Postoperative marijuana use and disordered eating among bariatric surgery patients.
Current literature is scarce in documenting marijuana use after bariatric weight loss surgery (WLS). The objective of this study was to explore the association among marijuana use patterns, disordered eating, and food addiction behaviors in patients 2 years after WLS. A university hospital in the United States. Participants (N = 50, mean age 28 y, standard deviation = 5.8) were administered a structured assessment that included the Addiction Severity Index, Yale Food Addiction Scale, Eating Disorder Examination Questionnaire, and Disordered Eating Questionnaire. Marijuana use was defined based on the Addiction Severity Index as current use (within 30 d), recent use (use in last year), and increased use (increased use since surgery). Data were analyzed using Fisher's exact tests and linear regression methods adjusting for age, gender, race/ethnicity, time since surgery, and change in body mass index. The majority of the sample was female (76%) and underwent Roux-en-Y gastric bypass (62%). Eighteen percent (18%) of the sample reported current marijuana use; 38% reported recent use; and 21.4% reported increased use post-WLS. A loss of controlled food intake was associated with current (P = .02) and increased post-WLS use (P = .01). Increased use and/or regular marijuana use predicted higher scores on eating disorder subscales compared with respective counterparts (P<.05). Current use did not significantly predict higher scores on the Yale Food Addiction Scale. Findings indicated marijuana use in post-WLS patients despite recommendations against use. A subgroup of WLS patients may be at risk for disordered eating post-WLS, particularly those who used marijuana before surgery, and should be closely monitored for several years post-WLS.


Evaluation of exogenous insulin homoeostasis by the artificial pancreas in insulin-dependent diabetes.
With the artificial pancreas used by the authors, insulin was delivered through a venous infusion and the rate of delivery was adjusted according to data provided by a continuous blood glucose monitor. After different trials we selected control algorithms integrating two parameters: instantaneous blood glucose concentration and increasing or decreasing patterns of blood glucose. A constant basal insulin infusion rate was added and improved the control of glycaemic excursions. Different parameters concerning exogenous insulin homoeostasis were determined. The delay to reach an insulin effect was 18+/-2 min and was shortened by a priming-dose at the beginning of the infusion. The insulin effect remained for 28+/-2 min after the infusion had been stopped, but differences were noted in the morning (21+/-2 min), in the afternoon (32+/-2 min) and during the night (25+/-3 min). Insulin needs were evaluated during meals. Related to the amount of carbohydrates, the doses fell from 0.53 units/hr/g of carbohydrate for breakfast to 0.15 for dinner. From these data, it appears that the efficiency of exogenous insulin exhibits a circadian rhythm.


Enhanced antibody responses to antigens presented on autologous erythrocytes.
On a dose basis, antigen coupled to autologous red blood cells is 1,000--10,000-fold more efficient at inducing an antibody response than the soluble form. More than one antigen can be coupled simultaneously to the same red blood cells. Under these circumstances, prior immunization with one antigen enhances the antibody response to the other antigen, provided both antigens are coupled to the same red cell. Thus, the technique of coupling antigens to red blood cells is a means of producing high-titred antisera without the use of adjuvant and also represents a useful procedure for preparing composite antigens for probing cell-cell interaction in the immune response.


[Longitudinal study of the gingival status during transitional dentition].
253 milk teeth with inflamed gingiva were observed for 19 months (on average) around the time of exfoliation and changeover to the secondary dentition. The criteria used were the gingival index by Löe and Silness, the intravital staining of glycogen with iodine solution by Zabinska and the plaque index by Quigley and Hein. In about one third of the cases, there was residual inflammation following loss of the milk teeth in the original area. With eruption of the permanent teeth, plaque level increased as did the degree of gingival inflammation. On full eruption of the permanent dentition the values fell under their former level.


Presidential address: E pluribus unum.
To promote the best possible overall pediatric surgical care, I think that this may be the time that we should consider making common cause with other surgical specialists who work in the pediatric age range. This will need cooperative organization in our hospitals, medical schools, and on the national level. We now need a combined strong voice to deal with the large organizations through which the policies and the funding are being decided. We must now "hang together, or we (and our patients) may all hang separately".


Structural analogues of cumambrin B from the flower of Chrysanthemum boreale.
The structural analogues of cumambrin B (1, 2, 3, 4) were isolated from the flower of Chrysanthemum boreale Makino. The structures of compounds were determined by two-dimensional 1H-1H COSY and 13C-1H COSY spectra with the aid of homonuclear and heteronuclear double resonance experiment. The stereochemistry of compounds has been verified from single crystal X-ray diffraction of cumambrin A (2). The antimicrobial activities of these guaianolides have been studied.


Genotyping Two Promoter Polymorphisms in the MIF Gene: A -794 CATT5-8 Microsatellite Repeat and a -173 G/C SNP.
Macrophage migration inhibitory factor (MIF) is an upstream proinflammatory cytokine encoded by a functionally polymorphic locus. The promoter region of the human MIF gene contains two polymorphisms. A variable nucleotide tandem repeat at position -794 comprises five to eight CATT repeats (referred to henceforth by numbers from 5 to 8, rs5844572). Gene reporter assays show a proportional increase in transcription with CATT repeat number; the 5-repeat allele leads to low expression, and the 6-, 7-, and 8-repeat alleles lead to correspondingly higher expression of MIF. A second MIF promoter polymorphism comprises a G-to-C single nucleotide polymorphism (SNP) at position -173 (rs755622), which is in strong linkage disequilibrium with -794 7-CATT and is associated with arthritis clinical severity and higher serum and synovial fluid MIF levels. This allele also has been reported to confer improved survival in patients with outpatient pneumonia. In this chapter, we will introduce the methods of genotyping CATT5-8 repeats and the MIF -173 G/C from human samples.


Unemployment and suicide. Evidence for a causal association?
To determine the independent associations of labour force status and socioeconomic position with death by suicide. Cohort study assembled by anonymous and probabilistic record linkage of census and mortality records. 2.04 million respondents to the New Zealand 1991 census aged 18-64 years. Suicide in the three years after census night. The age adjusted odds ratios (95% confidence intervals) of death by suicide among 25 to 64 year olds who were unemployed compared with employed were 2.46 (1.10 to 5.49) for women and 2.63 (1.87 to 3.70) for men. Similarly increased odds ratios were observed for the non-active labour force compared with the employed. Strong age only adjusted associations of suicide death with the socioeconomic factors of education (men only), car access, and household income were observed. Compared with those who were married on census night, the non-married had odds ratios of suicide of 1.81 (1.22 to 2.69) for women and 2.08 (1.66 to 2.61) for men. In a multivariable model the association of socioeconomic factors with suicide reduced to the null. However, marital status and labour force status remained strong predictors of suicide death. Unemployment was also strongly associated with suicide death among 18-24 year old men. Sensitivity analyses suggested that confounding by mental illness might explain about half, but not all, of the association between unemployment and suicide. Being unemployed was associated with a twofold to threefold increased relative risk of death by suicide, compared with being employed. About half of this association might be attributable to confounding by mental illness.


MRI of benign hyperplasia in the nasopharynx: is there an association with Epstein-Barr virus?
To evaluate whether there is an association between persistently positive plasma Epstein-Barr virus (EBV) DNA and the presence and the change in benign hyperplasia. One hundred and seventeen participants with positive-plasma EBV-DNA, but without NPC from previous nasopharyngeal carcinoma (NPC) screening, underwent follow-up magnetic resonance imaging (MRI) and plasma EBV-DNA after 2 years. Logistic regression was used to analyse associations between MRI (benign hyperplasia on the follow-up MRI and change from 2 years earlier), and plasma EBV-DNA, smoking, and age. At follow-up, EBV-DNA positivity and smoking were independent parameters for the presence of benign hyperplasia (p=0.027 and 0.023 respectively). Compared with participants in whom EBV-DNA became negative (n=44/117 37.6%), those in whom EBV-DNA remained positive (n=73/117 62.4%) had a greater risk of benign hyperplasia developing (previous MRI normal), being stable or processing (52/73 71.2% versus 18/44 40.9%; p=0.001). These results suggest a potential link between benign hyperplasia on MRI and the EBV. As EBV contributes to NPC oncogenesis, future MRI research is warranted to determine if persistent benign hyperplasia is a risk marker for development of NPC.


Effects of hormonal treatment on the contralateral descended testis in unilateral cryptorchidism.
One of the therapeutic options in the treatment of cryptorchidism is hormonal therapy with luteinizing hormone releasing hormone (LHRH) and/or human chorionic gonadotropin (HCG); concerns have, however, been raised regarding its safety. The purpose of this study was to demonstrate that hormonal therapy improves the abnormal histology of the contralateral descended testis without harming the germ cells. Patients with unilateral cryptorchidism were randomized into two groups: those treated with orchiopexy alone and those treated with LHRH long acting analog and HCG. Biopsies taken from contralateral descended testes were analyzed and compared with controls. The number of germ cells per tubule in contralateral testes of patients treated with orchiopexy alone is significantly lower than the number of germ cells in testes of patients with spontaneously descended testes (P<0.0001). Hormonal therapy did not have any adverse effect upon the histology of the contralateral testis, but in fact improved it. Seven weeks of hormonal therapy induced a rise in the number of germ cells per tubule (P<0.05). It was also beneficial for the number of adult dark spermatogonia per tubule and the number of primary spermatocytes, although these differences did not reach statistical significance. The contralateral testis in patients with unilateral cryptorchidism is abnormal. Hormonal therapy improves the histopathology of the contralateral testis without harming the germ cells.


