Micro-costing analysis of suspected lower respiratory tract infection care in a French emergency department.
In the context of budgetary constraints faced by healthcare systems, the medical-economic evaluation of care strategies becomes essential. In particular, valuing consumed resources in the overcrowded emergency departments (EDs) has become a priority to adopt more efficient approaches in treating the growing number of patients. However, precisely measuring the cost of care is challenging. While bottom-up micro-costing is considered the gold standard, its practical application remains limited. The objective was to accurately estimate the ED care cost for patients consulting in a French ED for suspected lower respiratory tract infection. The authors conducted a cost analysis using a bottom-up micro-costing method. Patients were prospectively included between January 1, and March 31, 2023. The primary endpoint was the mean cost of ED care. Resources consumed were collected using direct observation method and cost data were obtained from information available at Strasbourg University Hospital. The mean cost of ED care was €411.68 (SD = 174.49). The cost elements that made the greatest contribution to the total cost were laboratory tests, labor, latency time, imaging and consumables. Considering this cost and the current epidemiological data on respiratory infections in France, the absence of valuation for outpatient care represents an annual loss of over 17 million euros for healthcare facilities. Micro-costing is a key element in valuing healthcare costs. The importance of accurately measuring costs, along with measuring the health outcomes of a defined care pathway, is to enhance the relevance of health economic evaluations and thus ensure efficient care.


Santalbic acid from quandong kernels and oil fed to rats affects kidney and liver P450.
Kernels of the plant Santalum acuminatum (quandong) are eaten as Australian 'bush foods'. They are rich in oil and contain relatively large amounts of the acetylenic fatty acid, santalbic acid (trans-11-octadecen-9-ynoic acid), whose chemical structure is unlike that of normal dietary fatty acids. When rats were fed high fat diets in which oil from quandong kernels supplied 50% of dietary energy, the proportion of santalbic acid absorbed was more than 90%. Feeding quandong oil elevated not only total hepatic cytochrome P450 but also the cytochrome P450 4A subgroup of enzymes as shown by a specific immunoblotting technique. A purified methyl santalbate preparation isolated from quandong oil was fed to rats at 9% of dietary energy for 4 days and this also elevated cytochrome P450 4A in both kidney and liver microsomes in comparison with methyl esters from canola oil. Santalbic acid appears to be metabolized differently from the usual dietary fatty acids and the consumption of oil from quandong kernels may cause perturbations in normal fatty acid biochemistry.


Visuospatial working memory, auditory discrimination, and attention.
The present study examined the degree to which tests of visuospatial storage capacity tap into domain-general storage and attention processes. This was done by comparing performance of visuospatial memory tasks with performance on sound-based sensory discrimination tasks. We found that memory task- and discrimination task performance both tapped into a cross-modality factor (visual and auditory). We further examined the degree to which this common variance could be explained by attention control and sustained attention. These attention factors accounted for roughly 60% of the variance in memory. This indicates that tests of visuospatial memory capacity reflect more than modality-specific memory.


A Case of Multiple Myeloma Presenting with Diabetes Insipidus.
Multiple myeloma (MM) can present with involvement of the central nervous system in the form of nerve palsy, plasma cell masses or, rarely, with endocrinological effects due to involvement of the pituitary gland. Usually, in such cases, the disease has a rapid progression and poor prognosis. We report a 52-year-old man who was admitted to the Kolkata Medical College, Kolkata, India, in 2016 with a prolonged low-grade fever and hypernatremia. Shortly afterwards, the patient began to complain of increased urinary frequency and drowsiness. The hypernatremia was treated with intranasal desmopressin and free water replacement. Serum protein electrophoresis and an immunofixation study revealed an immunoglobulin G-κ monoclonal band. Magnetic resonance imaging of the pituitary gland revealed the absence of a posterior bright spot and spotty infiltration of the pituitary fossa. A bone marrow biopsy confirmed a diagnosis of cranial diabetes insipidus due to posterior pituitary MM infiltration.


