Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study.
The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.


H-type hypertension is a risk factor for chronic total coronary artery occlusion: a cross-sectional study from southwest China.
Chronic total coronary occlusion (CTO) is serious and the "last bastion" of percutaneous coronary intervention. Hypertension and hyperhomocysteinemia (HHCY) are synergistic and significantly increase cardiovascular event risk. The relationship between H-type hypertension and CTO remains unclear; thus, this cross-sectional study investigated this potential association. Between January 2018 and June 2022, 1446 individuals from southwest China were recruited to participate in this study. CTO was defined as complete coronary artery occlusion persisting for over three months. H-type hypertension was defined as hypertension with plasma homocysteine levels ≥ 15 µmol/L. Multivariate logistic regression models were applied to assess the association between H-type hypertension and CTO. Receiver operating characteristic (ROC) curves were generated to determine the accuracy of H-type hypertension in predicting CTO. Of the 1446 individuals, 397 had CTO, and 545 had H-type hypertension. After multivariate adjustment, the odds ratio (OR) for CTO in individuals with H-type hypertension was 2.3-fold higher (95% CI 1.01-5.26) than that in healthy controls. The risk of CTO is higher in individuals with H-type hypertension than in those with isolated HHCY and hypertension. The area under the ROC curve for CTO was 0.685 (95% CI, 0.653-0.717) for H-type hypertension. In southwest China, H-type hypertension is significantly related to the occurrence of CTO. This retrospective study was registered with the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2100050519.2.2).


Usual and unusual radiologic manifestations of acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection in children.
AIDS is being recognized with ever-increasing frequency in children. This article includes a discussion of the common radiographic manifestations of AIDS as well as some rarely encountered problems. It is hoped that with heightened awareness of this spectrum of radiographic findings, radiologists may contribute to a prompt diagnosis of AIDS so that appropriate short-term therapy and counseling may be instituted.


Trends in Risk Factors and Treatments in Patients With Stable Ischemic Heart Disease Seen at Cardiology Clinics Between 2006 and 2014.
Chronic ischemic heart disease is the most prevalent of all cardiovascular diseases. Patients are at high risk of complications. In recent decades, changes may have occurred in the clinical characteristics of the disease, its treatment and control of risk factors. A direct comparison of 2 national registries of patients with chronic ischemic heart disease carried out in 2006 (n=1583) and 2014 (n=1110). We observed statistically significant differences between the 2 registries, with a higher percentage of men and smokers in the 2014 registry, but a lower prevalence of diabetes mellitus and hypertension. Heart failure and stroke were more prevalent in the 2006 registry. Patients in the 2014 registry had better results for lipid profile, blood glucose, creatinine, and glomerular filtration rate. We observed higher use of recommended drugs for secondary prevention and an increased percentage of patients receiving optimal medical therapy, from 32.5% to 49.5% (P<.01). Use of high-intensity statin doses also increased from 10.5% to 42.8% (P<.01). We found better control of some risk factors (improved dyslipidemia, heart rate, and blood glucose in patients with diabetes) but worse blood pressure control. The clinical profile of patients with chronic ischemic heart disease is similar in the 2 registries. There has been an improvement in patients' medical therapy and dyslipidemia control, blood glucose, and heart rate, but there is still much room for improvement in the control of other cardiovascular risk factors.


Mechanism of selectivity in ion-pair high-performance liquid chromatography of aminoglycoside antibiotics using perfluorinated pairing ions.
The behaviour of perfluorinated carboxylic acids as pairing ions for the chromatography of the aminoglycoside antibiotics was studied. As with perhydrogenated pairing ions, the capacity factor can be modified according to the percentage of organic modifier and the nature and concentration of perfluorinated pairing ion in the mobile phase. The special selectivity effect observed with trifluoroacetic acid was investigated and interpreted as a concerted mechanism involving ionic and hydrophobic interactions.


Antireflection coating of barriers to enhance electron tunnelling: exploring the matter wave analogy of superluminal optical phase velocity.
The tunnelling of electrons through barriers is important in field emission sources and in interconnects within electronic devices. Here we use the analogy between the electromagnetic wave equation and the Schrodinger equation to find potential barriers that, when added before an existing barrier, increase the transmission probability. A single pre-barrier of negative potential behaves as a dielectric "antireflection coating", as previously reported. However, we obtain an unexpected and much greater enhancement of transmission when the pre-barrier has a positive potential of height smaller than the energy of the incident electron, an unfamiliar optical case, corresponding to media with superluminal phase velocities as in dilute free electron media and anomalous dispersion at X-ray frequencies. We use a finite difference time domain algorithm to evaluate the transmission through a triangular field emission barrier with a pre-barrier that meets the new condition. We show that the transmission is enhanced for an incident wavepacket, producing a larger field emission current than for an uncoated barrier. Examples are given of available materials to enhance transmission in practical applications. The results are significant for showing how to increase electron transmission in field emission and at interconnects between dissimilar materials in all types of electronic devices.


[The effect of ethanol-applications on uric acid-metabolism in minipigs (author's transl)].
The effect of several drugs on minipigs was examined over a period of upto 3 months. The drugs applied were: ethanol, etacryn acid (per os), ethanol, maleic acid, physiological NaCl--solution (by infusion). The creatinin-, uric acid-, lactat- and haematocrit-values of the serum and blood as well as the creatinin- and uric-excretion were followed. For ethanol and maleine acid an increase of the creatinin- and uric acid-excretion was found. This was accompanied by an increase of the haematocrit value. If the diuresis was augmented by certain substances, a more or less pronounced uricosuria was found. The measured values will be discussed, especially how the renal function may be involved.


Retraction Note: Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix.
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41467-020-19968-3.


Crystal structure of (4-cyano-pyridine-κN){5,10,15,20-tetrakis[4-(benzoyloxy)phenyl]porphyrinato-κ(4) N}zinc-4-cyano-pyridine (1/1).
In the title compound, [Zn(C72H44N4O8)(C6H4N2)]·C6H4N2 or [Zn(TPBP)(4-CNpy]·(4-CNpy) [where TPBP and 4-CNpy are 5,10,15,20-(tetra-phenyl-benzoate)porphyrinate and 4-cyano-pyridine, respectively], the Zn(II) cation is chelated by four pyrrole-N atoms of the porphyrinate anion and coordinated by a pyridyl-N atom of the 4-CNpy axial ligand in a distorted square-pyramidal geometry. The average Zn-N(pyrrole) bond length is 2.060 (6) Å and the Zn-N(4-CNpy) bond length is 2.159 (2) Å. The zinc cation is displaced by 0.319 (1) Å from the N4C20 mean plane of the porphyrinate anion toward the 4-cyano-pyridine axial ligand. This porphyrinate macrocycle exhibits major saddle and moderate ruffling and doming deformations. In the crystal, the [Zn(TPBP)(4-CNpy)] complex mol-ecules are linked together via weak C-H⋯N, C-H⋯O and C-H⋯π inter-actions, forming supra-molecular channels parallel to the c axis. The non-coordinating 4-cyano-pyridine mol-ecules are located in the channels and linked with the complex mol-ecules, via weak C-H⋯N inter-actions and π-π stacking or via weak C-H⋯O and C-H⋯π inter-actions. The non-coordinating 4-cyano-pyridine mol-ecule is disordered over two positions with an occupancy ratio of 0.666 (4):0.334 (4).


Selective Oxidation of Glycerol to Dihydroxyacetone over Au/CuxZr1-xOy Catalysts in Base-Free Conditions.
In this paper, a series of Cu-Zr mixed metal oxide-supported Au catalysts were prepared by deposition-precipitation and evaluated for selective oxidation of glycerol to dihydroxyacetone (DHA) in base-free conditions. The best catalytic performance was obtained with DHA selectivity of up to 95% and yield of 70% in 4 h, 50 °C and PO2 = 0.2 MPa over the Au/Cu0.95Zr0.05 and Au/Cu0.9Zr0.1 catalysts. Combined with the characterization results of Brunauer-Emmett-Teller, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature programmed desorption, it was proposed that the content of Au0, the size of Au, and the basicity of the catalyst affected the glycerol conversion and DHA selectivity. After the catalyst was recycled four times, the glycerol conversion decreased by about 14% which might result from the carbon deposition or the byproduct adsorption and the agglomeration of Au particle.


The medical risks of obesity.
Obesity is associated with a number of medical conditions that lead to increased morbidity and increased mortality. Both the National Institutes of Health and the World Health Organization define obesity as a body mass index (BMI) > or = 30 kg/m2 and overweight as a BMI 25-30. The most common conditions associated with obesity are insulin resistance, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, gallstones and cholecystitis, sleep apnea and other respiratory dysfunction, and the increased incidence of certain cancers. These are discussed below.


Factors increasing the risk of inappropriate vancomycin therapy in ICU patients: A prospective observational study.
Vancomycin trough levels are frequently subtherapeutic in intensive care unit (ICU) patients. The aim of this study was to identify patients at risk of therapeutic failure defined as vancomycin area-under-the-curve0-24 /minimum inhibitory concentration (AUC0-24 /MIC) <400, and to examine possible effects of different MICs, the variability in renal clearance and continuous renal replacement therapy (CRRT), and the relevance of vancomycin therapy. A prospective observational study of ICU patients ≥ 18 years at initiation of vancomycin therapy was conducted from May 2013 to October 2015. The patients were divided into four groups according to renal function and CRRT-mode as follows: normal- or augmented renal clearance and continuous venovenous hemodialysis or -hemofiltration. Vancomycin peak and trough levels were measured at 24, 48, and 72 hours after therapy initiation. Relevance of vancomycin therapy was retrospectively evaluated based on microbiological results. Eighty-three patients were included, median age 54.5 years, 74.5% male, SAPS II score 46, and 90 day mortality 28%. Vancomycin therapy was initiated on ICU-day 8 (IQR, 5-12), with a median treatment time of 7.5 (IQR, 5-12) days. AUC0-24 /MIC > 400 was reached in 81% and 8% with MIC = 1 and 2 mg/L respectively. The CRRT groups had higher AUC0-24 /MIC-ratios than the non-CRRT groups (P < .001). Augmented renal clearance increased the risk of AUC0-24 /MIC < 400, independent of MIC-value. Initiation of vancomycin therapy was retrospectively considered relevant in 28 patients (34%). A MIC-value >1 mg/L and augmented renal clearance, were factors increasing the risk of therapeutic failure. Vancomycin treatments could have been omitted or shortened in most of these patients.