Diffuse large B-cell lymphoma in octogenarians aged 85 and older can benefit from treatment with curative intent: a report on 129 patients prospectively registered in the Elderly Project of the Fondazione Italiana Linfomi (FIL).
Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.


Reperfusion in acute myocardial infarction: effect of timing and modulating factors in experimental models.
Timely reperfusion of ischemic myocardium in experimental animals halts the advancing transmural "wavefront" of ischemic cell death and thereby limits myocardial infarct size by limiting its transmural extent. The time window of opportunity for such salvage in most experimental models of regional ischemia is the first 3 hours. The number of myocytes that can be salvaged by reperfusion decreases exponentially during this period, such that at 3 hours, reperfusion limits infarct size by only about 10%. The rate of lethal ischemic cell injury and therefore the amount of myocardium that can be salvaged by reperfusion after a particular duration of ischemia is dependent both on the degree of blood flow deficit and the rate of ischemic metabolism. In experimental animal models, several interventions, including hypothermia, calcium antagonists, and "ischemic preconditioning," have been shown to reduce the rate of ischemic metabolism and to limit myocardial infarct size when assessed after a defined period of ischemia and reperfusion. Hypothetically, interventions that could prevent additional myocyte necrosis caused by some deleterious aspects of reperfusion ("lethal reperfusion injury") also could serve as valuable adjunctive therapy. However, studies of therapies designed to prevent lethal reperfusion injury have produced conflicting results. Thus, the concept that lethal reperfusion injury occurs remains controversial. Experimental evidence indicates that reperfusion accelerates both the initial inflammatory response and later process of infarct repair. Late reperfusion of infarcts in dogs, which does not limit myocardial infarct size, appears to accelerate the replacement of necrotic myocardium by scar without altering the size of the final scar.


Prevalence of asymptomatic malaria infection and use of different malaria control measures among primary school children in Morogoro Municipality, Tanzania.
Malaria is a public health problem in Tanzania affecting all age groups. It is known that school children are the age group most commonly infected with malaria parasites. Their infections are usually asymptomatic, go unnoticed and thus never get treated, result in anaemia, reduced ability to concentrate and learn in school and if fallen sick may lead to school absenteeism. Effective malaria control requires frequent evaluation of effectiveness of different malaria interventions. A cross-sectional study design involving 317 out of 350 school children aged 6-13 years from five primary schools within municipality was conducted. Multistage cluster sampling and simple random sampling methods were used to obtain primary school and study participants, respectively. Finger-prick blood samples were collected for Plasmodium parasite detection by malaria rapid diagnostic test (mRDT) and haemoglobin level assessment by Easy Touch(®) GHb system machine. A questionnaire was administered to assess use of insecticide-treated nets (ITNs) and anti-malarial drugs. The prevalence of asymptomatic malaria was 5.4 % (95 % CI 3.3-8.6 %) and anaemia was 10.1 % (95 % CI 7.2-13.9 %). School children aged 6-9 years were more affected by malaria than those aged 10-13 years. The proportion of ITNs used was 90.6 % (95 % CI 86.3-93.9 %) while that of artemisinin combination therapy (ACT) was 71.9 % (95 % CI 66.2-77.1 %). Findings show existence of asymptomatic malaria and walking anaemia among primary school children in Morogoro municipality. The majority of school children reported use of ITNs and ACT for malaria control. These findings provide a rationale for using schools and school children to assess effectiveness of malaria interventions.


The prognostic yield of biomarkers harvested in chemotherapy-naive stage II colon cancer: can we separate the wheat from the chaff?
The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction. However, few such biomarkers have reached widespread clinical utility. For the clinician swimming in the sea of emerging biomarkers, it may be hard to recognize the true floating aid from the surrounding debris in the search for more precise decision-making. Proposed markers include microsatellite instability (MSI), KRAS mutations and BRAF mutations, but a number of gene panels and consensus molecular subtypes are proposed for clinical prediction and prognostication as well. While several studies suggest such biomarkers or panels to have a prognostic role in subgroups of patients, a number of studies are reported in heterogeneous groups with in part discordant findings, which again distorts the predictive and prognostic ability of each marker. Lack of homogeneous cohorts, underpowered studies in strict subgroups and challenges in analytical and clinical validity may hamper the progress towards widespread clinical utility. The harvest of prognostic biomarkers in colon cancer has yielded a huge number of candidates for which it is now time to separate the wheat from the chaff.


Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model.
We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part of several phase II protocols and the majority received treatment with intermediate dose subcutaneous IL-2 and interferon-alpha. Neutrophil and monocyte counts, lactate dehydrogenase (LDH), number of metastatic sites, location of metastases and performance status were all statistically significant prognostic factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P<0.001, hazard ratio 2.8), elevated neutrophil counts (P=0.02, hazard ratio 1.4) and a performance status of 2 (P=0.008, hazard ratio 1.6) as independent prognostic factors for poor survival. An elevated monocyte count could replace an elevated neutrophil count. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the three independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 12.6 months (95% confidence interval (CI), 11.4-13.8), 6.0 months (95% CI, 4.8-7.2) and 3.4 months (95% CI, 1.2-5.6), respectively. The low-risk group encompassed the majority of long-term survivors, whereas the patients in the high-risk group with a very poor prognosis should probably not be offered IL-2-based immunotherapy.


Experimental data on the development of "Post-installed Screw Pullout test" for in-situ investigation of concrete strength.
This data article describes the datasets obtained during the development phase of "Post-installed Screw Pullout (PSP) test", a new in-situ test for concrete strength assessment. The datasets presented focus on the results obtained in mortar samples. The presented PSP test method is based on a post-installed screw being pulled from the parent material. To implement this, the screws installed in mortar sample were loaded to failure and the responses were recorded in the form of load-displacement curves. The samples were tested for two types of screw under different test conditions, with variables that included hole depth, hole diameter and mortar strength. These datasets are associated with the article "The Post-installed Screw Pullout Test: Development of a Method for Assessing In-situ Concrete Compressive Strength" (Al-Sabah et al., 2020).


Surgical technic for the resection of internal carotid aneurysms using an internal shunt.
A technic for reconstruction of the internal carotid artery after resection of carotid aneurysms is presented. Reconstruction is performed over an internal shunt using a vein or Dacron patch. Total interruption of cerebral circulation is usually less than three minutes. The technic is described in detail. Oculoplethysmographic and phonoangiographic follow-up studies demonstrate normal carotid flow.


Effect of pregnancy on the speaking voice.
The study aims to investigate the vocal symptoms and acoustic changes in pregnant women pre- and postpartum in comparison to the controls. A total of 25 pregnant women who presented for delivery were enrolled in this study. Twenty-one nonpregnant women were matched as controls. Vocal symptoms such as hoarseness, vocal fatigue, and aphonia were assessed. Acoustic analysis included fundamental frequency (F(0)), habitual pitch, relative average perturbation (RAP), shimmer, noise-to-harmony ratio (NHR), and maximum phonation time (MPT). There were no significant differences in the incidence of vocal symptoms in pregnant women versus controls. However, vocal fatigue was more prevalent in the pregnant group. With respect to the acoustic parameters, there was a significant decrease in the MPT at term. The rest of the variables were comparable. Postpartum, the MPT significantly increased and there was an increase in F(0) and a significant decrease in the voice turbulence index (VTI). Pregnant women have more vocal fatigue and a reduction in MPT compared to the controls. Immediately after delivery, there is a significant increase in MPT.


PI3K/Akt-dependent transcriptional regulation and activation of BMP-2-Smad signaling by NF-kappaB in metastatic prostate cancer cells.
Bone morphogenetic proteins (BMPs) exert osteoinductive effects in prostate cancer (PC) via uncharacterized mechanisms. In this study, we investigated whether the nuclear transcription factor NF-kappaB, implicated in PC metastasis, is involved in transcriptional regulation and activation of BMP-2 or BMP-4/Smad signaling in PC cells. NF-kappaB inhibition was achieved by IkappaBalpha super-repressor adenoviral vector and activation was monitored by EMSA and reporter assays. BMP expression and activation was measured by PCR and reporter assays. Promoter binding assay was performed by chromatin immunoprecipitation (ChIP) assay. Smad1/5/8 phosphorylation was measured by Western blot analysis. PCR and chimeric BMP-2 and BMP-4 luciferase assays demonstrate that NF-kappaB confers robust and selective activation of BMP-2 in p65 overexpressing or rhTNF-alpha-stimulated PC cells. Inhibition of NF-kappaB significantly reduced transcript levels and autocrine production of BMP-2 by rhTNF-alpha stimulated C4-2B cells and to a lesser extent by the parental LNCaP cells. Selective inhibition of PI3K/Akt suppressed the NF-kappaB-induced BMP-2 promoter activity. Furthermore, suppression of NF-kappaB activation decreased the transcript levels and BMP-2-induced phosphorylation of Smad1/5/8, critical downstream targets of BMP-2 signaling in PC cells. Notably, the activation of BMPRII by BMP-2 is required for modulation of Smad activation by NF-kappaB in PC cells. Based on ChIP analysis, the transcriptional regulation of BMP-2 gene by NF-kappaB may be partially attributed to binding to kappab site on the BMP-2 promoter. The data suggest that PI3K/Akt-NF-kappaB axis may promote PC bone metastasis in part by regulating transcription and activation of the BMP-2-Smad signaling cascade in osteotropic PC cells.


