index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_1055_16072
AIMS The objective of our study was to evaluate the role of mineral and bone metabolism disorders associated with chronic kidney disease (MBD-CKD) in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus (T1DM) of long duration. METHODS We investigated 96 patients with T1DM of long duration, with CKD at different stages (0-5), including patients on hemodialysis (HD) and with kidney transplantation (KT). Along with overall clinical examination, we assessed markers of MBD (calcium, phosphorus, parathormone, vitamin D, fibroblast growth factor (FGF) 23) and levels of cardiac injury marker (atrial natriuretic peptide, NT-proBNP). Multispiral computer tomography with Agatston index calculation was also included. RESULTS Decreased kidney function was associated with increased of levels phosphorus, parathormone, FGF 23, and vitamin D deficiency, with the highest deviation from the reference ranges seen in patients on HD with a very high risk of cardiovascular events. In KT patients with satisfactory graft function, these parameters were at the same levels as in patients with CKD stages 0-4. Progression of cardiovascular pathology was accompanied by elevation of NT-proBNP levels as CKD duration increased, decreased glomerular filtration rate, and were correlated with the main parameters of mineral homeostasis. The severity of coronary arteries calcification was associated with patient age and duration of T1DM and arterial hypertension. CONCLUSIONS Development and progression of kidney dysfunction is accompanied by MBD, a significant factor in progression of cardiac pathology, which remains a major cause of mortality in this patient population.
pubmed_1055_16072
pubmed_1052_1159
Spindle and kinetochore-associated protein 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. SKA1 is required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. Recently, SKA1 has been highlighted as a biomarker in some types of cancers, however, the precise role of SKA1 in gastric cancer remains unknown. In order to investigate the role of SKA1 in gastric cancer, the expression levels of SKA1 were analyzed in 56 gastric cancer samples and 54 non-neoplastic samples by immunohistochemistry, and we found SKA1 was significantly overexpressed in gastric cancer tissues. Moreover, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in the human gastric cancer cell line MGC80-3. Functional analysis indicated that SKA1 silencing significantly inhibited cell proliferation and colony formation, as determined by MTT and colony formation assays. The depletion of SKA1 in MGC80-3 cells also led to S phase cell cycle arrest. These results suggest that SKA1 could be used for gastric cancer early diagnosis as a biomarker. It is possible to enable a potential therapy based on targeting SKA1.
10.1007/s11010-014-1999-1
pubmed_143_23520
(R)-m-Nitrophenyl-1,2-ethanediol (m-NPED) is a versatile and highly value-added chiral building block for the synthesis of some bioactive compounds, such as (R)-Nifenalol. To efficiently produce (R)-m-NPED through the enantioconvergent hydrolysis of racemic (rac-) m-nitrostyrene oxide (m-NSO) using the whole resting cells of Escherichia coli/pCold-pveh2 intracellularly expressing PvEH2, an epoxide hydrolase from Phaseolus vulgaris, two reaction systems were investigated. In the Na2 HPO4 -NaH2 PO4 buffer (50 mmol l-1 , pH 7·0) system, merely 15 mmol l-1 rac-m-NSO was successfully subjected to enantioconvergent hydrolysis, producing (R)-m-NPED with 86·0% enantiomeric excess (eep ) and 177·6 mg l-1  h-1 space-time yield (STY). The experimental result indicated that there is inhibitory effect of rac-m-NSO at high concentration on PvEH2. To efficiently increase the concentration of rac-m-NSO and the STY of (R)-m-NPED, petroleum ether was first selected to construct an organic/aqueous two-phase system. Then, both the volume ratio (vo /vb ) of petroleum ether to phosphate buffer and the weight ratio (wc /ws ) of E. coli/pCold-pveh2 dry cells to rac-m-NSO were optimized as 2 : 8 and 5 : 1, respectively. In the optimized petroleum ether/phosphate buffer two-phase system, the enantioconvergent hydrolysis of rac-m-NSO at 40 mmol l-1 (6·6 mg ml-1 ) was carried out at 25°C for 12 h using 33·0 mg ml-1 vacuum freeze-dried cells of E. coli/pCold-pveh2, producing (R)-m-NPED with 87·4% eep , 82·3% yield and 502·4 mg l-1  h-1 STY. SIGNIFICANCE AND IMPACT OF THE STUDY: Epoxide hydrolases play a crucial role in producing enantiopure epoxides and/or vicinal diols. However, numerous biocatalytic reactions of organic compounds, such as epoxides, in aqueous phase suffered various restrictions. Herein, the enantioconvergent hydrolysis of rac-m-NSO in two reaction systems was investigated using the whole cells of Escherichia coli/pCold-pveh2. As a result, the concentration of rac-m-NSO and the space-time yield of (R)-m-NPED in organic/aqueous two-phase system were significantly increased, when compared with those in aqueous phase. To our knowledge, this is the first report about the production of (R)-m-NPED from rac-m-NSO at an elevated concentration by PvEH2 in the two-phase system.
10.1111/lam.13258
pubmed_382_11405
Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. The activities of pyrimethamine, trimethoprim, sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfamethoxazole, sulfamethazine, and sulfathiazole were examined against developing S. neurona merozoites in bovine turbinate cell cultures. A microtiter plate host cell lesion based assay was used to determine the effects of agents on developing merozoites. A cell culture flask assay was used to determine if selective concentrations of the agents killed or only inhibited development of S. neurona. Pyrimethamine was coccidiocidal at 1.0 microg/ml and trimethoprim was coccidiocidal at 5.0 microg/ml. None of the sulfonamides had activity when used alone at 50.0 or 100.0 microg/ml. Combinations of sulfonamides (5.0 or 10.0 microg/ml) with 0.1 microg/ml pyrimethamine demonstrated improved activity.
10.1016/s0304-4017(99)00020-5
pubmed_518_7275
We are developing synthetic polymers for pharmaceutical and medical applications. These applications can be broadly grouped on how the polymer will be utilized e.g. material, excipient or molecule. Our focus is to develop polymers with more defined structures that are based on biological, physicochemical and/or materials criteria. Strategies are being developed to more efficiently optimize structure-property correlations during preclinical development. We describe two examples of our research on pharmaceutical polymer development: narrow molecular weight distribution (MWD) homopolymeric precursors which can be functionalized to give families of narrow MWD homo- and co-polymers, and hydrolytically degradable polymers.
10.1211/0022357011776612
pubmed_250_636
The purpose of this study was to determine the effects of beta-alanine supplementation and high-intensity interval training (HIIT) on electromyographic fatigue threshold (EMG(FT)) and efficiency of electrical activity (EEA). A total of 46 men completed four, 2-min work bouts on a cycle ergometer. Using bipolar surface electrodes, the EMG amplitude was averaged and plotted over the 2-min. The resulting slopes were used to calculate EMG(FT) and EEA. Following initial testing, all participants were randomly assigned to either placebo (PL; n = 18), beta-alanine (BA; n = 18) or control groups (CON; n = 10). Following randomization, participants engaged in 6 weeks of HIIT training. Significant improvements in EMG(FT) and EEA resulted for both training groups. In conclusion, HIIT appeared to be the primary stimulus effecting EMG(FT) or EEA, suggesting adaptations from HIIT may be more influential than increasing skeletal muscle carnosine levels on delaying fatigue in recreationally active men.
10.1007/s00421-008-0911-7
pubmed_1051_24221
Fluorescence in situ hybridization analysis (FISH) using a CBFB breakapart probe is widely used to detect CBFB rearrangement (CBFBr) in cases of acute myeloid leukemia (AML). However, detection of 3'CBFB deletion (3'CBFBdel) often poses a challenge for interpretation, and the clinical importance of 3'CBFBdel associated CBFBr remains largely unknown. We identified 16 AML patients with 3'CBFBdel, 11 (69%) of which were confirmed to have CBFB::MYH11 fusion. These 11 patients presented with de novo AML; 10 showed myelomonocytic differentiation, 8 had a prominent eosinophilic component, and 7 showed characteristic eosinophils with basophilic granules. Next generation sequencing showed mutations in 7/8 patients, 5 with KRAS/NRAS, 3 with FLT3-TKD, but none with KIT mutations. Except for one patient who died 5 days after diagnosis of AML, all 10 patients received chemotherapy and achieved remission initially. However, within 3 years, 5 (50%) patients had relapsed, of whom, 1 died and 4 received hematopoietic stem cell transplant. After a median follow-up of 76 months, 3 patients died and 8 were alive in complete remission. Our study shows that detection of 3'CBFBdel is not equivalent to unbalanced CBFB rearrangement, and therefore, an alternative confirmatory test is warranted. AML with 3'CBFBdel/CBFBr often shows similar pathological features to AML with inv(16), but appears to have different mutation profiles and a higher risk of relapse requiring hematopoietic stem cell transplant.
10.1007/s00277-022-04767-1
pubmed_419_23480
BACKGROUND Various products are available for lightening hair. There are no data on which applications are actually used in hairdressing, impeding proper estimation of actual exposure and necessary preventive measures. OBJECTIVES To assess information about availability, usage and formulation of lightening preparations in the German hairdressing trade. METHODS A market survey was conducted and hairdressers were surveyed by online questionnaires. RESULTS Of 783 hairdressers clicking the link, 565 hairdressers (91.2% female, mean age of 40.2 ± 11.7 years) from all German states responded (response rate: 72.2%). The questionnaire survey has shown that available hair-lightening preparations in the German hairdressing trade are (multiple selection possible): dust-free (88.5%) and non-dust-free bleaching powders (22.1%), bleaching creams (41.9%), high-lifting hair colour creams (88.8%) and normal hair colour creams (58.4%). Five hundred eighteen (91.7%) hairdressers favour lightening hair with powder. The market survey revealed that bleaching powders and creams contain potassium persulfate, ammonium persulfate and sodium persulfate or combinations of these persulfate salts. CONCLUSIONS Hairdressers are exposed to various hair-lightening applications containing different chemicals. Preventive measures need to address adverse skin and respiratory effects. Implementation of targeted health education already in early career stages (i.e., apprenticeship) seems advisable and can be maintained by refresher trainings.
10.1111/cod.14242
pubmed_796_7404
The occurrence of re-expansion pulmonary oedema immediately after excision of a pleural histiocytoma is described.
10.1136/thx.44.8.682
pubmed_163_5786
The thoughts that come to mind when viewing a face depend partly on the face and partly on the viewer. This basic interaction raises the question of how much common ground there is in face-evoked thoughts, and how this compares to viewers' expectations. Previous analyses have focused on early perceptual stages of face processing. Here we take a more expansive approach that encompasses later associative stages. In Experiment 1 (free association), participants exhibited strong egocentric bias, greatly overestimating the extent to which other people's thoughts resembled their own. In Experiment 2, we show that viewers' familiarity with a face can be decoded from their face-evoked thoughts. In Experiment 3 (person association), participants reported who came to mind when viewing a face-a task that emphasises connections in a social network rather than nodes. Here again, viewers' estimates of common ground exceeded actual common ground by a large margin. We assume that a face elicits much the same thoughts in other people as it does in us, but that is a mistake. In this respect, we are more isolated than we think.
10.1016/j.cognition.2021.104955
pubmed_1053_16843
A second case of the unique lipid-rich cell thyroid adenoma is described complemented by detailed lipid analysis. New observations were made. The cytoplasm of the tumour cells contained scattered, aggregated sudanophil crystals; under polarized light the frozen, unstained sections exhibited numerous birefringent lipid crystals; electron microscopy provided further evidence that the clear cell appearance was due to intracellular lipid droplets with scanty glycogen particles. Comparative lipid analysis by thin layer chromatography and high-pressure liquid chromatography (HPLC) revealed quantitative and qualitative differences in lipid composition of tumour cells when compared with goitre cells from normal thyroid gland and subcutane fat. Qualitative differences in triglyceride composition (by HPLC) between tumour cells and subcutaneous fat indicated that the fat accumulation in the follicle cells was not a result of simple storage, but an expression of altered intracellular lipid metabolism.
10.1007/BF01600145
pubmed_512_3287
BACKGROUND In recent years, meters for continuous monitoring of interstitial fluid glucose have been introduced to help people with type 1 diabetes mellitus (T1DM) to achieve better control of their disease. OBJECTIVE The objective of this project was to summarise the evidence on the clinical effectiveness and cost-effectiveness of the MiniMed(®) Paradigm™ Veo system (Medtronic Inc., Northridge, CA, USA) and the Vibe™ (Animas(®) Corporation, West Chester, PA, USA) and G4(®) PLATINUM CGM (continuous glucose monitoring) system (Dexcom Inc., San Diego, CA, USA) in comparison with multiple daily insulin injections (MDIs) or continuous subcutaneous insulin infusion (CSII), both with either self-monitoring of blood glucose (SMBG) or CGM, for the management of T1DM in adults and children. DATA SOURCES A systematic review was conducted in accordance with the principles of the Centre for Reviews and Dissemination guidance and the National Institute for Health and Care Excellence Diagnostic Assessment Programme manual. We searched 14 databases, three trial registries and two conference proceedings from study inception up to September 2014. In addition, reference lists of relevant systematic reviews were checked. In the absence of randomised controlled trials directly comparing Veo or an integrated CSII + CGM system, such as Vibe, with comparator interventions, indirect treatment comparisons were performed if possible. METHODS A commercially available cost-effectiveness model, the IMS Centre for Outcomes Research and Effectiveness diabetes model version 8.5 (IMS Health, Danbury, CT, USA), was used for this assessment. This model is an internet-based, interactive simulation model that predicts the long-term health outcomes and costs associated with the management of T1DM and type 2 diabetes. The model consists of 15 submodels designed to simulate diabetes-related complications, non-specific mortality and costs over time. As the model simulates individual patients over time, it updates risk factors and complications to account for disease progression. RESULTS Fifty-four publications resulting from 19 studies were included in the review. Overall, the evidence suggests that the Veo system reduces hypoglycaemic events more than other treatments, without any differences in other outcomes, including glycated haemoglobin (HbA1c) levels. We also found significant results in favour of the integrated CSII + CGM system over MDIs with SMBG with regard to HbA1c levels and quality of life. However, the evidence base was poor. The quality of the included studies was generally low, often with only one study comparing treatments in a specific population at a specific follow-up time. In particular, there was only one study comparing Veo with an integrated CSII + CGM system and only one study comparing Veo with a CSII + SMBG system in a mixed population. Cost-effectiveness analyses indicated that MDI + SMBG is the option most likely to be cost-effective, given the current threshold of £30,000 per quality-adjusted life-year gained, whereas integrated CSII + CGM systems and Veo are dominated and extendedly dominated, respectively, by stand-alone, non-integrated CSII with CGM. Scenario analyses did not alter these conclusions. No cost-effectiveness modelling was conducted for children or pregnant women. CONCLUSIONS The Veo system does appear to be better than the other systems considered at reducing hypoglycaemic events. However, in adults, it is unlikely to be cost-effective. Integrated systems are also generally unlikely to be cost-effective given that stand-alone systems are cheaper and, possibly, no less effective. However, evidence in this regard is generally lacking, in particular for children. Future trials in specific child, adolescent and adult populations should include longer term follow-up and ratings on the European Quality of Life-5 Dimensions scale at various time points with a view to informing improved cost-effectiveness modelling. STUDY REGISTRATION PROSPERO Registration Number CRD42014013764. FUNDING The National Institute for Health Research Health Technology Assessment programme.