Validation of the Staff Attitudes to Nutritional Nursing Care Geriatric scale in Italian.
To validate the Staff Attitudes to Nutritional Nursing Care Geriatric scale in Italian, a tool created in Sweden to measure nurses' attitudes towards nutritional care in older people. Malnutrition in institutionalized older people is a serious problem having negative impact on patient outcomes. It is reported in the literature that nurses have negative attitudes towards nutritional care. Forward and back-translation were carried out to build the Italian version of the tool. Content and face validity were then examined by pilot study. Test-retest reliability with Spearman's rho (rs) correlation, intraclass correlation (ICC) and internal consistency reliability with Cronbach's α were assessed. Differences between test-rest were assessed by t-test. Linguistic and semantic adaptation of the tool into Italian was successful. Thirty-three nurses skilled in caring for older patients did pilot testing and 46 test-retesting. SANN-G GITA-scale achieved good content and face validity, good internal consistency reliability (Cronbach's α = 0.85) and acceptable stability [rs = 0.75, P = 0.001; ICC = 0.76, 95% confidence interval (CI) 0.63-0.86; P = 0.001]. The t-test showed no significant difference between test and retest results, confirming stability of the tool (t(64) = -0.98; P = 0.33). The process of adaptation of the scale from Swedish to Italian language was successful. Thus, the SANN-GITA scale can be useful to assess attitudes of nursing staff to nutritional care in the Italian context. This tool will allow the identification of areas where Italian nurses have negative attitudes and where to implement strategies to improve overall nutritional care.


Antifungal activity of plant extracts against Colletotrichum lagenarium, the causal agent of anthracnose in cucumber.
Colletotrichum lagenarium is an important plant-pathogenic fungus that causes anthracnose of cucumber, a disease that is widespread under both greenhouse and field cultivation. To find a promising method for the control of this disease, extracts of eight plants from China were screened in the study presented here. The results showed that the extract of Cinnamomum camphora (L.) Presl had significantly greater inhibitory activity against C. lagenarium than the other seven plant extracts tested in vitro. At 5 days after inoculation in a potted seedling experiment, C. camphora extract demonstrated 95% control of C. lagenarium at a concentration of 16 mg mL⁻¹, and the MIC₅₀ was 2.596 mg mL⁻¹. Microscopic observation showed that this extract had a significant impact on the morphology of the fungus, leading to shorter hyphae that were more branched; this observation was associated with the inhibition of mycelial growth. Stability assays revealed that the extract was relatively stable at 80 °C, under acidic conditions and when exposed to light and short periods of UV radiation. These results demonstrated that the extract from C. camphora could be used as a potent phytochemical fungicide.


Extent of increase in intracellular calcium concentration in electrically stimulated chick embryo heart cells does not depend on resting intracellular calcium concentration.
Using Fura-2 digital imaging microscopy, we found two cell populations in chick embryo heart with different resting intracellular calcium concentration ([Ca2+]i). Electrical stimulation of the cells led to the same increase in [Ca2+]i in both cell types, e.g. from 118 +/- 24 nM up to a peak of 243 +/- 67 nM (SD, n = 18) and from 44 +/- 15 nM up to a peak of 135 +/- 59 nM (SD, n = 13) in cells with high and low resting [Ca2+]i, respectively. All the cells showed the same rate of decline in [Ca2+]i. Due to synchronic stimulation and contraction, this method is suitable to measure [Ca2+]i transients at a high time resolution in individual cells.


Synergistic autoinhibition and activation mechanisms control kinesin-1 motor activity.
Kinesin-1 activity is regulated by autoinhibition. Intramolecular interactions within the kinesin heavy chain (KHC) are proposed to be one facet of motor regulation. The KHC also binds to the kinesin light chain (KLC), which has been implicated in both autoinhibition and activation of the motor. We show that the KLC inhibits the kinesin-microtubule interaction independently from the proposed intramolecular interaction within KHC. Cargo-adaptor proteins that bind the KLC stimulated processive movement, but the landing rate of activated kinesin complexes remained low. Mitogen-activated protein 7 (MAP7) enhanced motility by increasing the landing rate and run length of the activated kinesin motors. Our results support a model whereby the motor activity of the kinesin is regulated by synergistic inhibition mechanisms and that cargo-adaptor binding to the KLC releases both mechanisms. However, a non-motor MAP is required for robust microtubule association of the activated motor. Thus, human kinesin is regulated by synergistic autoinhibition and activation mechanisms.


Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion.
No data exist on the trigger for platelet transfusions in adult thrombocytopenic patients with acute leukemia undergoing lumbar puncture (LP). We reviewed the records of 66 patients with acute leukemia (median age 38 years, range 18-68) who have been treated in our institution for 6 years. A total of 195 LPs were performed. No serious hemorrhagic complications occurred, but there was a significant trend towards a higher percentage of traumatic procedures, defined as the occurrence of >500 erythrocytes per high-power field, in patients with lowest platelet counts ( p<0.005). Although not associated with serious clinical bleeding events in this study, the increased occurrence of traumatic procedures may indicate an increased risk for more serious hemorrhagic complications, implying a trigger not lower than 20x10(9)/L for prophylactic transfusions of platelets in adult patients with acute leukemia undergoing LP.


Recurrent meningeal malignant tumor: Assessment of differences in the solitary fibrous tumor/hemangiopericytoma spectrum through a case report.
Solitary fibrous tumors (SFTs) are neoplasms that grow from mesenchymal fusiform cells. In the central nervous system, meninges are the common origin of these neoplasms. Although literature reports mostly SFT as benign neoplasm, malignancy data have been described in recurrences or metastatic lesions. Definitive diagnosis includes immunohistochemical profiles assessing cellular positivity for CD34, vimentin, CD99 and Bcl-2. Recent studies have demonstrated NAB2-STAT6 gene fusion as a distinct molecular feature of SFT with overexpression of the fusion protein NAB2-STAT6 in nuclei of these cells. Since several years, pathologists have grouped SFT and hemangiopericytomas (HPC) as different phenotypes of the same entity although both neoplasms do not share numerous features. This article, based on a case of a recurrent malignant SFT, aims to emphasize differences in the SFT/HPC spectrum due to the diagnostic, therapeutic and prognostic implications.


The RG2 rat glioma model.
The ethylnitrosourea-induced cell line RG2 grows very well in infinite cell culture in vitro, and provides a simple, reproducible glioma model when inoculated into the brains of syngeneic Fischer 344 rats. We have used this tumor model in a series of therapy studies. We here report our experiences of the untreated (= tumor bearing control) animals, e.g. in terms of the techniques employed and also the growth, histology and effects upon the blood-brain barrier of the tumors. Weight loss as a measure of systemic effects during tumor development is also described. The RG2 model has considerable potential as a suitable tool for experimental neuro-oncology.


Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells.
The mechanism of the inhibitory effect of anti-GD2 ganglioside (GD2) 14G2a mouse monoclonal antibody (mAb) on human neuroblastoma cells survival was studied in vitro. It was recently shown in IMR-32 cells that death induced by this antibody exhibited several characteristics typical of apoptosis. In this study we used cytotoxixity assays, qRT-PCR and immunoblotting to evaluate the response of several human neuroblastoma cell lines to the anti-GD2 14G2a mAb. We showed that the mAb decreases all three aurora kinases expression and phosphorylation in IMR-32 and LA-N-1 cells. Most importantly, we show, that MK-5108 specific aurora A kinase inhibitor decreases neuroblastoma cell survival, and when used in combination with the mAb, significantly potentiates cytotoxicity against IMR-32, CHP-134, and LA-N-5 neuroblastoma cells in vitro. It was shown that downregulation of aurora A kinase by the therapeutic antibody is associated with decreased levels of MYCN protein in cytoplasm, and induced expression of PHLDA1 and P53 proteins.


Assessment of the potential germ cell mutagenicity of industrial and plant protection chemicals as part of an integrated study of genotoxicity in vitro and in vivo.
An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.


Combined cisplatin and carboplatin chemotherapy for treatment of advanced epithelial ovarian cancer.
The primary goal of this trial was to evaluate the clinical activity and the toxicity of a combination of cisplatin and carboplatin for women with advanced-stage epithelial ovarian cancer. Fifty-one consecutive evaluable patients with untreated stage III and IV epithelial ovarian cancer received 360 mg/m2 carboplatin on Day 1 and 50 mg/m2 cisplatin on Day 2 administered intravenously every 28 days for six cycles. Drug doses were adjusted for hematologic toxicity based on nadir counts during the prior therapy course. Dose levels included 300-400 mg/m2 carboplatin and 50-75 mg/m2 cisplatin. Second-look surgery was optional. Endpoints were clinical response, surgical response, progression-free survival, and survival. Of 8 patients with measurable disease, 3 (37.5%) had a clinical compete response, and 3 (37.5%) had a clinical partial response, for an overall clinical response rate of 75%. Of 39 patients who began chemotherapy with abnormal serum levels of CA 125, 31 (79%) achieved normalization of CA 125 at the completion of chemotherapy. Thirteen patients underwent second-look laparotomy. Of these, 7 (54%) had a pathological compete response, and 2 (15%) had a partial response. The median progression-free survival was 14 months, and the overall median survival was 32.5 months. Neutropenia and thrombocytopenia were the main dose-limiting toxicities. In addition, 9 patients developed grade 2 and 3 developed grade 3 ototoxicity. This regimen is very active against advanced-stage epithelial ovarian cancer. The degree of ototoxicity observed is worrisome, but such toxicity may be ameliorated by limiting the dose of cisplatin and increasing the dose of carboplatin.