Hydrogen peroxide (H2O2) as a source of dissolved oxygen in COD-degradation respirometric experiments.
Two different re-oxygenation techniques (aeration and hydrogen peroxide addition) were compared in respirometric experiments. As similar results were obtained in both cases, it was concluded that the addition of hydrogen peroxide does not modify the oxygen uptake rate of the biomass, under either endogenous or feeding conditions. It was hypothesized that under those experimental conditions (inhibition of nitrification with ATU), hydrogen peroxide alters neither the biomass metabolism nor the biodegradability of the tested substrates. The oxygen uptake rates obtained with the aeration system were often more scattered due to the adhesion of fine bubbles after the switch off of the aeration. Moreover, the transfer rate of oxygen to the solution is faster in the case of hydrogen peroxide addition.


Premedication with orally administered lorazepam in adults undergoing ERCP: a randomized double-blind study.
Restlessness often complicates ERCP and may be a reason for premature termination of the procedure. Our purpose was to evaluate whether a premedication with orally administered lorazepam could reduce the need for sedatives and improve sedation quality. Randomized double-blind trial. Therapeutic ERCP with an intravenous sedation containing midazolam, propofol, and S(+)-ketamine. 95 inpatients (aged 20-91 years). 1 mg of lorazepam (n=47) or placebo (n=48) given orally before ERCP. Total amount of administered propofol. Heart rate, blood pressure, number of oxygen desaturations, and states of restlessness did not differ between the groups. The same amount of midazolam was administered in both groups. There was no significant difference in the total amount of propofol to achieve adequate sedation (lorazepam vs placebo: 71+/-5 vs 63+/-4 microg/kg/min, mean+/-SE). Paradoxically, patients pretreated with lorazepam even needed more propofol in the early phase of sedation (275+/-39 vs 159+/-37 microg/kg in minutes 5-10, P<.05) and the total amount of ketamine administered was higher in this group as well (15.8+/-1.4 vs 11.3+/-1.2 microg/kg/min, P<.05). In both groups there were high rates of satisfaction with the course of the procedure evaluated both by the endoscopists and the patients. The trial failed to show an advantage of an oral premedication with lorazepam. The amount of sedatives administered in the lorazepam group even tended to be higher. A premedication with lorazepam may be counterproductive when followed by sedation containing another benzodiazepine.


Occurrence of gustducin-immunoreactive cells in von Ebner's glands of guinea pigs.
An immunohistochemical examination of guinea-pig taste buds in vallate papillae revealed gustducin-immunoreactive cells in the area of von Ebner's glands, minor salivary glands. Since there have been no reports describing those cells in these locations for other species, we investigated these glands in order both to localize the cells and compare their immunoreactive characteristics with corresponding cells in the vallate taste buds. The gustducin-immunoreactive cells coincided with cells containing no secretory granules in the end portion of the glands, which was supported by the electron-microscopic immunocytochemistry. Double immunofluorescence microscopy confirmed these cells to be entirely immunopositive to type III inositol 1,4,5-triphosphate receptor (IP3R-3), phospholipase Cβ2 (PLCβ2), and villin and also partly immunopositive to neuron-specific enolase (NSE) and calbindin D-28K. The gustducin-immunoreactive cells in the vallate taste buds exhibited completely the same immunoreactivities for these five molecules. Accordingly, the present results give credence to a consideration that the gustducin-immunnoreactive cells in both locations are identical in function(s) e.g., chemo-reception.


The impact of a quality improvement initiative to reduce denture loss in an acute hospital.
Background Denture loss is a significant problem for patients admitted to hospital in the UK. Initiatives aimed at staff and patients have been introduced at many hospitals to try and reduce and solve this issue.Aim This investigation aimed to evaluate the impact of a quality improvement programme on denture loss at an acute hospital, including the reasons dentures were reported as lost or broken and who reported them.Method Information on dentures which were lost or broken was collected in an acute hospital between 2016-2021 and included the number of losses, the reason for the loss/breakage and who reported them. The number of complaints and financial reimbursement related to denture loss was also obtained from the trust for the same period.Results In total, 123 dentures were reported as lost or broken between 2016-2021. The most commonly reported reasons for loss were patient transfers between wards, being left on hospital trays, or when patients were sleeping. Patients or carers are more likely to report a lost denture compared to hospital staff. Reimbursement paid by the trust for denture incidents is much lower than the numbers reported.Conclusion Creating a single reporting pathway for denture loss and implementing methods to reduce denture loss led to an increase in the numbers of dentures reported as lost. This is likely to be attributed to an increased awareness of reporting pathways. Denture loss is a significant financial burden to the NHS, in addition to causing patients and families distress and is most likely under-reported in many hospitals.


Appropriate use of intravenous proton pump inhibitors in the management of bleeding peptic ulcer.
Rebleeding from peptic ulcers is a major unsolved problem in the management of acute upper gastrointestinal bleeding. Our goal was to review what is known and what remains to be learned about the effectiveness of antisecretory therapy for acute upper gastrointestinal bleeding. We reviewed the data regarding the effectiveness of endoscopic therapy, the prediction of those at increased risk for rebleeding, and the effectiveness of antisecretory drug therapy in preventing rebleeding with or without endoscopic hemostasis. Proton pump inhibitor therapy without endoscopic hemostasis is ineffective clinically for stopping bleeding or preventing rebleeding. Endoscopic hemostasis remains the cornerstone of therapy. The data are consistent with the notion that reliable maintenance of the intragastric pH at > or = 6 after endoscopic hemostasis is associated with the lowest rebleeding rates. H2-receptor antagonists are ineffective for achieving this goal. Intermittent bolus and oral administration of proton pump inhibitors are equivalent and fail to achieve this goal, which can only be accomplished by bolus administration of a proton pump inhibitor (e.g., 80 mg) followed by a constant infusion (e.g., 8 mg/hr). Whether the combination of endoscopic hemostasis and pH control is equal or superior to selected second-look endoscopy is unknown. A treatment algorithm is suggested.


Simvastatin attenuates cardiopulmonary bypass-induced myocardial inflammatory injury in rats by activating peroxisome proliferator-activated receptor γ.
Statins have been shown to downregulate the systemic inflammatory response after cardiopulmonary bypass. However, the role of statins as anti-inflammatory agents in heart tissue remains unknown. The aim of this study was to test whether statin pretreatment attenuates local inflammatory cytokines production in heart and to explore whether the underlying mechanism involves peroxisome proliferator-activated receptor (PPAR) γ. A rat model of cardiopulmonary bypass was established. The animals were pretreated with simvastatin 5 mg/kg/day or 10 mg/kg/day for 7 days before operation. The serum concentration and myocardial level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 was evaluated by enzyme linked immunosorbent assay. The polymorphonuclear neutrophils accumulation in heart tissue was determined by myeloperoxidase activity assay. The activity of nuclear factor (NF)-κB and PPARγ in the heart was determined by electrophoretic mobility shift assay. The myocardial PPARγ expression was also examined by immunohistochemistry. The systemic and local TNF-α, IL-6 and MCP-1 were all significantly elevated after cardiopulmonary bypass. In contrast, simvastatin pretreatment significantly decreases the serum and myocardial expression level of above cytokines, myocardial myeloperoxidase activity and myocardial NF-κB activity. However, there was an evident increase in the activity and expression of PPARγ. In conclusion, simvastatin pretreatment not only attenuates acute systemic and local inflammatory response induced by cardiopulmonary bypass. The anti-inflammatory effect of simvastatin in myocardium may be partly related to the activation of PPARγ and inhibition of NF-κB.


Oxidative and apoptotic effects of lambda-cyhalothrin modulated by piperonyl butoxide in the liver of Oreochromis niloticus.
The aim of this study was to investigate the toxic effects of pyrethroid pesticide lambda-cyhalothrin in the presence of piperonyl butoxide as a modulator in the liver of juvenile Oreochromis niloticus. LC(50) (96h) value of lambda-cyhalothrin was determined as 2.901μg/L for O. niloticus. The fish were exposed to 0.48μg/L (1/6 of the 96-h LC(50)) lambda-cyhalothrin and 10μg/L piperonyl butoxide for 96-h and 15-d. tGSH, GSH, GSSG, Hsp70 and TBARS contents, GPx, GR, GST and caspase-3 enzymes activities were determined. Lambda-cyhalothrin caused increases in tGSH, GSH, TBARS contents, and GST activity. Piperonyl butoxide treatment with lambda-cyhalothrin caused significant increases in tGSH GSH, Hsp70, TBARS contents, and GPx and GST activities while caspase-3 activity was decreased. The results of the present study revealed that lambda-cyhalothrin caused oxidative stress which upregulated GSH and GSH-related enzymes. Piperonyl butoxide increased the oxidative stress potential and apoptotic effects of lambda-cyhalothrin.


Retraction: a narrative review of long noncoding RNA: insight into neural ischemia/reperfusion mediated by two pathophysiological processes of injury and repair.
[This retracts the article DOI: 10.21037/atm-22-268.].