10.3310/hta20170
pubmed_78_23730
Dose-escalated chemotherapy has proven utility in a variety of treatment settings, including preparative regimens before bone marrow or hematopoietic stem cell transplantation. However, the potential damage imposed by aggressive regimens on the marrow microenvironment warrants further investigation. In the present study, we tested the hypothesis that dose-escalated chemotherapy, with etoposide as a model chemotherapeutic agent, activates the transforming growth factor beta-1 (TGF-beta1) signaling pathway in bone marrow stromal cells. After high-dose etoposide exposure in vitro, Smad3 protein was phosphorylated in a time-and dose-dependent manner in marrow-derived stromal cells, coincident with the release of active and latent TGF-beta1 from the extracellular matrix. Phosphorylation was modulated by p38 kinase, with translocation of Smad3 from the cytoplasm to the nucleus subsequent to its phosphorylation. Etoposide induced activation of TGF-beta1 followed the generation of reactive oxygen species and required matrix metalloproteinase-2 (MMP-2) protein availability. Chemotherapy effects were diminished in MMP-2(-/-) knockout stromal cells and TGF-beta1 knockdown small interfering RNA-transfected stromal cells, in which phosphorylation of Smad3 was negligible after etoposide exposure. Stable transfection of a human MMP-2 cDNA into bone marrow stromal cells resulted in elevated phosphorylation of Smad3 during chemotherapy. These data suggest TGF-beta1/p38/Smad3 signaling cascades are activated in bone marrow stromal cells after dose-escalated chemotherapy and may contribute to chemotherapy-induced alterations of the marrow microenvironment.
10.1634/stemcells.2004-0354
pubmed_1037_14967
OBJECTIVES To determine the incidence and predictive factors of acute kidney injury (AKI) after off-pump lung transplantation. DESIGN A retrospective cohort study. SETTING The operating room and intensive care unit. PARTICIPANTS Adult patients who underwent lung transplant without cardiopulmonary bypass or extracorporeal membrane oxygenator between 2006 and 2016 at the Vanderbilt University Medical Center. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The presence of postoperative AKI was assessed by the Kidney Disease: Improving Global Outcomes criteria in the first seven postoperative days. Multivariate logistic regression analysis was used to determine the independent predictive factors of AKI. One hundred forty-eight patients were included in the final analysis, of whom 63 (42.6%) subsequently developed AKI: 43 (29.0%) stage 1, ten (6.8%) stage 2, and ten (6.8%) stage 3. Patients who had AKI had a longer hospital length of stay (12 days [interquartile range (IQR): 10-17] vs ten days [IQR: 8-12], p < 0.001). For every one-year increase in age, the odds of AKI decreased by 8% (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.87-0.98, p = 0.008). The odds of having AKI in patients with bilateral lung transplant was lower than patients with unilateral transplant (OR 0.09, 95% CI: 0.01-0.63, p = 0.015). Additionally, a diagnosis of chronic obstructive pulmonary disease increased the odds of AKI by four-fold compared with a diagnosis of idiopathic pulmonary fibrosis (OR 4.73, 95% CI: 1.44-15.56, p = 0.011). CONCLUSIONS AKI is a common complication after off-pump lung transplantation and is associated with increased hospital length of stay. Younger age, unilateral lung transplant, and diagnosis of chronic obstructive pulmonary disease are independently associated with AKI.
10.1053/j.jvca.2021.09.021
pubmed_121_12561
PURPOSE To evaluate whether or not continuous positive airway pressure (CPAP) treatment in pregnancies complicated by obstructive sleep apnea (OSA) is associated with a decrease in hypertensive disorders of pregnancy. METHODS This was a retrospective cohort study of perinatal outcomes in women who underwent objective OSA testing and treatment as part of routine clinical care during pregnancy. Where diagnostic criteria for OSA were reached (respiratory event index (REI) ≥ 5 events per hour), patients were offered CPAP therapy. Obstetrical outcomes were compared between the control group (no OSA), the group with untreated OSA (OSA diagnosed, not CPAP compliant), and the group with treated OSA (OSA diagnosed and CPAP compliant), with CPAP compliance defined as CPAP use ≥ 4 h, 70% of the time or greater. A composite hypertension outcome combined diagnoses of gestational hypertension (gHTN) and preeclampsia (PreE) of any severity. RESULTS The study comprised outcomes from 177 completed pregnancies. Our cohort was characterized by obesity, with average body mass indices > 35 kg/m2, and average maternal age > 30 years old. CPAP was initiated at an average gestational age of 23 weeks (12.1-35.3 weeks), and average CPAP use was 5.9 h (4-8.5 h). The composite hypertension outcome occurred in 43% of those without OSA (N = 77), 64% of those with untreated OSA (N = 77), and 57% of those with treated OSA, compliant with CPAP (N = 23) (p = 0.034). CONCLUSION Real-world data in this small study suggest that CPAP therapy may modulate the increased risk of hypertensive complications in pregnancies complicated by OSA.
10.1007/s11325-022-02669-0
pubmed_1003_3185
In the present study, electrophysiological recordings were made from hippocampal slices obtained from mice overexpressing galanin under the promoter for the platelet-derived growth factor-B (GalOE mice). In these mice, a particularly strong galanin expression is seen in the granule cell layer/mossy fibers. Paired-pulse facilitation (PPF) of excitatory postsynaptic field potentials (fEPSPs) at the lateral perforant path (LPP)-dentate gyrus synapses was elicited in the dentate gyrus after stimulation with different interpulse intervals. Slices from young adult wild-type (WT) animals showed significant PPF of the 2nd EPSP evoked with paired-pulse stimuli, while PPF was reduced in slices from young adult GalOE mice, as well as aged WT mice, but were not observed at all in slices from aged GalOE animals. Application of the putative galanin antagonist M35 increased PPF in slices from aged WT mice as well as from adult and aged GalOE mice, but had no effect in slices taken from young adult WT mice. These data indicate that galanin is involved in hippocampal synaptic plasticity, in particular in age-related reduction of synaptic plasticity in the LPP input to the dentate gyrus. Galaninergic mechanisms may therefore represent therapeutic targets for treatment of age-related memory deficits and Alzheimer's disease.
10.1016/j.npep.2005.02.005
pubmed_258_26257
BACKGROUND The correlation between intraocular pressure (IOP) and the magnetic resonance imaging (MRI) parameters in thyroid-associated ophthalmopathy (TAO) patients was explored. METHODS This study included 82 eyes in 41 TAO patients who had a large difference in the IOP between each eye. We measured the T2 relaxation time (T2RT) of the extraocular muscles (EOMs), the orbital fat, and the area of the EOMs. RESULTS There was a positive correlation between IOP and exophthalmos, the clinical activity score (CAS), the T2RT (of the medial rectus (MR)), the area of the MR, inferior rectus (IR) and lateral rectus, and the mean area. We established a regression model with IOP as the dependent variable, and the area of the IR was statistically significant. CONCLUSIONS High IOP in TAO patients was positively correlated with the degree of exophthalmos and EOM inflammation (especially the inferior rectus). The state of the EOMs in an orbital MRI may partially explain high IOP and provide the necessary clinical information for subsequent high IOP treatment.
10.3390/jcm11143981
pubmed_777_3630
This phase II study evaluated the efficacy and safety of combination chemotherapy with paclitaxel, cisplatin, and 5-fluorouracil (5-FU) in advanced gastric cancer. Patients with histologically confirmed gastric adenocarcinoma were eligible for the study. Paclitaxel (175 mg/m(2)) and cisplatin (75 mg/m(2)) were given as a 1-hr intravenous infusion on day 1, followed by 5-FU (750 mg/m(2)) as a 24-hr continuous infusion for 5 days. This cycle was repeated every 3 weeks. Forty-five eligible patients (median age, 56 yr) were treated in this way. Of the 41 patients in whom efficacy was evaluable, an objective response rate (ORR) was seen in 51.2% (95% CI, 0.35-0.67), a complete response in two, and a partial response in 19 patients. The median progression free survival was 6.9 months (95% CI, 5.86-7.94 months), and the median overall survival was 12.7 months (95% CI, 9.9-15.5). The main hematological toxicity was neutropenia and greater than grade 3 neutropenia was observed in twelve patients (54%). Febrile neutropenia developed in three patients (6.8%). The major non-hematological toxicities were asthenia and peripheral neuropathy, but most of patients showed grade 1 or 2. In conclusion, combination chemotherapy with paclitaxel, cisplatin, and 5-FU is a promising regimen, and was well tolerated in patients with advanced gastric cancer.
10.3346/jkms.2008.23.4.586
pubmed_978_6528
The prevalence of primary repeat cesareans in the 37th and 38th weeks of gestation and the highest rate of premature births explain the shorter duration of pregnancy associated with this mode of delivery. In cases where ecbolics were administered labour was prolonged and the rate of secondary repeat cesareans was higher. Late rupture of the amniotic sac seems to increase the chances of successful vaginal delivery. Biparietal cranial diameter had no influence on the mode of delivery; significantly higher values were found only in cases of cranial-pelvic incongruity. The frequency of primary repeat cesareans increased in proportion to the age of the mother. The time interval since the previous cesarean delivery is of no importance. Birth weights were lower in the group of elective repeat cesareans owing to lower gestational age. It does not always appear justified to rule out a vaginal birth in cases of twins. Regional anesthesia is not a contraindication.
pubmed_978_6528
pubmed_496_4350
Neuroendocrine tumors of the intestinal tract have low malignant potential but can result in decreased survival if they spread to the liver. The estimated 5-year survival of patients with liver metastases from neuroendocrine tumor is only 20%. Further, morbidity related to the Carcinoid Syndrome and other endocrine symptoms may also greatly reduce the quality of life. Treatment options for liver neuroendocrine tumor include long-acting somatostatin receptor antagonists (LAR), inteferon-alpha, chemotherapy and hepatic artery embolisation with and without chemotherapy. Surgical resection is feasible in select patients, but it may result in major morbidity and even mortality. In our series of 18 patients with liver neuroendocrine tumors, there was no operative mortality and acceptable morbidity. All 10 patients with the Carcinoid syndrome had complete amelioration of symptoms and the 5-year actuarial survival was 80%. Aggressive major surgery for liver neuroendocrine tumor metastases can be performed safely with acceptable mortality by experienced surgeons. Results have been similar for patients with gastrinoma and pancreatic neuroendocrine tumors. Surgical resection appears to result in outstanding long-term survival and amelioration of symptoms. It should be the first-line therapy for patients with liver neuroendocrine tumors in whom the tumor can be completely removed.
10.1016/j.bpg.2005.04.003
pubmed_444_634
OBJECTIVE In 2008, integrated thoracic residency programs (IP) for cardiothoracic (CT) training were created in response to a decline in CT trainees. However, few studies have reported on trends in the CT training pathway since the inception of IPs. This manuscript examines the current trends related to the overall number of surgical trainees entering CT surgery training following the introduction of IPs into the National Resident Match Program (NRMP). DESIGN Main and specialty match data were gathered from NRMP annual reports between 2008 and 2018. Descriptive statistics were used to analyze program size, applications, and filled and unfilled positions for IPs and traditional CT residency programs. Pearson's correlation coefficient was used to determine associations between program variables. SETTING NRMP main and specialty match in 2008 to 2018. PARTICIPANTS Participants of the NRMP main and specialty match in 2008 to 2018. RESULTS IPs increased from 2 programs offering 3 positions in 2008 to 28 programs offering 36 positions in 2018. However, during the same time period, the number of available traditional CT residency positions have decreased by 29% (130 to 92). As the number of IPs increased, there was a significant decrease in the number of traditional CT residency positions (ρ = -0.95, p < 0.001). Although, the overall number of CT residency programs (traditional and IP) remained largely unchanged, the proportion of filled CT residency positions increased from 67.7% in 2008 up to 97.7% in 2018. CONCLUSION The IP training format has shown success in increasing the number of trainees entering into CT training programs. Consideration should be given to increasing the number of IP positions or increase interest in CT among general surgery residents to increase the number of CT surgery trainees with the goal of increasing the size of the future CT workforce.
10.1016/j.jsurg.2020.08.008
pubmed_836_6778
Twenty-five patients with pituitary lesions were operated on by image-guided transsphenoidal surgery (TSS) using the Mehrkoordinaten Manipulator (MKM) navigation system. The cases included 21 cases of pituitary adenomas, 2 cases of craniopharyngioma and 2 cases of Rathke's cleft cyst. All operations were performed through the sublabial approach under an operative microscope. In some cases, an endoscope was used for the observation of the residual tumor and surrounding structures. The tumors and surrounding important structures such as the internal carotid arteries, the basilar artery, and the optic nerves were precisely localized, and mechanical error was less than 2 mm in almost all cases. In 3 early cases of pituitary adenoma, the patient's head was moved slightly during the insertion of the nasal speculum; in these cases, the resulting error was more than 2 mm. In evaluating the procedures, we determined that the most useful benefit of the MKM system compared with other systems is that the navigation information is not only displayed on the monitor, but also presented in the operative field under the microscope. Therefore, the surgeon can obtain the navigation information without removing his eyes from the operative field under the microscope. The most important drawback to the system is its bulky size.