Cost-effectiveness analysis of phone reminders for outpatient magnetic resonance imaging (MRI) appointments in Singapore.
Due to long wait times, rising demand and limited resources for Magnetic Resonance Imaging (MRI) services, phone call reminders were implemented as an intervention to increase scanner utilisation and improve non-attendance at the radiology department in Changi General Hospital, Singapore. This study aims to evaluate the impact of phone reminders on outpatient MRI non-attendance rate as well as the operational efficiency and savings of this intervention through cost-effectiveness analysis. MRI outpatient records from January to December 2020 (pre-intervention period) and January to December 2021 (post-intervention period) were retrospectively obtained from the hospital systems. Non-attendance rates, costs and savings following the intervention were compared. Outpatient appointment non-attendance rates reduced from 12.85% to 8.93% after intervention. Following the phone reminders, 2,953 patients (21.69%) decided to cancel or reschedule their appointments. Based on the 91.07% attendance rate (100% - 8.93%), another 2689 slots were recovered from the cancellation of these appointments and were given to other patients. The reduction in non-attendance rates (3.92%) after the intervention translates to an increase in attendance of 533 patients while the net revenue generation with the phone reminder intervention was $387,179. Cost analysis indicates that phone reminders provide an inexpensive, easily implemented and personalised method to help increase adherence and improve appointment attendance. Reminding patients by phone calls two day before their appointments also leads to better optimization of appointment slots from cancelations and re-scheduling that can be used to allocate these appointments to other patients.


Kidney Transplantation Outcomes From Donors After Controlled Circulatory Death: A Comparison With Expanded Criteria Brain Death Donors.
The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list have led to an expansion of the acceptance criteria, such as donors after controlled cardiac death (cDCD) and donors after brain death with expanded criteria (DBD-EC). Some concerns and doubts about survival outcomes achieved with these allografts are still present. Our aim was to compare transplant outcomes from cDCD vs DBD-EC. A retrospective single-center observational study including all kidney transplant (KT) donors from all cDCD and DBD-EC (>60 years) from January 2015 to January 2022 was performed. We analyzed clinical characteristics, early clinical outcomes, and patient and graft survival rates. 129 cDCD and 166 DBD-EC KT recipients were included. The median follow-up was 30,2 months. DBD-EC were older and had more comorbidities than cDCD. KTs from cDCD and DBD-EC showed similar rates of delayed graft function and primary nonfunction. Patient survival at 1 year was similar (85% DBD-EC vs 90% cDCD, P = .32). Death-censored graft survival at 1 year was similar among young cDCD (18-59 years) and elderly DBD (60-69 years; 97% vs 92.3%, P = .2). Recipient age and expanded criteria in KT from cDCD were related to worse early graft outcomes. The outcomes achieved with KT from cDCD were similar to those observed in older and more comorbid DBD donors. This assumption is worth consideration when choosing the most suitable donor for each recipient.


Whole deletion of CYP2A6 gene (CYP2A6AST;4C) and smoking behavior.
The relationship between nicotine metabolism of CYP2A6 and the smoking behavior in a Japanese population was investigated. The CYP2A6 genotypes were determined by the PCR method. There was a significant difference in the frequency of the CYP2A6AST;4C allele, which is a whole deleted allele for the human CYP2A6 gene, between smokers and nonsmokers. The frequency of the CYP2A6AST;4C allele was higher in nonsmokers than in smokers, whereas the frequency of CYP2A6AST;1A/AST;1B heterozygotes with a higher activity of nicotine metabolism was lower. In this study it was suggested that the CYP2A6AST;4C allele may prevent the carrier from smoking and the CYP2A6AST;1A/AST;1B heterozygote may be at risk for developing smoking behavior.


Non-thermal atmospheric plasma treatment of onychomycosis in an in vitro human nail model.
Onychomycosis affects almost 6% of the world population. Topical azoles and systemic antifungal agents are of low efficacy and can have undesirable side effects. An effective, non-invasive therapy for onychomycosis is an unmet clinical need. Determine the efficacy threshold of non-thermal atmospheric plasma (NTAP) to treat onychomycosis in an in vitro model. A novel toe/nail-plate model using cadaver nails and agarose media inoculated with Candida albicans was exposed to a range of NTAP doses. Direct exposure of C albicans and Trichophyton mentagrophytes to 12 minutes of NTAP results in complete killing at doses of 39 and 15 kPulses, respectively. Onset of reduced viability of C albicans to NTAP treatment through the nail plate occurs at 64 kPulses with 10× and 100× reduction at 212 and 550 kPulses, respectively. NTAP is an effective, non-invasive therapeutic approach to onychomycosis that should be evaluated in a clinical setting.


Detection of swine-origin influenza A (H1N1) viruses using a localized surface plasmon coupled fluorescence fiber-optic biosensor.
Swine-origin influenza A (H1N1) virus (S-OIV) was identified as a new reassortant strain of influenza A virus in April 2009 and led to an influenza pandemic. Accurate and timely diagnoses are crucial for the control of influenza disease. We developed a localized surface plasmon coupled fluorescence fiber-optic biosensor (LSPCF-FOB) which combines a sandwich immunoassay with the LSP technique using antibodies against the hemagglutinin (HA) proteins of S-OIVs. The detection limit of the LSPCF-FOB for recombinant S-OIV H1 protein detection was estimated at 13.9 pg/mL, which is 10(3)-fold better than that of conventional capture ELISA when using the same capture antibodies. For clinical S-OIV isolates measurement, meanwhile, the detection limit of the LSPCF-FOB platform was calculated to be 8.25 × 10(4)copies/mL, compared with 2.06 × 10(6)copies/mL using conventional capture ELISA. Furthermore, in comparison with the influenza A/B rapid test, the detection limit of the LSPCF-FOB for S-OIV was almost 50-fold in PBS solution and 25-fold lower in mimic solution, which used nasal mucosa from healthy donors as the diluent. The findings of this study therefore indicate that the high detection sensitivity and specificity of the LSPCF-FOB make it a potentially effective diagnostic tool for clinical S-OIV infection and this technique has the potential to be applied to the development of other clinical microbe detection platforms.


Growth of Vetiveria zizanioides and Phragmities australis on Pb/Zn and Cu mine tailings amended with manure compost and sewage sludge: a greenhouse study.
The Lechang lead/zinc (Pb/Zn) mine and Dabao Shan copper (Cu) mine are located at the north of Guangdong Province in southern China. The residual tailings were permanently stored in tailings ponds which required revegetation to reduce their impact on the environment. A greenhouse study was conducted to evaluate the feasibility of using Vetiveria zizanioides (vetiver) and Phragmities australis (common reed) for the reclamation of Pb/Zn and Cu mine tailings and to evaluate the effects of organic amendments using manure compost (11.00, 22.03, 44.05 and 88.10 t/ha) and sewages sludge (11.00, 22.03, 44.05 and 88.10 t/ha) on the revegetation of these tailings. The results revealed that the applications of manure compost or sewage sludge not only increased N, P and K concentrations, but also decreased DTPA-extractable Pb and Zn contents in Pb/Zn tailings and DTPA-extractable Cu contents in Cu tailings. For Pb/Zn mine tailings, application of sewage sludge increased the yields of both species (highest yield at 44.05 t/ha), but not manure compost. For Cu mine tailings, application of manure compost (highest yield for both species at 44.05 and 22.03 t/ha for vetiver and common reed accordingly) or sewage sludge (highest yield at 22.03 and 44.05 t/ha for vetiver and common reed accordingly) increased the yield of both species. In general, vetiver achieved a higher yield when compared with common reed, under the same treatment. Plant tissue analysis showed that application of manure compost and sewage sludge could significantly reduce Pb uptake and accumulation, but not Cu in both vetiver and common reed.


Structure-based design and synthesis of a series of hydroxamic acids with a quaternary-hydroxy group in P1 as inhibitors of matrix metalloproteinases.
Examination of the S1 area of the active site of pro-stromelysin has led us to the design of novel and potent inhibitors of matrix metalloproteinases containing constrained quaternary-hydroxy group at P1. The synthesis and biological activity of these compounds with variations at P1', P2', and P3' will be described.


Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1.
Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT). PH1 is a clinically and genetically heterogeneous disorder. The aim of our study was to analyze and characterize the mutational spectrum of PH1 in Tunisian patients. Molecular studies of 146 Tunisian patients suspected with PH were performed by PCR/Restriction fragment length polymorphism (RFLP) to detect seven mutations described as the most common. Direct sequencing for the 11 exons was performed in patients in whom any mutation was not identified. The genetic diagnosis of PH1 was confirmed in 62.3% of patients. The first molecular approach based on PCR/restriction enzyme test was positive in 37.6% of patients, whereas the second molecular approach based on whole gene sequencing was successful in 24% of cases. Twelve pathogenic mutations were detected in our cohort. Two mutations were novel, and five were detected for the first time in Tunisians. The three most frequent mutations were p.Ile244Thr, p.Gly190Arg, and c.33dupC, with a frequency of 43.4%, 21.4%, and 13.1%, respectively. The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients.


