Chromium removal at neutral pHs via electrochemical Cr(VI) reduction and subsequent Cr(III) adsorption with MoS2 nanoflowers-modified graphite felt.
The operation performance and stability of electrochemical Cr(VI) reduction are strongly restricted at neutral pHs (e.g., drinking water and groundwater) by the high Cr(VI) oxidation potentials and cathode passivation of Cr(OH)3 precipitates. Herein, we fabricated MoS2 nanoflowers-modified graphite felt (GF-MoS2) to construct the electrochemical apparatus (EA) and adsorption column (AC), attempting to stable and effective Cr(VI) removal at neutral pHs via electrochemical Cr(VI) reduction and subsequent Cr(III) adsorption. In EA with a sequential oxidation-reduction process, Cr(VI)-contaminated influent (5 mg/L) at neutral pHs (6.0-8.0) was oxidized first by anode to generate large amounts of H+ ions via H2O oxidation, decreasing the pH of anode-oxidized influent to ∼2.5 at 2.6 V and 1000 L/m2/h. Subsequently, the acidic anode-oxidized influent was further reduced by GF-MoS2 cathode, promoting significantly Cr(VI) reduction via decreasing Cr(VI) oxidation potentials and alleviating Cr(III) precipitation on cathode. These results enabled the stable and effective operation of GF-MoS2-based EA with almost Cr(VI) reduction to Cr(III). With further assembling GF-MoS2-based AC, Cr(III) species in EA effluent were easily adsorbed or intercepted by GF-MoS2, achieving undetectable Cr species in AC effluent. Combination techniques of GF-MoS2-based electrochemical reduction and adsorption can be an effective approach for remediating Cr(VI)-contaminated water at neutral pHs.


Nasal insertion depths for neonatal intubation.
Data on the depth of nasal intubation in neonates are rare, although this is the preferred route in some countries. Therefore, recommendations on optimal nasal intubation depths based on gestational age (GA) and weight are desirable. We determined the distances between the middle of thoracic vertebrae 2 (T2) and the tip of the endotracheal tube in 116 X-rays from nasally intubated neonates. The intubation depth (tip to nostril distance) that was documented in the digital patient's file was then corrected for this distance to reach an optimal nasal insertion depth. Results were plotted against the infant's GA and weight. GA-based and birthweight-based charts and formulas for the nasal intubation depth in infants with a GA between 24 and 43 weeks and body weight between 400 and 4500 g were created. Generated data may help in predicting optimal insertion depths for nasal intubation in neonates.


Low serum calcium and phosphorus and their clinical performance in detecting COVID-19 patients.
This study aimed to evaluate the clinical performance of low serum calcium and phosphorus in discriminative diagnosis of the severity of patients with coronavirus disease 2019 (COVID-19). We conducted a single-center hospital-based study and consecutively recruited 122 suspected and 104 confirmed patients with COVID-19 during January 24 to April 25, 2020. Clinical risk factors of COVID-19 were identified. The discriminative power of low calcium and phosphorus regarding the disease severity was evaluated. Low calcium and low phosphorus are more prevalent in severe or critical COVID-19 patients than moderate COVID-19 patients (odds ratio [OR], 15.07; 95% confidence interval [CI], 1.59-143.18 for calcium; OR, 6.90; 95% CI, 2.43-19.64 for phosphorus). The specificity in detecting the severe or critical patients among COVID-19 patients reached 98.5% (95% CI, 92.0%-99.7%) and 84.8% (95% CI, 74.3%-91.6%) by low calcium and low phosphorus, respectively, albeit with suboptimal sensitivity. Calcium and phosphorus combined with lymphocyte count could obtain the best discriminative performance for the severe COVID-19 patients (area under the curve [AUC] = 0.80), and combined with oxygenation index was promising (AUC = 0.71). Similar discriminative performances of low calcium and low phosphorus were found between suspected and confirmed COVID-19 patient. Low calcium and low phosphorus could indicate the severity of COVID-19 patients, and may be utilized as promising clinical biomarkers for discriminative diagnosis.


A novel type of allosteric regulation: functional cooperativity in monomeric proteins.
Cooperative functional properties and allosteric regulation in cytochromes P450 play an important role in xenobiotic metabolism and define one of the main mechanisms of drug-drug interactions. Recent experimental results suggest that ability to bind simultaneously two or more small organic molecules can be the essential feature of cytochrome P450 fold, and often results in rich and complex pattern of allosteric behavior. Manifestations of non-Michaelis kinetics include homotropic and heterotropic activation and inhibition effects depending on the stoichiometric ratios of substrate and effector, changes in the regio- and stereospecificity of catalytic transformations, and often give rise to the clinically important drug-drug interactions. In addition, functional response of P450 systems is modulated by the presence of specific and non-specific effector molecules, metal ions, membrane incorporation, formation of homo- and hetero-oligomers, and interactions with the protein redox partners. In this article we briefly overview the main factors contributing to the allosteric effects in cytochromes P450 with the main focus on the sources of cooperative behavior in xenobiotic metabolizing monomeric heme enzymes with their conformational flexibility and extremely broad substrate specificity. The novel mechanism of functional cooperativity in P450 enzymes does not require substantial binding cooperativity, rather it implies the presence of one or more binding sites with higher affinity than the single catalytically active site in the vicinity of the heme iron.


[Lewis antigen and diabetes].
The Lewis negative (Le a--b--) red blood cell phenotype was observed three times more frequently in 170 diabetics (29%) irrespective of their clinical type and in 27 non-diabetics low insulin responders to glucose than in 100 controls (10%). This difference could not be accounted for by factors influencing the serological typing ("ABH secretion and ABO groups) nor by the geographic origin of the populations tested. The Lewis substances are primarly soluble antigens present in blood, saliva, others fluids and absorbed on red blood cells. In 50 diabetics saliva was also analysed. Blood cell and saliva results were concordant allowing to interpret the Lewis negative blood cell phenotype as reflecting the absence of Lewis antigen. The higher frequency of Lewis negative phenotype was not related to the severity or the duration of the diabetes and therefore was unlikely to depend on metabolic factors. The similarity between the results for juvenile and maturity onset diabetes seems to indicate that these two clinical types of diabetes are genetically related. Furthermore, the same results obtained in low insulin responders afford additional support for considering these subjects as potential diabetics. It probably indicates, in the diabetic population, an increased frequency of le/le genotype or of one or several genes inhibiting the expression of Le.


Three distinct forms of rat brain protein kinase C: differential response to unsaturated fatty acids.
Although the three distinct forms of protein kinase C isolated from rat brain soluble fraction are structurally very similar, they respond differently to free unsaturated fatty acids such as arachidonic acid to exhibit their catalytic activity. Type I enzyme encoded by gamma-sequence, as predicted by cDNA clone analysis, responds to these fatty acids only slightly, whereas Type III enzyme determined by alpha-sequence is activated by free unsaturated fatty acids in the presence of Ca2+ in a comparable manner to phosphatidylserine plus diacylglycerol. Type II, a mixture of two enzymes encoded by beta I- and beta II-sequence, resulting from alternative splicing, shows properties in between those of Type I and Type III. Some of these forms of protein kinase C may function at a relatively later phase of cellular responses when large amounts of unsaturated fatty acids and Ca2+ are mobilized.


Determination of mono-O-acetylated N-acetylneuraminic acids in human and rat sera by fluorometric high-performance liquid chromatography.
A simple, rapid, and highly sensitive fluorometric high-performance liquid chromatographic method for the determination of N-acetylneuraminic acid and its mono-O-acetyl derivatives in human and rat sera is described. The neuraminic acids, released by hydrolysis of serum in 2 M acetic acid, are converted with 1,2-diamino-4,5-methylenedioxybenzene, a fluorogenic reagent for alpha-keto acids, to highly fluorescent derivatives without the occurrence of O-acetyl migration and de-O-acetylation. The derivatives are separated isocratically within 25 min by reversed-phase chromatography using a TSK gel ODS-120T column. The limits of detection are 57-192 fmol in a 10-microliters injection volume at a signal-to-noise ratio of 3. This sensitivity permits precise determination of the neuraminic acids in 5 microliters of human and rat sera.


Hyponatremic-Hypertensive Syndrome in Ovarian Paraganglioma.
Hyponatremic-hypertensive syndrome (HHS) is characterized by combination of polyuria, polydipsia, hypertension, hyponatremia and hypokalemia in association with unilateral renal artery stenosis. A 10-year- old girl presented with polyuria, polydipsia, hypertension, hyponatremia, hypokalemia and proteinuria. Ultrasonography with doppler study revealed bilateral normal renal arteries. Completed tomography of abdomen detected a left adnexal mass, which was later confirmed as ovarian paraganglioma on histopathology. After tumor excision, polyuria subsided and blood pressure normalized. Hyponatremic-Hypertensive Syndrome does not always result from unilateral renal artery stenosis. High index of clinical suspicion with appropriate imaging technique may clinch rare endocrine causes of hypertension, like paraganglioma.