10.1055/s-2003-39340
pubmed_1008_2456
We studied 40 infertile couples in whom cervical hostility was the only known cause of infertility, and 18 fertile women. IgA, IgG and IgM together with alpha-2-macroglobulin and albumin were measured in the cervicovaginal secretions and serum using the Mancini radial diffusion technique. IgA and IgG were present in the cervicovaginal secretions of all the women and the concentrations found did not differ significantly in the two groups. Levels of IgM were significantly higher in the infertile group. The ratio of protein levels in cervicovaginal fluid to serum levels were calculated using the formulae of Donovan et al (1970). Locally-produced IgA, IgG and IgM were found in more of the infertile women and in greater amounts than in the fertile women. Class specific anti-immunoglobulin antibodies conjugated to inert particles were used to selectively remove specific classes of immunoglobulin from the cervicovaginal secretions. Removal of a particular immunoglobulin class or all three resulted in less inhibition than either IgG or IgM. In infertile women with locally produced IgA and IgG, there was greater inhibition of sperm migration than in those women who lacked locally produced immunoglobulins.
10.1111/j.1471-0528.1980.tb04427.x
pubmed_720_11949
The aim of the present study was to analyze lung adenocarcinoma-associated microarray data and identify potentially crucial genes. The gene expression profiles were downloaded from the Gene Expression Omnibus database and 6 datasets, of which 2 were discarded and 4 were retained, were preprocessed using packages in the R computing language. Subsequently, Gene Set Enrichment Analysis (GSEA) and meta-analysis was used to screen the common pathways and differentially expressed genes at the transcriptional level. The genes detected from GSEA through The Cancer Genome Atlas databases were subsequently examined, and the crucial genes by survival data were identified. Pathways of the crucial genes were obtained using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the online website Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, and the pathways of crucial genes that were upregulated or downregulated were matched using the Venn method to identify the common crucial pathways. Furthermore, on the basis of the common crucial pathways, key genes that are closely associated with the development and progression of lung adenocarcinoma were identified with the KEGG pathway of DAVID. Additional information was obtained through Gene Ontology annotation. A total of two key pathways, including cell cycle and DNA replication, as well as 12 key genes [DNA polymerase δ subunit 2, DNA replication licensing factor MCM4, MCM6, mitotic checkpoint serine/threonine-protein kinase BUB1, BUB1β, mitotic spindle assembly checkpoint protein MAD2A, dual specificity protein kinase TTK, M-phase inducer phosphatase 1, cell division control protein 45 homolog, cyclin-dependent kinase inhibitor 1C, pituitary tumor-transforming gene 1 protein and polo-like kinase 1] were identified. These key pathways and genes may be studied in future studies involving gene transfection/knockdown, which may provide insights into the prognosis of lung adenocarcinoma. Additional studies are required to confirm their biological function.
10.3892/ol.2019.10236
pubmed_714_12369
Detection of fetal scalp cysts may pose diagnostic challenges in terms of differentiating between structures whose origin is ectodermal, so presumed benign, and neuroectodermal, potentially having neurological significance. We describe the first case of a fetal scalp dermoid cyst to be detected antenatally and discuss the concept of sequested meningoceles which may not have neurological consequence but can be associated with other structural abnormalities.
10.1002/(sici)1097-0223(199912)19:12<1157::aid-pd711>3.0.co;2-1
pubmed_574_17257
We newly synthesized a pivaloyloxymethyl ester of ofloxacin (OFLX-PVM) as prodrug in order to avoid the chelate formation between new quinolone and metal cations such as Al3+, Mg2+, Ca2+, or Fe2+ in the gastrointestinal tract. This compound was rapidly hydrolyzed in an incubation experiment by 43% in plasma, by 92% in small intestinal mucosal homogenates, and by 97% in liver homogenates during 0.5 h incubation, but was resistant to hydrolysis by pancreatic enzymes. In everted gut sac experiments, this compound was efficiently absorbed even in the presence of aluminium ion, whereas the absorption of ofloxacin (OFLX) was decreased significantly by the presence of aluminium ion. Minimal inhibitory concentration (MIC) values of OFLX-PVM were far higher than OFLX. Effects of aluminium hydroxide on the oral bioavailability of OFLX and OFLX-PVM were investigated in rabbits. The area under the plasma concentration-versus-time curve from zero to 24 h (AUC0-24h) following oral administration of OFLX was decreased significantly by 47.6% by combined administration with aluminium hydroxide, but AUC0-24h values of OFLX-PVM coadministered with and without aluminium hydroxide were similar to that of OFLX alone. These observations indicate that this new compound is likely to offer a prodrug for avoidance of interaction between new quinolone and metal cations.
10.1248/bpb.16.594
pubmed_661_15542
There are few studies of the breakdown of language in specific dementias and there is some dispute that language pathology in brain failure is comparable to that of focal lesions. It is recognized that while aphasic language is a disturbance of receptive and propositional speech, disturbances of "InnerLanguage" disrupt the planning and regulatory basis of behavior. This paper presents a comparison of three pathological groups to match normal controls and suggest that in its initial stages reduced cognitive performances in Alzheimers type Dementia and Korsakow Psychosis on non verbal measures maybe a further of the regulatory role of inner speech comparison with traumatic Aphasia which more clearly exists on a deficit of verbal comprehension and expression.
pubmed_661_15542
pubmed_1046_15048
PURPOSE Chimeric antigen receptor (CAR) T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete Tregs, these regimens are nonspecific, toxic, and provide only a narrow window before Tregs repopulate hosts. Importantly, CARs have also been shown to inadvertently potentiate Tregs by providing a source of IL2 for Treg consumption. We explored whether disruption of the IL2 axis would confer efficacy against solid tumors without the need for lymphodepletion. EXPERIMENTAL DESIGN We developed second- (CD28z) and third- (CD28-4-1BBz) generation CARs targeting EGFRvIII. To eliminate secretion of IL2, 2 amino acid substitutions were introduced in the PYAP Lck-binding motif of the CD28 domain (ΔCD28). We evaluated CARs against B16 melanomas expressing EGFRvIII. RESULTS CD28z CARs failed to engraft in vivo. Although 4-1BB addition improved expansion, CD28-4-1BBz CARs required lymphodepletion to treat solid tumors. CARs deficient in Lck signaling, however, significantly retarded tumor growth without a need for lymphodepletion and this was dependent on inclusion of 4-1BB. To evaluate CAR vulnerability to Tregs, we lymphodepleted mice and transferred CARs alone or with purified Tregs. Cotransfer with Tregs abrogated the efficacy of CD28-4-1BBz CARs, whereas the efficacy of ΔCD28-4-1BBz CARs remained unperturbed. CONCLUSIONS In the absence of lymphodepletion, CARs targeting solid tumors are hindered by Treg immunosuppression and poor persistence. Here, CARs were modified to circumvent Treg suppression and to simultaneously improve in vivo engraftment. Modified CARs treated solid tumors without a need for lymphodepletion.
10.1158/1078-0432.CCR-18-1211
pubmed_958_14908
Through the use of their hands, their intelligence, and their compassion, midwives have traditionally taken a noninterventionist approach to labor and childbirth. Therapeutic Tough, known by its practitioners as simply TT, is a contemporary healing modality through which a practitioner's hands are used to facilitate healing. Midwives and practitioners of TT share an appreciation of the value of a holistic and noninterventionist approach to maintaining patient health. This article explores the potential use of TT as a tool to complement the practice of midwifery. It provides an explanation of the theories underlying TT, the history of its development, and the process involved in its practice. Additionally, the results of studies both supportive and critical of the practice of TT are analyzed. Finally, possible applications of TT to the practice of midwifery are suggested.
10.1016/s0091-2182(99)00039-7
pubmed_596_14302
BACKGROUND AND PURPOSE The present study aimed to devise a simple scale to predict very poor outcome after tissue plasminogen activator (t-PA) therapy using clinical and MRI factors. METHODS Consecutive stroke patients treated with t-PA within 3 h of onset were studied prospectively. Clinical factors and MRI findings independently associated with very poor outcome (modified Rankin Scale score 4-6) at 3 months after t-PA therapy were assessed. RESULTS The subjects were 117 patients. Multivariate logistic regression analysis revealed the following independent factors associated with very poor outcome: time from stroke onset to treatment ≥140 min (OR 2.790, 95% CI 1.082-7.193; p = 0.0337), baseline National Institutes of Health Stroke Scale score ≥20 (OR 3.794, 95% CI 1.199-12.009; p = 0.0233), glucose ≥180 mg/dl (OR 3.288, 95% CI 1.126-9.600; p = 0.0295), internal carotid artery occlusion (OR 6.187, 95% CI 5.090-18.354; p = 0.0129) and M1 susceptibility vessel sign (OR 6.379, 95% CI 1.194-34.074; p = 0.030). Those 5 variables were selected in the scale, with each factor as 1 point. Frequencies of patients with a very poor outcome for each score were as follows: score 0, 26.3%; score 1, 30.6%; score 2, 70.0%, and score 3-5, 100%. CONCLUSION A clinical scale using clinical and MRI factors can predict very poor outcome in t-PA patients.
10.1159/000327690
pubmed_293_12556
BACKGROUND The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover. OBJECTIVE To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses. METHODS The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II-IV patients with QRS >120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality. RESULTS Among 41 patients enrolled (aged 64 ± 13 years, 38% female, LVEF 28%, QRS 168 ± 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n = 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 ± 22 ms vs 164 ± 25 ms [TR], P < .001;124 ± 19 ms vs 162 ± 24 ms [PP], P < .001). A trend toward higher echocardiographic response was also observed (80 vs 57% [TR], P = .14; 91% vs 54% [PP], P = .078). No significant differences in CV hospitalization or mortality were observed. CONCLUSIONS Patients receiving His-CRT on-treatment demonstrated superior electrical resynchronization and a trend toward higher echocardiographic response than BiV-CRT. Larger prospective studies may be justifiable with refinements in patient selection and implantation techniques to minimize crossovers.
10.1016/j.hrthm.2019.05.009
pubmed_377_17457
When grown in green light, Fremyella diplosiphon strain UTEX 481 produces the red-colored protein phycoerythrin (PE) to maximize photosynthetic light harvesting. PE is composed of two subunits, CpeA and CpeB, which carry two and three phycoerythrobilin (PEB) chromophores, respectively, that are attached to specific Cys residues via thioether linkages. Specific bilin lyases are hypothesized to catalyze each PEB ligation. Using a heterologous, coexpression system in Escherichia coli, the PEB ligation activities of putative lyase subunits CpeY, CpeZ, and CpeS were tested on the CpeA and CpeB subunits from F. diplosiphon. Purified His(6)-tagged CpeA, obtained by coexpressing cpeA, cpeYZ, and the genes for PEB synthesis, had absorbance and fluorescence emission maxima at 566 and 574 nm, respectively. CpeY alone, but not CpeZ, could ligate PEB to CpeA, but the yield of CpeA-PEB was lower than achieved with CpeY and CpeZ together. Studies with site-specific variants of CpeA(C82S and C139S), together with mass spectrometric analysis of trypsin-digested CpeA-PEB, revealed that CpeY/CpeZ attached PEB at Cys(82) of CpeA. The CpeS bilin lyase ligated PEB at both Cys(82) and Cys(139) of CpeA but very inefficiently; the yield of PEB ligated at Cys(82) was much lower than observed with CpeY or CpeY/CpeZ. However, CpeS efficiently attached PEB to Cys(80) of CpeB but neither CpeY, CpeZ, nor CpeY/CpeZ could ligate PEB to CpeB.
10.1074/jbc.M111.284281
pubmed_289_23934
Histopathological interpretation of semimembranosus muscle samples from an adult Warmblood mare with clinical signs suggestive of exertional rhabdomyolysis and intermittent mild elevations in muscle enzyme activities revealed abundant sarcoplasmic vacuoles in all fibre-types containing fine, apparently proteinaceous debris. Vacuolar contents stained lightly with PAS, but did not appear to contain amylopectate, lipid or acid phosphatase and their periphery was unstained with dystrophin immunohistochemistry. Electron microscopy revealed that vacuoles were not membrane bound. No vacuoles were detected in muscle samples evaluated at post mortem following 4 months of rest. To our knowledge, this is the first report of a presumed primary vacuolar myopathy in a horse.
pubmed_289_23934
pubmed_291_11703
In a randomised, cross-over study, we compared the use of the Airtraq , Airway Scope and Macintosh laryngoscopes by paramedics for tracheal intubation in three simulated prehospital scenarios. Fifty-four paramedics were invited to take part. When evaluated in a difficult airway manikin, median IQR [range] time to intubation with the Airtraq (21 (16-37 [6-80] s) and Airway Scope (16 (5-75 [12-23] s) was shorter than that with the Macintosh laryngoscope (39 (25-54 [7-120] s; p < 0.0001). The success rate within 30 s was greater with the Airtraq (61%) and Airway Scope (93%) than with the Macintosh laryngoscope (22%; p < 0.0001). When used for a standard intubation and in the sitting position, we found minimal differences among the three laryngoscopes. We conclude that the Airway Scope and Airtraq have significant advantages over the Macintosh laryngoscope and that of the two, the Airway Scope is the more effective device to use in the prehospital environment.