Synthesis of polyadenylate-containing RNA in vitro in permeable cells of Escherichia coli B.
As a starting point for the study of the biosynthesis of polyadenylated RNA in bacteria, the characteristics of RNA synthesis by cells of Escherichia coli B made permeable to small molecules by treatment with toluene were examined. Such cells mediated the incorporation of radiolabeled ribonucleoside triphosphates into RNA in a reaction that was sensitive to inhibitors of RNA polymerase and required the simultaneous presence of the four ribonucleoside triphosphates. Between 10 to 15% of the RNA synthesized under these conditions was polyadenylated as shown by affinity chromatography on oligo(dT)-cellulose. The presence of orthophosphate or dADP, inhibitors of polynucleotide phosphorylase, had no effect on the reaction and the rate of RNA synthesis was indistinguishable in the polynucleotide phosphorylase-deficient strain PR-7 and in its otherwise isogenic parent strain PR-100. The poly(A) tracts associated with the newly synthesized RNA could be isolated after exhaustive digestion with pancreatic and T1 ribonucleases and accounted for 14% of the poly(A)-RNA. At least 74% of the poly(A) sequences were located at the 3' ends of RNA molecules and their weight-average length was 48 nucleotide residues. The size distribution of total RNA and poly(A)-RNA synthesized in the toluenized cell system was similar to that of the corresponding pulse-labeled fractions derived from growing cultures. The sequence complexity of poly(A)-RNA and unadenylated RNA synthesized in toluenized cells with [alpha-32P]CTP as the labeled substrate was analyzed by hybridization to fragments of Escherichia coli B DNA generated by digestion with EcoRI restriction endonuclease and immobilized on nitrocellulose sheets. Both RNA fractions hybridized with many DNA fractions, the hybridization patterns being similar with poly(A)-RNA and unadenylated RNA. This indicated that many different types of RNA transcripts synthesized in toluenized cells were subject to polyadenylation, but that polyadenylation was incomplete so that each transcript was present in both an adenylated and an unadenylated state.


External validation of a machine learning classifier to identify unhealthy alcohol use in hospitalized patients.
Unhealthy alcohol use (UAU) is one of the leading causes of global morbidity. A machine learning approach to alcohol screening could accelerate best practices when integrated into electronic health record (EHR) systems. This study aimed to validate externally a natural language processing (NLP) classifier developed at an independent medical center. Retrospective cohort study. The site for validation was a midwestern United States tertiary-care, urban medical center that has an inpatient structured universal screening model for unhealthy substance use and an active addiction consult service. Unplanned admissions of adult patients between October 23, 2017 and December 31, 2019, with EHR documentation of manual alcohol screening were included in the cohort (n = 57 605). The Alcohol Use Disorders Identification Test (AUDIT) served as the reference standard. AUDIT scores ≥5 for females and ≥8 for males served as cases for UAU. To examine error in manual screening or under-reporting, a post hoc error analysis was conducted, reviewing discordance between the NLP classifier and AUDIT-derived reference. All clinical notes excluding the manual screening and AUDIT documentation from the EHR were included in the NLP analysis. Using clinical notes from the first 24 hours of each encounter, the NLP classifier demonstrated an area under the receiver operating characteristic curve (AUCROC) and precision-recall area under the curve (PRAUC) of 0.91 (95% CI = 0.89-0.92) and 0.56 (95% CI = 0.53-0.60), respectively. At the optimal cut point of 0.5, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.66 (95% CI = 0.62-0.69), 0.98 (95% CI = 0.98-0.98), 0.35 (95% CI = 0.33-0.38), and 1.0 (95% CI = 1.0-1.0), respectively. External validation of a publicly available alcohol misuse classifier demonstrates adequate sensitivity and specificity for routine clinical use as an automated screening tool for identifying at-risk patients.


Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening.
Early diagnosis is very important to improve the survival rate of patients with gastric cancer (GC), especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of GC. In this study, we explored whether MIC-1 can improve the detection rate of early GC. We screened 8257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4, and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4, and PG1/PG2, and its role in early GC diagnosis and the assessment of the risk of precancerous lesions have also been studied. Based on endoscopic and histopathological findings, 55 participants had GC, 566 participants had low-grade neoplasia, and 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in GC serum samples as compared to controls (P < .001). The sensitivity of serum MIC-1 for GC diagnosis was much higher than that of CA-199 (49.1% vs 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4, and PG1/PG2 in distinguishing early-stage GC (AUC: 72.9% vs 69.5%, 67.5%, 44.0%, respectively). Serum MIC-1 is significantly elevated in most patients with early GC. MIC-1 can serve as a novel diagnostic marker of early GC and value the risk of GC.


Regioselective ruthenium catalyzed hydrohydroxyalkylation of dienes with 3-hydroxy-2-oxindoles: prenylation, geranylation, and beyond.
The direct conversion of secondary to tertiary alcohols via ruthenium(0) catalyzed C-C coupling of substituted 3-hydroxy-2-oxindoles with various dienes is described. Coupling occurs in a completely regioselective manner in the absence of stoichiometric byproducts.


Coagulation abnormalities in the carbohydrate-deficient glycoprotein syndrome: case report and review of the literature.
The carbohydrate-deficient glycoprotein syndromes are a group of recently described autosomal recessive, metabolic defects affecting multiple systems. The disorder is caused by inefficient posttranslational glycosylation of glycoproteins. Patients with the syndrome present early in life with psychomotor retardation, seizures, hypotonia, and stroke-like episodes. They also have dysmorphic features including almond-shaped eyes, constant squint, inverted nipples, and buttock fat pads. One of the features of the syndrome is coagulopathy, and we report here a patient who presented with a prolonged activated partial thromboplastin time, and was subsequently diagnosed with the carbohydrate-deficient glycoprotein syndrome. We also summarize the results of five previously published studies of the coagulation system in these patients. Most of the reported patients are deficient in factor XI, protein C, antithrombin III, and protein S. Other coagulation proteins are less frequently affected. Both bleeding and thrombosis have been observed, yet the cause of the stroke-like episodes remains speculative. The carbohydrate-deficient glycoprotein syndrome is an increasingly recognized multisystem disorder affecting hemostasis, and thus will involve clinical hematologists as part of a multidisciplinary team caring for patients with the syndrome.


Ab initio study of a biradical radiationless decay channel of the lowest excited electronic state of cytosine and its derivatives.
A theoretical model for the ultrafast S1-->S0 internal conversion of cytosine is presented, in which a state switch from the initially prepared 1pipi* state to the out-of-plane deformed excited state of biradical character controls the rate of the S1(1pipi*) decay. This mechanism successfully accounts for the dramatically longer S1 lifetimes of 5-fluorocytosine and N-acetylcytosine relative to cytosine. The replacement of the C5 hydrogen atom by a methyl group is predicted to lead to a substantial, but not dramatic, increase in the S1 lifetime, also consistent with experiment. It is this ability to correctly predict the substituent effects that distinguishes the present model from the previously proposed mechanisms.


Evaluating the effect of high-density measurement mode on patient-specific quality assurance for head and neck cancer with ArcCHECK.
The high-density measurement (HDm) mode of the ArcCHECK device can achieve a twofold resolution enhancement compared to the standard measurement (Sm) mode. The aim of this study was to evaluate the effect of HDm on the gamma passing rate (GPR) for the patient-specific quality assurance (PSQA) in head and neck cancer. We retrospectively evaluated 30 patients who underwent volumetric modulated arc therapy (VMAT) for head and neck cancer. Absolute gamma analysis was performed on Sm and HDm data. We also investigated correlations between the modulation complexity score for VMAT (MCSv) and differences in the GPR between the two measurement modes. The global GPR of Sm and HDm was 81.0% ± 8.4% and 82.6% ± 7.6% for the 2%/2 mm criterion, 94.0% ± 4.1% and 94.9% ± 3.6% for the 3%/2 mm criterion, and 96.6% ± 2.4% and 97.0% ± 2.4% for the 3%/3 mm criterion, respectively. HDm slightly improved GPR (p < 0.01) for the 2%/2 mm criterion. Differences in GPR between Sm and HDm for the 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria were 1.6% ± 3.0%, 0.8% ± 2.0%, and 0.4% ± 1.2%, respectively. No correlation was identified between the MCSv and the difference in GPR between Sm and HDm. Despite an improvement in GPR with HDm, the difference in GPR between Sm and HDm was approximately 2% even when the tighter criteria were used. Moreover, the change in the GPR between Sm and HDm did not depend on plan complexity. Thus, the effect of HDm on GPR is limited for the PSQA in VMAT for head and neck cancer.


Patient preferences for systemic sclerosis treatment: A descriptive study within an Italian cohort.
The aim of this study is to ascertain systemic sclerosis patients' preferences regarding the formulations of the medications they use. We undertook questionnaires and interviews aimed at understanding systemic sclerosis patients' preferences with respect to the medications they used. Among 160 systemic sclerosis patients, we found that the majority does not have difficulty taking their medication. However, preferences were identified (81.25% - 65/80 - preferred oral meds and 47.50% - 38/80 - disliked rectal/vaginal meds), as well as some systemic sclerosis patients have significant difficulties using their medications. In fact, factors such as swallowing and fine finger motion difficulties were frequent, while intravenous/intramuscular/subcutaneous medicines were usually not preferred because they are felt as inconvenient (intravenous = 33.4% and subcutaneous/intramuscular = 10%) or painful (intravenous = 37.50% and subcutaneous/intramuscular = 10%). Most systemic sclerosis patients are able to take their medication despite having some difficulties. However, as there were clear preferences, we could improve patients' adherence to drug therapy if taking these preferences into account.


Ethyl carbamate regulate esters degradation by activating hydrolysis during Baijiu ripening.
The presence of ethyl carbamate in traditional fermented food is a public health concern for the FDA. The effect of forced photoirradiation (0-150,000 lx) and thermal stress (4, 25, 40 °C) on ethyl carbamate (0-150 μg/L) on physiological characteristics of Baijiu, such as esters content, photochemical degradation, and hydrogen-bond interaction efficiency were monitored by ultra high performance liquid chromatography quadrupole-orbitrap and the dynamic changes by digital foodomics analysis. Furthermore, 748 trace components covering 11 subclasses were identified in Baijiu and 71 esters were screened by Spearman's correlation, fold changes, P values and VIP values. A forward stepwise multiple regression and discriminant analysis were performed for predicting the content of esters from appearance characteristics obtained by foodomics analysis, reaching R-square values up to 0.91. A reduction of the present variation in ethyl lactate, ethyl caproate, diethyl succinate, ethyl oleate and ethyl linoleate concentration could possibly result in a better understanding of the ethyl carbamate effects. Ethyl carbamate was found to cause esters hydrolysis through inter-molecular interaction in various species of alcoholic drinks. It was demonstrated that the light exposure level and thermal intensity applied for ethyl carbamate-spiked Baijiu samples did not unambiguously influence esters concentration in Baijiu. Future research should focus on moderate light exposure level and thermal stress and should aim at reducing natural ethyl carbamate by more closely controlling the esters content of the ripening degree.