The assessment of L- and M-cone specific electroretinographical signals in the normal and abnormal human retina.
Electroretinography (ERG) is a non-invasive method that can contribute to a description of the functional organization of the human retina under normal and pathological circumstances. The physiological and pathophysiological processes leading to an ERG signal can be better understood when the cellular origins of the ERG are identified. The ERG signal recorded at the cornea is initiated by light absorption in the photoreceptors which leads to activity in the photoreceptors and in their post-receptoral pathways. Light absorption in distinct photoreceptor types may lead to different ERG responses caused either by differences between the photoreceptors or between their post-receptoral pathways. The description of contributions of the different photoreceptor types to the ERG may therefore give more detailed insight in the origins of the ERG. Such a description can be obtained by isolating the responses of a single photoreceptor type. Nowadays, careful control of differently colored light sources together with the relatively well-known cone and rod fundamentals enables a precise description and control of photoreceptor excitation. Theoretically, any desired combination of photoreceptor excitation modulation can be achieved, including conditions in which the activity in only one photoreceptor type is modulated (silent substitution). In this manner the response of one photoreceptor type is isolated without changing the state of adaptation. This stimulus technique has been used to study the contribution of signals originating in the different photoreceptor types to the human ERG. Furthermore, by stimulating two or more photoreceptor types simultaneously, the interaction between the different signals can be studied. With these new techniques results of measurements in healthy subjects and patients with retinal diseases can be compared. This approach should ultimately help to develop better diagnostic tools and result in a fuller description of the changes and the pathophysiological mechanisms in retinal disorder. Finally, data obtained with cone and rod specific stimuli may lead to a reinterpretation of the standard ERG used in a clinical setting.


Commercial heparin solution investigated in vitro after reported impaired nerve function in a patient.
Exposure to commercial heparin solution caused rapid conduction failure in frog sciatic nerve preparations. The toxic substance was not the heparin itself, but the 0,5% phenol preservative. Phenol solutions with concentrations between 0,1% and 5% caused a dose-dependent nerve failure, which manifested as a progressive decline in compound action potential amplitude. Care must be taken in the administration of any solution preserved with phenol, to prevent nerve damage.


The rise of resilient healthcare research during COVID-19: scoping review of empirical research.
The COVID-19 pandemic has presented many multi-faceted challenges to the maintenance of service quality and safety, highlighting the need for resilient and responsive healthcare systems more than ever before. This review examined empirical investigations of Resilient Health Care (RHC) in response to the COVID-19 pandemic with the aim to: identify key areas of research; synthesise findings on capacities that develop RHC across system levels (micro, meso, macro); and identify reported adverse consequences of the effort of maintaining system performance on system agents (healthcare workers, patients). Three academic databases were searched (Medline, EMBASE, Scopus) from 1st January 2020 to 30th August 2022 using keywords pertaining to: systems resilience and related concepts; healthcare and healthcare settings; and COVID-19. Capacities that developed and enhanced systems resilience were synthesised using a hybrid inductive-deductive thematic analysis. Fifty publications were included in this review. Consistent with previous research, studies from high-income countries and the use of qualitative methods within the context of hospitals, dominated the included studies. However, promising developments have been made, with an emergence of studies conducted at the macro-system level, including the development of quantitative tools and indicator-based modelling approaches, and the increased involvement of low- and middle-income countries in research (LMIC). Concordant with previous research, eight key resilience capacities were identified that can support, develop or enhance resilient performance, namely: structure, alignment, coordination, learning, involvement, risk awareness, leadership, and communication. The need for healthcare workers to constantly learn and make adaptations, however, had potentially adverse physical and emotional consequences for healthcare workers, in addition to adverse effects on routine patient care. This review identified an upsurge in new empirical studies on health system resilience associated with COVID-19. The pandemic provided a unique opportunity to examine RHC in practice, and uncovered emerging new evidence on RHC theory and system factors that contribute to resilient performance at micro, meso and macro levels. These findings will enable leaders and other stakeholders to strengthen health system resilience when responding to future challenges and unexpected events.


Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning.
The ADAMs (a disintegrin and metalloprotease) are a family of membrane-anchored glycoproteins capable of shedding a multitude of proteins from the cell surface. Although ADAMs are being considered as crucial modulators of physiological and pathophysiological processes, their roles in neuronal death/survival are largely unexplored. In the present study, changes in brain expression of ADAM15 and ADAM17 (TACE) have been quantitatively examined in rats in response to injurious severe hypoxia (SH) and in animals which acquired hypoxic tolerance through preconditioning to mild hypoxia prior SH. SH persistently up-regulated ADAM15 mRNA and protein levels in hippocampus and neocortex but not in thalamus or hypothalamus. This effect was not observed in the preconditioned rats tolerant to SH. In contrast, hippocampal levels of ADAM17 mRNA and neocortical levels of ADAM17 mRNA and protein were largely reduced following SH in non-preconditioned rats. Hypoxic preconditioning prevented down-regulation of the adam17 gene and considerably enhanced ADAM17 protein expression in hippocampus and neocortex in response to SH. The present findings implicate ADAM15 in the processes of neuronal hypoxic injury. On the other hand, these results also provide evidence for a pro-survival neuroprotective role of ADAM17 and its engagement in the process of preconditioning-induced hypoxic tolerance. The analysis of the protein levels of soluble and membrane-bound forms of APP in the neocortex and hippocampus of rats subjected to SH and SH with preconditioning has demonstrated that an increased ADAM17 expression in preconditioned animals 24h after hypoxia corresponded to a higher level of soluble form of APP and a reduction of the membrane bound fraction which reflects the role of ADAM17 in APP shedding.


Dental impactions related to pseudoxanthoma elasticum.
Pseudoxanthoma elasticum is a rare genetic disorder causing degeneration and calcification of elastic fibers, leading to injuries in the skin, retina, and cardiovascular system. This report describes a case of a 30-year-old woman whose diagnosis of pseudoxanthoma elasticum was confirmed after a skin biopsy. The patient presented at the Clinical Management Unit of the Department of Oral and Maxillofacial Surgery, Virgen del Rocio Hospital (Seville, Spain) with pain related to a semi-erupted lower first molar. Radiologic examination disclosed multiple dental impactions. Cases of oligodontia, amelogenesis imperfecta, and mucosal lesions related to pseudoxanthoma elasticum were found in the current literature, but there were no reports of multiple dental impactions.


A fully automated contour detection algorithm the preliminary step for scatter and attenuation compensation in SPECT.
Contour detection is an important step in information extraction from nuclear medicine images. In order to perform accurate quantitative studies in single photon emission computed tomography (SPECT) a new procedure is described which can rapidly derive the best fit contour of an attenuated medium. Some authors evaluate the influence of the detected contour on the reconstructed images with various attenuation correction techniques. Most of the methods are strongly affected by inaccurately detected contours. This approach uses the Compton window to redetermine the convex contour: it seems to be simpler and more practical in clinical SPECT studies. The main advantages of this procedure are the high speed of computation, the accuracy of the contour found and the programme's automation. Results obtained using computer simulated and real phantoms or clinical studies demonstrate the reliability of the present algorithm.


Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance.
The possible relationships between biochemical measurements and both densitometric and radiographic indexes of skeletal fragility were evaluated in 65 postmenopausal women with monoclonal gammopathy of undetermined significance (MGUS). There was a significantly higher prevalence of vertebral fractures in the MGUS group compared with a control population (P < or = 0.001). The MGUS patients were then grouped according to the presence or absence of at least one mild vertebral fracture. Patients with fractures (Fx, n=34) were older (62.8 +/- 6.1 years), with long-standing disease (8.8 +/- 7.1 years) when compared with those without fractures (NFx, n=31; 59.7 +/- 5.0 years, P < or = 0.05 and 5.8 +/- 4.1 years, P < or = 0.05). The receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio was higher in Fx compared with NFx (0.092 +/- 0.018 vs. 0.082 +/- 0.020; P < or = 0.05). Lumbar spine (0.811 +/- 0.14 vs. 0.956 +/- 0.12 g/cm2), femoral neck (0.660 +/- 0.09 vs. 0.747 +/- 0.10 g/cm2) and total bone mineral density (BMD) (0.788 +/- 0.11 vs. 0.884 +/- 0.11 g/cm2) were lower (all P < or = 0.001) in FxMGUS compared with Nfx patients. Receiver operating characteristic curves identified lumbar BMD as the variable that best predicted vertebral fractures (area under the curve 0.817; 95% confidence interval, 0.713-0.921). This study provides an indication for the measurement of BMD in MGUS patients, as a means of predicting vertebral fractures, especially in those that are asymptomatic. Patients with prevalent fractures should undergo pharmacological treatment to prevent further fractures.


Short-term prediction of safety and operation impacts of lane changes in oscillations with empirical vehicle trajectories.
Lane changes made during traffic oscillations on freeways largely affect traffic safety and could increase collision potentials. Predicting the impacts of lane change can help to develop optimal lane change strategies of autonomous vehicles for safety improvement. The study aims at proposing a machine learning method for the short-term prediction of lane-changing impacts (LCI) during the propagation of traffic oscillations. The empirical lane-changing trajectory records were obtained from the Next Generation Simulation (NGSIM) platform. A support vector regression (SVR) model was trained in this study to predict the LCI on the crash risks and flow change using microscopic traffic variables such as individual speed, gap and acceleration on both original lanes and target lanes. Sensitivity analyses were conducted in the SVR to quantify the contributions of correlative lane changing factors. The results showed that the trained SVR model achieved an accuracy of 72.81 % for the risk of crashes and 95.34 % in predicting the flow change. The sensitivity analysis explored the optimal speed and acceleration for the lane changer to achieve the lowest time integrated time-to-collision (TIT) value for safety maximization. Finally, we compared the LCI for motorcycles, automobiles and trucks as well as the LCI for both lane-changing directions (from left to right and from right to left). It was found that motorcycles conducted lane changes with smaller gaps and larger speed differences, which brings the highest crash risks. Passenger cars were found to be the safest when they conduct lane changes. Lane changes to the right had more negative impacts on traffic flow and crash risks.