Molecular characterization of a novel His333Arg variant of human protoporphyrinogen oxidase IX.
Variegate porphyria is caused by mutations in the protoporphyrinogen oxidase IX (PPOX, EC 18.104.22.168) gene, resulting in reduced overall enzymatic activity of PPOX in human tissues. Recently, we have identified the His333Arg mutation in the PPOX protein (PPOX(H333R)) as a putative founder mutation in the Moroccan Jewish population. Herein we report the molecular characterization of PPOX(H333R) in vitro and in cells. Purified recombinant PPOX(H333R) did not show any appreciable enzymatic activity in vitro, corroborating the clinical findings. Biophysical experiments and molecular modeling revealed that PPOX(H333R) is not folded properly and fails to adopt its native functional three-dimensional conformation due to steric clashes in the vicinity of the active site of the enzyme. On the other hand, PPOX(H333R) subcellular distribution, as evaluated by live-cell confocal microscopy, is unimpaired suggesting that the functional three-dimensional fold is not required for efficient transport of the polypeptide chain into mitochondria. Overall, the data presented here provide molecular underpinnings of the pathogenicity of PPOX(H333R) and might serve as a blueprint for deciphering whether a given PPOX variant represents a disease-causing mutation.


Comparison of brachiocephalic angiography and IVDSA in the same group of patients.
In this investigation for the first time conventional angiography (CA) and intravenous digital subtraction angiography (IVDSA) of the aortic arch and brachiocephalic vascular territory is compared in the same group of 25 patients. The quality of the image derived from IVDSA is inferior to that of CA and, moreover, varies with the location. If sufficiently good, IVDSA has an accuracy of 81 to 91% in comparison to CA for stenotic lesions depending on the site. Ulcerations are missed more frequently than with CA. Discrepancies between IVDSA and CA are caused mainly by misregistration. According to our investigation there are multiple stenotic lesions in the brachiocephalic territory in 84% of the patients. Adequate assessment of the need for surgery in symptomatic patients can therefore only be made after complete visualization of the aortic and brachiocephalic vascular territory. If non-invasive methods, like duplex-scanning, cannot fulfill this requirement, IVDSA is the only semi-invasive method that can provide the information. It is therefore desirable to improve IVDSA technique in the near future instead changing to intra-arterial DSA (IADSA). Now already the advantages outweight the drawbacks.


Anti-inflammatory efficacy and relevant SAR investigations of novel chiral pyrazolo isoquinoline derivatives: Design, synthesis, in-vitro, in-vivo, and computational studies targeting iNOS.
Isoquinoline alkaloids are a rich source of multimodal agents with distinctive structural specificity and various pharmacological activities. In the present report, we propose a combination of design, synthesis, computational study, primary in-vitro screening using the lipopolysaccharide (LPS)-induced RAW 264.7 cell line, and in-vivo evaluation in mice models as a novel approach to speed up anti-inflammatory drugs discovery. The nitric oxide (NO) inhibitory effect of new compounds revealed that all of them displayed the potent NO inhibitory ability in a dose-dependent manner with no obvious cytotoxicity. A series of the model compounds 7a, 7b, 7d, 7f, and 7g have been identified as the most promising, with IC50 values of 47.76 μM, 33.8 μM, 20.76 μM, 26.74 μM, and 47.8 μM respectively in LPS-induced RAW 264.7 cell line. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. Western blotting data of 7d identified that our synthesized compounds can down-regulate and suppress the expression of the key inflammatory enzyme, inducible nitric oxide synthase (iNOS). These results suggested that synthesized compounds may be potent anti-inflammatory agents, inhibiting the NO-release, in turn, iNOS inflammatory pathways. Furthermore, in-vivo anti-inflammatory detection via xylene-induced ear edema in mice revealed that these compounds could also inhibit swelling in mice, with model compound 7h showing an inhibition activity (64.4%) at a concentration of 10 mg/kg comparable to the reference drug celecoxib. Molecular docking results showed that shortlisted compounds (7b, 7c, 7d, 7e, and 7h) had a potential binding affinity for iNOS with low energies, with S-Score to be -7.57, -8.22, -7.35, -8.95, -9.94 kcal/mol, respectively. All results demonstrated that the newly synthesized chiral pyrazolo isoquinoline derivatives are highly potential anti-inflammatory agents.


Pneumolysin stimulates production of tumor necrosis factor alpha and interleukin-1 beta by human mononuclear phagocytes.
Human peripheral blood monocytes and a human monocyte cell line were exposed to the toxin pneumolysin. Pneumolysin-exposed cells produced significantly larger amounts of tumor necrosis factor alpha and interleukin-1 beta than cells not exposed to the toxin. The viability of cells was not affected by the concentrations of pneumolysin used in the experiments.


Anticonvulsant efficacy of L-deprenyl (selegiline) during chronic treatment in mice: continuous versus discontinuous administration.
We have previously reported that L-deprenyl (selegiline), an irreversible inhibitor of monoamine oxidase type B (MAO-B), exerts anticonvulsant activity against different seizure types in mice and rats. The anticonvulsant effect of L-deprenyl was rapid in onset but short lasting, arguing in favor of other, reversible mechanisms of L-deprenyl as a basis for the anti-seizure activity. For further evaluation, we administered L-deprenyl continuously via subcutaneously implanted osmotic minipumps in mice and determined the threshold for myoclonic seizures induced by i.v. infusion of pentylenetetrazol repeatedly during prolonged treatment, with treatment periods lasting from 2 to 4 weeks. For comparison with continuous administration via minipumps, L-deprenyl was injected once daily at a dose (10 mg/kg) known to produce complete and irreversible inhibition of MAO-B and anticonvulsant effects after acute administration in rodents. Continuous administration of L-deprenyl, 50 or 100 mg/kg per day, led to a progressive increase in seizure threshold in the absence of any observable adverse effects, while administration of 10 mg/kg per day via minipumps was devoid of any significant anticonvulsant effect. When 10 mg/kg were administered once daily in the afternoon for 4 weeks and the seizure threshold was determined repeatedly in the morning, no significant anticonvulsant effect was observed. The data argue against a critical role of MAO-B inhibition in the anticonvulsant activity of L-deprenyl but suggest that other, reversible biochemical and cellular effects known to occur at higher doses of this drug are involved in this respect. In view of the short half-life of L-deprenyl, these reversible effects can only be maintained during chronic treatment when the drug is given continuously such as via implanted minipumps.


The location of antigenic sites on the surface of the nematode parasite Strongyloides ratti reactive to antibody-directed cellular cytotoxicity from both macrophages and eosinophils from the natural host.
Heat-treated and untreated sera from rats immune to Strongyloides ratti are capable of arming both immune and non-immune macrophages and eosinophils in vitro. These cells are capable of killing larvae of the parasite. Electron microscopy has indicated multi-point attachment of the cells to the epicuticular transverse grooves of the larvae within 4 and 24 h of incubation at 37 degrees.


The Haphazard Pattern in Grade-3 Endometrioid Carcinoma Is Associated with Poor Prognosis and Tumor Lymphocyte Infiltration.
The aim of this study was to examine the associations among the haphazard invasive patterns, defined as directionless infiltration into the myometrium; expression of key proteins; tumor infiltrative lymphocytes (TILs); and the prognosis of gade-3 endometrioid carcinoma (G3EC). Between 1990 and 2013, patients with G3EC who underwent surgery at our hospital were identified. Invasive patterns were classified into either haphazard, infiltrative, or expansile patterns. The estrogen, progesterone, androgen receptor, cytokeratin 5/6, epidermal growth factor receptor, E-cadherin, snail-2, vimentin, ZEB1, chromogranin A, synaptophysin, MLH1, MSH2, MSH6, and PMS2 levels were evaluated by immunochemical analysis. The degree of strong or weak lymphocyte infiltration (LI) were evaluated using zone formation of LI at the invasive front. Haphazard, infiltrative, and expansile patterns were discovered in 8 (18%), 6 (13%), and 31 (69%) cases, respectively. Cases with the haphazard patterns were diagnosed at a more advanced stage (p < 0.01) and recurred more frequently (p < 0.01). There were statistical differences in progression-free survival (PFS) and overall survival (OS) between the three groups (PFS; p < 0.01: OS; p < 0.01). In multivariate analysis, only the haphazard pattern was found to be an independent, worse prognostic factor of PFS (Hazard ratio (HR) =10.8, p < 0.01) and OS (HR = 23.3, p < 0.01). Furthermore, the haphazard invasive pattern was related with weak LI (p < 0.01) but not with the expression of all proteins analyzed. The haphazard pattern was found to be a worse prognostic factor and was associated with weak LI in G3EC. The aggressive feature of G3EC might be associated with LI but not tumor biology.


Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression.
Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity. The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. Four single-dose studies were conducted in 75 healthy volunteers. Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 μg octreotide were administered. We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion. Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 h × ng/ml); and median time ≥ 0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively. The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly.


A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy.
Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease. A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized. Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients. 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.