High purity and yield of natural Tregs from cord blood using a single step selection method.
Natural regulatory T cells (Tregs), characterized as CD4 CD25high Foxp3+, have been described as paramount contributors in immuno-regulation and self-tolerance. CD4 and CD25 have been the main markers used for their isolation, resulting in cells with potent suppressive properties. Nevertheless, low purity and yield continue to be an issue when attempting thorough characterizations and/or up scaling to bigger models and for clinical trials. Here we present a single-step methodology optimized for cord blood CD25+ isolation, using magnetic microbeads that achieves a reproducible purity of 89% for CD4 CD25high CD127low. These cells showed a more consistent suppressive effect in mixed lymphocyte cultures. In addition, the proportion of contaminating effector T cells was < 9% whilst the yield of Tregs was doubled compared to the standard protocol. Gating on CD4 CD25high CD127low populations post isolation showed better correlation with suppressive efficacy compared to CD4 CD25+ gate. These data should facilitate the clinical scale-up of this procedure to obtain consistent Tregs for clinical application and research.


Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.
Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.


Experimental (-) emetine myopathy. Ultrastructural and morphometric observations.
The ultrastructural changes induced by (-) emetine hydrochloride were studied in two skeletal muscles of the rat. (-) Emetine was administered at a dose level of 2 mg/kg for periods ranging from one to four weeks. Changes were noted after the one week stage and were progressive with all muscle components appearing to be affected. Myofibrillar changes included Z line streaming, rod formation, myofilament loss and contraction clumping. Mitochondrial degeneration was detected, but the most striking feature of the induced myopathy was the extensive membrane proliferation. The membranes were considered to be involved in the isolation of sarcoplasmic constitutents in the production of autophagic vacuoles. Morphometry was carried out in order to quantify some of the changes in the fibre components.


Contribution of radionuclide imaging to radiation oncology.
Radionuclide imaging has been helpful to oncologists in the initial evaluation and follow-up of patients with primary and metastatic disease. With the introduction of ultrasound and computed tomography, there has been some reduction in the number of radionuclide imaging procedures. These imaging modalities should be used to complement one another. With the introduction of single-photon emission computed tomography in clinical nuclear medicine, there will be a significant improvement in the sensitivity, accuracy, and quantitative ability to detect abnormal lesions. There are intensive efforts in the development of tumor imaging using new agents. Specific antibodies for surface tumor antigens can be labeled with radioisotopes and used as tools for screening primary tumors and metastatic lesions. Therefore, for the present, radionuclide imaging will continue to contribute to clinical oncology.


Effects of turbulence modelling on prediction of flow characteristics in a bench-scale anaerobic gas-lift digester.
Flow in a gas-lift digester with a central draft-tube was investigated using computational fluid dynamics (CFD) and different turbulence closure models. The k-ω Shear-Stress-Transport (SST), Renormalization-Group (RNG) k-∊, Linear Reynolds-Stress-Model (RSM) and Transition-SST models were tested for a gas-lift loop reactor under Newtonian flow conditions validated against published experimental work. The results identify that flow predictions within the reactor (where flow is transitional) are particularly sensitive to the turbulence model implemented; the Transition-SST model was found to be the most robust for capturing mixing behaviour and predicting separation reliably. Therefore, Transition-SST is recommended over k-∊ models for use in comparable mixing problems. A comparison of results obtained using multiphase Euler-Lagrange and singlephase approaches are presented. The results support the validity of the singlephase modelling assumptions in obtaining reliable predictions of the reactor flow. Solver independence of results was verified by comparing two independent finite-volume solvers (Fluent-13.0sp2 and OpenFOAM-2.0.1).


A biosensor based on oriented immobilization of an engineered l-glutamate oxidase on a screen-printed microchip for detection of l-glutamate in fermentation processes.
This paper describes an amperometric biosensor utilizing an engineered l-glutamate oxidase for glutamate monitoring in microbial fermentation processes. We designed a general immobilization strategy that utilized a chitin-binding domain (ChBD-tag) as a biotether to further immobilize l-glutamate oxidase (GLOX) in an oriented manner on a screen-printed Prussian blue nanocube microchip (PB/SPC) with the biopolymer chitosan. The improved l-glutamate biosensor exhibited an enhanced sensitivity of 53.4 µA L mmol-1 cm-2 and a linear range from 25 µmol/L to 300 µmol/L with a detection limit of 9 µmol/L, and retained 95 % of its initial activity after two weeks of usage. In addition, the as-prepared biosensor was applied for real-time monitoring of food ingredient l-glutamate concentration during the fermentation process, which was in good agreement with that of high-performance liquid chromatography (HPLC). Above all, the l-glutamate biosensor prepared by this method had high analytical performance, and could fully realize real-time and high-efficiency monitoring in glutamate fermentation.


CHCHD2 Regulates Mitochondrial Function and Apoptosis of Ectopic Endometrial Stromal Cells in the Pathogenesis of Endometriosis.
Endometriosis is a disease that involves dysfunction of mitochondria, imbalance of proliferation, and apoptosis. Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a major mitochondrial protein which could regulate the mitochondrial function and apoptosis in various tumor cells, promote migration and then lead to tumor progression. This study aimed to explore the role of CHCHD2 on endometriosis. We investigated the expression of CHCHD2 in ectopic and eutopic endometrium tissues of patients with endometriosis and normal endometrium tissues. Furthermore, CHCHD2 was downregulated to explore the corresponding change of mitochondrial function and morphology, mitochondrial-mediated apoptosis pathway, and proliferation and migration of ectopic endometrial stromal cells. Our results demonstrated that the mRNA and protein expression levels of CHCHD2 were significantly increased in eutopic and ectopic endometrium tissues compared with the normal endometrium tissues. The knockdown of CHCHD2 could cause mitochondrial dysfunction, including the opening of mitochondrial permeability transition pore, loss of mitochondrial membrane potential and the release of cytochrome c, and morphological damage. In addition, CHCHD2 down-expression could also lead to inhibition of cell proliferation, decrease of migration ability, and aggravation of mitochondrial-mediated apoptosis. Together, these findings suggest that increased expression of CHCHD2 in endometriotic tissues may contribute to the pathogenesis of endometriosis via regulating mitochondrial function and apoptosis, and CHCHD2 may be a potential target for interrupting the development of endometriosis.


Delayed repair of flexor profundus tendon in the palm (zone 3) with superficialis transfer.
Transfer of a flexor superficialis tendon was done in an attempt to restore flexor profundus function, as a secondary procedure, in the palm (zone 3) in 16 hands. These were cases in which direct repair was not possible. Eight patients achieved a total active motion (TAM) above 200 degrees and two more were above 180. Of those eight with TAM above 200 degrees four required a secondary tenolysis to improve to that level. Transfers in six patients were regarded as failures. Failures were associated with a poor tendon bed and noncompliant patients. This is a procedure that has limited indication in a cooperative patient with a good tendon bed who reports late with both flexor tendons cut in zone 3.


Micro-aeration and leachate recirculation for the acceleration of landfill stabilization: Enhanced hydrolytic acidification by facultative bacteria.
The long duration of landfill stabilization is one of the challenges faced by municipalities. In this paper, a combination of micro-aeration and leachate recirculation is used to achieve rapid degradation of organic matter in landfill waste. The results showed that the content of volatile fatty acids (VFAs) in the hydrolysis phase increased significantly and could enter the methanogenic phase quickly. Until the end of the landfill, the removal rates of chemical oxygen demand (COD), total phosphorus (TP) and ammonia nitrogen (NH4+-N) by micro-aeration and leachate recirculation reached 80.17 %, 48.30 % and 48.56 %, respectively, and the organic matter degradation rate reached 50 %. Micro-aeration and leachate recirculation enhanced the abundance of facultative hydrolytic bacteria such as Rummeliibacillus and Bacillus and the oxygen tolerance of Methanobrevibacter and Methanoculleus. Micro-aeration and leachate recirculation improved the organic matter degradation efficiency of landfill waste by promoting the growth of functional microorganisms.


Elucidating the degradation mechanism of a self-degradable dextran-based medical adhesive.
We developed a self-degradable medical adhesive, LYDEX, consisting of periodate-oxidized aldehyde-functionalized dextran (AD) and succinic anhydride-treated ε-poly-l-lysine (SAPL). After gelation and adhesion of LYDEX by Schiff base bond formation between the AD aldehyde groups and SAPL amino groups, molecular degradation associated with the Maillard reaction is initiated, but the detailed degradation mechanism remains unknown. Herein, we elucidated the degradation mechanism of LYDEX by analyzing the main degradation products under typical solution conditions in vitro. The degradation of the LYDEX gel with a sodium periodate/dextran content of 2.5/20 was observed using gel permeation chromatography and infrared and 1H NMR spectroscopy. The AD ratio in the AD-SAPL mixture increased as the molecular weight decreased with the degradation time. This discovery of LYDEX self-degradability is useful for clarifying other polysaccharide hydrogel degradation mechanisms, and valuable for the use of LYDEX in medical applications, such as hemostatic or sealant materials.