[Hypersynchronous EEG activity and conditioned avoidance reflexes in rats].
The influence of dimethylsulfolane on active avoidance conditioning with simultaneous registration of EEG was investigated. Dimethylsulfolane, which shows some pharmacological properties of pentylenetetrazole causes a decrease of the amount of conditioned reactions. There was no strong correlation between the impairment of learning ability and the number of EEG spindle discharges after dimethylsulfolane.


Psychometric evaluation of a new patient-completed questionnaire for evaluating anal incontinence symptoms and impact on quality of life: the ICIQ-B.
A psychometrically robust patient-completed questionnaire for anal incontinence, which reflects issues of importance to both clinicians and patients, was lacking for assessment purposes. This study aimed to determine the psychometric properties of a new questionnaire developed to address this need, the International Consultation on Incontinence Questionnaire-Bowels module. Qualitative studies were used to refine the developmental version of the questionnaire. Quantitative studies were conducted to evaluate its psychometric properties. Patients were invited to complete the questionnaire via postal administration. Two hundred sixty-one patients with known bowel symptoms participated in the study (244 females, 17 males; mean age, 59.7 years (range, 24-92)). The aspects of validity were evaluated in comparison with available evidence, responses to existing instruments, and physiological findings. Reliability was assessed through repeat administration of the questionnaire and evaluation of internal consistency by the Cronbach α coefficient. Responsiveness following treatment was evaluated by the use of the Wilcoxon signed rank test. Exploratory factor analysis was used to derive the final version of the questionnaire with evidence from the above studies. The final questionnaire contains 17 questions arranged in 3 scored domains: bowel pattern, bowel control, and quality of life, with 4 unscored items included to evaluate important issues from a clinical or patient perspective. The questionnaire demonstrated acceptable validity, "good" to "very good" reliability, and reasonable response to changes in symptom and quality-of-life status following intervention. Response rates varied according to location. The International Consultation on Incontinence Questionnaire Bowel module is a psychometrically robust, self-report instrument for the evaluation of anal incontinence and its impact on quality of life. It is suitable for use in individuals with anal incontinence of varying causes. It includes a scoring system for use in clinical practice and research.


Diagnostic efficacy of backscattering intensity measurements in optical coherence tomography of cervical intraepithelial dysplasia.
The aim of this study was to determine the diagnostic efficacy of backscattering intensity measurements in optical coherence tomography in identifying different grades of cervical intraepithelial dysplasia. OCT images were taken from 153 unsuspicious and suspicious areas of 30 fresh conisation and hysterectomy specimens, evaluated by two blinded investigators using a six-grade classification (normal, inflammation, CIN1, CIN2, CIN3, squamous carcinoma) and later compared to the corresponding histology. Differences between judgments based on either the histology or the OCT images were investigated employing Correspondence Analysis (CA). Further, we explored the extent as to which backscattering intensity profiles of OCT images contained the essential information required for a reliable and valid diagnosis, using Linear Discriminant Analysis (LDA). The CA of histology- and OCT-based judgments suggests that the diagnostic process may be characterized in terms of two stochastically independent underlying ("latent") variables, the first of them reflecting the definiteness with which CIN classes are identified, the second reflecting a bias towards diagnosing inflammation on the side of the OCT-based judgments. This finding is supported by the results of LDAs, where histology and OCT categorizations differ in particular with respect to the positions of inflammation and CIN1. Possibly, a second canonical variable has to be assumed accounting for the evaluation of carcinoma. The systematic differences between histology-based and OCT-based diagnoses suggest that the use of available information is influenced by perceptual and/or cognitive biases. Apart from this it seems that the profiles appear to provide a remarkably large amount of information determining the main course of the diagnostic process.


Standing male equine urogenital endoscopic surgery.
Standing laparoscopy in the horse was used initially as a diagnostic tool to assist in the diagnosis of a cryptorchid testicle. Now, this technique is also used for treatment of cryptorchid testicles. The focus of this article is the standing laparoscopic cryptorchidectomy, the most common laparoscopic procedure performed on the male equine urogenital tract. Advantages, disadvantages, instrumentation, and general procedure are discussed.


Functional hepatic recovery after xenotransplantation of cryopreserved fetal liver cells or soluble cell-factor administration in a cirrhotic rat model: are viable cells necessary?
Chronic liver failure results in the decrease of the number of functioning hepatocytes. It dictates the necessity of using exogenous viable cells or/and agents that can stimulate hepatic regenerative processes. Fetal liver contains both hepatic and hematopoietic stem cells with high proliferative potential, which may replace damaged cells. Also, immature cells produce fetal-specific factors which may support the injured liver. Our aim was to test the ability of human fetal liver cells and cell-free fetal-specific factors of non-hepatic origin to stimulate recovery processes in an experimental model of carbon tetrachloride-induced cirrhosis in rats. Cirrhotic rats were intrasplenically injected with fetal liver cells (1 x 10(7) cells/0.3 mL medium) or cell-free fetal-specific factors (0.3 mL/1 mg protein). Control groups received medium alone. Serum indexes, hepatic functions, and morphology were evaluated for 15 days. Human fetal liver cell transplantation was shown to abrogate the mortality of cirrhotic animals, to improve serum markers, and to restore liver mitochondrial function and detoxification. Morphological patterns of liver recovery were observed by histology. In comparison, an injection of fetal-specific factors produced similar functional recovery, whilst a more limited liver regeneration was observed by histology. The positive effects of fetal liver cell and cell-free fetal-specific factors in experimental cirrhosis may result from the presence of stage-specific factors activating hepatocellular repair.


Dosimetry and Toxicity Outcomes in Patients Treated with Hypofractionated Regional Nodal Irradiation for Breast Cancer: What is the Best Dose-Volume Limit to Minimize Risks of Radiation Pneumonitis?
Although published data have supported the use of hypofractionated regional nodal irradiation (HF-RNI) for breast cancer, limited dosimetric data exist to evaluate predictors of lung toxicity. The ongoing RT CHARM trial limits the percentage of ipsilateral lung volume that receives ≥18 Gy to 35 to 40%. We assessed dosimetry, toxicity, and disease outcomes in patients with breast cancer treated with HF-RNI with a particular focus on pneumonitis. We retrospectively reviewed all patients with breast cancer treated with HF-RNI (40-43 Gy in 15-16 fractions) after either lumpectomy or mastectomy at The University of Pittsburgh Medical Center from September 2018 to December 2021 to collect dosimetric and outcomes data. All post-radiation therapy chest computed tomography (CT) scans were manually reviewed for evidence of acute (≤6 months postradiation) or chronic (>6 months postradiation) pneumonitis. One-hundred-ninety-one patients qualified with a median follow-up of 20.3 months (range, 5.1-42.2). Acute grade 1 (G1) pneumonitis was observed in 6.8% of the overall cohort (13 of 191 patients) and 39.4% of the patients (13 of 33) who received a chest CT ≤6 months postradiation therapy. Only 1 patient developed acute G2 pneumonitis. Chronic G1 pneumonitis was observed in 29.8% of the overall cohort (57 of 191 patients) and 77% of patients (57 of 74 patients) who received a chest CT >6 months postradiation therapy. No patients developed acute G3+ or chronic G2+ pneumonitis. Rates of symptomatic pneumonitis were low in this cohort of patients treated with HF-RNI, even with integration of HER2/neu-directed therapy, chemotherapy, hormone therapy, and internal mammary nodal irradiation. Lung V20Gy <26% appeared safe in this cohort to limit symptomatic pneumonitis, though this is not meant to represent the safe upper limit. Given the low event rate of symptomatic pneumonitis, data from larger cohorts will be needed to assess dosimetric predictors and the safe upper limit of lung dose.


Use of a modified symptom distress scale in assessment of the cancer patient.
Symptom distress was assessed in a heterogeneous sample of cancer patients using a modified version of the McCorkle and Young (Cancer Nurs. 1, 373-378, 1978) Symptom Distress scale based on a linear analogue self-assessment (LASA) scale. Validity was assessed. Reliability, based on estimation of internal consistency (Cronbach's coefficient alpha), was high (alpha = 0.97) showing the tool to be reliable and effective in assessment of symptom distress. Of the 120 patients included 73% indicated significant distress from at least one symptom, 55% from two or more and 28% from at least five. Only 25% were suffering widespread or advanced disease suggesting that the incidence of symptom distress is not, of necessity, dependent on the extent of disease. The results obtained using the modified index were compared with those previously obtained by McCorkle and Young (1978) and showed marked similarities between the different cancer patient populations. This indicates that the modified scale is no less effective in assessing symptom distress but this has considerable advantages due to its simplicity and ease of administration.


Highly stereoselective syntheses of syn- and anti-1,2-amino alcohols.
The reduction of N-protected amino ketones can be carried stereoselectively to produce either the syn- or anti-amino alcohol diastereomer. Carbamate-protected amino ketones can be reduced predictably and selectively to anti-amino alcohols with LiAlH(O-t-Bu)3 in ethanol at -78 degrees C. N-Trityl-protected amino ketones can be reduced selectively to syn-amino alcohols with LiAlH(O-t-Bu)3 in THF at -5 degrees C.


The effect of halothane general anaesthesia on platelet function.
Major craniofacial surgery has the potential for very large blood loss, frequently greater than one blood volume. In order that an assessment could be made of any deficiencies of platelet function or coagulation, tests were performed at intervals during the operation. None of the coagulation parameters showed variation below normal limits during the operation, but in vitro platelet aggregation showed significant decreases to several agonists.