S-acylation of the Wnt receptor Frizzled-5 by zDHHC5 controls its cellular localization and synaptogenic activity in the rodent hippocampus.
Proper localization of receptors for synaptic organizing factors is crucial for synapse formation. Wnt proteins promote synapse assembly through Frizzled (Fz) receptors. In hippocampal neurons, the surface and synaptic localization of Fz5 is regulated by neuronal activity, but the mechanisms involved remain poorly understood. Here, we report that all Fz receptors can be post-translationally modified by S-acylation and that Fz5 is S-acylated on three C-terminal cysteines by zDHHC5. S-acylation is essential for Fz5 localization to the cell surface, axons, and presynaptic sites. Notably, S-acylation-deficient Fz5 is internalized faster, affecting its association with signalosome components at the cell surface. S-acylation-deficient Fz5 also fails to activate canonical and divergent canonical Wnt pathways. Fz5 S-acylation levels are regulated by the pattern of neuronal activity. In vivo studies demonstrate that S-acylation-deficient Fz5 expression fails to induce presynaptic assembly. Our studies show that S-acylation of Frizzled receptors is a mechanism controlling their localization and function.


Radiobiology of pions in comparison with other heavy particles.
Our recent data on late effects of pions in spinal cord, lung and rectum in rodents is presented with reference to other high-LET radiations. Unlike high-LET radiations such as neutrons and neon ions, the RBE for late effects of pions (up to 1.5) is not found to be significantly different from acute effects. Because of the potential of matching treatment volume (especially by using dynamic treatments) to the target volume by using pions and heavy ions, it is of utmost importance to study the tolerance of normal tissues to late effects as a function of volume. Such knowledge combined with pion and heavy ion dynamic treatment could lead to a further step in heavy particle radiotherapy.


Embolization of a Large Intracoronary Thrombus During ST-Segment Elevation Myocardial Infarction.
Aspiration thrombectomy was performed to retrieve intact thrombus in a 69-year-old woman. Bradycardia and hypotension rapidly resolved. Balloon angioplasty was performed at the site of proximal RCA in-stent restenosis with improved angiographic appearance and TIMI 3 flow in the major branches.


Microbiota abnormalities in inflammatory airway diseases - Potential for therapy.
Increasingly the development of novel therapeutic strategies is taking into consideration the contribution of the intestinal microbiota to health and disease. Dysbiosis of the microbial communities colonizing the human intestinal tract has been described for a variety of chronic diseases, such as inflammatory bowel disease, obesity and asthma. In particular, reduction of several so-called probiotic species including Lactobacilli and Bifidobacteria that are generally considered to be beneficial, as well as an outgrowth of potentially pathogenic bacteria is often reported. Thus a tempting therapeutic approach is to shape the constituents of the microbiota in an attempt to restore the microbial balance towards the growth of 'health-promoting' bacterial species. A twist to this scenario is the recent discovery that the respiratory tract also harbors a microbiota under steady-state conditions. Investigators have shown that the microbial composition of the airway flora is different between healthy lungs and those with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease as well as cystic fibrosis. This is an emerging field, and thus far there is very limited data showing a direct contribution of the airway microbiota to the onset and progression of disease. However, should future studies provide such evidence, the airway microbiota might soon join the intestinal microbiota as a target for therapeutic intervention. In this review, we highlight the major advances that have been made describing the microbiota in chronic lung disease and discuss current and future approaches concerning manipulation of the microbiota for the treatment and prevention of disease.


Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa.
Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP. Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina. Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways. Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice.


Etoposide plus cisplatin chemotherapy improves the efficacy and safety of small cell lung cancer.
According to the statistical data of GLOBOCAN in 2020, the incidence of lung cancer ranks third worldwide. Approximately 60%-70% of newly diagnosed patients with small cell lung cancer (SCLC) has already progressed to extensive-stage SCLC (ES-SCLC). SCLC is sensitive to chemotherapy and radiotherapy, but prone to secondary drug resistance. At present, chemotherapy is the mainstay of treatment for ES-SCLC. This study is designed to evaluate the efficacy and safety of etoposide plus platinum in the treatment of SCLC. A retrospective analysis was performed on 112 patients with SCLC admitted to the China-Japan Union Hospital of Jilin University from 2016 to 2018. According to treatment methods, the patients were divided into an EL group (etoposide plus lobaplatin, n = 53) and an EP group (etoposide plus cisplatin, n = 59). The short-term efficacy (objective response rates and disease control rates) and 2-year survival rates were observed. The two groups were compared in terms of serum levels of pro-gastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) before and after treatment. The incidence of adverse reactions was also compared. The quality of life (QOL) of patients was compared by measuring the Karnofsky Performance Status (KPS) scale. The risk factors affecting treatment efficacy were analyzed by multivariate Logistics analysis. Patients in the EL group had similar objective response rate (ORR) and disease control rate (DCR) to those in the EP group. The 2-year survival prognosis (median survival time) between the two groups was not significantly different. After treatment, serum levels of ProGRP, NSE, VEGF and MMP-9 in both groups decreased remarkably, with no remarkable differences between the two groups. The EL group had a remarkably lower incidence of adverse reactions than the EP group. In the EP group, the KPS scores after 6 cycles of treatment were remarkably higher than those after 2 cycles of treatment. ProGRP, NSE, VEGF and MMP-9 were independent risk factors affecting the efficacy of patients with SCLC. With equivalent efficacy, EP regimen is safer than EL regimen in the treatment of SCLC, which suggests that etoposide plus platinum has better clinical application value for SCLC.


Coping with unemployment--a contribution to the understanding of women's unemployment.
The aim of this paper was to contribute to the understanding of women's unemployment with emphasis on individual reactions in terms of their significance and context. The study was carried out within the methodological tradition of grounded theory. Thirty-six unemployed women were interviewed. The reactions to unemployment were seen in relation to two, systematically generated core variables: 'the relation to wage labour' and 'the relation to alternative activities'. Four different groups of unemployed were identified in light of their relations to these two core variables. They were called 'the give-uppers', 'the clenchers', 'the refocusers' and 'the ambivalents'. Serious effects of unemployment were found among the give-uppers and the clenchers. The refocusers on the other hand, enjoyed their lives and had replaced the loss of work with other meaningful activities.


Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects.
The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.


Study on the expression of the rate constant α of the creep equation by modified θ projection applied to turbine materials.
It is well-known that the creep equation obtained by the modified θ projection [2] describes well from the primary creep region to the tertiary creep region. However, unlike the power law such as that applied by the Bailey-Norton method, the stress variables and temperature variables are not found in the equation coefficients. Therefore, the users of this equation must find functions containing temperature variables and stress variables to display the equation coefficients. Thus, among the three coefficients A, α, and B included in the equation of the modified θ projection, the rate constant α, which exerts the largest influence on the curvature and the minimum creep strain rate of the creep curve [3], was selected as the object of investigation. Moreover, by considering the Cr-Mo-V steel and the Ni-based superalloy as examples, the expression of α was investigated. As a result, it was found that the discrete cosine transform and series can be applied not only to the coefficients of the creep equation but also to the creep equation itself. It is very important that the Fourier transform, which is considered to be applicable only to periodic functions, can be applied to non-periodic functions like a creep equation or its coefficients without apodizing such as windowing [9].


Ferritin in human liver cells of homozygous beta-thalassaemia: ultrastructural observations.
Homozygous beta-thalassaemia is a disease in which there is a progressive iron overload from infancy to death in early adulthood. Liver biopsies from 10 patients in various stages of this disease were examined by electron microscopy. A number of round or oval lysosomal structures, containing lamellae different from myelin figures, were seen in all patients, including those with minimal iron overload. Ferritin molecules were seen either in relationship with the lamellae forming arrays, or in paracrystalline arrangement, or with no organized form. There were practically no ferritin molecules in sub-cellular compartments other than cell sap and lysosomes. The density of cell sap ferritin was constant beyond infancy, but the number of iron-laden lysosomes increased with age. The stages in the process of iron seclusion, seen even in advanced phases of iron overload, are described. Ferritin is thought to accumulate in lysosomes by a transmembraneous movement, but other explanations are considered.


Characterizing tree trait variance over spatiotemporal scales.
Beyond the study of the mean, functional ecology lacks a concise characterization of trait variance patterns across spatiotemporal scales. Traits are measured in different ways, using different metrics, and at different spatial (and rarely temporal) scales. This study expands on previous research by applying a ubiquitous and widely used empirical model-Taylor's Power Law-to functional trait variance with the goal of identifying general patterns of trait variance scaling (the behavior of trait variance across scales). We compiled data on tree seedling communities monitored over 10 years across 213 2 m2 plots and functional trait data from a subtropical forest in Puerto Rico. We examined trait-based Taylor's Power Law at nested spatial and temporal scales. The scaling of variance with the mean was idiosyncratic across traits suggesting that the drivers of variation are likely to differ across traits that may make variance scaling theory elusive. However, slopes varied more in space than through time, suggesting that spatial environmental variability may have a larger role in driving trait variance than temporal variability. Empirical models that characterize taxonomic patterns across spatiotemporal scales, like Taylor's Power Law, can provide an insight into the scaling of functional traits, a necessary next step toward a more predictive trait-based ecology.


An automatic counter for autoradiographed cells in Petri dishes.
A simple automatic counting device for cells on Petri dishes is described. The device is tested up to 1 x 10(4) cells (0.01 m)-2 and counts linearly without coincidence error. The counting time for each dish is c. 3-4 min including the time required to place the dish in the apparatus.