10.1111/j.1365-2044.2010.06514.x
pubmed_574_15710
This article examines the influence that attributions of personal responsibility for infection with the human immunodeficiency virus have on service and policy responses to the epidemic. A model of attributed responsibility is proposed that classifies social judgments of another person's behavior that take into account the extent to which the behavior caused the situation, the person knew or should have known the potential consequences of the behavior, the person intended to engage in the behavior, and factors over which the person had little or no control might have influenced the behavior. Research has shown that attributions of responsibility lead to increased anger, decreased empathy, and a diminished willingness to offer help to others in need. The author concludes that awareness of attributions of responsibility may help reduce their discriminatory effects at all levels of social work practice.
pubmed_574_15710
pubmed_140_16013
OBJECTIVE Introduction: One of the most important indicators of the professional training of future dentists, their competitiveness is the development of professional interaction. The aim of the article is to update the content of the training of future dentists to engage in professional interaction. PATIENTS AND METHODS Materials and methods: The study, completed during 2015-2018, was attended by 292 students of the specialty "Stomatology". The research uses the following methods: theoretical - analysis, synthesis, systematization and synthesis of scientific literature; empirical - testing, survey, monitoring, pedagogical experiment to find out the effectiveness of the developed content of training future dentists; methods of mathematical statistics. RESULTS Results and conclusions: For realization of the research purpose it was specially developed a discipline "Professional interaction of dentists" which is aimed at the realization of the tasks: the acquisition of future dentists theoretical knowledge on problems of communication and interaction; increasing the need for communication, implementing a variety of interactions; the formation of future dentists readiness for the implementation of professional interaction, positive communicative attitude to team interaction and receiving satisfaction from it. The program results of the study of the indicated discipline are presented, content of its modules is disclosed. Interactive forms which are used in the process of training future dentists (trainings, business games, problem situations, etc.) and teaching methods (dialogue-discussion, polygon, brainstorming, method of ideas generation, situational dialogues, etc.) are described. The components of future dentist's readiness for professional interaction are developed: motivational, cognitive, operational and personal. The results of the pedagogical experiment, which proved the effectiveness of the implementation of the special course "Professional Interaction of Dentists», are presented. Statistical analysis of the results of the study made it possible to establish that after studying the special course in the experimental group there was a noticeable significant increase in the number of students assigned to the high level, in addition, the number of future dentists with a low level was significantly reduced.
pubmed_140_16013
pubmed_48_19396
BACKGROUND Gastric neuroendocrine neoplasms (G-NENs) are uncommon, and data on their management is limited. We here investigated the clinicopathological characteristics, surgical and survival outcomes in G-NENs among Chinese. Moreover, we will discuss their prognostic value. METHODS From existing databases of the West China Hospital, we retrospectively identified 135 consecutive patients who were surgically treated and pathologically diagnosed as G-NENs from January 2009 to August 2015. RESULTS This entire cohort comprised 98 males and 37 females, with a median age of 60 years. Twenty-five patients underwent endoscopic resection, while 110 patients underwent open/laparoscopic surgery. Thirty-nine patients had neuroendocrine tumor G1 (NET G1), seven patients had neuroendocrine tumor G2 (NET G2), 69 patients had neuroendocrine carcinoma G3 (NEC G3) and 20 patients had mixed adenoneuroendocrine carcinoma (MANEC). The median survival was not achieved for both NET G1 and NET G2 versus 19 months (range 3-48) for NEC G3 and 10.5 months (range 3-45) for MANEC. The 3-year survival rates for stage I, II, III, and IV were 91.1 %, 78.6 %, 51.1 % and 11.8 %, respectively (P < 0.001). As for the prognostic analysis, both surgical margin and the newly updated World Health Organization (WHO) classification were independent predictors of overall survival (OS). CONCLUSIONS G-NENs are a kind of rare tumors, and patients with NET G3 and MANEC have unfavorable prognosis even surgically treated. Moreover, surgical margin and the new 2010 WHO criteria are closely associated with OS for G-NENs.
10.1186/s12876-016-0505-5
pubmed_498_8335
In many scientific fields, there is an interest in understanding the way in which chemical networks evolve. The chemical networks which researchers focus upon have become increasingly complex, and this has motivated the development of automated methods for exploring chemical reactivity or conformational change in a "black-box" manner, harnessing modern computing resources to automate mechanism discovery. In this work, we present a new approach to automated mechanism generation which couples molecular dynamics and statistical rate theory to automatically find kinetically important reactions and then solve the time evolution of the species in the evolving network. The key to this chemical network mapping through combined dynamics and ME simulation approach is the concept of "kinetic convergence", whereby the search for new reactions is constrained to those species which are kinetically favorable at the conditions of interest. We demonstrate the capability of the new approach for two systems, a well-studied combustion system and a multiple oxygen addition system relevant to atmospheric aerosol formation.
10.1021/acs.jctc.1c00335
pubmed_637_21068
We studied the fate and toxicity of two types of CeO2 NPs (bare or citrate-coated) in environmentally relevant conditions, using large indoor microcosms. Long-term exposure was carried out on a three-leveled freshwater trophic chain, comprising microbial communities as primary producers, chironomid larvae as primary consumers, and amphibian larvae as secondary consumers. Whereas coated NPs preferentially sedimented, bare NPs were mainly found in the water column. However, mass balance indicated low recovery (51.5%) for bare NPs, indicating possible NP loss, against 98.8% of recovery for coated NPs. NPs were rather chemically stable, with less than 4% of dissolution. Chironomid larvae ingested large amounts of NPs and were vectors of contamination for amphibian larvae. Although bioaccumulation in amphibian larvae was important (9.47 and 9.74 mg/kg for bare and coated NPs, respectively), no biomagnification occurred through the trophic chain. Finally, significant genotoxicity was observed in amphibian larvae, bare CeO2 NPs being more toxic than citrate-coated NPs. ᅟ.
10.1007/s11356-017-9346-1
pubmed_154_7134
The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light. In particular, two major issues have seen considerable progress in the past decade. First, the pathways that provide visceral sensation to conscious perception at a cortical level have been elucidated in both animals and humans. The nociceptive system runs in parallel to the pathways carrying visceral sensation from the cranial nerves and may be considered in itself a component of visceral sensation. Second, structures in the central nervous system that generate patterns of autonomic response have been identified. These pattern generators are located at multiple levels of the central nervous system, and they can be combined in temporal and spatial patterns to subserve a wide range of behavioral needs.
10.1146/annurev.neuro.25.032502.111311
pubmed_1043_2794
Between 1968 and 1975, the authors studied at the Institut Curie the value of fine needle aspiration cytology in the follow-up of breast cancers, which have been previously treated with definitive irradiation (182 cases) or lumpectomy and post-operative irradiation (20 cases). The cytologic results have been compared to the pathologic aspects of the surgical specimens. The cytologic procedure was made when the tumor decrease was incomplete or too slow, or when, after a free interval, was noted in the irradiated breast a tissue reaction clinically and radiologically indefinite. The post-therapeutic investigation interested 202 cases of breast carcinoma. Compared to the histologic result, the cytologic results proved to be: -- identical. . . . . . . in 170 cases (84%) -- false benign . . . . . in 4 cases (2%) -- false malignant . . . . in 4 cases (2%) -- insufficient cell material in 24 cases (12%) The high rate of correct cytologic diagnosis and the very low rate of wrong results prove the value and interest of the fine needle aspiration cytology for residual tumor masses or for recurrences in irradiated breast cancers.
pubmed_1043_2794
pubmed_1048_8664
We examine theoretically the spreading of a viscous liquid drop over a thin film of uniform thickness, assuming the liquid's viscosity is regulated by the concentration of a solute that is carried passively by the spreading flow. The solute is assumed to be initially heterogeneous, having a spatial distribution with prescribed statistical features. To examine how this variability influences the drop's motion, we investigate spreading in a planar geometry using lubrication theory, combining numerical simulations with asymptotic analysis. We assume diffusion is sufficient to suppress solute concentration gradients across but not along the film. The solute field beneath the bulk of the drop is stretched by the spreading flow, such that the initial solute concentration immediately behind the drop's effective contact lines has a long-lived influence on the spreading rate. Over long periods, solute swept up from the precursor film accumulates in a short region behind the contact line, allowing patches of elevated viscosity within the precursor film to hinder spreading. A low-order model provides explicit predictions of the variances in spreading rate and drop location, which are validated against simulations.
10.1098/rspa.2016.0270
pubmed_1044_26200
A scaffold is one of the most significant implants for treating bone injury, while the precise control of stem cell proliferation and differentiation within a scaffold is still challenging. In this work, a composite scaffold was designed to be capable of recruiting endogenous stem cells, stimulating osteogenic differentiation and achieving significant bone repair function. The designed SiCP + SF@PFS silica-calcium phosphate composite scaffold was obtained by mixing the peptide PFS containing silk fibroin solution with the SiCP scaffold, and treating with horseradish peroxidase and H2O2. The results showed that the composite scaffold was able to release the PFS peptide continuously to induce the migration of mesenchymal stem cells. Meanwhile, cell proliferation and osteogenic differentiation were also improved after being seeded on the scaffold. In the cranial defect rat model, the composite scaffold was able to recruit CD29+ and CD90+ cells one week after implantation around the injury sites. The results of Micro-CT, H&E staining, Masson's staining and immunohistochemical staining indicated that the composite scaffold was able to promote new bone formation significantly.
10.1039/d2tb00687a
pubmed_628_5464
A pharmacokinetic study based on the distribution of radioactivity from the double labelled S-adenosyl-L-methionine (SAM) has been carried out by oral administration of the liposoluble stable salt [methyl-(14)C, 8-(3)H]SAM N-ole-1-oyltaurate to rats. The SAM sulfate p-toluensulfonate salt, the only SAM salt at present commercialized as drug, was chosen as reference compound to have a comparative pharmacokinetic analysis. The metabolism of the SAM is characterised by a differential use of the two labelled moieties by the various organs, liver being the most active in metabolizing the sulfonium compound with a preferential uptake of the methyl-(14)C fragment. The radioactivity detected after the administration of [methyl-(14)C, 8-(3)H]SAM N-ole-1-oyltaurate is, in all the organs examined, two times higher than the [methyl-(14)C, 8-(3)H]SAM sulfate p-toluensulfonate compound, attesting that the liposoluble [methyl-(14)C, 8-(3)H]SAM N-ole-1-oyltaurate is provided with better bioavailability.
10.1016/s0378-5173(01)00858-4
pubmed_832_13854
We aimed to investigate the relationship between non-perfusion on ultra-widefield angiography (UWF FA) and aqueous cytokine levels and central macular thickness (CMT) in eyes with branch retinal vein occlusion (BRVO). Thirty-five eyes with treatment-naïve BRVO were included. Non-perfusion area (NPA) for partial and complete ischemia was manually segmented and the ischemic index (ISI) for each was calculated using stereographically projected UWF FA for four different retinal zones. Partial and complete ischemia had different regional predominance. Partial ischemia was predominant in the posterior regions, while complete ischemia was predominant in the periphery. And partial ischemic area, located posterior to far periphery, showed significant correlation with central macular thickness and concentrations of angiogenic and inflammatory cytokines, while complete ischemic area showed no correlation with any of the parameters. Taken together, partial but not complete ischemia, particularly in the more posterior retina, was associated with higher cytokine levels and more severe macular edema in eyes with BRVO. These findings would help us to better understand the different clinical significance of ischemia in BRVO depending on the severity and regional distribution.
10.1038/s41598-020-79522-5
pubmed_571_12041
The mitochondrial anti-viral signaling protein (MAVS), also known as CARDIF, IPS-1, KIAA1271 and VISA, is a mitochondria associated protein that regulates type I interferon production through coordinated activation of NF-kappaB and IRF3. The N-terminal CARD domain of MAVS interacts with RIGI helicase of upcapped RNA detection and the putative TRAF2 and TRAF6 binding motifs modulate protein interaction for NF-kappaB activation. MAVS is encoded by a single gene composed of 6 exons but is generally detected as multiple protein bands after separation by SDS-PAGE. In an effort to identify MAVS variants with diverse biological functions, we isolated three splicing variants and named them MAVS 1a (exon 2 deletion), 1b (exon 3 deletion) and 1c (exon 6 deletion), respectively. MAVS 1a and 1b, due to a frame shift by exon deletion, encode 131 and 124 aa residues, respectively. Except the first 39 aa residues encoded by exon 1, MAVS 1a does not share sequence homology with known proteins, it instead contains a putative TRAF2-binding motif and interacts with TRAF2 and RIP1. MAVS 1b shares the first 97 residues with wt MAVS and 27 aa residues of unknown protein. Unlike MAVS that activates both NF-kappaB and IRF3 pathways, expression of MAVS 1b selectively activates an IFNbeta but not an IL8 promoter. MAVS 1b interacts with RIP1 and FADD and exhibits anti-viral activity against VSV infection. This study uncovers MAVS splicing variants of diverse biological function.
10.1016/j.molimm.2007.11.018
pubmed_888_876
The Sin3 proteins are evolutionarily conserved co-repressors (CoR) that function as mediators of gene repression for a variety of transcriptional silencers. The paired amphipathic helices of Sin3A were identified and studied as protein-protein interacting domains. Previously we have shown the interaction of Sin3A with the CoR Alien in vivo and in vitro. Here, we show that Alien and Sin3A reside together in vivo with the vitamin D3 receptor on the human 24-hydroxylase (CYP24) promoter containing vitamin D3 response elements by chromatin immunoprecipitation. We delineated and characterized the interaction domains of Sin3A with Alien. Interestingly, the highly conserved region (HCR) of Sin3A, which has not yet been functionally characterized, interacts with Alien. The HCR encompasses only 134 amino acids, shares more than 80% identity with Sin3B and binds to the N-terminus of Alien, which harbours a transferable silencing function. Functionally, co-expression of Sin3A enhances Alien-mediated gene repression and overexpression of the HCR alone leads to the inhibition of Alien-mediated repression and to the induction of the endogenous CYP24 promoter. Our results therefore indicate a novel functional role of the Sin3 HCR and give novel insights into Alien-mediated gene repression.
10.1093/nar/gkh621
pubmed_1046_16477
Spatially resolved diffuse reflectance spectroscopy (srDRS) is a well-established technique for noninvasive, in vivo characterization of tissue optical properties toward diagnostic applications. srDRS has a potential for depth-resolved analysis of tissue, which is desired in various clinical situations. However, current fiber-based and photodiode-based systems have difficulties achieving this goal due to challenges in sampling the reflectance with a high enough resolution. We introduce a compact, low-cost architecture for srDRS based on the use of a multipixel imaging sensor and light-emitting diodes to achieve lensless diffuse reflectance imaging in contact with the tissue with high spatial resolution. For proof-of-concept, a prototype device, involving a commercially available complementary metal-oxide semiconductor coupled with a fiber-optic plate, was fabricated. Diffuse reflectance profiles were acquired at 645 nm at source-to-detector separations ranging from 480  μm to 4 mm with a resolution of 16.7  μm. Absorption coefficients (μa) and reduced scattering coefficients (μs') of homogeneous tissue-mimicking phantoms were measured with 4.2  ±  3.5  %   and 7.0  ±  4.6  %   error, respectively. The results obtained confirm the potential of our approach for quantitative characterization of tissue optical properties in contact imaging modality. This study is a first step toward the development of low-cost, wearable devices for skin condition diagnosis in vivo.
10.1117/1.JBO.23.11.115003
pubmed_226_21320
BACKGROUND To evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost. METHODS Patients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0. RESULTS Between 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months. CONCLUSIONS Accelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease.
10.1186/s13014-021-01976-2
pubmed_197_21004
"Dose-painting" radiotherapy allows for a heterogeneous delivery of radiation within the tumour volume by targeting radioresistant areas defined by functional imaging. Within gross tumour volume, it is possible to define one or more target volumes based on biology (biological target volume [BTV]) and to apply a strategy of intensity modulated radiation therapy (IMRT) that will deliver a higher dose to these regions. In this review of the literature, we will highlight the biological elements responsible for radioresistance, and how to image them, then we will detail the radiotherapy techniques necessary for this approach, before presenting clinical results in various situations (head and neck tumours, prostate, brain tumours, etc.). Despite many difficulties that make dose-painting IMRT unusable in routine nowadays, biology-guided radiation therapy represents one of the major pathways of development of radiotherapy in the coming years.