A strategy of hypothermic circulatory arrest for difficult heart transplant postventricular assist device.
Donor heart and ventricular assist device excision can be extremely difficult at the time of heart transplant. We present a strategy of hypothermic circulatory arrest established with ventricular assist device cannulas for difficult heart transplants. The device inlet or outlet cannulas already in place, or both, are used to complement the safe cannulation sites available. This approach permits controlled excision of the recipient heart and device, easy access to convert to standard ascending aorta and bicaval cannulation, and minimizes the donor graft anoxia time. Two case reports are presented.


A theoretical study of cis-trans isomerisation in H-ZSM5: probing the impact of cluster size and zeolite framework on energetics and structure.
In this study the results from a series of calculations are reported that probe the influence of the QM cluster size and the extended framework treatment in ONIOM calculations. This is done by comparing the differences in the structures and energetics obtained during simulations of cis-trans isomerisation of butene in H-ZSM-5 at varying level of accuracy. Seven different models have been employed; 3T, 5T and 10T DFT cluster models, and to more effectively encode the extended framework of ZSM-5; 3T:46T, 5T:46T, 10T:46T DFT:MM ONIOM models, and a 46T DFT cluster model. The results show that irrespective of the exact QM cluster size, relatively small gasphase clusters show clear limitations due to the neglect of the extended framework. In particular, the structural and electronic implications of using the different zeolite models have been rigorously assessed using the multivariate statistical method principal components analysis (PCA).


Hemisplenectomy for giant splenic cysts in children.
To analyse the clinical features and outcome following surgery of giant splenic cysts in children, all patients presenting to a children's hospital over the years 1987-1996 were reviewed. Variables analysed included presenting symptoms, method of diagnosis, operative procedure, and complications. Six patients (aged 8-16 years) presented with abdominal pain or a large abdominal mass. Ultrasound examination demonstrated large (>5 cm) unilocular splenic cysts. Five of the six children underwent hemisplenectomy without complication or blood transfusion. The remaining patient had an infected cyst, for which total splenectomy was necessary because of major intraoperative haemorrhage. Hemisplenectomy is based on accurate dissection of the splenic hilum with clear knowledge of the intracapsular vascular anatomy of the spleen. Preoperative vaccination is recommended in the event that splenectomy is required. This retrospective review concludes that hemisplenectomy for splenic cysts is a safe procedure in children.


Temperature Prediction Model for Bone Drilling Based on Density Distribution and In Vivo Experiments for Minimally Invasive Robotic Cochlear Implantation.
Surgical robots have been proposed ex vivo to drill precise holes in the temporal bone for minimally invasive cochlear implantation. The main risk of the procedure is damage of the facial nerve due to mechanical interaction or due to temperature elevation during the drilling process. To evaluate the thermal risk of the drilling process, a simplified model is proposed which aims to enable an assessment of risk posed to the facial nerve for a given set of constant process parameters for different mastoid bone densities. The model uses the bone density distribution along the drilling trajectory in the mastoid bone to calculate a time dependent heat production function at the tip of the drill bit. Using a time dependent moving point source Green's function, the heat equation can be solved at a certain point in space so that the resulting temperatures can be calculated over time. The model was calibrated and initially verified with in vivo temperature data. The data was collected in minimally invasive robotic drilling of 12 holes in four different sheep. The sheep were anesthetized and the temperature elevations were measured with a thermocouple which was inserted in a previously drilled hole next to the planned drilling trajectory. Bone density distributions were extracted from pre-operative CT data by averaging Hounsfield values over the drill bit diameter. Post-operative [Formula: see text]CT data was used to verify the drilling accuracy of the trajectories. The comparison of measured and calculated temperatures shows a very good match for both heating and cooling phases. The average prediction error of the maximum temperature was less than 0.7 °C and the average root mean square error was approximately 0.5 °C. To analyze potential thermal damage, the model was used to calculate temperature profiles and cumulative equivalent minutes at 43 °C at a minimal distance to the facial nerve. For the selected drilling parameters, temperature elevation profiles and cumulative equivalent minutes suggest that thermal elevation of this minimally invasive cochlear implantation surgery may pose a risk to the facial nerve, especially in sclerotic or high density mastoid bones. Optimized drilling parameters need to be evaluated and the model could be used for future risk evaluation.


Chemotherapy for metastatic carcinoid tumors: experiences with 32 patients and a review of the literature.
An analysis of results of chemotherapy in 32 patients with metastatic carcinoid tumors was carried out. The most frequently used chemotherapeutic agent was 5-fluorouracil (5-FU) followed by nitrosoureas in combination with 5-FU or with cyclophosphamide. Adriamycin (used as adriamycin-DNA complex) alone or in combination with other drugs was used in seven patients. Seven partial responses were observed, five of them occurring in the patients receiving adriamycin-containing regimens. Based on these findings, adriamycin deserves further evaluation in metastatic carcinoid tumors.


Erratum: Ramirez-Medina, E.; et al. Evaluation in Swine of a Recombinant African Swine Fever Virus Lacking the MGF-360-1L Gene. Viruses 2020, 12, 1193.
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Feasibility study of porous media for treating oily sludge with self-sustaining treatment for active remediation technology.
Oil sludge is the primary pollutant produced by the petroleum industry, which is characterized by large quantities, difficult disposal, and high toxicity. Improper treatment of oil sludge will pose a severe threat to the human living environment. Self-sustaining treatment for active remediation (STAR) technology has a specific potential for treating oil sludge, with low energy consumption, short remediation time, and high removal efficiency. Given the low smoldering porosity, poor air permeability, and poor repair effect of oil sludge, this paper considered coarse river sand as the porous medium, built a smoldering reaction device, conducted a comparative study on smoldering experiments of oil sludge with and without river sand, and studied the key factors affecting smoldering of oil sludge. The study shows that the repair effect is greatly improved by adding river sand, increasing the pore, and improving air permeability, and the total petroleum hydrocarbon removal rate reaches more than 98%, which meets the requirements of oil sludge treatment. When the mass ratio of oil sludge to river sand (sludge-sand ratio) is 2:1, the flow velocity is 5.39 cm/s, and the particle size of the medium is 2-4 mm. In addition, the best conditions for smoldering occur. The average peak temperature, average propagation speed, and average removal efficiency are relatively high. The peak temperature occurs in a short time; the heating time is also short, and the heat loss is low. Moreover, the generation of toxic and harmful gases is reduced, and secondary pollution is hindered. The experiment indicates that the porous media play a crucial role in the smoldering combustion of oil sludge.


[Pulmonary eosinophilic granuloma associated with recurrent pneumothorax: report of a case].
A 25-years-old male, current smoker, was referred to our department for treatment of the right pneumothorax due to pulmonary eosinophilic granuloma. He underwent thoracoscopic partial resection of the right lung. Immunostaining of the specimen revealed a lot of Langerhans cells positive for S 100 protein, suggesting active lesion. After cessation of smoking, no recurrence of pneumothorax or progression of disease have been observed for 13 months.


A behavioural study of neuroglobin-overexpressing mice under normoxic and hypoxic conditions.
Neuroglobin (Ngb), a neuron-specific heme-binding protein that binds O2, CO and NO reversibly, and promotes in vivo and in vitro cell survival after hypoxic and ischaemic insult. Although the mechanisms of this neuroprotection remain unknown, Ngb might play an important role in counteracting the adverse effects of ischaemic stroke and cerebral hypoxia. Several Ngb overexpressing mouse models have confirmed this hypothesis; however, these models were not yet exposed to in-depth behavioural characterisations. To investigate the potential changes in behaviour due to Ngb overexpression, heterozygous mice and wild type (WT) littermates were subjected to a series of cognitive and behavioural tests (i.e., the SHIRPA primary screening, the hidden-platform Morris water maze, passive avoidance learning, 47h cage activity, open field exploration, a dark-light transition box, an accelerating rotarod, a stationary beam, a wire suspension task and a gait test) under normoxic and hypoxic conditions. No significant behavioural differences were found between WT and Ngb-overexpressing mice at three months old. However, one-year-old Ngb-overexpressing mice travelled more distance on the stationary beam compared with WT littermates. This result shows that the constitutive overexpression of Ngb might counteract the endogenous decrease of Ngb in crucial brain regions such as the cerebellum, thereby counteracting age-induced neuromotor dysfunction. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.


Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.
Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. Immunolabeling experiments and transmission electron microscopy of the sciatic nerve from one of the affected individuals revealed a lack of myelin. Functional tests using affected individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein. This is consistent with previous studies reporting arthrogryposis in Lgi4-deficient mice due to peripheral hypomyelination. This study adds to the recent reports implicating defective axoglial function as a key cause of AMC.