[A method for studying spinal reflex arcs among muscles in the human upper limb: a post-stimulus time-histogram technique].
A post-stimulus time-histogram (PSTH) technique has been used for studying spinal reflex arcs in humans. In the PSTH technique, effects of the reflex arcs on the motoneuron excitability are examined by analyzing changes in firing probabilities of a motor unit after conditioning stimuli to afferent fibers. Recent studies with the PSTH technique have demonstrated reflex arcs mediated by low threshold muscle afferent fibers (group I afferents) among muscles in the human upper limb. The results have shown several differences of the reflex arcs between the human upper limb and animal forelimb. This paper has described the PSTH technique. Comparisons of the reflex arcs between humans and animals have been also described.


Brain structure across the lifespan: the influence of stress and mood.
Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood, and their interplay in the brain gray and white matter (WM) structure. We showed the critical impact of age in the WM volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.


The Diagnostic Accuracy of Bone Marrow Biopsy Versus PET/CT Scan in Identifying Bone Marrow Involvement in Diffuse Large B Cell Lymphoma Patients at a Cancer Hospital.
Background It is of great importance to assess bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) for staging, prognostic, and therapeutic purposes. The gold standard method used for the identification of bone marrow involvement is bone marrow biopsy (BMB), but it has certain drawbacks. In recent years, positron emission tomography/computed tomography (PET/CT) has become a highly effective method in the diagnosis and staging of lymphoma. Objective The objective of this study is to estimate the diagnostic accuracy of PET/CT in identifying bone marrow involvement in DLBCL patients in a cancer care hospital in Lahore, using BMB as a reference standard. Methods This descriptive cross-sectional study was conducted at the Department of Pathology of Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) from January 1, 2013, to December 31, 2018. A retrospective data of 146 patients fulfilling the inclusion and exclusion criteria was retrieved from the hospital information system (HIS). The inclusion criteria include patients aged 18-80 years, of either gender, and with a confirmed diagnosis of DLBCL on tissue biopsy. The exclusion criteria include patients who had started chemotherapy or radiotherapy for DLBCL or were using granulocyte colony-stimulating factor (G-CSF) prior to their PET/CT scan. All patients underwent PET/CT and BMB, and the diagnostic accuracy of PET/CT was calculated, with BMB taken as the reference standard. Results The mean age of cases was 52.73 ± 16.27 years. There were 95 (65.1%) male and 51 (34.9%) female cases, with a high male-to-female ratio. In the present study, 32.19% of cases had bone marrow involvement on BMB, and 34.2% of cases had bone marrow involvement on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy of PET/CT were found to be 93.61%, 93.93%, 88%, 96.88%, and 93.84%, respectively. Conclusion It is concluded that PET/CT scan has good sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. So, it is suggested to choose this non-invasive technique because the presence of a disease in extra-medullary space can also be detected and the evaluation of bone marrow in the whole body can be performed. PET/CT scan is an effective imaging modality in the detection of bone marrow involvement in DLBCL patients, and its relative advantages over bone marrow biopsy might conclude this to be a preferred technique.


Unrestricted component count in multiphase lattice Boltzmann: A fugacity-based approach.
Studies of multiphase fluids utilizing the lattice Boltzmann method (LBM) are typically severely restricted by the number of components or chemical species being modeled. This restriction is particularly pronounced for multiphase systems exhibiting partial miscibility and significant interfacial mass exchange, which is a common occurrence in realistic multiphase systems. Modeling such systems becomes increasingly complex as the number of chemical species increases due to the increased role of molecular interactions and the types of thermodynamic behavior that become possible. The recently introduced fugacity-based LBM [Soomro et al., Phys. Rev. E 107, 015304 (2023)2470-004510.1103/PhysRevE.107.015304] has provided a thermodynamically consistent modeling platform for multicomponent, partially miscible LBM simulations. However, until now, this fugacity-based LB model had lacked a comprehensive demonstration of its ability to accurately reproduce thermodynamic behavior beyond binary mixtures and to remove any restrictions in a number of components for multiphase LBM. In this paper we closely explore these fugacity-based LBM capabilities by showcasing comprehensive, thermodynamically consistent simulations of multiphase mixtures of up to ten chemical components. The paper begins by validating the model against the Young-Laplace equation for a droplet composed of three components. The model is then applied to study mixtures with a range of component numbers from one to six, showing agreement with rigorous thermodynamic predictions and demonstrating linear scaling of computational time with the number of components. We further investigate ternary systems in detail by exploring a wide range of temperature, pressure, and overall composition conditions to produce various characteristic ternary diagrams. In addition, the model is shown to be unrestricted in the number of phases as demonstrated through simulations of a three-component three-phase equilibrium case. The paper concludes by demonstrating simulations of a ten-component, realistic hydrocarbon mixture, achieving excellent agreement with thermodynamics for both flat interface vapor-liquid equilibrium and curved interface spinodal decomposition cases. This study represents a significant expansion of the scope and capabilities of multiphase LBM simulations that encompass multiphase systems of keen interest in engineering.