Kupffer's vesicle in Fundulus heteroclitus: a scanning and transmission electron microscope study.
Kupffer's vesicle, a transitory organ peculiar to teleost embryos, was investigated in embryos of Fundulus heteroclitus by scanning electron microscopy. The roof of the vesicle is constructed to rather large columnar cells which are in continuity wiht hypoblast cells. Each of the roof cells is adorned with a single long cilium which emerges from a depression in the center of the surface and extends into the cavity of the vesicle. Studies with a transmission electron microscope confirm and extent these observations. The surface of the roof of the vesicle variously exhibits the presence of droplets and viscous and/or filamentous material. The exposed surface, however, sometimes appears clean and somtimes appears to have undergon partial destruction. The periblast floor of the vesicle is characterized by the presence of numerous folds and/or microvillus projections into the cavity of the vesicle. A filamentous precipitate is sometimes present. These observations are discussed in terms of the possible functional significance of this unique evanescent organ of the teleost embryo.


Hybrid Monte Carlo estimators for multilayer transport problems.
This paper introduces a new family of hybrid estimators aimed at controlling the efficiency of Monte Carlo computations in particle transport problems. In this context, efficiency is usually measured by the figure of merit (FOM) given by the inverse product of the estimator variance Var[ξ] and the run time T: FOM := (Var[ξ] T)-1. Previously, we developed a new family of transport-constrained unbiased radiance estimators (T-CURE) that generalize the conventional collision and track length estimators [1] and provide 1-2 orders of magnitude additional variance reduction. However, these gains in variance reduction are partly offset by increases in overhead time [2], lowering their computational efficiency. Here we show that combining T-CURE estimation with conventional terminal estimation within each individual biography can moderate the efficiency of the resulting "hybrid" estimator without introducing bias in the computation. This is achieved by treating only the refractive interface crossings with the extended next event estimator, and all others by standard terminal estimators. This is because when there are index-mismatched interfaces between the collision location and the detector, the T-CURE computation rapidly becomes intractable due to the large number of refractions and reflections that can arise. We illustrate the gains in efficiency by comparing our hybrid strategy with more conventional estimation methods in a series of multi-layer numerical examples.


The association between TP53 Arg72Pro polymorphism and lung cancer susceptibility: evidence from 30,038 subjects.
The TP53 codon 72 polymorphism has been associated with the individual susceptibility to lung cancer. However, the association remains uncertain and varies with ethnicity, smoking status, cancer histology, and stage. We performed a meta-analysis to evaluate the relationship between TP53 Arg72Pro polymorphism and lung cancer susceptibility basing on 15,647 lung cancer patients and 14,391 controls from 36 published literatures. We also performed stratified analysis in populations of different ethnicities, smoking statuses, lung cancer stages, and histological types. The analysis showed a significantly increased lung cancer susceptibility among Pro allele carriers (P < 0.001, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.1-1.19), especially for smokers (P < 0.001, OR = 1.29, 95% CI = 1.12-1.47). Stratified analysis indicated that Pro72 elevates lung cancer susceptibility in Asians, while it has no effect on lung cancer risk of Caucasians. Moreover, Pro carriers present an increased risk of developing squamous cell carcinoma and adenocarcinoma, instead of large cell carcinoma and small cell carcinoma. Interestingly, patients with the Pro allele seemed to be diagnosed with lung cancer at the early stages (stage I-II, P = 0.008, OR = 1.2, 95% CI = 1.05-1.37). Our results suggest that the Pro allele acts as a risk factor for development of lung cancer, especially for smokers and Asians.


DNA repair inhibitors and radiotherapy.
Radiotherapy (RT) is one of the main cancer treatments and grows in importance due to improved techniques. DNA damage caused by ionizing radiation creates DNA strand breaks that trigger an intervention of DNA repair pathways involving numerous proteins and enzymes. In recent years, we have identified DNA repair inhibitors as targets for inhibiting cellular repair systems and thus causing cell death. Combining RT with these DNA repair inhibitors appears to be a new approach for cancer treatment, but safety and real efficiency of this combination in practice is unclear. Numerous trials are underway in various diseases and initial results are promising overall, yet remain controversial.


Systematic review: the safety and tolerability of pharmacological agents for treatment of irritable bowel syndrome--a European perspective.
To use an evidence-based approach to evaluate the safety and tolerability of the treatments available for irritable bowel syndrome (IBS), or in clinical development, in Europe. A separate review appraises the evidence for the efficacy of these therapies. A literature search (for 1980 to 2005) was completed for all relevant clinical trial data and other articles which included safety information on the use of pharmacological IBS therapies. Clinical trials were scored according to the level of safety information, and adverse event incidence reported when possible. The tolerability of many of the agents used to treat IBS in Europe is poorly understood. However, serotonergic agents, such as tegaserod and alosetron, which are currently unavailable in Europe, have undergone rigorous assessment in IBS and their benefits have been established. Following initial marketing of alosetron for use in patients with IBS with diarrhoea, concerns about severe constipation and ischaemic colitis resulted in restriction of its use to women with severe IBS symptoms. This highlights the importance of post-marketing surveillance and post-marketing studies in refining the therapeutic indication of new IBS therapies, which will help to identify appropriate recipients for the drug and establish the impact of adverse reactions in clinical practice. There is a significant lack of data on the safety and tolerability of the therapies currently used routinely to treat IBS in Europe. The newer agents have undergone rigorous assessment, such that their benefits and risks in treating IBS are established. Defining their place among the spectrum of available therapies remains challenging when the benefits and risks of the older treatments are so poorly characterized.


Regulation and role of p21-activated kinase 3 by corticotropin-releasing factor in mouse pituitary.
Corticotropin-releasing factor (CRF) is a major regulatory peptide in the hypothalamic-pituitary-adrenal (HPA) axis under stress conditions. In response to stress, CRF, produced in the hypothalamic paraventricular nucleus, releases adrenocorticotropic hormone (ACTH) from the anterior pituitary (AP). ACTH in turn stimulates the release of glucocorticoid from the adrenal glands. Glucocorticoid then inhibits hypothalamic production of CRF and pituitary production of ACTH. Mice lacking a functional gene for CRF (CRF KO) showed severe impairment of the HPA axis, indicating that CRF is required for its regulation. We applied oligonucleotide microarray analysis to the AP of CRF KO to identify gene expression induced by CRF. Twenty-four genes showed less than 60% expression in CRF KO compared with normal mice. Real-time PCR analysis revealed that p21-activated kinase 3 (Pak3), prohormone convertase type 1 (PC1), and CRF-binding protein (BP) mRNA expression levels were increased by CRF in AP cells. Both Pak3 and PC1 were also increased by dexamethasone in AP cells, while CRF-BP mRNA levels were reduced. Therefore, both Pak3 and PC1 mRNA levels would be regulated by both CRF and glucocorticoids. Pak3 knockdown inhibited CRF-induced cell viability in AtT-20 cells, suggesting the important role of Pak3 in the proliferation of corticotrophs.


Surgical treatment of extraluminal pelvic recurrence from rectal cancer: oncological management and resection techniques.
Local recurrence (LR) after curative surgery for rectal cancer occurs in 4 to 33% of cases especially with suboptimal surgery (non-TME). For numerous patients, diagnosis of LR is done at late stage of the disease because of the high rate of asymptomatic patients. MRI and PET-scan are the most performing exams to assess the local and general extension, with high diagnostic accuracy (sensibility 85% and specificity 92%). For extraluminal pelvic recurrences from rectal cancer, pelvic exenterations alone or with irradiation (preoperative and/or intraoperative) can afford a R0 resection rate ranging from 30% to 45% with acceptable morbidity. Morbidity and mortality rates are high for total exenteration and abdominosacral resection. After curative surgery, 5-year global survival from 30% to 40% is observed. Careful selection of patients with better preoperative status before resection is needed to achieve more curative resections and increase long-term survivor rates.


Failure to detect immune complexes in the secondary stage of pityriasis rosea.
Thirty-three patients with pityriasis rosea were studied with regard to the possible presence of circulating and cutaneously deposited immune complexes. The levels of circulating immune complexes, determined by a solid-phase C1q-binding assay, were not different from those of healthy control individuals. The levels were similar in samples obtained during the initial and during the remission stages of the disease. Cutaneous deposits of immunoglobulin and/or complement were found in only 5 of 33 patients. This study does not support of concept that circulating immune complexes are important for the development of the secondary skin lesions in pityriasis rosea.


Response surface methodology modeling to improve degradation of Chlorpyrifos in agriculture runoff using TiO2 solar photocatalytic in a raceway pond reactor.
This paper deals with the use of a raceway pond reactor (RPR) as an alternative photoreactor for solar photocatalytic applications. Raceway pond reactors are common low-cost reactors which can treat large volumes of water. The experiments were carried out with TiO2 in the agriculture effluent spiked with Chlorpyrifos (CPF) at circumneutral pH. The Response Surface Methodology (RSM) was used to find the optimum process parameters to maximize CPF oxidation from the mathematical model equations developed in this study using R software. By ANOVA, p-value of lack of fit > 0.05 indicated that, the equation was well-fitted. The theoretical efficiency of CPF removal, under the optimum oxidation conditions with UV solar energy of around 697 ± 5.33 lux, was 84.01%, which is in close agreement with the mean experimental value (80 ± 1.42%) confirming that the response model was suitable for the optimization. As far as the authors know, this is the first study of CPF removal using RPR in agriculture runoff at circumneutral pH.