[Easing the patients' trajectories from private practice to hospital: One-year experiment of the RAPIDO project].
Internal medicine departments manage patients referred by emergency departments or private practitioners. Considering the overcrowding of emergency departments and lack of beds for inpatients, this specialty must be part of an "ambulatory shift", particularly by strengthening the links between community and hospital medicine. Our objective was to evaluate a new care pathway in internal medicine at Nîmes university hospital. Our department has developed the RAPIDO project (Réseau d'Aide à la PrIse en Charge Diagnostique et d'Orientation). The referring general practitioner contacts a senior internist on a dedicated phone line. After careful evaluation, he may offer a consultation within 15 days. A summary report is then given to the patient. Between November 2020 and November 2021, 254 patients were seen via RAPIDO. The average call-consultation time period was 6.4 (±4.5) days, for symptoms lasting for 2 weeks to 3 months in 43% (n=109) of cases. The reason for the call was a suspicion of systemic disease in 28% of cases (n=84), or a dysfunction of an organ in 16%. A diagnosis was made in 89% of cases. The budget of the whole procedure was balanced. A quick internal medicine consultation pathway for general practitioners seems to be a relevant, feasible and economically viable healthcare trajectory, which can be transposed to any type of healthcare institution, as soon as sufficient human resources are dedicated.


Human neurocysticercosis: comparison of enzyme immunoassay capture techniques based on monoclonal and polyclonal antibodies for the detection of parasite products in cerebrospinal fluid.
Current diagnosis of neurocysticercosis relies mostly on computerized tomography and nuclear magnetic resonance, with detection of antibodies being confirmatory rather than decisive. An assay which detects parasite products in cerebrospinal fluid would conclusively demonstrate a current infection and could be important when decisions regarding treatment must be made. Cerebrospinal fluid from patients with neurocysticercosis was used in 4 enzyme immunoassay capture tests designed to detect parasite products. Of the systems tested, one, based on the use of a monoclonal antibody reactive with a surface and secretion component of the metacestode, was particularly promising, giving a sensitivity of 72%. The assay has the double advantage of a very low background and a proved specificity for the products of living cysticerci. The other 3 systems (monoclonal anti-vesicular fluid antibody, polyclonal antibody against a saline extract and polyclonal anti-antigen B antibody) were less sensitive. Results with the anti-antigen B system support the proposal that products of low immunogenicity are the most appropriate targets for the serological detection of the parasite.


Impact factors of orthopaedic journals between 2000 and 2010: trends and comparisons with other surgical specialties.
The impact factors (IF) of orthopaedic journals is an important component in determining the future of orthopaedic research funding. We aim to characterise the trend in journal IF over the last decade and draw comparisons with other surgical specialties. We conducted an analysis of impact factors from Journal Citation Reports between 2000 and 2010. Between 2000 and 2010 the number of orthopaedic journals increased from 24 to 41, more than any other surgical specialty and the mean IF increased from 0.842 to 1.400. Journals printed in the English language had a significantly higher IF in the year 2010 (1.64 vs. 0.33, p = 0.01) than those printed in other languages. English language journals published in the US had significantly higher mean 2010 IF (1.932 vs. 1.243, p = 0.025) than those published in Europe, and this had changed compared with 2000 mean IF (0.978 Vs. 0.704, p = 0.360). Orthopaedics was ranked sixth out of 11 surgical subspecialties in 2000 but dropped to seventh out of 11 in 2010. The quality of orthopaedic journals has significantly increased over the last decade and this has been accompanied by a rise in mean IF. It is important that orthopaedics continues to improve the quality of research, which may help orthopaedic researchers secure funding in the future.


Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non-small cell lung cancer cells via p53-p21 signaling pathway.
As a regulator of cell cycle, cell division cycle-associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported. In our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan-Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD-1, PD-L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53-p21 pathway and regulates the cell cycle. CDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase. In conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53-p21 signaling pathway, participating in the development and progression of NSCLC patients.


Changes in cardiac repolarisation during spontaneous nocturnal hypoglycaemia in subjects with type 1 diabetes: a preliminary report.
Experimental studies have revealed that hypoglycaemia can result in morphological changes in electrocardiographic repolarisation in subjects with type 1 diabetes. However, the influence of spontaneous nocturnal hypoglycaemia on repolarisation morphology in a 'real life' situation is not clear. Adults with type 1 diabetes (n = 11) underwent continuous glucose monitoring with a subcutaneous sensor and digital 12-lead ECG recording for three nights. T-wave morphology was analysed with custom-made software during both hypoglycaemia (glucose <3.5 mmol/l at least 20 min) from ten consecutive heart beats in the middle of the deepest hypoglycaemia and from a control nonhypoglycaemic period (glucose ≥5.0 mmol/l) from the same recording. In the comparison of 10 hypoglycaemia-control pairs, heart rate (65 ± 12 beats/min during normoglycaemia versus 85 ± 19 beats/min during hypoglycaemia, p = 0.028) increased and the QTc interval (439 ± 5 vs. 373 ± 5 ms, respectively, p = 0.025) decreased significantly during hypoglycaemia. The spatial QRS-T angle (TCRT) was reduced, and the roughness of the T-wave loop (T-E) increased significantly (p = 0.037 for both) in the patients during hypoglycaemia. In adults with type 1 diabetes, spontaneous nocturnal hypoglycaemia results in morphological changes and increased heterogeneity of global cardiac repolarisation. These changes may contribute to the risk of 'dead in bed' syndrome encountered in young individuals with type 1 diabetes.


Multiple HLA associations and disease susceptibility.
A strong association between a particular HLA antigen and a given disease may mask a secondary, weaker association. Applying a stepwise analysis to published HLA-DR frequencies in rheumatoid arthritis demonstrates an increased frequency of DRI not otherwise apparent.


Influence of light-cured luting agents and associated factors on the color of ceramic laminate veneers: A systematic review of in vitro studies.
The luting agent plays a significant role in the appearance of ceramic laminate veneers (CLV), allowing improved/stable shade matching with adjacent teeth. A systematic review was conducted to investigate the influence of light-cured luting agents and color-associated factors aiming to draw guidelines for stable shade matching of CLV. The paper has also given an overview of the compositional characteristics of all luting agents and ceramic systems whose performance was presented herein. A search of in vitro studies that quantitatively investigated the influence of light-cured luting agents on the color of CLV was conducted. PubMed/MedLine, Cochrane Library, SciVerse Scopus and Web of Science databases were explored until December 2017 with no year limit. Data regarding the effect of light-cured luting agent, ceramic systems, effect of background, accelerated aging and surface treatments on color change were collected. A meta-analysis was not possible due to heterogeneity of data. After duplicates' removal, 3630 studies were identified, 48 were selected for full-text analysis, and 21 remaining papers met the inclusion criteria and were included in this systematic review. Considering the shade aspects of luting agents, translucency and value showed the greatest visible color differences for CLVs. The effect of luting agent shade on the color of veneers is greatly affected by ceramic thickness and opacity.


Paper 3: Selecting rapid review methods for complex questions related to health policy and system issues.
Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues.We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews.The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions.


Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice.
Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 micrograms) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 micrograms) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP(dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5D-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.


Dynamic changes in CCAN organization through CENP-C during cell-cycle progression.
The kinetochore is a crucial structure for faithful chromosome segregation during mitosis and is formed in the centromeric region of each chromosome. The 16-subunit protein complex known as the constitutive centromere-associated network (CCAN) forms the foundation for kinetochore assembly on the centromeric chromatin. Although the CCAN can be divided into several subcomplexes, it remains unclear how CCAN proteins are organized to form the functional kinetochore. In particular, this organization may vary as the cell cycle progresses. To address this, we analyzed the relationship of centromeric protein (CENP)-C with the CENP-H complex during progression of the cell cycle. We find that the middle portion of chicken CENP-C (CENP-C(166-324)) is sufficient for centromere localization during interphase, potentially through association with the CENP-L-N complex. The C-terminus of CENP-C (CENP-C(601-864)) is essential for centromere localization during mitosis, through binding to CENP-A nucleosomes, independent of the CENP-H complex. On the basis of these results, we propose that CCAN organization changes dynamically during progression of the cell cycle.


Understanding the Unique Electronic Properties of Nano Structures Using Photoemission Theory.
Newly emerging experimental techniques such as nano-ARPES are expected to provide an opportunity to measure the electronic properties of nano-materials directly. However, the interpretation of the spectra is not simple because it must consider quantum mechanical effects related to the measurement process itself. Here, we demonstrate a novel approach that can overcome this problem by using an adequate simulation to corroborate the experimental results. Ab initio calculation on arbitrarily-shaped or chemically ornamented nano-structures is elaborately correlated to photoemission theory. This correlation can be directly exploited to interpret the experimental results. To test this method, a direct comparison was made between the calculation results and experimental results on highly-oriented pyrolytic graphite (HOPG). As a general extension, the unique electronic structures of nano-sized graphene oxide and features from the experimental result of black phosphorous (BP) are disclosed for the first time as supportive evidence of the usefulness of this method. This work pioneers an approach to intuitive and practical understanding of the electronic properties of nano-materials.


Chloride-salinity as indicator of the chemical composition of groundwater: empirical predictive model based on aquifers in Southern Quebec, Canada.
The present study first describes the variations in concentrations of 12 chemical elements in groundwater relative to salinity levels in Southern Quebec (Canada) groundwater systems, and then uses this data to develop an empirical predictive model for evaluating groundwater chemical composition relative to salinity levels. Data is drawn from a large groundwater chemistry database containing 2608 samples. Eight salinity classes were established from lowest to highest chloride (Cl) concentrations. Graphical analyses were applied to describe variations in major, minor, and trace element concentrations relative to salinity levels. Results show that the major elements were found to be dominant in the lower salinity classes, whereas Cl becomes dominant at the highest salinity classes. For each of the major elements, a transitional state was identified between domination of the major elements and domination of Cl. This transition occurred at a different level of salinity for each of the major elements. Except for Si, the minor elements Ba, B, and Sr generally increase relative to the increase of Cl. The highest Mn concentrations were found to be associated with only the highest levels of Cl, whereas F was observed to be more abundant than Mn. Based on this analysis of the data, a correlation table was established between salinity level and concentrations of the chemical constituents. We thus propose a predictive empirical model, identifying a profile of the chemical composition of groundwater relative to salinity levels, to help homeowners and groundwater managers evaluate groundwater quality before resorting to laborious and costly laboratory analyses.