Effects of posture on the physiology of gastric emptying: a magnetic resonance imaging study.
Gastric contents empty from the stomach despite frequent changes in body position. The mechanism that maintains gastric emptying independent of position is poorly understood. The aim of this study was to determine the effects of body position on gastric emptying and motor function. Twelve volunteers were investigated in seated position (SP) and upside-down position (UDP) after ingestion of 300 ml water. Magnetic resonance imaging provided a non-invasive assessment of gastric emptying and volumes, intragastric distribution and peristaltic function. A marked difference in distal/proximal intragastric distribution between UDP and SP was present (7% versus 40%; p < 0.01). Gastric-emptying time was similar but emptying pattern was linear in UDP and exponential in SP. Peristalsis was slower in UDP than SP (2.75 versus 2.96 min-1; p < 0.01), but no correlation was found between peristaltic frequency and the rate of gastric emptying in either position. Postprandial volume response (gastric relaxation) was greater in UDP than SP (280 versus 250 ml; p < 0.05). A correlation was found between gastric relaxation and gastric-emptying time in SP (r2=0.46) but not in UDP. The stomach maintains the rate of gastric emptying despite radical changes in body position and intragastric distribution of gastric contents. In SP, hydrostatic pressure (modulated by gastric tone) dictates the gastric emptying. In UDP, gastric emptying also appears to be mediated by continuous adaptation of gastric tone. These findings provide support for the hypothesis that the mechanism of gastric emptying resembles a "pressure pump" rather than a "peristaltic pump".


Gingival swelling in a 13-year-old girl with multiple recurrences.
We present a challenging case of gingival swelling that recurred several times in 3.5 years in a 13-year-old girl. Histologic evaluation of the initial biopsy revealed groups of epithelioid cells surrounded by lymphocytes in the submucosal fibrous connective tissue, and it was diagnosed as noncaseating granulomatous inflammation. With the tissue specimens from subsequent multiple excisions and several immunohistochemical studies, the diagnoses evolved to benign cellular infiltrate of undetermined origin, epithelioid hemangioma, proliferating endothelial cell neoplasm of uncertain biologic potential, atypical vascular tumor, epithelioid hemangioendothelioma, and kaposiform hemangioendothelioma. We discuss the list of differential diagnoses from various pathologists and propose our diagnosis of epithelioid hemangioendothelioma based on its clinical behavior, histologic features, and immunohistochemical findings.


Weight reduction after gastroplasty: the predictive value of surgical, metabolic, and psychological variables.
Twenty-one grossly obese patients (mean body weight 126 kg, range 93-190 kg) were treated with gastroplasty ad modum Gomez. Eighteen months after surgery the average weight loss was 30.4 kg (range 1-71 kg); about 80 per cent of this weight loss represented loss of body fat. Mean weight loss of the entire programme, including preoperative weight reduction was 34.4 kg (range 1-71 kg). Dilation of the pouch and/or channel occurred in 14 patients and was generally discovered 6-12 months after operation. The wide range in weight reduction could not be unequivocally attributed to technical-surgical factors. Although the patients with the least weight reduction had all developed channel dilation, several patients with excellent weight loss also showed dilation of the pouch and/or channel. An extensive psychological investigation performed before surgery demonstrated more signs of sensitivity and denial in the unsuccessful patients; the successful ones were more dependent and tended to live in a supportive social environment. The unsuccessful patients were younger and their estimated alcohol consumption was higher. A number of morphological and biochemical variables including body weight, fat cell size, and variables reflecting thyroid function, lipid and glucose metabolism, and adipose tissue metabolism were not related to subsequent weight loss.


Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.
Wee1 tyrosine kinase regulates mitosis by carrying out the inhibitory tyrosine 15 phosphorylation of Cdc2 M-phase inducing kinase. Schizosaccharomyces pombe Wee1 is a large protein, consisting of a C-terminal catalytic domain of approximately 350 amino acids preceded by a N-terminal domain of approximately 550 residues. The functional properties of the Wee1 N-terminal domain were investigated by expressing truncated forms of Wee1 in S. pombe. Both positive and negative regulatory domains were identified. Sequences important for Wee1 function were mapped to a central region (residues 363-408). This region is not required for kinase activity or nuclear localization, suggesting it may be involved in substrate recognition. The negative regulatory domain resides in the N-terminal third of Wee1, Wee1 constructs lacking this domain are more effective at delaying mitosis than wild-type Wee1. The negative regulatory domain contains clusters of potential Cdc2 phosphorylation sites. Investigations to monitor the abundance of Wee1 mRNA and protein during the cell cycle were also carried out.


Factors Affecting Sampling Strategies for Design of an Effects-Directed Analysis for Endocrine-Active Chemicals.
Effects-directed analysis (EDA) is an important tool for identifying unknown bioactive components in a complex mixture. Such an analysis of endocrine-active chemicals (EACs) from water sources has promising regulatory implications but also unique logistical challenges. We propose a conceptual EDA (framework) based on a critical review of EDA literature and concentrations of common EACs in waste and surface waters. Required water volumes for identification of EACs under this EDA framework were estimated based on bioassay performance (in vitro and in vivo bioassays), limits of quantification by mass spectrometry (MS), and EAC water concentrations. Sample volumes for EDA across the EACs showed high variation in the bioassay detectors, with genistein, bisphenol A, and androstenedione requiring very high sample volumes and ethinylestradiol and 17β-trenbolone requiring low sample volumes. Sample volume based on the MS detector was far less variable across the EACs. The EDA framework equation was rearranged to calculate detector "thresholds," and these thresholds were compared with the literature EAC water concentrations to evaluate the feasibility of the EDA framework. In the majority of instances, feasibility of the EDA was limited by the bioassay, not MS detection. Mixed model analysis showed that the volumes required for a successful EDA were affected by the potentially responsible EAC, detection methods, and the water source type, with detection method having the greatest effect on the EDA of estrogens and androgens. The EDA framework, equation, and model we present provide a valuable tool for designing a successful EDA. Environ Toxicol Chem 2020;39:1309-1324. © 2020 SETAC.


Underreporting of minor transfusion reactions in cancer patients.
Minor adverse reactions following transfusion of blood components to cancer patients are not uncommon. Reporting these minor reactions to the transfusion service needs a careful evaluation. The objectives of this study were to closely monitor the transfusion reactions that occurred and had not been reported to the transfusion service and to evaluate the process by which the medical and nursing staff recognized and managed these reactions. We prepared a questionnaire with the nursing staff of a selected inpatient unit that addressed important questions, such as signs and symptoms during the transfusion, premedications given, process for physician notification, recommended action, and blood component implicated. Charts of the patients were reviewed, and the process was monitored for a 6-month period. A total of 58 cases were completed and analyzed. Platelet concentrates were transfused in 43 cases (74.1%), packed red blood cells in 9 cases (15.6%), and fresh frozen plasma in 6 cases (10.3%). Minor adverse reactions that were documented included chills in 11 cases (19.0%), low-grade fever in 11 cases (19.0%), hives and itching in 24 cases (41.4%), nausea and vomiting in 1 case (1.7%), and headaches and nonspecific mild pains in 11 cases (19.0%). Transfusions had been resumed in 27 cases (46.6%) and stopped completely in 13 cases (22.4%). Twenty-seven of 58 (46.6%) were first-time events. We conclude that underreporting of minor transfusion reactions, such as a febrile nonhemolytic transfusion reaction and allergic reactions, exists. To ensure safety to our cancer patients who are transfusion-dependent, we suggest that careful evaluation of any suspected transfusion reaction event should be referred to the transfusion medicine physicians who will evaluate each case and discuss it with the attending physician. This process will prevent detrimental, acute transfusion reactions.