10.1016/j.canrad.2010.06.005
pubmed_87_11332
AIM In childhood, severe psychomotor impairment (SPMI) is associated with profound sleep disturbances. With the help of newly developed and validated measures, we systematically assessed how much a child's sleep disturbance affects parental sleep and quality of life (QoL) in this specific patient group. METHOD Parents and their children with SPMI were enrolled from three outpatient centers and one in-patient center in Germany. We administered a set of questionnaires to the parents that addressed their child's sleep quality, the sleep disturbance-related parental burden, and the impact on both parental sleep and QoL. Additional questionnaires were used to gather data describing our sample group to allow for comparison with published norms. RESULTS Parents of 214 children, adolescents, and young adults with SPMI (114 males, 100 females; mean age 10y 5mo, SD 5y 6mo, range 0.1-25y) responded to the questionnaire set (response rate of 66%). We found severe impairment of parental health status and QoL. More than 50% of the parents suffered from a sleep disorder (e.g. prolonged sleep latency, shortened sleep duration). Sleep disturbances in children, adolescents, and young adults correlated strongly with parental sleep disturbances, parental impairment of physical and mental functioning, parental social functioning, and parental working ability. INTERPRETATION Sleep-related difficulties have a significant sociomedical impact on the parents of children, adolescents, and young adults with complex neurological diseases. Typically, parents are severely affected in various aspects of daily living. There is a need for novel diagnostic and therapeutic approaches that match the complex sociomedical needs of these patients and their families.
10.1111/dmcn.12530
pubmed_559_6202
BACKGROUND The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been explored as a gene delivery vehicle for a variety of mammalian cell lines. However, the transient expression nature due to its incapability to replicate in mammalian cells and insufficient transduction efficiency limit its application. METHODS Recombinant baculovirus vectors containing genetic elements from Epstein-Barr virus (EBV), OriP and EBNA-1, which are essential for the episomal maintenance of the EBV genome in latently infected cells, were constructed and tested for their ability to sustain and express transgene (enhanced green fluorescence protein (egfp)) in mammalian cells. RESULTS The recombinant baculovirus containing OriP and EBNA-1 genes driven by the cytomegalovirus (CMV) promoter was capable of persisting in a significant proportion of infected mammalian cells, HEK293, Vero, Cos-7, and Hone-1, without any selective pressure. In HEK293, the expression of EGFP lasted for 60 days with markedly enhanced expression level. The persistence of baculovirus genome correlated with the expression of EBNA-1. CONCLUSIONS The improved baculovirus vector could mediate prolonged and enhanced foreign gene expression in some mammalian cells. Furthermore, an adequate level of the EBNA-1 protein was essential for the maintenance of the OriP-containing baculovirus genome. The new vector has potential for use in gene therapy.
10.1002/jgm.978
pubmed_426_14564
Clinical dietitians' time and expertise have been allocated much more efficiently at Fairview General Hospital through computer analysis of information that is readily available in existing mainframe programs. Other health care institutions may be able to achieve similar results by examining information about patient populations and diet orders stored in their computers.
pubmed_426_14564
pubmed_507_21504
This paper presents the development of a fast multi-residue method for the determination of 49 pharmaceuticals and 6 metabolites from different therapeutic classes in water resources by means of Ultra-performance liquid chromatography (UPLC) coupled to tandem mass spectrometry. The use of the UPLC technology enabled all the 55 compounds to be separated chromatographically in less than 9min (6.3min positive mode and 2.7min negative mode) and with a total analysis time of 18min when considering column conditioning. Improved resolution, sensitivity and a reduction of matrix effects were obtained under these conditions. Unequivocal identification and quantification of the target compounds was also performed by using the dual acquisition modes of the hybrid triple quadrupole-linear ion trap (QqLIT) system. Triple quadrupole mode by means of selected reaction monitoring (SRM) was used for quantification, whilst a second SRM transition together with information-dependent analysis (IDA) experiments was used for confirmation. Additionally, one general, single solid-phase extraction (SPE) method was developed by using Oasis HLB cartridges. Quality parameters of the method in wastewaters were established obtaining a fast, robust, reproducible and cost-effective method for all the target pharmaceuticals. Finally, the optimized SPE-UPLC/QqLIT method was used for the analysis of the target compounds in wastewaters from Spain. Thirty-one out of fifty-five compounds were identified in the samples collected.
10.1016/j.chroma.2009.11.007
pubmed_1059_1393
In the present paper, morphologic studies on experimental echinococcosis are reported. Following i.p. infection of gerbils (Meriones unguiculatus) with Echinococcus multilocularis scolices, the development of cysts within the internal organs of the experimental animals could be readily visualized by scanning electron microscopy.
10.1007/BF00380525
pubmed_87_9229
Ternary Pt-Ru-Ni deposits on glassy carbon substrates, Pt-Ru(Ni)/GC, have been formed by initial electrodeposition of Ni layers onto glassy carbon electrodes, followed by their partial exchange for Pt and Ru, upon their immersion into equimolar solutions containing complex ions of the precious metals. The overall morphology and composition of the deposits has been studied by SEM microscopy and EDS spectroscopy. Continuous but nodular films have been confirmed, with a Pt ÷ Ru ÷ Ni % bulk atomic composition ratio of 37 ÷ 12 ÷ 51 (and for binary Pt-Ni control systems of 47 ÷ 53). Fine topographical details as well as film thickness have been directly recorded using AFM microscopy. The composition of the outer layers as well as the interactions of the three metals present have been studied by XPS spectroscopy and a Pt ÷ Ru ÷ Ni % surface atomic composition ratio of 61 ÷ 12 ÷ 27 (and for binary Pt-Ni control systems of 85 ÷ 15) has been found, indicating the enrichment of the outer layers in Pt; a shift of the Pt binding energy peaks to higher values was only observed in the presence of Ru and points to an electronic effect of Ru on Pt. The surface electrochemistry of the thus prepared Pt-Ru(Ni)/GC and Pt(Ni)/GC electrodes in deaerated acid solutions (studied by cyclic voltammetry) proves the existence of a shell consisting exclusively of Pt-Ru or Pt. The activity of the Pt-Ru(Ni) deposits toward methanol oxidation (studied by slow potential sweep voltammetry) is higher from that of the Pt(Ni) deposit and of pure Pt; this enhancement is attributed both to the well-known Ru synergistic effect due to the presence of its oxides but also (based on the XPS findings) to a modification effect of Pt electronic properties.
10.3389/fchem.2014.00029
pubmed_876_6374
A widely held view is that, to elicit adaptive immune responses, most protein antigens must be given with adjuvants that activate the innate immune system. It has also been proposed that the immune system is tolerant to idiotypes (Id) of the syngeneic primary antibody (Ab) repertoire. We now show that among 73 purified noncomplexed secretory IgM monoclonal antibodies (mAb), 4 (5.5%) elicited high levels of IgG Ab against the Id even though no adjuvant was added. The responses were controlled by H2-linked immune response genes. IgG1, but no IgG2a or IgG2b, anti-Id Ab were detected, indicating involvement of T helper type 2 (Th2) cells. All 4 IgM mAb are likely germ-line gene-encoded, and 1 was shown to represent a recurrent Id. After endotoxin depletion the most potent immunogen of the 4 still provoked robust humoral anti-Id responses. The results suggest that a natural protein of the primary IgM Ab repertoire can be immunogenic without an adjuvant.
10.1002/1521-4141(200107)31:7<2143::aid-immu2143>3.0.co;2-1
pubmed_530_8004
Escherichia coli is a pathogen of major importance in swine and public health. To determine the prevalence of Shiga toxigenic E. coli (STEC) and enteropathogenic E. coli (EPEC), samples were collected from the feces and carcasses of swines. In total, 441 samples were collected in four samplings, of which 141 samples tested positive for either the stx1, stx2, and/or eae genes. From the positive samples, one STEC and 15 atypical EPEC (aEPEC) isolates were obtained, and all originated from the same sampling. In addition to eae, lpfA(O157/OI-141), ehxA, toxB, and lpfA(O113) were present in the aEPEC isolates. The only stx2-containing isolate carried stx2e and belonged to serotype O103:HNT. Resistance to four or more antimicrobials was found in almost half of the isolates, and some isolates shared the same fingerprint patterns by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). The presence of certain virulence genes and the high level of resistance to antimicrobials, as well as the possible fecal contamination of carcasses showed that some of the isolates are of public health concern.
10.1089/fpd.2012.1206
pubmed_560_23904
Fatigue after myocardial infarction (MI) has been found to be distressing. A person's self-efficacy will influence his/her health behavior and plays an active role in tackling illness consequences. This study investigated associations between fatigue, disturbed sleep, general self-efficacy, and health-related quality of life (HRQoL) in a sample of 145 respondents admitted to hospital for MI two years earlier. The aim was to identify the predictive value of general self-efficacy and to elucidate mediating factors between self-efficacy and HRQoL. General self-efficacy measured four months after MI was positively related to HRQoL after two years. In tests of indirect effects, fatigue meditated the effects between self-efficacy and the physical and the mental dimension of HRQoL, respectively. The indirect effect of disturbed sleep went through that of fatigue. To conclude, patients who suffer from post-MI fatigue may need support aimed at helping them increase their self-efficacy as well as helping them adapt to sleep hygiene principles and cope with fatigue, both of which will have positive influences on HRQoL.
10.1080/13548506.2011.608807
pubmed_656_5207
BACKGROUND The aim of this study was to provide information about the spread and characteristics of the vancomycin-resistant Enterococcus faecium isolates (VREfm) in Turkey. METHODS Seventy-one nonduplicate consecutive isolates of VREfm were obtained from various clinical specimens of inpatients treated at university or training hospitals in seven regions of Turkey. Further characteristics included antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA, and multilocus sequence typing (MLST) of selected isolates. The presence of vancomycin resistance and virulence genes (esp and hyl) was investigated by polymerase chain reaction (PCR). RESULTS All VREfm isolates had MICs to vancomycin of ≥32 mg/L and contained the vanA gene. The presence of esp gene was identified in 64 and hyl in eight VREfm isolates. All VREfm showed the multiresistance phenotype, including ampicillin (99%), penicillin (99%), imipenem (99%), ciprofloxacin (87%), moxifloxacin (87%), erythromycin (97%), streptomycin (86%), gentamicin (82%), tetracycline (70%), and teicoplanin (99%). All were susceptible to tigecycline while quinupristin-dalfopristin (97%) and linezolid (93%) were the most active other agents. Analysis of the PFGE profiles showed that 53 (74.6%) VREfm isolates shared a similar electrophoretic profile, designed as type 1, and were closely related (>85%). The sequence type was identified by MLST in 44 VRE isolates with unrelated or closely related PFGE patterns. MLST revealed that nosocomial spread of VREfm resulted from dissemination of lineage C1 E faecium clones. Sequence types ST78, ST203, and ST117 were the most frequently isolated. This is the first report of ST733 around the world. CONCLUSIONS Lineage C1 clones are disseminated among clinical VREfm isolates in seven different regions in Turkey. Regarding VREfm isolates, the worldwide epidemic strains are in circulation in Turkey.
10.1002/jcla.23541
pubmed_51_6828
The prevalence of fluorosis is mainly due to the consumption of more fluoride (F(-1)) through drinking water, vegetables, and crops. The objective of the study was mapping of F(-1) endemic area of Newai Tehsil, Tonk district, Rajasthan, India. For the present study, water, soil (0-45 cm), and vegetation samples were collected from 17 villages. Fluoride concentration in water samples ranged from 0.3 to 9.8 mg/l. Out of 17 villages studied, the amounts of F(-1) content of eight villages were found to exceed the permissible limits. Labile F(-1) content and total F(-1) content in soil samples ranges 11.00-70.05 mg/l and 50.3-179.63 μg g(-1), respectively. F(-1) content in tree species was found in this order Azadirachta indica 47.32-55.76 μg g(-1) > Prosopis juliflora 40.16-49.63 μg g(-1) > Acacia tortilis 34.39-43.60 μg g(-1). While in case of leafy vegetables, F(-1) content order was Chenopodium album 54.23-98.42 μg g(-1) > Spinacea oleracea 30.41-64.09 μg g(-1) > Mentha arvensis 35.48-51.97 μg g(-1). The order of F(-1) content in crops was found as 41.04 μg g(-1) Pennisetum glaucum > 13.61 μg g(-1) Brassica juncea > 7.98 μg g(-1) Triticum sativum in Krishi Vigyan Kendra (KVK) farms. Among vegetation, the leafy vegetables have more F(-1) content. From the results, it is suggested that the people of KVK farms should avoid the use of highly F(-1) containing water for irrigation and drinking purpose. It has been recommended to the government authority to take serious steps to supply drinking water with low F(-1) concentration for the fluorosis affected villages. Further, grow more F(-1) hyperaccumulator plants in F(-1) endemic areas to lower the F(-1) content of the soils.
10.1007/s10661-012-2683-0
pubmed_768_11666
BACKGROUND Germany, like many other countries, will soon have a shortage of qualified doctors. One reason for the dissatisfaction amongst medical residents are the relatively unstructured residency training programs despite increasing importance of outcome-based education. The aim of our study was to identify characteristics and requirements for good teaching during anesthesiology residency training from the resident's point of view. METHODS A consensus workshop with residents from all medical universities in Germany was held. Participants were allocated to one of the three topics, chosen based on a 2009 nationwide evaluation of residency. The three topics were (A) characteristics of helpful/good teachers, (B) characteristics of helpful/good conditions and (C) characteristics of helpful/good curricular structure. Each group followed a nominal group technique consensus process to define and rank characteristics for a good residency. RESULTS 31 (79.5%) resident representatives were present. The consented results put emphasis on the importance of structured curricula including transparent goals and objectives, in training formative assessments and quality assurance measures for the program. Residents further long for trained trainers with formal teaching qualifications and protected teaching time. CONCLUSIONS Good residency training requires careful consideration of all stakeholders' needs. Results reflect and extend previous findings and are at least to some degree easily implemented. These findings are an important step to establish a broader consensus within the discipline.