Spinal and Peripheral Mechanisms Individually Lead to the Development of Remifentanil-induced Hyperalgesia.
The present study was performed to determine neuronal loci and individual molecular mechanisms responsible for remifentanil-induced hyperalgesia. The effect of methylnaltrexone (MNX) on remifentanil-induced behavioral hyperalgesia was assessed to distinguish contributions of the peripheral and/or central nervous system to remifentanil-induced hyperalgesia. Phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) in the dorsal root ganglion (DRG) neurons after remifentanil infusion, and the effect of a p38MAPK inhibitor on remifentanil-induced hyperalgesia were analyzed to investigate involvement of p38MAPK in the peripheral mechanisms of remifentanil-induced hyperalgesia. Spinal levels of prodynorphin mRNA after remifentanil infusion, and the effect of the BK2 bradykinin receptor antagonist on remifentanil-induced hyperalgesia were investigated to assess potential spinal mechanisms. The effects of MNX and BK2 antagonists on remifentanil-induced exacerbation of post-incisional hyperalgesia were also investigated using behavioral analysis. Remifentanil infusion induced hyperalgesia in the early (4 h to 2 days) and late (8-14 days) post-infusion periods. MNX inhibited hyperalgesia only during the early post-infusion period. p38MAPK phosphorylation was observed in the DRG neuron, and the p38MAPK inhibitor inhibited hyperalgesia during the early post-infusion period. Prodynorphin expression increased in the spinal cord, and a BK2 antagonist inhibited hyperalgesia during the late post-infusion period. Remifentanil-induced exacerbation of incisional hyperalgesia was inhibited by MNX and the BK2 antagonist. The present study demonstrated that remifentanil activates peripheral and spinal neurons to promote chronologically distinctive hyperalgesia. p38MAPK phosphorylation in the DRG neuron leads to peripherally-driven hyperalgesia during the early post-infusion period, while spinal dynorphin-bradykinin signaling promotes hyperalgesia during the late post-infusion period.


Blm10 binds to pre-activated proteasome core particles with open gate conformation.
Blm10 is bound to the yeast proteasome core particle, a crucial protease of eukaryotic cells [corrected]. Two gates, at both ends of the CP, control the access of protein substrates to the catalytic cavity of the CP. Normally, substrate access is auto-inhibited by a closed gate conformation unless regulatory complexes are bound to the CP and translocate protein substrates in an ATP-dependent manner. Here, we provide evidence that Blm10 recognizes pre-activated open gate CPs, which are assumed to exist in an equilibrium with inactive closed gate CP. Consequently, single-capped Blm10-CP shows peptide hydrolysis activity. Under conditions of disturbed CP assembly, as well as in open gate mutants, pre-activated CP or constitutively active CP, respectively, prevail. Then, Blm10 sequesters disordered and open gate CP by forming double-capped Blm10(2)-CP in which peptide hydrolysis activity is repressed. We conclude that Blm10 distinguishes between gate conformations and regulates the activation of CP.


Dysregulation of aversive signaling pathways: a novel circuit endophenotype for pain and anxiety disorders.
Aversive experiences activate dedicated neural instructive pathways which trigger memory formation and change behavior. The strength of these aversive memories and the degree to which they alter behavior is proportional to the intensity of the aversive experience. Dysregulation of aversive learning circuits can lead to psychiatric pathology. Here we review recent findings elucidating aversive instructive signaling circuits for fear conditioning. We then examine how chronic pain as well as stress and anxiety disrupt these circuits and the implications this has for understanding and treating psychiatric disease. Together this review synthesizes current work on aversive instructive signaling circuits in health and disease and suggests a novel circuit based framework for understanding pain and anxiety syndromes.


Clinical relevance of the blanking period on late recurrence after catheter ablation of atrial fibrillation.
Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p < .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p < .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively). The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.


Temporal relationship between human and canine visceral leishmaniasis in an urban area in southeastern Brazil: An application of the ARIMAX model.
Visceral leishmaniasis (VL) is a neglected disease of public and animal health importance. With the urbanization of the disease, there is evidence of a temporal correlation between the occurrence of human (HVL) and canine (CVL) visceral leishmaniasis, usually with cases in dogs preceding those in humans. In this context, the objective of this study was to develop a time series model suitable for canine-human transmission of Leishmania infantum. Monthly cases of HVL and CVL from 2006 to 2018 in Belo Horizonte, Minas Gerais, Brazil, were evaluated, and monthly health indicators were calculated for HVL and CVL, i.e., incidence coefficient (HVL_IC) and proportion of seropositive dogs (PSD), respectively. The temporal relationship was evaluated using an autoregressive integrated moving average with exogenous variable (ARIMAX) model for two different periods (January 2006-August 2013 and September 2013-December 2018). During the 13 years studied, 1115 new cases of HVL and 103,358 dogs seropositive for CVL were recorded. HVL_IC and PSD exhibited decreasing trends throughout the first study period (January 2006-August 2013). According to the ARIMAX model adjusted for this period, there was a temporal relationship between HVL_IC and PSD, with HVL_IC being influenced by HVL_IC for the last two and five months and by PSD for the third previous month. For the second study period (September 2013-December 2018), it was not possible to fit an ARIMAX model. This study highlights the improvements made by VL surveillance since 2006 in Belo Horizonte and contributes to a better understanding of the epidemiology of the disease by public health policy-makers, doctors and veterinarians involved in the prevention and control of zoonoses.


Studies on the mechanism of the stimulation of polymerase II-catalyzed RNA synthesis by mercury compounds.
The specific stimulation of alpha-amanitin-sensitive RNA synthesis in isolated nuclei by methyl mercury (Frenkel, G. D., and Randles, K. (1982) J. Biol. Chem. 257, 6275-6279) has been further investigated. Using the method of alkaline hydrolysis/uridine analysis to determine the number of RNA chains growing in vitro, it was found that the stimulation could not be accounted for by an increase in the number of growing chains. The stimulatory effect of heparin (Coupar, B. E. H., and Chesterton, C. J. (1977) Eur. J. Biochem. 79, 525-533), was found to be additive with that of methyl mercury at saturating concentrations of the latter. Various detergents were found to affect RNA synthesis per se and to modify the stimulatory effect of methyl mercury, suggesting that the stimulation by methyl mercury requires a degree of structural integrity of some nuclear components. The ability of a number of other mercury compounds to stimulate RNA synthesis was investigated. None of the inorganic compounds examined, i.e. HgCl2, HgSO4, and Hg(ClO4)2, stimulated synthesis. Among the alkyl organic compounds tested in addition to methyl mercury, ethyl mercury also stimulated RNA synthesis, but dimethylmercury did not. Among the aryl compounds tested, phenylmercury did not stimulate synthesis whereas p-hydroxymercuribenzoate and p-hydroxymercuribenzenesulfonate did. N-Ethylmaleimide, a nonmercurous sulfhydryl reagent, was found to have only weak ability to stimulate RNA synthesis, compared to a comparable mercury-containing sulfhydryl reagent, p-hydroxymercuribenzoate. The stimulatory effect of the latter was, however, effectively competed out by the former, indicating that sulfhydryl binding is necessary for the stimulation but not sufficient. This conclusion was reinforced by experiments which utilized a model system to measure the ability of various mercury compounds to compete with N-ethylmaleimide in binding to cysteine. The results showed that even compounds such as phenylmercury and the inorganic mercurials, which are unable to stimulate RNA synthesis, are able to bind to a sulfhydryl group.


New discrete-time fractional derivatives based on the bilinear transformation: Definitions and properties.
In this paper we introduce new discrete-time derivative concepts based on the bilinear (Tustin) transformation. From the new formulation, we obtain derivatives that exhibit a high degree of similarity with the continuous-time Grünwald-Letnikov derivatives. Their properties are described highlighting one important feature, namely that such derivatives have always long memory.


Effects of chemoradiotherapy and chemotherapy on survival of patients with locally advanced pancreatic cancer: A meta-analysis of randomized controlled trials.
To comparatively evaluate chemoradiotherapy (CRT) and chemotherapy (CT) for the treatment of locally advanced pancreatic cancer (LAPC) by meta-analysis.A literature search was performed until August 2016 to identify comparative studies assessing survival rates and complications. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined with the fixed or random effects model.Five randomized controlled trials (RCTs) met the defined inclusion criteria. A total of 593 patients were included, with 295 and 298 treated with CRT and CT, respectively. Overall survival showed no statistically significant difference in patients treated with CRT and CT at 6, 12, 18, and 24 months (respectively: OR = 1.13, 95% CI: 0.60-2.17; OR = 1.15, 95% CI: 0.53-2.52; OR = 1.13, 95% CI: 0.43-2.95; OR = 1.07, 95% CI: 0.67-1.72). Meanwhile, CRT had higher rates of grade 3 to 4 adverse events (nausea and vomiting, OR = 2.74, 95% CI: 1.36-5.52; diarrhea, OR = 4.28, 95% CI: 1.16-15.71).The data are not sufficient to change from CT to CRT in the treatment of patients with LAPC and thus clinical discretion is required until more data is accumulated.