Statistical methods for the meta-analysis of diagnostic tests must take into account the use of surrogate standards.
Evaluating the performance of a new diagnostic test presents a challenge if the conventional "gold" standard is invasive, hazardous, or expensive, especially if that test has been supplanted in usual clinical practice by a "silver" standard test that is more acceptable and perhaps only slightly suboptimal. In such a case, a systematic literature review will typically uncover a mix of study types, some using the gold and some the silver. We sought to develop and compare statistical methods to account for this kind of heterogeneity in performing a meta-analysis. We compared the performance of estimation methods based on generalized mixed models which incorporate heterogeneity, especially choice of reference test, and random between-study variation in sensitivity and specificity with more conventional methods which neglect the differences in reference tests. Computer simulations were conducted to assess bias and root mean square error of point estimates and coverage of interval estimates. Methods ignoring the difference in reference tests severely underestimated sensitivity and specificity under the assumption of conditional independence. Bias was substantial even for references with small departure from the standard and persisted with increasing sample size. Coverage of interval estimates was far from nominal level. In the presence of varying reference tests, avoidance of bias and invalid confidence intervals for diagnostic performance requires applying a model that accounts for differences in reference test and heterogeneity among studies.


Se-doping dependence of the transport properties in CBE-grown InAs nanowire field effect transistors.
We investigated the transport properties of lateral gate field effect transistors (FET) that have been realized by employing, as active elements, (111) B-oriented InAs nanowires grown by chemical beam epitaxy with different Se-doping concentrations. On the basis of electrical measurements, it was found that the carrier mobility increases from 103 to 104 cm2/(V × sec) by varying the ditertiarybutyl selenide (DtBSe) precursor line pressure from 0 to 0.4 Torr, leading to an increase of the carrier density in the transistor channel of more than two orders of magnitude. By keeping the DtBSe line pressure at 0.1 Torr, the carrier density in the nanowire channel measures ≈ 5 × 1017 cm-3 ensuring the best peak transconductances (> 100 mS/m) together with very low resistivity values (70 Ω × μm) and capacitances in the attofarad range. These results are particularly relevant for further optimization of the nanowire-FET terahertz detectors recently demonstrated.PACS: 73.63.-b, 81.07.Gf, 85.35.-p.


Dissociation of neural correlates of verbal and non-verbal visual working memory with different delays.
Dorsolateral prefrontal cortex (DLPFC), posterior parietal cortex, and regions in the occipital cortex have been identified as neural sites for visual working memory (WM). The exact involvement of the DLPFC in verbal and non-verbal working memory processes, and how these processes depend on the time-span for retention, remains disputed. We used functional MRI to explore the neural correlates of the delayed discrimination of Gabor stimuli differing in orientation. Twelve subjects were instructed to code the relative orientation either verbally or non-verbally with memory delays of short (2 s) or long (8 s) duration. Blood-oxygen level dependent (BOLD) 3-Tesla fMRI revealed significantly more activity for the short verbal condition compared to the short non-verbal condition in bilateral superior temporal gyrus, insula and supramarginal gyrus. Activity in the long verbal condition was greater than in the long non-verbal condition in left language-associated areas (STG) and bilateral posterior parietal areas, including precuneus. Interestingly, right DLPFC and bilateral superior frontal gyrus was more active in the non-verbal long delay condition than in the long verbal condition. The results point to a dissociation between the cortical sites involved in verbal and non-verbal WM for long and short delays. Right DLPFC seems to be engaged in non-verbal WM tasks especially for long delays. Furthermore, the results indicate that even slightly different memory maintenance intervals engage largely differing networks and that this novel finding may explain differing results in previous verbal/non-verbal WM studies.


Exploration of Brazilian biodiversity and selection of a new oleaginous yeast strain cultivated in raw glycerol.
The objective of this study was to use glycerol generated from the synthesis of biodiesel to study the oleaginous potential of wild yeasts. An initial selection was performed via a rapid and qualitative technique by staining with Sudan Black B. Initially 129 yeasts were present, from which 5 were selected and cultivated in liquid medium containing pure or raw glycerol. The yeast LEB-M3, isolated from the Pantanal, presented lipid content of 20.46% and 56.58% for cultivation in pure and raw glycerol, respectively. This strain was genotypically identified as Candida sp. The fatty acid profile showed predominance of oleic acid (C18:1), 57.35% for cultivation in pure glycerol, and in raw glycerol linoleic acid (C18:2) was predominant (46.0%). It was possible to select a yeast with high lipid concentrations 9.14 g/L and fatty acid profile similar to vegetable oils commonly used in the synthesis of biodiesel.


Home oxygen management of neonatal chronic lung disease in Western Australia.
To describe the course and management of infants with neonatal chronic lung disease who were discharged home on low-flow supplemental oxygen. Retrospective case series in Western Australia. Fifty-six neonates born in the 6 year period 1987-92 inclusive were discharged home on supplemental oxygen. The median gestational age was 27 weeks (range 22-40), median birthweight 865 g (range 450-3350), median oxygen flow rates 125 mL/min (range 30-850). The median corrected age at discharge was 1 month (range term-9.5) and this had decreased throughout the study period. Acute hospital readmissions were common (36 of 56, 64%). The majority of these admissions were for wheezing illnesses. Three infants died. The median corrected age at weaning from day oxygen was 4 months (range term-33) and from night oxygen was 6 months (range 2-38). Monitoring of oxygen saturation in air, in low-flow oxygen and in the overnight sleep study were important non-invasive guides in deciding when patients were ready for discharge, reducing the oxygen flow rate and when oxygen could be ceased, respectively. The home oxygen programme enables infants with neonatal chronic lung disease to be discharged home earlier, is safe, and well accepted by parents and community health care workers.


Systematic Comparison of Muscle Ultrasound Thickness in Polyneuropathies and Other Neuromuscular Diseases.
We have aimed to assess whether muscle thickness ultrasound (US) shows differences between patients with chronic inflammatory demyelinating polyneuropathy (CIDP), chronic axonal polyneuropathy (CAP), and other neuromuscular (NM) diseases compared to controls and to each other. We performed a cross-sectional study from September 2021 to June 2022. All subjects underwent quantitative sonographic evaluation of muscle thickness in eight relaxed muscles and four contracted muscles. Differences were assessed using multivariable linear regression, correcting for age and body mass index (BMI). The study cohort consisted of 65 healthy controls, and 95 patients: 31 with CIDP, 34 with CAP, and 30 with other NM diseases. Both relaxed and contracted muscle thickness in all patient groups were lower than in the healthy controls, after controlling for age and body mass index (BMI). Regression confirmed that the differences persisted between patient groups and healthy controls. Differences between patient groups were not apparent. The current study shows that muscle ultrasound thickness is not specific in NM disorders, but shows a global reduction in thickness compared with healthy controls after corrections for age and BMI.


Medical and legal evaluations of the retained foreign bodies in Turkey.
Like other countries, the physicians accusation that might be right or wrong, have increased nowadays in Turkey. Even all precautions are taken in the operation theatre, there are still some cases in which foreign bodies are retained in the abdominal cavity. It is not likely for the cases of retained foreign bodies in the abdominal cavity to be considered as an acceptable complication. Therefore, the surgeon must keep in mind that in such situations they are going to be judged as faulty both in the civil courts and in the courts of first instance. In this study incidences, causes and legal outcomes of the foreign bodies that are left behind in the abdominal cavity in Turkey are discussed.


[3H]imipramine binding of protein nature in human platelets: inhibition by 5-hydroxytryptamine and 5-hydroxytryptamine uptake inhibitors.
The nature of [3H]imipramine binding to human platelets was investigated. Desipramine and 5-hydroxytryptamine (5-HT) displaced the same amount of binding and the binding was sensitive to protease treatment. The nature of pharmacological inhibition of [3H]imipramine binding was investigated in saturation experiments. Increases in KD without changes in Bmax were noted with the addition of 5-HT, desipramine, norzimeldine, or 5-methoxytryptoline. Reductions in Bmax without alterations in KD were obtained when citalopram or clomipramine was added. It is concluded that the [3H]imipramine binding site in human platelets is of protein nature and that this binding site contains the substrate recognition site for 5-HT uptake. In addition, [3H]imipramine and other 5-HT uptake inhibitors have bonds to other parts of the 5-HT uptake carrier or to the surrounding lipid membrane. This additional binding outside the substrate recognition site is not one single site but most likely represents sites that are specific for the chemical structure of each uptake inhibitor, respectively.


Aortoiliac morphologic correlations in aneurysms undergoing endovascular repair.
The feasibility of endovascular aneurysm repair depends on morphologic characteristics of the aortoiliac segment. Knowledge of such characteristics is relevant to safe deployment of a particular device in a single patient and to development of new devices for use in patients with a broader spectrum of anatomic variations. We evaluated findings on computed tomography scans for 277 patients being considered for endovascular aneurysm repair. Aortic neck length and angulation estimates were generated with three-dimensional trigonometry. Specific centerline points were recorded, corresponding to the aorta at the celiac axis, lowest renal artery, cranial aspect of the aneurysm sac, aortic terminus, right hypogastric artery origin, and left hypogastric origin. Aortic neck thrombus and calcium content were recorded, and neck conicity was calculated in degrees. Statistical analysis was performed with the Spearman rank correlation. Data are expressed as median and interquartile range. Median diameter of the aneurysms was 52 mm (interquartile range, 48-59 mm) in minor axis and 56 mm (interquartile range, 51-64 mm) in major axis, and median length was 88 mm (interquartile range, 74-103 mm). Median proximal aortic neck diameter was 26 mm (interquartile range, 22-29 mm), and median neck length was 30 mm (interquartile range, 18-45 mm). The common iliac arteries were similar in diameter (right artery, 16 mm [interquartile range, 13-20 mm]; left artery, 15 mm [interquartile range, 11-18 mm]) and length (right, 59 mm [interquartile range, 50-69 mm]; left, 60 mm [interquartile range, 49-70 mm]). Median angulation of the infrarenal aortic neck was 40 degrees (interquartile range, 29-51 degrees), and median angulation of the suprarenal segment was 45 degrees (interquartile range, 36-57 degrees). By gender, sac diameter, proximal neck diameter, and iliac artery diameter were significantly larger in men. Significant linear associations were identified between sac diameter and sac length, neck angulation, and iliac artery diameter. As the length of the aneurysm sac increased the proximal aortic neck length decreased. Conversely, as the sac length decreased sac eccentricity increased. Mural thrombus content within the neck increased with increasing neck diameter. There is considerable variability in aortoiliac morphologic parameters. Significant associations were found between various morphologic variables, links that are presumably related to a shared pathogenesis for aberration in aortoiliac diameter, length, and angulation. Ultimately this information can be used to develop new endovascular devices with broader applicability and improved long-term results.