10.3205/000190
pubmed_548_13889
CONTEXT The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned. OBJECTIVE This study aimed to determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS US community-dwelling adults years of older (n = 2843) enrolled onto the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range. MAIN OUTCOME MEASURES Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death were measured. RESULTS No departures from linearity were detected. Higher TSH was negatively associated (P = .03) and higher FT4 was positively associated (P = .007) with mortality. Higher FT4 was associated with atrial fibrillation (P < .001) and heart failure (P = .004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (P < .05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure, and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all P < .05). Total T3 was not associated with any outcome. CONCLUSIONS Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people.
10.1210/jc.2014-3586
pubmed_792_3045
PURPOSE Genetic instability plays a major role in multi-stage carcinogenesis. Ionizing radiation induces delayed genetic instability which can be transmitted to the clonal offspring of the irradiated cell, so it is of considerable importance to determine whether radiation-induced genetic instability contributes to radiation-leukaemogenesis. RESULTS The experimental data obtained using radiation-induced leukaemias in mouse models were reviewed, and an attempt was made to distinguish between the instability detectable in de novo cancers and that which is associated with ionising radiation. Genetic lesions identified in mouse leukaemias include non-clonal chromosomal aberrations, loss of heterozygosity, and minisatellite/microsatellite mutations. CONCLUSIONS Studies of mouse radiation-induced leukaemias have detected evidence of genetic instability. However, with few exceptions, most of this instability was also observed during de novo multi-stage carcinogenesis. This raises the possibility that radiation induces ongoing genetic instability that is functionally indistinguishable to that implicated in de novo tumour progression.
10.1080/095530098140989
pubmed_596_24403
Traditionally alcohol has been used by the military to cope with the intense stress of battle but also as a way of mediating the transition from the heightened experience of combat to routine safety. The use of alcohol has divided medical opinion. Some doctors viewed it as wholly harmful to both social and occupational function and to health, while others argued that alcohol had a specific role in lifting morale, aiding unit cohesion and protecting soldiers from adjustment disorders. Although alcoholism has always been identified as incompatible with military service, the effects of habitual heavy drinking among military personnel are less well understood. Recent studies have suggested that young single males and those who have undergone particularly stressful experiences are at greatest risk of misusing alcohol. These associations, observed in the aftermath of recent conflicts in Iraq and Afghanistan, have again raised questions about the place of alcohol in military culture.
10.3109/09540261.2010.550868
pubmed_337_15197
The transtibial technique is the most relevant among many surgical techniques for posterior cruciate ligament reconstruction, and many types of fixation devices are used for tibial fixation according to the technique and the length of the graft. However, bone density in the fixation areas should be taken into consideration when choosing the fixation device to achieve rigid and stable fixation. However, density is not a substantial issue for anteromedial cortical fixation using a cortical suspension device. We describe tibial fixation with a TightRope RT (Arthrex, Naples, FL), which is a cortical suspension device, in anatomic transtibial posterior cruciate ligament reconstruction.
10.1016/j.eats.2015.10.008
pubmed_740_17089
BACKGROUND Few trauma guidelines evaluate and recommend anesthesiology practices and there are no trauma anesthesia-specific guidelines. There is no information on how anesthesiologists perceive clinical practice patterns. Our objective was to understand the perceptions of anesthesiologists regarding trauma anesthesia practices. METHODS A survey assessing anesthesia management of trauma patients was distributed to 21,491 anesthesiologists. A subset of 10 of these questions was subsequently reviewed by a trauma anesthesiology focus group through a 3-round web-based Delphi process. A question was deemed to have respondent consensus if the response with the highest percentage of agreement was unchanged between rounds 1 and 2. RESULTS A total of 2360 anesthesiologists (11% response rate) responded to the survey. Results demonstrated that the practitioners' answers conflicted with existing surgical trauma society recommendations (ie, when to transfuse component therapy), and several areas that lacked any guidelines, resulted in response variability among anesthesiologists where not 1 answer achieved >75% agreement (ie, intubation technique of choice for patients with uncleared cervical spine). Thirteen trauma anesthesiologists participated in round 1 (response rate 100%), and 12 responded in rounds 2 and 3 (response rate 92%) of the Delphi process. None of the questions received 100% agreement. Consensus was achieved on 9 of 10 statements pertaining to trauma anesthesia care. Consensus was not reached on the intubating technique in a hemodynamically unstable patient with an uncleared cervical spine with deficits. Delphi participant opinion conflicted with existing guidelines on 2 statements: the use of cricoid pressure, and when to begin blood component therapy. CONCLUSIONS There are several important areas of trauma anesthesia practice where guidelines do not exist and several where existing guidelines are not endorsed by the majority of practitioners who completed our survey. The lack of consensus on trauma anesthesia management and the variation in survey responses demonstrate a need to develop evidence-based trauma anesthesia guidelines.
10.1213/ANE.0000000000002863
pubmed_190_5071
Whole-genome duplication events have driven to a large degree the evolution of angiosperm genomes. Although the majority of redundant gene copies after a genome duplication are lost, subfunctionalization or gene balance account for the retention of gene copies. The Arabidopsis 80S ribosome represents an excellent model to test the gene balance hypothesis as it consists of 80 ribosomal proteins, all of them encoded by genes belonging to small gene families. Here, we present the isolation of mutant alleles of the APICULATA2 (API2) and RPL36aA paralogous genes, which encode identical ribosomal proteins but share a similarity of 89% in their coding sequences. RPL36aA was found expressed at a higher level than API2 in the wild type. The loss-of-function api2 and rpl36aa mutations are recessive and affect leaf development in a similar way. Their double mutant combinations with asymmetric leaves2-1 (as2-1) caused leaf polarity defects that were stronger in rpl36aa as2-1 than in api2 as2-1. Our results highlight the role of combined haploinsufficiency and purifying selection in the retention of these paralogous genes in the Arabidopsis genome.
10.1038/srep04122
pubmed_891_25542
We report a case of a pancreatic ductal adenocarcinoma (PDAC) presenting synchronously with a paraganglioma (PGL) in a Whipple reaction specimen. The patient was a 72-year-old female with a history of breast and vulvar cancer. The simultaneous occurrence of two synchronous tumours in the pancreas was striking. Due to the presence of PGL and multiple meta- and synchronous tumours, the patient was referred to genetic counselling. Tumour tissue from the vulvar carcinoma, the PDAC and the PGL was analysed by targeted next-generation sequencing (NGS) of 161 cancer-related genes and by whole exome sequencing (WES). Peripheral blood was also examined by NGS and WES. These genetic analyses revealed germline polymorphisms in AXIN2 (NM_004655.4:c 0.2272 G>A; p.Ala758Thr), BRCA2 (NM_000059.3:c.9976 A>T; p.Lys3326Ter), NCOR1 (NM_006311.4:c 0.6544 G>A; p.Ala2182Thr) and SPTA1 (NM_003126.3:c 0.373 G>A; p.Ala125Thr) and somatic mutations of KRAS (NM_033360.3;c 0.35 G>A; p.Gly12Asp) and TP53 (NM_000546.5; c.602delT; p.Leu201CysfsTer46) in the PDAC and of TP53 (NM_000546.5; c 0.733 G>A; p.Gly245Ser) and TERT (NM_198253.2; c.-124 C>T; promotor region) in the vulvar carcinoma. Breast carcinoma tissue was not available for genetic analysis. The results of the genetic analyses did not explain the presence of multiple tumours in this patient, despite a slightly increased risk of breast cancer associated with the identified BRCA2 polymorphism. To our knowledge, this is the first report of the synchronous occurrence of PDAC and PGL. This case emphasizes the importance of thorough macroscopic examination of pancreatic resection specimens, as coexisting neoplasms may otherwise be missed.
10.1016/j.prp.2021.153590
pubmed_336_659
OBJECTIVES Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. METHODS A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. RESULTS Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. CONCLUSIONS Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.
10.1371/journal.pone.0086200
pubmed_882_11653
OBJECTIVES The development of transplant arteriosclerosis, the hallmark feature of heart transplant rejection, is associated with a chronic immune response and also influenced by an initial injury to the graft through ischaemia and reperfusion. Hypoxia-inducible transcription factor (HIF)-1 pathway signalling has a protective effect against ischaemia-reperfusion injury and has already been demonstrated to ameliorate allograft nephropathy in previous animal studies. Therefore, the aim of this study was to investigate the effect of stabilization of hypoxia-inducible transcription factors with a prolyl-hydroxylase domain (PHD) inhibitor on transplant arteriosclerosis in an experimental aortic allograft model. METHODS MHC-class I mismatched C.B10-H2(b)/LilMcdJ donor thoracic aortas were heterotopically transplanted into the abdominal aorta of BALB/c mice. Donor animals received a single dose of the PHD inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40 mg/kg) or vehicle i.p. 4 h before transplantation. Intragraft HIF accumulation after ICA treatment was detected by immunohistochemistry before and after cold ischaemia (n = 5). Grafts were harvested 30 days after transplantation and analysed by histology (n = 7) and immunofluorescence (n = 7). In addition, intragraft mRNA expression for cytokines, adhesion molecules and growth factors was determined on Day 14 (n = 7). RESULTS Donor preconditioning with ICA resulted in HIF accumulation in the aorta and induction of the HIF target genes vascular endothelial growth factor and transforming growth factor-beta. Vascular lesions were present in both experimental groups. However, there was significantly reduced intimal proliferation in preconditioned grafts when compared with vehicle controls [intimal proliferation 31.3 ± 8% (ICA) vs 55.3 ± 20% (control), P < 0.01]. In addition, experimental groups revealed a down-regulation of E-selectin (-57%) and MCP1 (-33%) expression after ICA pretreatment compared with controls, going along with decreased T-cell [1.4% CD4+ T-cell infiltration vs 8.4% (control) and 4.9% CD8+ T-cell infiltration vs 10.7% (control)], dendritic cell (0.6% dendritic cells infiltration vs 1.9% infiltration(control)] and macrophage infiltration [4.8% macrophages (ICA) vs 10.9% (control)] within vascular grafts. CONCLUSIONS These data of an animal transplant model show that the pharmaceutical activation of HIF with endogenous up-regulation of protective target genes leads to adaptation of the graft to low oxygen-saturation and hereby attenuates the development of transplant arteriosclerosis and allograft injury. Pharmaceutical inhibition of PHDs appears to be a very attractive strategy for organ preservation that deserves further clinical evaluation.
10.1093/icvts/ivv352
pubmed_1010_6329
BACKGROUND APOC3 is important in lipid transport and metabolism with limited studies reporting genetic sequence variations in specific ethnic groups. The present study aimed to analyze the full APOC3 sequence among Kuwaiti Arabs and test the association of selected variants with lipid levels and BMI. METHODS Variants were identified by Sanger sequencing the entire APOC3 gene in 100 Kuwaiti Arabs. Variants and their genotypes were fully characterized and used to construct haplotype blocks. Four variants (rs5128, rs2854117, rs2070668, KUAPOC3N3 g.5196 A > G) were selected for testing association with serum lipid levels and BMI in a cohort (n = 733). RESULTS APOC3 sequence (4.3 kb) of a Kuwaiti Arab was deposited in Genbank (accession number KJ437193). Forty-two variants including 3 novels were identified including an "A" insertion at genomic positions 116,700,599-116,700,600 (promoter region) and two substitutions in intron 1 at genomic positions 116,700,819 and 116,701,159. Only three variants, (rs5128, rs2854117, and rs2070668) were analyzed for association of which rs5128 showed a trend for association with increased BMI, TG and VLDL levels that was further investigated using multivariate analysis. A significant association of rs5128 with BMI (p <  0.05) was observed following a dominant genetic model with increased risk by an OR of 4.022 (CI: 1.13-14.30). CONCLUSION The present study is the first to report sequence analysis of APOC3 in an Arab ethnic group. This study supports the inclusion of rs5128 as a marker for assessing genetic risk to dyslipidemia and obesity and the inclusion of the novel variant g.5196 A > G for population stratification of Arabs.
10.1186/s12944-019-1165-6
pubmed_1001_19886
Previous studies have shown that jaw reflexes and activity patterns of the jaw muscles were modulated in the presence of jaw muscle pain. However, there is no study comparing the modulatory effects on the jaw reflexes induced by noxious stimulation to the jaw muscle. To clarify this, effects of the application of mustard oil (MO), an inflammatory irritant, into the temporalis (jaw-closing) muscle on (1) jaw-opening reflex evoked by tooth pulp stimulation (TP-evoked JOR) as a nociceptive reflex, (2) jaw-opening reflex evoked by inferior alveolar nerve stimulation as a non-nociceptive reflex and (3) jaw-closing reflex evoked by trigeminal mesencephalic nucleus stimulation as a proprioceptive reflex were investigated in anesthetized rats. The MO application induced suppression of all reflexes, and the effect on the TP-evoked JOR was more prominent than on the other reflexes. To elucidate the involvement of endogenous opioid system for the suppressive effect, a systemic administration of naloxone following the MO application was conducted. The MO-induced suppressive effect on the TP-evoked JOR was reversed by the naloxone administration. The results suggest that noxious stimulation to the jaw muscle modulate jaw reflexes particularly for the nociceptive jaw-opening reflex, and the modulatory effect includes both facilitatory and inhibitory aspects. The results also suggest that pain modulatory systems such as the endogenous opioid system play a crucial role in the suppression of the nociceptive transmissions related to nociceptive reflexes, and in some pathological states, defense reflexes may not be evoked properly.
10.1016/j.brainres.2005.02.003
pubmed_885_19777
The Arabidopsis LOB-domain (LBD) gene family is composed by 43 members divided in two classes based on amino acid conservation within the LOB-domain. The LOB domain is known to be responsible for DNA binding and protein-protein interactions. There is very little functional information available for most genes in the LBD family and many lbd single mutants do not exhibit conspicuous phenotypes. One plausible explanation for the limited loss-of-function phenotypes observed in this family is that LBD genes exhibit significant functional redundancy. Here we discuss an example of one phylogenetic subgroup of the LBD family, in which genes that are closely related based on phylogeny exhibit distinctly different expression patterns and do not have overlapping functions. We discuss the challenges of using phylogenetic analyses to predict redundancy in gene families.
10.4161/psb.22320
pubmed_109_9604
Thh design of a plug-holder unit for electrode implants is described. The plug-holder attaches to the stereotaxic and facilitates the insertion of the electrode contact pins into the plug by retaining the connector plug in a fixed rigid position. In addition, it prevents the accidental breakage of contact lead wires which can normally occur during the contact pin insertion procedure. The unit is inexpensive and simple to construct.