Clinicopathological analysis and prognostic treatment study of angiosarcoma of the breast: a SEER population-based analysis.
Breast angiosarcoma is a rare malignancy of endovascular origin, accounting for less than 1% of all mammary cancers. Our aim was to explore clinicopathological features and the factors associated with prognosis. We extracted information from the Surveillance, Epidemiology, and End Results Program (SEER) for all patients with breast angiosarcoma between 2004 and 2015. Chi-square analysis was used to compare the clinicopathological features in all patients. Overall survival (OS) was assessed using the Kaplan and Meier method. Univariate and multivariate analyses were performed to evaluate the factors associated with prognosis. A total of 247 patients were included in the analyses. The median OS of patients with primary breast angiosarcoma (PBSA) and secondary breast angiosarcoma (SBAB) was 38 months and 42 months, respectively. The 1-, 3- and 5-year OS with PBSA was 80%, 39%, and 25%, respectively, and the 1-, 3- and 5-year OS with SBAB was 80%, 42%, and 34%, respectively. Multivariate analysis revealed that tumor size (p = 0.001), tumor grade (p < 0.001), tumor extension (p = 0.015), and tumor spread (p < 0.001) were statistically significant factors for OS. Partial mastectomy with radiation (HR = 0.160, 95% CI, 0.036-0.719, p = 0.016), partial mastectomy with chemotherapy (HR = 0.105, 95% CI, 0.011-1.015, p = 0.052), and partial mastectomy (HR = 0.125, 95% CI, 0.028-0.583, p = 0.007) were related to significantly better OS outcomes in primary angiosarcoma. Primary breast angiosarcoma has a better clinical phenotype than secondary breast angiosarcoma. Although overall survival was not statistically significant, primary breast angiosarcoma was better than secondary breast angiosarcoma with systemic therapy. Depending on the outcome of survival, partial mastectomy is effective in treating primary breast angiosarcoma.


MicroRNA Expression Profiling Predicts Nodal Status and Disease Recurrence in Patients Treated with Curative Intent for Colorectal Cancer.
Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making.


Prostate lymphoscintigraphy for sentinel lymph node identification in canines: reproducibility, uptake, and biokinetics depending on different injection strategies.
At present there are neither clinical nor experimental data available on the influence of technical details on the quality and reproducibility of prostate lymphoscintigraphy. Six adult fox hounds received repeated transrectal ultrasound guided intraprostatic injections of a technetium 99m labeled nanocolloid to prove the influence of different techniques of injection (one central injection in both prostate lobes vs two peripheral injections in both lobes) on tracer accumulation in sentinel lymph nodes (SLN) and other organs. The reproducibility of the favored technique was examined and in a last step it was subject to scrutiny following a reduction of the injected volume to 1% of the prostate volume. The number of scintigraphically visualized SLN varied between four and seven. They were located in the region of the internal and external iliac vessels, presacrally, paravesically, and directly paraprostatically. In five of six cases, the localization was reproducible both with the central application of an identical volume as well as with the volume reduced central injection. Tracer accumulation of SLNs and other organs varied enormously. We expect that with the combination of both injection techniques, even with the reduced injection volume, an optimized prostate lymphoscintigraphy will be the outcome.


Bicarbonate activates glycolysis and lactate production in corneal endothelial cells by increased pHi.
Recent studies have shown that lactate coupled water flux is the underlying mechanism of the corneal endothelial pump, which is highly dependent on the presence of bicarbonate. In this study we test the hypothesis that the increased intracellular pH (pHi) caused by bicarbonate stimulates glycolytic activity and the production of lactate by endothelial cells. Primary cultures of bovine corneal endothelial cells (BCEC) were incubated in bicarbonate-free (BF) ringer, a high [HEPES] ringer, and bicarbonate-rich (BR) ringer all at pH 7.5. Lactate production and glucose consumption were greatest in BR>HEPES >BF. Similarly, pHi was greatest in BR>HEPES>BF. Increasing pHi with NH4Cl also increased lactate production in BF or BR, indicating that the increased lactate production in BR is not due to HCO3- itself. Glucose transport capacity, as measured by 2-N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino-2-Deoxyglucose (2-NBDG) uptake was unaffected by the three incubation conditions. Using Laconic, a FRET sensor for lactate, we found that intracellular [lactate] increased immediately and transiently when cells were switched from BF to BR perfusion indicating increased lactate production with subsequent matching of efflux. Moreover, induction of acute lactate influx by perfusion pulses of 10 mM lactate increased intracellular [lactate] significantly faster in BF than in BR, consistent with higher lactate production and efflux in BR. In summary, our results indicate that glycolytic flux and lactate production increase in BR due to increased pHi, consistent with the well-known pH sensitivity of phosphofructokinase, the rate limiting enzyme in glycolysis.


Dynamics of cell rounding during detachment.
Animal cells undergo repeated shape changes, for example by rounding up and respreading as they divide. Cell rounding can be also observed in interphase cells, for example when cancer cells switch from a mesenchymal to an ameboid mode of cell migration. Nevertheless, it remains unclear how interphase cells round up. In this article, we demonstrate that a partial loss of substrate adhesion triggers actomyosin-dependent cortical remodeling and ERM activation, which facilitates further adhesion loss causing cells to round. Although the path of rounding in this case superficially resembles mitotic rounding in involving ERM phosphorylation, retraction fiber formation, and cortical remodeling downstream of ROCK, it does not require Ect2. This work provides insights into the way partial loss of adhesion actives cortical remodeling to drive cell detachment from the substrate. This is important to consider when studying the mechanics of cells in suspension, for example using methods like real-time deformability cytometry (RT-DC).


Genome-wide identification, characterization, interaction network and expression profile of GAPDH gene family in sweet orange (Citrus sinensis).
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that plays important roles in multiple cellular processes including phytohormone signaling, plant development, and transcriptional regulation. Although GAPDH genes have been well characterized in various plant species such as Arabidopsis, tobacco, wheat, rice, and watermelon, comprehensive analysis has yet to be completed at the whole genome level in sweet orange (Citrus sinensis). In this study, six GAPDH genes distributed across four chromosomes were identified within the sweet orange genome. Their gene structures, conserved subunits, and subcellular localization were also characterized. Cis-element analysis of CsGAPDHs' promoter regions and the results of dark treatments indicate that CsGAPDH may be involved in photosynthesis. CsGAPDH genes expressed either in a tissue-specific manner or constitutively were ultimately identified along with their expression response to phosphorus deficiency treatments. In addition, a dual-luciferase transient assay was performed to reveal the transcriptional activation of CsGAPDH proteins. Gene Ontology (GO) analysis for proteins interacting with CsGAPDHs helped to uncover the roles these CsGAPDHs play in other plant processes such as citrus seed germination. This study provides a systematic analysis of the CsGAPDH gene family in the sweet orange genome, which can serve as a strong foundation for further research into the biochemical properties and physiological functions of CsGAPDHs.


Modulation of calcium responses by altered peptide ligands in a human T cell clone.
To determine whether altered peptide ligands (APL) affect calcium signaling events, we investigated changes in intracellular calcium concentration ([Ca2+]i) in human T cell clone stimulated with either the fully agonistic peptide M12p54-68, the partially agonistic analogue E63V or the simple antagonistic analogue E58M. Both E63V and E58M stimulated a Ca2+ response in approximately 40% of T cells, whereas M12p54-68 did so in approximately 70% of T cells. The most predominant pattern of a Ca2+ increase induced by M12p54-68 was a small sinusoidal peak followed by a sustained high response. The most frequent pattern of calcium response induced by E63V was a continuous high response without a preceding sinusoidal peak, whereas that induced by E58M was large with frequent oscillations. Genistein, an inhibitor of the protein tyrosine kinases (PTK), markedly inhibited the wild-type peptide-induced increase in [Ca2+]i, whereas it marginally inhibited the response induced by E63V or E58M. In contrast, GF109203X, a protein kinase C (PKC)-specific inhibitor, markedly inhibited the E63V- or E58M-induced Ca2+ response, whereas it marginally affected the wild peptide-induced Ca2+ response. Furthermore, in nominal Ca2+-free medium, the E58M-induced Ca2+ response was almost completely blocked, while the M12p54-68- or E63V-induced responses were only partially inhibited. Our results suggest that the Ca2+ response induced by the fully agonistic peptide depends on activation of the genistein-sensitive signaling pathway, including PTK, whereas the Ca2+ response to a simple antagonistic APL completely depends on extracellular Ca2+ and activation of the GF109203X-sensitive signaling pathway, including PKC. These differences in the CA2+i response in recognition of different APL may parallel the unique T cell activation patterns induced by APL in human T cells.


Some aspects of household diet and family income problems in Transkei.
Apparent levels of household diet, perceptions of diet and food production, rural water supplies, attitudes to birth control, and household incomes and expenditure of families in rural areas in Transkei were studied. The results revealed problems of deficiencies in family energy intake and low incomes, such that at least 40% of rural families were living in a state of poverty. There is urgent need for an integrated development approach aimed at fulfilling basic needs.


Retracted: Analysis of Interventional Application Effect of Ultrasound-Guided QLB and TAPB in the Treatment and Analgesia of Patients Undergoing Laparoscopic Colorectal Surgery.
[This retracts the article DOI: 10.1155/2022/4199868.].


Well-maintained responses of acetylcholine release and blood flow in the cerebral cortex to focal electrical stimulation of the nucleus basalis of Meynert in aged rats.
Responses of extracellular acetylcholine (ACh) release and blood flow in the cerebral cortex in the parietal lobe following focal electrical stimulation of the nucleus basalis of Meynert (NBM) ipsilateral to the parietal cortex were compared in healthy adult (6-8 months) and aged (27-28 months) Fischer-344 rats anesthetized with halothane. The focal electrical stimulation of the NBM produced an increase in the ACh release and blood flow in the parietal cortex in both the adult and aged rats. The increased responses of ACh and blood flow observed in the healthy, adult rats were well maintained in the aged rats.


Crystal structure of a variable region segment of Leptospira host-interacting outer surface protein, LigA, reveals the orientation of Ig-like domains.
Leptospiral immunoglobulin-like (Lig) protein family is a surface-exposed protein from the pathogenic Leptospira. The Lig protein family has been identified as an essential virulence factor of L. interrogan. One of the family members, LigA, contains 13 homologous tandem repeats of bacterial Ig-like (Big) domains in its extracellular portion. It is crucial in binding with the host's Extracellular matrices (ECM) and complement factors. However, its vital role in the invasion and evasion of pathogenic Leptospira, structural details, and domain organization of the extracellular portion of this protein are not explored thoroughly. Here, we described the first high-resolution crystal structure of a variable region segment (LigA8-9) of LigA at 1.87 Å resolution. The structure showed some remarkably distinctive aspects compared with other closely related Immunoglobulin domains. The structure illustrated the relative orientation of two domains and highlighted the role of the linker region in the domain orientation. We also observed an apparent electron density of Ca2+ ions coordinated with a proper interacting geometry within the protein. Molecular dynamic simulations demonstrated the involvement of a linker salt bridge in providing rigidity between the two domains. Our study proposes an overall arrangement of Ig-like domains in the LigA protein. The structural understanding of the extracellular portion of LigA and its interaction with the ECM provides insight into developing new therapeutics directed toward leptospirosis.