O-glycosylation of the extracellular domain of pollen class I formins modulates their plasma membrane mobility.
In plant cells, linkage between the cytoskeleton, plasma membrane, and cell wall is crucial for maintaining cell shape. In highly polarized pollen tubes, this coordination is especially important to allow rapid tip growth and successful fertilization. Class I formins contain cytoplasmic actin-nucleating formin homology domains as well as a proline-rich extracellular domain and are candidate coordination factors. Here, using Arabidopsis, we investigated the functional significance of the extracellular domain of two pollen-expressed class I formins: AtFH3, which does not have a polar localization, and AtFH5, which is limited to the growing tip region. We show that the extracellular domain of both is necessary for their function, and identify distinct O-glycans attached to these sequences, AtFH5 being hydroxyproline-arabinosylated and AtFH3 carrying arabinogalactan chains. Loss of hydroxyproline arabinosylation altered the plasma membrane localization of AtFH5 and disrupted actin cytoskeleton organization. Moreover, we show that O-glycans differentially affect lateral mobility in the plasma membrane. Together, our results support a model of protein sub-functionalization in which AtFH5 and AtFH3, restricted to specific plasma membrane domains by their extracellular domains and the glycans attached to them, organize distinct subarrays of actin during pollen tube elongation.


Genetic susceptibility to infection-mediated preterm birth.
Preterm birth is a heterogeneous disorder that is responsible for significant neonatal morbidity and mortality. Intrauterine infection is implicated in a significant proportion of preterm birth-particularly in early gestation. Epidemiologic evidence supports a genetic component to infection overall and preterm birth in particular. Furthermore, a number of studies examining genes involved in pathogen recognition and our response to pathogens suggest a genetic susceptibility to infection-mediated preterm birth. On the whole, however, these studies have been difficult to replicate and explain only a small portion of the phenotypic variation in preterm birth. Given this, methodological considerations are emphasized to improve our understanding of the genetic susceptibility to infection-mediated preterm birth.


Effect of an Individually Tailored and Home-Based Intervention in the Chronic Phase of Traumatic Brain Injury: A Randomized Clinical Trial.
Traumatic brain injury (TBI) can cause long-lasting and heterogeneous difficulties that require an individually tailored approach to rehabilitation. However, high-quality studies of treatment options in the chronic phase of TBI are lacking. To evaluate the effect of a home-based, individualized, and goal-oriented rehabilitation intervention in the chronic phase of TBI. This study was an intention-to-treat parallel-group assessor-blinded randomized clinical trial with 1:1 randomization to an intervention or control group. Participants included adults in southeastern Norway who had sustained a TBI more than 2 years earlier, lived at home, and had ongoing TBI-related difficulties. A population-based sample of 555 individuals were invited, and 120 were included. Participants were assessed at baseline, 4 months, and 12 months after inclusion. Specialized rehabilitation therapists provided the intervention in patients' homes or via video conference and telephone. Data collection was conducted between June 5, 2018, and December 14, 2021. The intervention group received an 8-session individually tailored and goal-oriented rehabilitation program over 4 months. The control group received usual care in their municipality. Preestablished primary outcomes were disease-specific health-related quality of life (HRQOL; measured by the Quality of Life After Brain Injury [QOLIBRI] overall scale) and social participation (measured by the Participation Assessment With Recombined Tools-Objective [PART-O] social subscale). Preestablished secondary outcomes included generic HRQOL (measured by the EuroQol 5-dimension 5-level [EQ-5D-5L] questionnaire), difficulty with TBI-related problem management (target outcomes; mean severity calculated across 3 main self-identified problem areas that were individually measured using a 4-point Likert scale), TBI symptoms (measured by the Rivermead Post Concussion Symptoms Questionnaire [RPQ]), psychological distress (depression and anxiety; measured by the Patient Health Questionnaire 9-item scale and the Generalized Anxiety Disorder 7-item scale [GAD-7], respectively), and functional competency (measured by the Patient Competency Rating Scale). Among 120 participants in the chronic phase of TBI, the median (IQR) age was 47.5 (31.0-55.8) years, and the median (IQR) time since injury was 4 (3-6) years; 85 (70.8%) were male. A total of 60 participants were randomized to the intervention group, and 60 were randomized to the control group. Between baseline and 12 months, no significant between-group effects were found for the primary outcomes of disease-specific HRQOL (QOLIBRI overall scale score: 2.82; 97.5% CI, -3.23 to 8.88; P = .30) or social participation (PART-O social subscale score: 0.12; 97.5% CI, -0.14 to 0.38; P = .29). At 12 months, the intervention group (n = 57) had significantly higher generic HRQOL (EQ-5D-5L score: 0.05; 95% CI, 0.002-0.10; P = .04) and fewer symptoms of TBI (RPQ total score: -3.54; 95% CI, -6.94 to -0.14; P = .04) and anxiety (GAD-7 score: -1.39; 95% CI, -2.60 to -0.19; P = .02) compared with the control group (n = 55). At 4 months only, the intervention group (n = 59) had significantly less difficulty managing TBI-related problems (target outcomes mean severity score: -0.46, 95% CI, -0.76 to -0.15; P = .003) compared with the control group (n = 59). No adverse events were reported. In this study, no significant results were observed for the primary outcomes of disease-specific HRQOL or social participation. However, the intervention group reported improvements in secondary outcomes (generic HRQOL and symptoms of TBI and anxiety) that were maintained at 12-month follow-up. These findings suggest that rehabilitation interventions could help patients even in the chronic phase of TBI. ClinicalTrials.gov Identifier: NCT03545594.


Study of retinal alterations in a high fat diet-induced type ii diabetes rodent: Meriones shawi.
Diabetic retinopathy is a common complication of type 2 diabetes and the leading cause of blindness in adults of working age. The aim of this work was to study the repercussions of high fat diet (HFD) induced diabetes on the retina of Meriones shawi (M.sh). Two groups of six M.sh each was studied. Group I was a normal control, fed with standard laboratory granules. In Group II, rodents received a HFD of enriched laboratory granules, for a period of 3 months. Body weight and plasma glucose were determined in the two groups. Retinal sections of the two groups were stained with the Hematoxylin-Eosin. Photoreceptors were identified by immunolabeling for rhodopsin (rods) and PNA (cones). Gliosis and microglial activation were identified by immunolabeling for GFAP and Iba-1. Labeling of calretinin and parvalbumin were also carried out to study the AII amacrine cells. Retinal layers thicknesses, gliosis, and specific neural cell populations were quantified by microscopy. The body weight (+77%) and plasma glucose (+108%) were significantly greater in the HFD rodents. Three months of HFD induced a significant loss of 38.77% of cone photoreceptors, as well as gliosis and an increase of 70.67% of microglial cells. Calcium homeostatic enzymes were depleted. This work shows that HFD in Meriones shawi induces a type II diabetes-like condition that causes loss of retinal neurons and photoreceptors, as well as gliosis. Meriones shawi could be a useful experimental animal model for this physiopathology particularly in the study of retinal neuro-glial alterations in Type II diabetes.


Transcriptome sequencing and differential expression analysis of natural and BTH-treated wound healing in potato tubers (Solanum tuberosum L.).
Wound healing is a representative phenomenon of potato tubers subjected to mechanical injuries. Our previous results found that benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) promoted the wound healing of potato tubers. However, the molecular mechanism related to inducible wound healing remains unknown. Transcriptomic evaluation of healing tissues from potato tubers at three stages, namely, 0 d (nonhealing), 5 d (wounded tubers healed for 5 d) and 5 d (BTH-treated tubers healed for 5 d) using RNA-Seq and differentially expressed genes (DEGs) analysis showed that more than 515 million high-quality reads were generated and a total of 7665 DEGs were enriched, and 16 of these DEGs were selected by qRT-PCR analysis to further confirm the RNA sequencing data. Gene ontology (GO) enrichment analysis indicated that the most highly DEGs were involved in metabolic and cellular processes, and KEGG enrichment analysis indicated that a large number of DEGs were associated with plant hormones, starch and sugar metabolism, fatty acid metabolism, phenylpropanoid biosynthesis and terpenoid skeleton biosynthesis. Furthermore, a few candidate transcription factors, including MYB, NAC and WRKY, and genes related to Ca2+-mediated signal transduction were also found to be differentially expressed during wound healing. Most of these enriched DEGs were upregulated after BTH treatment. This comparative expression profile provided useful resources for studies of the molecular mechanism via these promising candidates involved in natural or elicitor-induced wound healing in potato tubers.