10.1016/0091-3057(76)90089-7
pubmed_468_5104
Several investigators have demonstrated that freshly harvested hepatocytes self-assemble into three-dimensional, compacted, freely suspended aggregates known as spheroids (1-3). These aggregates have smooth, undulating surfaces and average approx 120 µm in diameter. Hepatocyte spheroids exhibit enhanced liver-specific activities and prolonged viability, compared to cells maintained as a monolayer (4,5). Extensive cell-cell contacts, tight junctions, and microvilli-lined channels that resemble bile canaliculi have been observed between hepatocytes in spheroids (6,7). Thus, these cells appear to mimic the morphology and ultrastructure of an in vivo liver lobule. Reorganization of hepatocytes into these three-dimensional structures is hypothesized to contribute to their enhanced liver-specific functions. Because of their enhanced function and tissue-like ultrastructure, hepatocyte spheroids show great promise for use in tissue-engineering applications and drug metabolism studies.
10.1385/0-89603-516-6:245
pubmed_789_11554
BACKGROUND Criteria for good candidate antigens for immunotherapy of acute myeloid leukemia are high expression on leukemic stem cells in the majority of patients with acute myeloid leukemia and low or no expression in vital tissues. It was shown in vaccination trials that Receptor for Hyaluronic Acid Mediated Motility (RHAMM/HMMR) generates cellular immune responses in patients with acute myeloid leukemia and that these responses correlate with clinical benefit. It is not clear however whether this response actually targets the leukemic stem cell, especially since it was reported that RHAMM is expressed maximally during the G2/M phase of the cell cycle. In addition, tumor specificity of RHAMM expression remains relatively unexplored. DESIGN AND METHODS Blood, leukapheresis and bone marrow samples were collected from both acute myeloid leukemia patients and healthy controls. RHAMM expression was assessed at protein and mRNA levels on various sorted populations, either fresh or after manipulation. RESULTS High levels of RHAMM were expressed by CD34(+)CD38(+) and CD34(-) acute myeloid leukemia blasts. However, only baseline expression of RHAMM was measured in CD34(+)CD38(-) leukemic stem cells, and was not different from that in CD34(+)CD38(-) hematopoietic stem cells from healthy controls. RHAMM was significantly up-regulated in CD34(+) cells from healthy donors during in vitro expansion and during in vivo engraftment. Finally, we demonstrated an explicit increase in the expression level of RHAMM after in vitro activation of T cells. CONCLUSIONS RHAMM does not fulfill the criteria of an ideal target antigen for immunotherapy of acute myeloid leukemia. RHAMM expression in leukemic stem cells does not differ significantly from the expression in hematopoietic stem cells from healthy controls. RHAMM expression in proliferating CD34+ cells of healthy donors and activated T cells further compromises RHAMM-specific T-cell-mediated immunotherapy.
10.3324/haematol.2012.065581
pubmed_567_14061
The Clara cell secretory protein (CCSP) gene is a cell-specific differentiation marker for the bronchiolar Clara cell. Previous studies suggest that CCAAT/enhancer binding protein (C/EBP)alpha is involved in controlling differentiation-dependent gene expression in the distal lung. In this study, immunofluorescence studies demonstrated high level expression of C/EBPdelta in the bronchiolar epithelium as well as lower levels of C/EBPalpha. Cotransfection studies in the lung epithelial cell line A549 showed that both C/EBPalpha and C/EBPdelta activate the murine CCSP gene and that a C/EBP-response element resides in the proximal CCSP promoter. C/EBPdelta exhibits an approximately 2-fold higher transactivation potential than does C/EBPalpha. DNase I footprint analyses revealed a footprint region located at -100 to -62 bp, corresponding to two C/EBP-binding sites. Mutation of either site resulted in abolished or strikingly reduced transactivation of the CCSP promoter by C/EBPalpha and C/EBPdelta, as well as impaired binding of both factors, indicating that the two C/EBP-binding sites form a compound response element. In electrophoretic mobility shift assays, it was shown that C/EBPalpha and C/EBPdelta can bind to both C/EBP sites, whereas in DNase I footprint analyses, the interaction of C/EBPalpha with the proximal site was weak. Furthermore, electrophoretic mobility shift assays demonstrated that C/EBPalpha and C/EBPdelta preferentially form heterodimers at both binding sites. Cotransfections with C/EBPalpha and C/EBPdelta together resulted in a superinduction of the CCSP promoter, indicating a regulatory role for the C/EBPalpha-C/EBPdelta heterodimers. Our findings demonstrate that C/EBPalpha and C/EBPdelta regulate the CCSP gene through a compound response element and suggest that these factors are important for the differentiation-dependent expression of CCSP.
10.1165/ajrcmb.22.4.3916
pubmed_204_14155
Dysfunction of the intestinal mucosal barrier of chicks caused by Salmonella pullorum is of great harm to the poultry industry. Probiotics are recognized for their beneficial health-promoting properties, promoting maintenance of bowel epithelial integrity and host immune system homeostasis. Our previous research showed that Lactobacillus casei protects jejunal mucosa from injury in chicks infected with S. pullorum. However, the specific mechanisms underlying its protective properties are still not fully understood. In the present study, we aimed to explore the mechanisms underlying the protective effects of L. casei on the intestinal mucosal barrier of chicks infected with S. pullorum through histological, immunological, and molecular biology methods. The results indicated that L. casei significantly reduced the diarrhea rate, increased the daily weight gain, and maintained normal levels of IgA, IgM, and IgG in the serum of chicks infected with S. pullorum. Furthermore, we found that L. casei markedly improved the immunity of gut mucosa by regulating cytokine and chemokine receptor balance, elevating the number of intraepithelial lymphocytes, and hence effectively restraining bowel inflammation. Strikingly, feeding of infected chicks with L. casei notably boosted interleukin-22 expression to activate the Wingless-Int pathway, moderated diamine oxidase and D-lactic acid levels, diminished the generation of myosin light chain kinase, and expanded tight junction protein levels (Zonulin-1 and Claudin-1), strengthening the function of the gut mucosal epithelium. In addition, experiments using 16S rDNA sequencing also demonstrated that L. casei immensely weakened the adhesion of S. pullorum, mainly manifesting as improved diversity of the intestinal microbiota in the V4 area of infected chicks. Taken together, these results show that the application of L. casei may be a good strategy to regulate the intestinal inflammatory response of chicks infected with S. pullorum, providing new perspectives in producing antibiotic substitutes in poultry farms.
10.1016/j.psj.2021.101283
pubmed_267_9226
A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity.
10.1128/iai.37.3.1181-1190.1982
pubmed_117_14907
BACKGROUND The estrogen receptor-1 (ESR1) gene encodes estrogen receptor-α, which is a major biomarker in the development of breast cancer. This study aimed to investigate the effect of ESR1 polymorphisms on breast cancer in Chinese Han women. MATERIALS AND METHODS We genotyped 4 candidate single nucleotide polymorphisms (SNPs) in ESR1 among 503 patients with breast cancer and 503 healthy people using the Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) under 4 genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1 expression analysis, respectively. RESULTS The T allele of rs9383938 in ESR1 was significantly associated with an increased breast cancer risk (OR, 1.26; 95% CI, 1.05-1.50; P = .013). In genetic models, rs9383938 increased breast cancer risk in the codominant model (OR, 1.54; 95% CI, 1.07-2.22; P = .021), the dominant model (OR, 1.31; 95% CI, 1.01-1.68; P = .040), and the additive model (OR, 1.24; 95% CI, 1.04-1.48; P = .017). Stratification analysis showed that rs9383938 and rs2228480 raised the breast cancer susceptibility in individuals aged younger than 52 years old. Rs1801132 of ESR1 was significantly associated with the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the allele model and genetic models (P < .05). CONCLUSIONS This study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in the Chinese Han population. Further mechanism studies are needed to confirm the contribution of ESR1.
10.1016/j.clbc.2020.10.003
pubmed_665_22370
Viable microorganisms were found in Miocene lacustrine clays of the cypris formation excavated from 200-m below the surface as spoil during open-cast brown coal mining (Sokolov Brown Coal Basin, North-Western Bohemia, Czech Republic). Both saprotrophic microfungi of the genera Penicillium, Verticillium, Cladosporium and Aspergillus as well as heterotrophic bacteria were isolated from an intact sediment cores. Heterotrophic bacteria were classified by the MIS Sherlock System as representatives of genera Nocardiopsis, Arthrobacter, Micrococcus, Kocuria, Rothia, Clavibacter, Bacillus, Paenibacillus, Brevibacillus, Microbacterium, Acinetobacter and Pseudomonas. A bacterium found among the strains had an atypical fatty acids profile enriched by branched fatty acids and polyunsaturated fatty acid (18:3 omega 6) and gave no MIS Sherlock match. Phospholipid fatty acids analysis indicates a relatively high (535 pmol g(-1)) but inhomogeneously distributed viable microbial biomass. Fatty acids analyses of non-fractioned lipids (representing viable, storage and dead biomass; 8390 pmol g(-1)) detected rich and homogenous profiles with fungal, bacterial and actinomycetal markers but no protozoan and algal fatty acids markers.
10.1007/s10482-005-9044-8
pubmed_295_3957
INTRODUCTION Despite targeted efforts globally to address childhood overweight/obesity, it remains poorly understood and challenging to manage. Physiotherapists have the potential to manage children with obesity as they are experts in movement and physical activity. However, their role remains unclear due to a lack of physiotherapy-specific guidelines. This scoping review aims to explore existing literature, critically appraising and synthesising findings to guide physiotherapists in the evidence-based management of childhood overweight/obesity. METHOD A scoping review was conducted, including literature up to May 2020. A review protocol exists on Open Science Framework at https://osf.io/fap8g/. Four databases were accessed including PubMed, Embase, CINAHL, Medline via OVID, with grey literature searched through google via "file:pdf". A descriptive synthesis was undertaken to explore the impact of existing interventions and their efficacy. RESULTS From the initial capture of 1871 articles, 263 intervention-based articles were included. Interventions included qualitative focused physical activity, quantitative focused physical activity and multicomponent interventions. Various outcome measures were utilised including health-, performance- and behaviour-related outcomes. The general trend for physiotherapy involvement with children who are obese appears to favour: 1) multicomponent interventions, implementing more than one component with environmental modification and parental involvement and 2) quantitative physical activity interventions, focusing on the quantity of bodily movement. These approaches most consistently demonstrated desirable changes across behavioural and health-related outcome measures for multicomponent and quantitative physical activity interventions respectively. CONCLUSION When managing children with obesity, physiotherapists should consider multicomponent approaches and increasing the quantity of physical activity, given consistent improvements in various obesity-related outcomes. Such approaches are well suited to the scope of physiotherapists and their expertise in physical activity prescription for the management of childhood obesity. Future research should examine the effect of motor skill interventions and consider the role of environmental modification/parental involvement as factors contributing to intervention success.
10.1371/journal.pone.0252572
pubmed_885_25204
BACKGROUND Plaster has been used for centuries as a stiffening agent to treat fractures and other musculoskeletal conditions that require rest, immobilization, or correction of a deformity. Despite modern metallurgy and internal stabilization, plaster casts and splints remain an important means of external stabilization. Casting is a dying art as modern internal and external fixation replace external immobilization. Proper casting technique is paramount. This manuscript outlines the history and chemistry of immobilization materials and techniques as well as the differences among them and the advantages and disadvantages of each. METHODS Historical references, peer-reviewed journals, textbooks, and primary sources were reviewed to provide data for this review. RESULTS The history of immobilization reveals a progressive development and refinement of materials that culminated in Mathijsen's plaster bandage in 1851. In 1798, calcium sulfate (plaster of Paris) was introduced. By 1927, crinoline rolls dipped in plaster treated with binding agents facilitated application. Synthetic casting "tapes" (45% polyurethane resin and 55% fiberglass) were introduced in the 1970s. Splinting techniques are ancient, with development spurred by treatment of war wounds. Plaster relies on soft-tissue contact to maintain rigidity. There are well-known advantages, disadvantages, and complications of plaster management. Casting materials all create an exothermic reaction. Burns are associated with water temperatures of &gt;24°C, more than eight layers (ply), and inadequate ventilation. The maximum water temperature must be lower with fiberglass casts. Plaster was the definitive management for most fractures for over 100 years until it was replaced by modern surgical techniques involving internal fixation in the latter part of the twentieth century. CONCLUSIONS Plaster casts and splints remain an important treatment method for acute and chronic orthopaedic conditions.
10.2106/JBJS.L.00183
pubmed_648_11003
M1 metallopeptidases regulate many important biological processes such as angiogenesis, tumour growth, hormone regulation, and immune cell development. Knowledge of substrate specificity mechanism in this family is valuable. An M1 peptidase from Deinococcus radiodurans (M1dr) with preference for bulky hydrophobic residues at N-terminus of peptide substrates was recently reported. In contrast to Escherichia coli aminopeptidase N, a previously characterized M1 peptidase, M1dr exhibits reduced activity towards peptides with N-terminal Arg or Ala residue. In order to illuminate structural basis of substrate specificity, we report several crystal structures of M1dr with different amino acids bound to the active site. Structural analysis indicated that the enzyme makes subtle adjustments to multiple residues leading to significant volume change of the active site cavity to accommodate residues of varying sizes (Leu to Trp). This study further reveals that the low preference for Arg at N-terminus of peptide substrate arises from a non-productive conformation in which many of the Arg molecules bind where they block the proton donor essential for the peptidase reaction. Hence, this study illuminates the substrate-binding mechanism and also reveals the structural basis for the substrate specificity of M1dr enzyme.