Conversion of poplar into bio-oil via subcritical hydrothermal liquefaction: Structure and antioxidant capacity.
Subcritical hydrothermal liquefaction of poplar was performed at 220-280 °C, and the liquid phase produced was extracted by ethyl acetate to obtain light oil (LO), which contained LO1 (water-soluble) and LO2 (ethyl acetate-soluble). The residue was further extracted with acetone to produce heavy oil (HO) and solid residue (SR). The highest bio-oil yield of 19.88% was obtained at 260 °C. The HO produced at 260 °C had the highest content of C (69.13%) and the higher heating value was 27.97 MJ/kg. The O/C and H/C ratios of LO were higher than those of HO due to less aromatics in LO. Oxidative inhibition rates of bio-oils, measured in DPPH-ethanol solution at a concentration of 0.1 mg/mL, reached 60.76% for LO1 while 90.29% and 90.85% for LO2 and HO, respectively. The bio-oil with good antioxidant activity can be utilized as an additive in bio-diesel to improve oxidation stability.


Programmed intermittent boluses vs continuous epidural infusion in labor using an adrenaline containing solution: A randomized trial.
Traditionally, epidural analgesia has been maintained using a continuous infusion (CEI) with the addition of patient-controlled boluses (PCEA). In recent years, programmed intermittent boluses (PIEB) has emerged as an alternative showing better efficacy in randomized studies. In this study, the aim was to test PIEB + PCEA vs CEI + PCEA using an epidural solution containing adrenaline. In total, 150 nulliparous and multiparous laboring women were randomized to maintain epidural analgesia with either PIEB + PCEA (5 ml bolus every hour, 5 ml PCEA bolus lockout 20 minutes) or CEI + PCEA (5 ml/h, 5 ml PCEA bolus, lockout 20 minutes) using a solution of bupivacaine 1mg/ml, fentanyl 2 mcg/ml and adrenaline 2 mcg/ml. The primary outcome was total hourly consumption of the epidural solution. Secondary outcomes included hourly pain scores, motor block at 60 minutes and 10 cm cervical dilation, maternal satisfaction, and the need for anesthetist intervention and time to this intervention. We found no differences in hourly drug consumption between the groups (mean 9.0 ml/h (SD 3.7) (CEI group) vs. 8.1 ml/h (SD 2.0) (PIEB group), P = .08). We found a significant difference in number of successfully administered PCEA boluses (mean no. 3.9 (SD 4.1) (CEI group) vs. 1.9 (SD 2.0) (PIEB group), P < .001). We found no significant differences in pain score, motor block, maternal satisfaction and the need for anesthetist intervention. In this study, we found no clinically relevant differences using PIEB + PCEA compared to CEI + PCEA when using an epidural solution containing adrenaline. For labor epidural analgesia infusions, to optimize the analgesic effect, additional programmed intermittent boluses can be used as an alternative to patient-controlled boluses only. In this clinical trial, no differences in drug consumption or analgesic effect was observed when comparing these two different epidural bolus controls programs.


The risk of preeclampsia rises with increasing prepregnancy body mass index.
To explore the dose-dependent relation between prepregnancy body mass index (BMI) and the risk of preeclampsia after adjusting for measured confounders. We studied 1179 primiparous women who enrolled at < 16 weeks' gestation into a prospective cohort study of the pathogenesis of preeclampsia. Multivariable logistic regression was used to quantify the independent effect of prepregnancy BMI on the risk of preeclampsia after adjusting for race and smoking status. BMI was specified as a restricted quadratic spline. Preeclampsia risk rose strikingly from a BMI of 15 to 30 kg/m(2). Compared with women with a BMI of 21, the adjusted risk of preeclampsia doubled at a BMI of 26 (odds ratio 2.1 [95% confidence interval, 1.4, 3.4]), and nearly tripled at a BMI of 30 (2.9 [1.6, 5.3]). Women with a BMI of 17 had a 57% reduction in preeclampsia risk compared with women with a BMI of 21 (0.43 [0.25, 0.76]), and a BMI of 19 was associated with a 33% reduction in risk (0.66 [0.50, 0.87]). These results indicate that preeclampsia risk rises through most of the BMI distribution. The dramatic elevation in overweight prevalence in the United States may increase preeclampsia incidence in the future.


Characterization of dominant-negative and temperature-sensitive mutants of tombusvirus replication proteins affecting replicase assembly.
The assembly of the viral replicase complex (VRC) on subcellular membranes is a key step in the replication process of plus-stranded RNA viruses. In this work, we have identified lethal and temperature sensitive (ts) point mutations within the essential p33:p33/p92 interaction domain of p33 and p92 replication proteins of Cucumber necrosis virus, a tombusvirus. Mutations within the p33:p33/p92 interaction domain also affected viral RNA recombination in yeast model host. An in vitro approach based on yeast cell free extract demonstrated that several p33 and p92 mutants behaved as dominant-negative during VRC assembly, and they showed reduced binding to the viral (+)RNA and affected activation of the p92 RdRp protein, while they did not directly influence (-) or (+)-strand synthesis. Overall, the presented data provide direct evidence that the p33:p33/p92 interaction domains in p33 and p92 are needed for the early stage of virus replication and also influence viral recombination.


A new model for production of chronic gastric ulcer by duodenogastric reflux in rats.
We have established an experimental model of chronic gastric ulcer, in rats which transection of the lower horizontal portion of the duodenum and anastomosis of the forestomach to the upper part of the jejunum caused regurgitation of all duodenal juice into the stomach. After 3, 6, 12, and 30 wk, all treated rats developed an ulcer in the prepyloric region on the lesser curvature of the stomach. More than half of the antrum was finally involved in the ulcer. Histologic studies revealed chronic ulcers quite similar to human ones. As a control series, transection at the pylorus failed to produce an ulcer. Although many papers have appeared regarding the experimental production of chronic gastric ulcer, most of the studies reported have applied chemicals, drugs, or mechanical injury to the gastric mucosa. Our model produced chronic regurgitation of duodenal juice as a natural phenomenon, and uniformly resulted in ulcer formation. Intragastric total bile acid concentrations were significantly elevated in the reflux group. Serum gastrin levels, the thickness of the fundic mucosa, and the height of fundic gland were also significantly increased. Thus, the detergent action of bile acids and the increased acid secretion were assumed to play an important role in ulcer formation. Further studies using this model are warranted on the pathogenesis of chronic peptic ulceration.


Regioselective synthesis of trisubstituted 2,3-dihydrofurans from donor-acceptor cyclopropanes or from reaction of the Corey ylide with alpha-sulfenyl-, alpha-sulfinyl-, or alpha-sulfonylenones.
[reactions: see text] Regioselective synthesis of 2,4,5- or 3,4,5-trisubstituted 2,3-dihydrofurans has been realized by using donor-acceptor cyclopropanes or by a Corey ylide reaction with alpha-sulfenyl-, alpha-sulfinyl-, or alpha-sulfonylenones. The method allowed a straightforward synthesis of the natural product calyxolane B.


Molecular approaches in the diagnosis of dermatophytosis.
Dermatophytosis is one of the most common infectious diseases in the world and can be caused by several dermatophyte species. These species are closely related in genetic structure in spite of different phenotypic and ecological features. The morphological similarity, variability, and polymorphism of dermatophytes have meant that species identification for dermatophytes is time consuming and requires a significant degree of knowledge and technological expertise. Molecular biology-based techniques have solved problems concerning the morphology-based identification of dermatophytes and have improved our knowledge on the epidemiology of dermatophytosis. Further development of molecular diagnosis of dermatophytosis requires the investigation of additional molecular markers for diagnostic tools targeting multiple loci as well as the improvement of techniques.


HLA-G expression in acute lymphoblastic leukemia: a significant prognostic tumor biomarker.
Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility class Ib antigen with multiple immune regulatory functions including the induction of immune tolerance in malignancies. The goal of our study was to investigate the expression of membrane form of HLA-G in acute lymphoblastic leukemia (ALL) before and after therapy in a trial to evaluate its role as a tumor escape mechanism and prognosis. So we measured its expression by reverse transcription (RT)-PCR in peripheral blood mononuclear cells of 25 (ALL) patients and 15 healthy controls and correlated our findings with a variety of clinical and laboratory variables and two important cytokines, IL-10 and INF-γ, and with natural killer (NK) cells. Serum levels of IL-10 and INF-γ were measured by ELISA. NK cells were quantitated by flow cytometry. The best cutoff values for the investigated markers were determined by ROC curve. The current study showed that membrane-bound HLA-G expression levels and positivity rates above the cutoff value 0.37 were significantly higher in ALL patients at diagnosis compared to after therapy and both showed significant higher levels than in normal control group (P < 0.01). Moreover, IL-10 and INF-γ serum levels were significantly elevated in ALL patients at time of diagnosis compared to healthy controls with a significant reduction in their levels in ALL patients after receiving chemotherapy. Membrane HLA-G expression showed a significant positive correlation with lactate dehydrogenase, peripheral and bone marrow blast cells and with IL-10 and INF-γ. The positive correlation of membrane HLA-G expression with both IL-10 and INF-γ serum levels supports the speculation that both cytokines may be involved in the control of HLA-G expression. HLA-G showed a negative correlation with NK cells confirming its importance in tumor escape through down-regulation of NK cells. In conclusion, HLA-G expression could be used as a prognostic tumor marker to monitor disease state and improvement in ALL.