A spatio-temporal dataset on food flows for four West African cities.
Gaining insight into the food sourcing practices of cities is important to understand their resilience to climate change, economic crisis, as well as pandemics affecting food supply and security. To fill existing knowledge gaps in this area food flow data were collected in four West African cities - Bamako (Mali), Bamenda (Cameroon), Ouagadougou (Burkina Faso), and Tamale (Ghana). The data cover, depending on the city, road, rail, boat, and air traffic. Surveys were conducted for one week on average during the peak harvest, lean, and rainy seasons, resulting in a dataset of over 100,000 entries for 46 unprocessed food commodities. The data collected includes information on the key types of transportation used, quantity, source, and destination of the food flows. The data were used to delineate urban foodsheds and to identify city-specific factors constraining rural-urban linkages. The data can also be employed to inform academic and policy discussions on urban food system sustainability, to validate other datasets, and to plan humanitarian aid and food security interventions.


Prevalence of undiagnosed autoimmune rheumatic diseases in the first trimester of pregnancy. Results of a two-steps strategy using a self-administered questionnaire and autoantibody testing.
To evaluate the prevalence of undiagnosed rheumatic diseases in the first trimester of pregnancy. We screened for rheumatic diseases in 1210 consecutive pregnant women during the first trimester of pregnancy using a 10-item questionnaire. A university hospital in northern Italy. One hundred and thirty-seven (11.3%) women who answered positively to at least one question constituted the cases and were compared with 107 negative controls. Cases and controls were tested for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibody, anti-beta2-glycoprotein I antibodies and lupus anticoagulant) and were evaluated by a rheumatologist for a definite diagnosis of rheumatic disease. Prevalence of undiagnosed rheumatic disease in the first trimester of pregnancy. The overall rate of positivity to the antibodies tested was 43.1% (59/137) among cases and 9.3% (10/107) in the controls (P < 0.001). A definitive diagnosis of rheumatic disease was made in 35 cases (25.5%) and in none of the controls (P <0.001). In stepwise logistic regression analysis, photosensitivity (adjusted OR 5.72; 95% CI 2.38-13.8), erythema or malar rash (adjusted OR 3.91; 95% CI 1.53-10) and history of two or more miscarriages (adjusted OR 5.6; 95% CI 1.55-20.6) were independent predictors of a definitive diagnosis of rheumatic disease (area under receiving operator curve = 0.814; 95% CI 0.76-0.86). Birthweight was lower (3180 g +/- 475 compared with 3340 g +/- 452, P= 0.008), and overall serious pregnancy complications (miscarriage, fetal growth restriction, delivery before 34 weeks of pregnancy and severe pre-eclampsia) were higher among cases (12/137) than controls (2/107) (adjusted OR 5.60; 95% CI 1.29-24.3; P= 0.021). A two-step screening process with a self-administered questionnaire proved to be a useful method to screen for undiagnosed rheumatic diseases during the first trimester of pregnancy.


Environmental impacts of various biomass supply chains for the provision of raw wood in Bavaria, Germany, with focus on climate change.
Wood biomass is considered a renewable raw product, but the supply chain of wood biomass involves non-renewable energy inputs, and thus possibly entailing environmental impacts. The objective of this study was to analyze different environmental impacts (GHG emissions, without biogenic CO2; primary energy consumption, non-renewable; particulate matter) caused by the provision of forest biomass for the four main tree species in Bavaria using Life Cycle Assessment (LCA) techniques. Based on forest growth simulations, a set of realistic forest biomass supply chains for Bavarian forestry conditions were modeled for the raw wood product system from site preparation to forest road and to plant/farm gate, respectively, analyzing the four different process groups: [A1] site preparation, [A2] site tending, [A3] biomass harvesting and [T] transport of biomass to plant/farm gate. Total GHG emissions of about 383,000tCO2-eq∗year(-1) (18.95kgCO2-eq∗m(-3)) are estimated for the Bavarian forestry sector (from site preparation to plant/farm gate) in the reference year 2013 indicating a share of 0.41% in the total GHG emissions of Bavaria. 0.035MJ of non-renewable energy has to be invested in order to provide 1MJ of woody biomass to plant/farm gate (267MJ∗m(-3)). One hundred and sixty six tons of particulate matter emissions per year are calculated for the Bavarian forestry sector in 2013 (0.008kgPM2.5-eq∗m(-3)). Our LCA results reveal that there is no single GHG emission value for raw wood but a broad range of possible GHG emissions for the Bavarian forestry. Most decisive parameters are forest road maintenance, biomass harvesting, forwarding and biomass transport, and GHG emissions are also notably influenced by tree species, age class, wood assortment and site quality. We recommend that environmental impact calculations should be implemented, for example in wood certification procedures as they are important key indicators for sustainable forest management.


Not Stromal Vascular Fraction (SVF) or Nanofat, but Total Stromal-Cells (TOST): A New Definition. Systemic Review of Mechanical Stromal-Cell Extraction Techniques.
The most important and greatest source in the body for regenerative cells is fat tissue. Obtaining regenerative cells from adipose tissue can be done in two ways: Enzymatic and mechanical. The regenerative cell cocktail obtained by the enzymatic method, including stem cells, is called Stromal vascular fracture (SVF). In the literature, there is no clear definition of regenerative cells obtained by mechanical method. We systematically searched the techniques and definitions for stromal cells obtained from adipose tissue by scanning different databases. To evaluate the mechanical stromal-cell isolation techniques and end products from adipose tissue. Systematic review of English and non-English articles using Embase, PubMed, Web of Science and Google scholar databases. Search terms included Nanofat, fragmented fat, mechanical stromal / stem cell, mechanical SVF, SVF gel. We screened all peer-reviewed articles related with mechanical stromal-cell isolation. Author performed a literature query with the aforementioned key words and databases. A total of 276 publications containing the keywords we searched were reached. In these publications, there are 46 different definitions used to obtain mechanical stromal cells. The term SVF is only suitable for enzymatic methods. A different definition is required for mechanical. The most used term nanofat is also not suitable because the product is not in both "fat" and in "nanoscale". We think that the term total stromal-cells would be the most appropriate definition since both extracellular matrix and all stromal cells are protected in mechanical methods.


Elemental surface concentration ratios and surface free energies of human enamel after application of chlorhexidine and adsorption of salivary constituents.
In vitro adsorption of chlorhexidine from a commercially available chlorhexidine-containing (0.12%) mouthrinse (Peridex) on both ground and polished and on saliva-coated enamel was studied by X-ray photoelectron spectroscopy and contact angle measurements. Furthermore, adsorption of salivary constituents was studied on chlorhexidine-treated enamel. Changes in the elemental surface composition obtained by X-ray photoelectron spectroscopy clearly demonstrated adsorption of chlorhexidine from the mouthrinse as indicated by increased N and C signals which were in all cases accompanied by a higher enamel surface free energy, estimated from the contact angle data. In addition, it was found that salivary constituents adsorb less to chlorhexidine-treated enamel than to ground and polished enamel and, moreover, that adsorbed salivary constituents were desorbed by chlorhexidine. In vivo, the effect of a 3-week use of chlorhexidine was compared with the use of a placebo and habitual oral hygiene of 10 volunteers by means of clinical contact angle measurements. Also in vivo adsorption of chlorhexidine yielded elevated surface free energies with respect to habitual oral hygiene or a placebo. Thus in vivo, the well-known favourable effects of the bactericidal properties of chlorhexidine completely overrule the unfavourable effects of high enamel surface free energies.


Antibiotics and collateral damage.
The precarious stability of the normal indigenous flora of the human gastrointestinal tract may be disturbed by a number of factors, but frequently and crucially by antibiotic therapy. This article explores recent insights on the collateral and ecologic effects of antibiotics on the microbiologic flora of the human body and the possible consequences of those effects, which are just beginning to be better understood. New data on this subject will not only help in designing better clinical trials but also begin to answer key questions about collateral damage.


Patients' experiences undergoing cancer surgery during the COVID-19 pandemic: a qualitative study.
This study aimed to understand patients' experiences undergoing cancer surgery during the COVID-19 pandemic. In response to COVID-19, many elective cancer surgeries were delayed creating a massive backlog of cases. Patients' experiences with surgical delays may inform healthcare systems' responses to the backlog of cases and guide preparations for future healthcare emergencies. This was a qualitative description study. Patients undergoing general surgery for cancer at two university-affiliated hospitals between March 2020 and January 2021 were invited to one-to-one interviews. Patients were purposefully selected using quota sampling until interviews produced no new information (i.e., thematic saturation). Interviews were conducted using a semi-structured guide and analyzed according to inductive thematic analysis. Twenty patients were included [mean age 64 ± 12.9; male (n = 10); surgical delay (n = 14); cancer sites: breast (n = 8), skin (n = 4), hepato-pancreato-biliary (n = 4), colorectal (n = 2), and gastro-esophageal (n = 2)]. When determining their willingness to undergo surgery, patients weighed the risk of COVID-19 infection against the urgency of their disease. Changes to the hospital environment (e.g., COVID-19 preventative measures) and deviations from expected treatment (e.g., alternative treatments, remote consultations, rescheduled care) caused diverse psychological responses, ranging from increased satisfaction to severe distress. Patients employed several coping strategies to mitigate distress, including eliciting reassurance from care providers, seeking information from unconventional sources, and reframing care interruptions. Changes in care during the pandemic elicited diverse psychological responses from patients undergoing cancer surgery. Coping was facilitated by consistent communication with providers, emphasizing the importance of patient-centered expectation setting as we prepare for the future within and beyond the pandemic.