A Multiplex Assay to Assess the Transaminase Activity toward Chemically Diverse Amine Donors.
The development of methods to engineer and immobilize amine transaminases (ATAs) to improve their functionality and operational stability is gaining momentum. The quest for robust, fast, and easy-to-use methods to screen the activity of large collections of transaminases, is essential. This work presents a novel and multiplex fluorescence-based kinetic assay to assess ATA activity using 4-dimethylamino-1-naphthaldehyde as an amine acceptor. The developed assay allowed us to screen a battery of amine donors using free and immobilized ATAs from different microbial sources as biocatalysts. As a result, using chromatographic methods, 4-hydroxybenzylamine was identified as the best amine donor for the amination of 5-(hydroxymethyl)furfural. Finally, we adapted this method to determine the apparent Michaelis-Menten parameters of a model immobilized ATA at the microscopic (single-particle) level. Our studies promote the use of this multiplex, multidimensional assay to screen ATAs for further improvement.


Thromboembolic complications with the cloth-covered Starr-Edwards aortic prosthesis in patients not receiving anticoagulants.
A comparison of the incidence of thromboembolic (TE) episodes was made in three groups of patient who underwent aortic valve replacement with the cloth-covered Starr-Edwards prostheses. Group 1 consisted of patients who received anticoagulants for either the entire period of follow-up or for a period of variable duration, after which these agents were no longer administered. When anticoagulants were stopped, 22 patients were categorized as Group 3 for study. Group 2 comprised patients who never received anticoagulants. Of the 147 patients followed in Group 1, 14 suffered one episode of TE. Six patients experienced major emboli; 3 of them died. Twenty of the 82 patients followed in Group 2 (no anticoagulants) suffered TE complications. There were 10 episodes of major emboli. Five of the 22 patients in Group 3 suffered an episode (all major) of TE. It is concluded from this study that anticoagulants should be given permanently to all patients with cloth-covered Starr-Edwards prostheses. Indeed, there is no period after operation when the incidence of TE is so low that anticoagulation may be safely discontinued.


Cardiac sympathoexcitation in heart failure.
Heart failure (HF) is a serious debilitating condition with poor survival rates and an increasing level of prevalence. The excessive sympatho-excitation that is a hallmark of heart failure has long-term effects that contribute to disease progression. The mechanisms causing the increase in renal sympathetic nerve activity (RSNA) have been extensively investigated in experimental models of heart failure, but there is less information on the factors causing the increase in cardiac SNA (CSNA). This review focuses on our recent investigations of the mechanisms driving the increased CSNA in an ovine rapid ventricular pacing model of HF. In conscious sheep with mild heart failure (ejection fraction 35-40%) the arterial baroreflex control of CSNA was normal. In contrast, the normal inhibition of CSNA with volume expansion was abolished in HF, indicating desensitisation of the cardiopulmonary mechano-reflex. Antagonism of central angiotensin AT1 receptors with losartan substantially reduced CSNA, demonstrating a critical role for the central renin-angiotensin system. Investigation of the role of the paraventricular nucleus of the hypothalamus (PVN), which plays a critical role in setting the increased RSNA in HF, demonstrated that the PVN did not maintain the increased CSNA in HF or the resting level of CSNA in normal animals. Furthermore, inhibition of the PVN in normal animals reversed the reduction in RSNA, but not CSNA, induced by volume expansion. These studies emphasise that the mechanisms controlling CSNA in the normal state, and causing the increase in HF, are different to those controlling sympathetic activity to the kidney.


Estradiol binding activity in epididymal cytosol of the turtle, Chrysemys picta.
Estrogen binding activity was investigated in the epididymis of the turtle, Chrysemys picta using DNA-cellulose affinity chromatography. A component binding estradiol-17 beta specifically with high affinity (Kd:8.0 X 10(-10) M) and limited capacity (20 fmol/mg protein) was demonstrated in the epididymal cytosol. In addition, binding of estradiol-17 beta was sensitive to excess (100-fold) diethylstilbestrol or natural estrogens (estradiol-17 beta, estrone, and estriol) but not to progesterone or androgens (testosterone and 5 alpha-dihydrotestosterone). The specific estrogen binding macromolecules eluted from DNA-cellulose columns sedimented at 4-5 S in linear 5-20% sucrose gradients. These characteristics suggest the presence of an estrogen receptor in this androgen target organ.


[Phenylpropanoids from Zanthoxylum species and their pharmacological activities: a review].
Phenylpropanoids are one of the major chemical constituents in Zanthoxylum species. They include simple phenylpropanoids, coumarins, and lignans and possess anti-tumor, anti-inflammatory, anti-platelet aggregation, anti-bacterial, anti-viral, insecticidal, and antifeedant activities. This review summarizes the chemical constituents and pharmacological activities from the Zanthoxylum plants in hopes of providing reference for the research and application of phenylpropanoids from this genus.


Inequities in COVID-19 vaccination coverage for adolescents with and without disability, national immunization Survey-Child COVID module, July 22, 2021-February 26, 2022.
Some people with disabilities are likely at increased risk of health impacts from coronavirus disease 2019 (COVID-19). To describe parent-reported COVID-19 vaccination status of adolescents (aged 13-17 years) and parental intent to get their child vaccinated, among adolescents with versus without disability. National Immunization Survey-Child COVID Module data from interviews conducted July 22, 2021-February 26, 2022, were analyzed to assess disability status and type and COVID-19 vaccination status for adolescents (n = 12,445). Prevalence estimates with 95% confidence intervals were calculated; T-tests were conducted. A lower percentage of adolescents with disability received ≥1 dose of COVID-19 vaccine compared to adolescents without disability (52.5% vs. 58.6%), [those with cognition (50.8%) or not performing errands independently (49.5%) disabilities were significantly lower]; and a higher percentage of parents reported intent to definitely vaccinate (9.9% vs. 6.5%) and definitely not vaccinate (14.9% vs. 11.8%) their adolescent. Among the unvaccinated adolescents, parents of those with disability were more likely to report difficulty getting their child vaccinated (19.1% vs. 12.9%), inconvenient vaccination-site operating hours (7.6% vs. 3.9%), difficulty knowing where to get their child vaccinated (7.2% vs. 2.7%), and difficulty getting to vaccination sites (6.0% vs. 3.0%), than parents of those without disability. Adolescents with disability had lower vaccination coverage compared to adolescents without disability. Parents of adolescents with disability reported higher intent to get their adolescents vaccinated, but among unvaccinated adolescents with disability, parents reported greater difficulty in accessing COVID-19 vaccines. Findings highlight the need for prioritized outreach to increase COVID-19 vaccination for this population.


Adding Mindfulness Practice to Exercise Therapy for Female Recreational Runners With Patellofemoral Pain: A Randomized Controlled Trial.
Considering current models that highlight the role of psychological components in pain management, mindfulness practice may be an effective strategy in the management of pain. To examine the effects of adding an 8-week mindfulness program to exercise therapy on the perceptions of pain severity, knee function, fear of movement, and pain catastrophizing of female recreational runners with patellofemoral pain (PFP). Randomized controlled clinical trial. University laboratory. Thirty female runners (age = 28.3 ± 7.08 years) with PFP were randomly assigned to the exercise or mindfulness-exercise group. The exercise-only group followed a protocol (18 weeks, 3 sessions/wk) that featured training modifications to help control injury-related symptoms. The mindfulness-exercise group received an 8-week mindfulness intervention in addition to the exercise protocol. The mindfulness component started 4 weeks before the exercise component; therefore, the 2 components overlapped during the first 4 weeks of the intervention. Usual pain, pain during stepping, and pain during running were assessed using visual analog scales. Functional limitations of the knee were assessed using the Knee Outcome Survey. Fear of movement, pain catastrophizing, and coping strategies were measured via the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, and the Coping Strategies Questionnaire, respectively. These outcomes were assessed at baseline, at week 9, and after 18 weeks. Pain during running, pain during stepping, and functional limitations of the knee were less for the mindfulness-exercise group than for the exercise-only group (P values < .05). The mindfulness-exercise group reported greater perceived treatment effects than the exercise-only group (P < .05). Pain catastrophizing was less and coping strategies were more favorable for mindfulness-exercise participants than for exercise-only participants (P values < .05). Mindfulness practice can be an effective adjunct to exercise therapy in the rehabilitation of PFP in recreational female runners.


Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS.
Motoneurons are selectively damaged in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Although the underlying mechanisms are not completely understood, increasing evidence indicates that motoneurons are particularly sensitive to disruption of mitochondria and Ca(2+)-dependent signalling cascades. Comparison of ALS-vulnerable and ALS-resistant neurons identified low Ca(2+)-buffering capacity and a strong impact of mitochondrial signal cascades as important risk factors. Under physiological conditions, weak Ca(2+) buffers are valuable because they facilitate rapid relaxation times of Ca(2+) transients in motoneurons during high-frequency rhythmic activity. However, under pathological conditions, weak Ca(2+) buffers are potentially dangerous because they accelerate a vicious circle of mitochondrial disruption, Ca(2+) disregulation and excitotoxic cell damage.