10.1016/j.ijbiomac.2019.12.239
pubmed_969_4916
The effects of two cardioselective beta-blockers metoprolol and atenolol (2 mg/kg, intravenously) on the activity of the sympathetic renal nerve as well as the sensitivity of the chronotropic and sympathetic components of the baroreceptor reflex tested by using phenylephrine or sodium nitroprusside. In the experiments on conscious Wistar rats only the more lipophilic agent metoprolol significantly decreased the baseline level of the activity of the sympathetic nerve by 15%. The sensitivity of the chronotropic baroreceptor reflex elicited by a decrease of arterial blood pressure with sodium nitroprusside was reduced significantly both by metoprolol and atenolol. The tendency towards a decrease of the sensitivity of the chronotropic reflex elicited by phenylephrine-induced elevation of blood pressure was noted. The baroreflectory modification of the sympathetic activity did not change significantly under the influence of metoprolol and atenolol. The presence of the central component of action (of metoprolol) and the peripheral component (of the studied beta-blockers) is concluded.
pubmed_969_4916
pubmed_417_1910
We have studied the fusion between voltage-clamped planar lipid bilayers and influenza virus infected MDCK cells, adhered to one side of the bilayer, using measurements of electrical admittance and fluorescence. The changes in currents in-phase and 90 degrees out-of-phase with respect to the applied sinusoidal voltage were used to monitor the addition of the cell membrane capacitance to that of the lipid bilayer through a fusion pore connecting the two membranes. When ethidium bromide was included in the solution of the cell-free side of the bilayer, increases in cell fluorescence accompanied tee admittance changes, independently confirming that these changes were due to formation of a fusion pore. Fusion required acidic pH on the cell-containing side and depended on temperature. For fusion to occur, the influenza hemagglutinin (HA) had to be cleaved into HA1 and HA2 subunits. The incorporation of gangliosides into the planar bilayers greatly augmented fusion. Fusion pores developed in four distinct stages after acidification: (a) a pre-pore, electrically quiescent stage; (b) a flickering stage, with 1-2 nS pores opening and closing repetitively; (c) an irreversibly opened stage, in which pore conductances varied between 2 and 100 nS and exhibited diverse kinetics; (d) a fully opened stage, initiated by an instantaneous, time-resolution limited, increase in conductance leveling at approximately 500 nS. The expansion of pores by stages has also been shown to occur during exocytosis in mast cells and fusion of HA-expressing cells and erythrocytes. We conclude that essential features of fusion pores are produced with proteins in just one of the two fusing membranes.
10.1085/jgp.102.6.1131
pubmed_552_20718
Two intermediates, A and B, have been identified in the selective oxidation of saturated hydrocarbons to ketones by Gif-type systems. Intermediate A has been characterized as an Fev species with a secondary iron sigma-bond to carbon; it is captured by four different reagents or transformed into the second intermediate, B, which hydrolyzes to form a secondary alcohol. A mu-oxo Fe2III dimer is proposed as a basis for Gif-type reactivity. If the first iron is involved in the synthesis of intermediate A, the second is used to oxidize intermediate B intramolecularly to a ketal, which on hydrolysis yields a ketone. The enzyme methane monooxygenase shows a remarkable similarity to Gif-type systems in its selective hydrocarbon oxidation, particularly in the case of adamantane.
10.1073/pnas.87.9.3401
pubmed_240_589
A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
10.5732/cjc.012.10088
pubmed_2_20815
BACKGROUND The FDA recently approved an anti-CTLA-4 antibody (Iplimumab) for the treatment of metastatic melanoma. This decision was based on Phase III results, which demonstrate that blocking this immune checkpoint provides a survival advantage in patients with advanced disease. As a single agent, ipilimumab is also being clinically evaluated in advanced (metastatic, castrate-resistant) prostate cancer and two randomized, placebo-controlled Phase III studies have recently completed accrual. METHODS We used a well-described genetically engineered mouse (GEM), autochronous prostate cancer model (Pro-TRAMP) to explore the relative sequencing and dosing of anti-CTLA-4 antibody when combined with a cell-based, GM-CSF-secreting vaccine (GVAX). RESULTS Our results show that combined treatment results in a dramatic increase in effector CD8 T cells in the prostate gland, and enhanced tumor-antigen directed lytic function. These effects are maximized when CTLA-4 blockade is applied after, but not before, vaccination. Additional experiments, using models of metastatic disease, show that incorporation of low-dose cyclophosphamide into this combined treatment regimen results in an additional pre-clinical benefit. CONCLUSIONS Together these studies define a combination regimen using anti-CTLA-4/GVAX immunotherapy and low-dose chemotherapy for potential translation to a clinical trial setting.
10.1186/1479-5876-11-89
pubmed_527_8116
Two zinc germanates incorporating bidentate-bridging organic amine ligands have been synthesized under solvothermal conditions by using the amines as solvents. Their structural features are infinite chains formed of edge-sharing ZnO(4)N trigonal bipyramids and unbranched vierer single layers with the composition [Ge(4)O(10)] and discrete ZnO(2)N(2) tetrahedra and unbranched zweier double chains with the composition [Ge(2)O(5)], respectively.
10.1021/ic1004825
pubmed_628_5727
It is generally accepted that cyclic nucleotides are key signaling molecules in the control of oocyte meiotic resumption. Given the role of phosphodiesterases (PDEs) in cyclic nucleotide degradation, this study was undertaken to investigate the properties and regulation of PDEs expressed in rat oocytes. Cilostamide-sensitive PDE3 was the major activity detected in denuded oocytes, whereas no PDE3 activity could be detected in cumulus cells. Moreover, comparable levels of PDE3 activity were measured in cumulus-oocyte complexes (COCs) and in denuded oocytes. The oocyte PDE was recovered in the soluble fraction of the homogenate and immunoprecipitated with a specific PDE3A antibody. A significant and transient increase (P < 0.05) in PDE3 activity was measured in the oocytes after 30 min of culture (70 min after isolation) compared with immediately after collection (10 min after isolation). Conversely, no changes in activity were observed when denuded oocytes or cumulus cells were incubated for up to 130 min. Evaluation of oocyte maturation indicated that only 10% of oocytes had resumed meiosis at the peak of the PDE3 activity. A significant increase (P < 0.05) in PDE3 activity was measured in COCs when follicle-enclosed oocytes were cultured in the presence of hCG. Again, this increase preceded oocyte maturation. In conclusion, these data demonstrate that PDE3A is the major PDE form expressed in mammalian oocytes. PDE3A activity increases prior to resumption of meiosis in both spontaneous and gonadotropin-stimulated maturation. These findings strongly support the hypothesis that an increase in oocyte PDE3A activity is one of the intraoocyte mechanisms controlling resumption of meiosis in rat oocytes, at least in vitro.
10.1095/biolreprod65.5.1444
pubmed_282_14208
This review article provides an overview of hybrid and nanocomposite materials used as biomaterials in nanomedicine, focusing on applications in controlled drug delivery, tissue engineering, biosensors and theranostic systems. Special emphasis is placed on the importance of tuning the properties of nanocomposites, which can be achieved by choosing appropriate synthetic methods and seeking synergy among different types of materials, particularly exploiting their nanoscale nature. The challenges in fabrication for the nanocomposites are highlighted by classifying them as those comprising solely inorganic phases (inorganic/inorganic hybrids), organic phases (organic/organic hybrids) and both types of phases (organic/inorganic hybrids). A variety of examples are given for applications from the recent literature, from which one may infer that significant developments for effective use of hybrid materials require a delicate balance among structure, biocompatibility, and stability.
10.2174/1381612823666170710160615
pubmed_994_3420
BACKGROUND Cardiac resynchronization therapy (CRT) relies on sufficient left ventricular (LV) pacing with safety margin to phrenic nerve stimulation (PNS). Previous studies introduced LV vector reprogramming in bipolar coronary sinus leads to optimize LV pacing and avoid PNS. We investigated the efficacy and reliability of quadripolar leads in CRT. METHODS The EffaceQ study enrolled 344 patients with de novo CRT implantation with a quadripolar LV lead in an observational, prospective multicenter study. The study was powered to demonstrate that in at least 90% of patients with an implanted quadripolar LV lead, a viable LV pacing configuration (LVPC) is available (primary end point: LV pacing threshold ≤2.5 V/0.5 ms, sufficient PNS margin). RESULTS Quadripolar leads were successfully implanted in 96% of patients. A total of 278 of 299 (93.0%) patients with complete data met the criteria for viable LVPC. With the use of traditional LVPCs, a viable LVPC would have been available (268 of 299 patients; P = 0.002) in significantly fewer patients (89.6%). In any LVPC, PNS was inducible in 65.0% of patients and 22.6% of patients reported PNS during ambulatory 3-month follow-up. LVPC reprogramming was performed in 49.8% of patients. PNS inducibility decreased from distal to proximal electrodes, whereas LV pacing thresholds increased from distal to proximal. At prehospital discharge, 5.9 ± 2.8 viable LVPCs were observed, stable during follow-up. The quadripolar electrode offered significantly more LVPC for LV optimization and PNS avoidance. CONCLUSION Quadripolar LV leads yield high numbers of patients with viable LVPCs and alternatives for noninvasive repositioning of LV pacing.
10.1111/pace.12664
pubmed_769_13000
AIM AND OBJECTIVE To study the radiological and functional outcomes as well as complications in the management of fractures involving both columns of the acetabulum using a single surgical approach. DESIGN Type IV, prospective clinical study. SETTING Level I trauma centre. MATERIALS AND METHODS Inclusion criteria were as follows: (a) patients over 20 year of age and (b) patients suffering from acetabular fractures involving both columns as per Letournel and Judet classification, namely transverse, transverse + posterior wall, T type, anterior column posterior hemi-transverse (ACPHT) and associated both columns. Exclusion criteria were as follows: (a) patient suffering from isolated anterior column, posterior column, anterior wall, posterior wall and posterior wall + column fractures; (b) patient who have undergone surgical procedures of the hip prior to trauma; and (c) compound acetabular fractures. A total of 23 patients having both column acetabulum fractures were included prospectively from June 2016 to December 2018 and followed up till 1 year postoperatively. Open reduction and internal fixation were performed through one of three described approaches, i.e., iliofemoral, Kocher-Langenbeck, and anterior intrapelvic or ilioinguinal. RESULTS Our study population consisted of 30.4% transverse, 39.1% associated both columns, 21.7% T type and 8.7% anterior column + posterior hemi-transverse. Of these, 65.2% were operated using the Kocher-Langenbeck approach, while 30.4% of patients required the anterior intrapelvic approach. The remaining 4.3% of patients were operated by the iliofemoral approach. Anatomic reduction was achieved in 100% of our study population with remaining displacement less than or equal to 1°mm. At 1-year follow-up, all fractures showed a satisfactory union with an excellent Matta index in 100% study subjects. Complications at 1 year included one case of foot drop, which was present preoperatively but failed to improve and one case of post-traumatic arthritis. Average Harris Hip score (HHS) and mean Merle D'Aubigne (MDA) scores suggested good clinical outcomes in the study population. CONCLUSIONS A single approach can be used to achieve good functional and radiological outcomes in carefully selected bicolumnar fractures of the acetabulum, with less approach-related morbidity. CLINICAL SIGNIFICANCE Traditionally, multiple approaches are used for acetabulum fractures involving both columns, but with proper patient selection, single approach can be used with good functional and surgical outcomes. HOW TO CITE THIS ARTICLE Patil A, Attarde DS, Haphiz A, et al. A Single Approach for Management of Fractures Involving Both Columns of the Acetabulum: A Case Series of 23 Patients. Strategies Trauma Limb Reconstr 2021;16(3):152-160.
10.5005/jp-journals-10080-1541
pubmed_636_13995
The mammalian epididymis plays a role in sperm maturation through its secretory activity. Among the proteins secreted by the epithelium, there are significant amounts of acid hydrolases. In most cell types, the normal distribution of lysosomal enzymes is mediated by mannose-6-phosphate receptors (MPRs). In this study, we analysed the expression and distribution of the cation-dependent MPR (CD-MPR) in epididymis from control, castrated or castrated rats with testosterone replacement. It was observed that expression of CD-MPR increased due to castration in all regions of the epididymis, which was reversed by injection of testosterone. We also measured the activity of α-mannosidase and observed that the castration tends to increase the retention of this enzyme in the tissue, which is reversed by the hormone replacement. In corpus, this resulted in a reduced secretion of the enzyme. Immunohistochemistry showed that CD-MPR has a supranuclear location (different from the cation-independent MPR), most likely in principal cells, and low reactivity in other cell types. The signal in castrated animals was more intense and tended to redistribute towards the apical cytoplasm. Thus, we concluded that expression and distribution of CD-MPR is affected by decrease of testosterone in rat epididymis, and this could change the distribution of lysosomal enzymes.
10.1111/and.12065
pubmed_629_22981
The results of chronic experiments on dogs showed that leu-enkephalin in doses 1, 7, and 9 microg/kg produced different effects on the gastric secretion and excretion on the background of various stimulants. The maximum protective effect of opiate was produced in a dose of 7 microg/kg. The peptide effect depended on the gastric secretion stimulator used: on the background of carbachol and pentagastrine, the activity of acidic and peptic factors was decreased and the protective factors of gastric juice were increased. In the case of histamine, leu-enkephalin increased the juice acidity and mucus secretion, but decreased the activity of pepsin and the excretion of ammonia from the stomach.
pubmed_629_22981
pubmed_608_14775
The big conductance Ca2+-dependent K+ channel, also known as BK, MaxiK, Slo1, or KCa1.1, is a ligand- and voltage-gated K+ channel. Although structure-function studies of the past decades, involving mutagenesis and electrophysiological measurements, revealed fine details of the mechanism of BK channel gating, the exact molecular details remained unknown until the quaternary structure of the protein has been solved at a resolution of 3.5 Å using cryo-electron microscopy. In this short review, we are going to summarize these results and interpret the gating model of the BK channel in the light of the recent structural results.
10.1139/cjpp-2018-0516
pubmed_75_14958
Subjectivity and observer variation in non-Hodgkin's lymphoma continues to plague current classification schemes. It was thought important to assess objectively derived morphometric data to see if three categories of follicular center cell (FCC) lymphomas, follicular small cleaved cell, follicular mixed small cleaved and large cell, and diffuse and nodular large cell, actually fall into distinctly separate classes based on nuclear parameters. Mean nuclear area, contour index and invagination depth of neoplastic lymphocytes, and the percentage of invaginated and clefted nuclear profiles in each example of FCC lymphoma were evaluated by three different approaches. Results obtained from distribution of the morphometric data in scatter diagrams, calculation of the overlap index, and linear regression values, all revealed considerable (but variable) degrees of overlap between the three FCC subtypes regardless of the nuclear parameter employed. Where separation between FCC lymphomas was maximal, although still incomplete, there was no consistent correlation between the nuclear parameter and the pair of FCC lymphomas being compared. At least in terms of nuclear morphological features, non-Hodgkin's lymphomas of FCC type seem to represent a continuum of one disease process. The information provides a basis for understanding some reasons underlying the problem of observer variation in non-Hodgkin's lymphoma.
10.1002/1097-0142(19861201)58:11<2477::aid-cncr2820581121>3.0.co;2-l
pubmed_1065_15275
This article presents the case report of a 31-year-old patient of mine with both an inflamed prostate gland and, unknown to his doctor, premature ejaculation, both of which were treated successfully by the antibiotic ciprofloxacin.
10.1080/009262300438760