Iron and cancer: more ore to be mined.
Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.


Study of the inhibitory effect of the product dihydroxyacetone on Gluconobacter oxydans in a semi-continuous two-stage repeated-fed-batch process.
The influence of the product inhibition by dihydroxyacetone (DHA) on Gluconobacter oxydans for a novel semi-continuous two-stage repeated-fed-batch process was examined quantitatively. It was shown that the culture was able to grow up to a DHA concentration of 80 kg m(-3) without any influence of product inhibition. The regeneration capability of the reversibly product inhibited culture from a laboratory-scale bioreactor system was observed up to a DHA concentration of about 160 kg m(-3). At higher DHA concentrations, the culture was irreversibly product inhibited. However, due to the robust membrane-bound glycerol dehydrogenase of G. oxydans, product formation was still active for a prolonged period of time. The reachable maximum final DHA concentration was as high as 220 kg m(-3). The lag phases for growth increased exponentially with increasing DHA threshold values of the first reactor stage. These results correlated well with fluorescence in situ hybridization (FISH) measurements confirming that the number of active cells decreased exponentially with increasing DHA concentrations.


Evaluation of functional parameters in the occlusion of complete denture wearers before and after prosthetic treatment.
The aim of the study was to evaluate functional parameters of the occlusion in complete denture wearers before and after prosthetic treatment. The sample used as the basis for the present study consisted of 50 healthy Caucasian patients (35 women and 15 men), aged from 44 to 86 years (mean=69.18±10), with a total deficiency of teeth. All patients received new complete dentures. Each patient underwent lateral radiograph with the presence of complete dentures, both before (initially existing dentures) and after the prosthetic treatment (new restorations). Cephalometric analysis was based on the Ricketts and McNamara criteria. In order to assess the functional parameters of the occlusion T-scan III analysis was conducted. The following parameters were measured: occlusion - and disclusion time. Statistically significant differences of functional parameters obtained before and 3 months after the treatment were noted in the whole study group. Both before and after therapy occlusion time was longer in women than in men. No statistically significant link was noted between functional parameters in occlusion and age of the patients, denture wearing time, and edentulous period. Some relationships were noted between occlusion time and cephalometric parameters associated with anterior facial height. Reconstruction of the surface of artificial teeth and vertical occlusal dimension affects the sustainability of parameters of occlusion and balance of forces in centric occlusion. The progressive shortening of occlusion time during the period of monitoring may be considered as a sign of progressive adaptation.


Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning.
Thyroid dysfunction, a common long-term complication following bone marrow transplantation (BMT), is frequently associated with total body irradiation (TBI) given in the pre-BMT conditioning protocol. We report our preliminary observation of the prevalence of thyroid dysfunction in children transplanted for primary immunodeficiency (PID) who were given cytoreductive conditioning with busulphan and cyclophosphamide, but without TBI. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (fT4) in 83 survivors transplanted between 1987 and 2002. We found nine children (10.8%) with clinical and/or biochemical thyroid dysfunction at 4 months to 4.5 years post-BMT of which three had positive antithyroid microsomal antibodies. Two patients were classified as primary and seven as compensated hypothyroidism (hyperthyrotropinaemia). Four patients with clinical features of hypothyroidism received replacement thyroxine, while five of the seven patients with compensated hypothyroidism remain off thyroxine because we suspect this may be a transient phenomenon. Abnormalities of thyroid function including severe primary hypothyroidism may occur post-BMT in children receiving chemotherapy conditioning without TBI. Thyroid function should be assessed regularly in this group of patients.


High-performance air-stable ambipolar organic field-effect transistor based on tris(phthalocyaninato) europium(III).
A novel sandwich-type tris(phthalocyaninato) europium triple-decker complex bearing peripheral electron-withdrawing groups (see center of figure) is used to fabricate a field-effect transistor by the quasi-Langmuir-Schaefer method. The air-stable, single-component ambipolar OFET device displays the best carrier properties of a device fabricated by solution processing of a single phthalocyanine derivative so far, which makes the complex very promising for applications in nanoelectronics.


TIGAR regulates DNA damage and repair through pentosephosphate pathway and Cdk5-ATM pathway.
Previous study revealed that the protective effect of TIGAR in cell survival is mediated through the increase in PPP (pentose phosphate pathway) flux. However, it remains unexplored if TIGAR plays an important role in DNA damage and repair. This study investigated the role of TIGAR in DNA damage response (DDR) induced by genotoxic drugs and hypoxia in tumor cells. Results showed that TIGAR was increased and relocated to the nucleus after epirubicin or hypoxia treatment in cancer cells. Knockdown of TIGAR exacerbated DNA damage and the effects were partly reversed by the supplementation of PPP products NADPH, ribose, or the ROS scavenger NAC. Further studies with pharmacological and genetic approaches revealed that TIGAR regulated the phosphorylation of ATM, a key protein in DDR, through Cdk5. The Cdk5-AMT signal pathway involved in regulation of DDR by TIGAR defines a new role of TIGAR in cancer cell survival and it suggests that TIGAR may be a therapeutic target for cancers.


Re-sequencing of a virulent strain of Campylobacter jejuni NCTC11168 reveals potential virulence factors.
In vitro passage of Campylobacter jejuni strains results in phenotypic changes and a general loss of virulence, as is the case with the genome-sequenced strain C. jejuni NCTC11168. Re-sequencing of a virulent strain of NCTC11168 identified 41 SNPs or indels involving 20 genes, four intergenic regions and three pseudogenes. The genes include six motility genes, two chemotaxis genes, three hypothetical genes and a capsule biosynthesis gene, which might have a critical role in C. jejuni virulence. Additionally, we found an insertion in both Cj0676 and Cj1470c, pseudogenes in avirulent NCTC11168, but functional proteins in virulent NCTC11168.


Early levels in blood of immunoglobulin M and natural killer cells predict outcome in nonseptic critically ill patients.
Critical illness results in derangements of all components of the immune response. Nonetheless, most of the efforts evaluating immune status in critically ill patients have been done in the field of sepsis. Here we have evaluated the immunity status at intensive care unit (ICU) admission in a cohort of nonseptic critically ill patients and its influence on their outcome. Ninety patients 18 years and older admitted to our ICU were studied for levels of immunoglobulin (Ig) G, IgM, IgA, CD3(+)CD4(+) T cells, CD3(+)CD8(+) T cells, B cells, natural killer (NK) cells, and C3 and C4 complement factors in peripheral blood in the next 24 hours after admission to the ICU. Patients with infection, sepsis, immunodeficiency, or concomitant immunosuppressive therapy were excluded. Levels of IgM, CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and B lymphocytes correlated inversely with age. In turn, levels of CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and C3 factor of the complement system correlated inversely with Acute Physiology and Chronic Health Evaluation II score. Multivariate Cox regression analysis censored at 28 days evidenced that levels of IgM played a protective role, whereas levels of NK cells behaved as a risk factor for mortality. Kaplan-Meier curves showed a cutoff of 58 mg/dL for IgM and 140 cells/mm(3) for NK cells. In conclusion, our results demonstrate that IgM plays a protective role in critically ill patients with no sepsis, whereas NK cell counts seem to play a deleterious one. Aging and severity at admission affect levels of key factors of the immune system in the blood of these patients.


An analysis of cholecystokinin-induced increase in acetylcholine output from cerebral cortex of the rat.
The effect of colecystokinin (CCK-8) on the release of ACh from the cerebral cortex was studied in urethane-anaesthetized rats with the cortical cup technique. The increase in output of ACh brought about by the administration of CCK-8 1.5 micrograms/kg (i.p.) was prevented by pretreatment with haloperidol (1 mg/kg i.p.) and by lesions of the nucleus basalis magnocellularis and substantia nigra but it was reduced only slightly by bilateral vagotomy. Conversely, none of the treatments abolished the decrease in output of ACh brought about by CCK-8 at a dose of 10 micrograms/kg (i.p.). Local injection of CCK-8 into the nucleus basalis had no effect. Therefore, CCK-8 appears to increase cortical cholinergic activity by indirectly stimulating the cholinergic neurones of the nucleus basalis through dopaminergic neurones.


A comparison of CT scan to transrectal ultrasound-measured prostate volume in untreated prostate cancer.
To compare CT and transrectal ultrasound (TRUS)-measured prostate volumes in patients with untreated prostate cancer. Between 1995 and 1999, 48 consecutive patients at the Portland Veterans Affairs Medical Center were treated with external beam radiotherapy. In 36 of these patients, TRUS and CT measurements of the prostate volume were obtained before treatment and <6 months apart. The TRUS volume was calculated using the prolate ellipsoid formula. The CT volume was calculated from the contours of the prostate drawn by one physician, who was unaware of the TRUS volume calculation, on axial CT images. The TRUS and CT prostate volume measurements correlated strongly (Pearson's correlation coefficient = 0.925, 95% confidence interval 0.856-0.961, p < 0.0001). The CT volume was consistently larger than the TRUS volume by a factor of approximately 1.5. In men with a TRUS prostate volume less than the median (<28 cm(3)), the CT/TRUS volume ratio was 1.7, and it was 1.4 for men whose volume was greater than the median. The CT volumes were correlated similarly with the TRUS volumes regardless of the CT slice interval. A strong correlation was found between CT scan and TRUS measurement of the prostate volume; however, CT consistently overestimated the prostate volume by approximately 50% compared with TRUS.