Interstitial cystitis-epidemiology, diagnostic criteria, clinical markers.
Knowledge of the epidemiology of interstitial cystitis (IC), the burden of the disease in the population, and the identification of possible risk factors remains largely fragmentary. The most reliable information comes from the few population-based studies that have appeared in the literature over the past 25 years, but two major issues urgently need to be addressed by appropriate epidemiologic studies: although studies find that only 10% of IC occurs in men, the hallmark symptoms of chronic prostatitis-pelvic pain, voiding dysfunction, and pain associated with sexual activity-overlap with those in men who carry the IC diagnosis. In addition, it is not known whether children suffer from the condition. The definition of IC is grounded in the symptomatology of pelvic pain and urinary frequency of a chronic nature and unexplained by any known urologic or other system pathology, but undue reliance on cystoscopic criteria has undoubtedly led to significant underdiagnosis. Efforts to identify clinical markers for diagnosis of IC are continuing and may lead the way to ascertaining the etiology and pathophysiology of IC.


Technical aspects of ultrasound imaging guidewires.
In many interventional catheterization laboratories around the world the use of intravascular ultrasound (IVUS) has become a routine addition to the catheter-based interventional procedures. IVUS catheters, for coronary use, typically of a size around 3 French, provide images that assist in diagnosing the coronary obstructive disease, choosing the most appropriate recanalization method, monitoring the recanalization process and evaluating the end result. The downside of the use of IVUS, apart from additional cost to the procedure, is the additional exchange of catheters during the procedure. Several designs of hybrid catheters have been proposed, combining IVUS imaging with a therapeutic de-obstruction method in one catheter. A more modular approach is to equip the guidewire with imaging capability. Such a guidewire would provide an image of the stenotic region as well as guide the recanalization catheter to its location. It will, however, require further miniaturization of the ultrasound imaging technology, which already is scaled down considerably to enable coronary imaging. In addition, the ultrasound imaging guidewire (UIG) would have to possess specific qualities in bending and torque to act as a true guidewire. A first step to modularity is the separately used 'imaging core', which is advanced into the guidewire lumen of a therapeutic catheter, but cannot guide this catheter to the desired location. The combination of both imaging and mechanical requirements would yield a true UIG, but constitutes major technical challenges.


University of Salford's £1.7m training facilities recreate real hospital environment.
The next generation of nurses and midwives will be honing their skills on manikins that can breathe, 'speak', sweat and blink at a £1.7 million training suite at the University of Salford.


High mobility group B proteins facilitate strong estrogen receptor binding to classical and half-site estrogen response elements and relax binding selectivity.
The estrogen receptor alpha (ER) is a ligand-dependent transcription factor that regulates the expression of estrogen-responsive genes. A key step in the activation process is the initial binding of the ER dimer to the estrogen response element (ERE). We examined the effect of the coactivator proteins, HMGB1 and HMGB2, in enhancing ER binding affinity to single and tandem EREs. Using EMSAs, both HMGB proteins are shown to enhance ER binding and induce cooperative ER binding on tandem ERE elements. We demonstrate that HMGB proteins facilitate strong ER binding to ERE consensus half-sites, exhibiting binding affinities comparable with ER binding to consensus ERE in the absence of HMGB proteins. These findings reveal that although HMGB proteins enhance binding affinity, they also relax ER binding specificity. Deoxyribonuclease I footprinting demonstrates that ER binds very differently to consensus ERE and ERE consensus half-sites, whereas both deoxyribonuclease I and exonuclease III digestions show that the presence of HMGB1/2 does not alter the DNA protection in ER/ERE complexes. Protease digestions of the complexes support this conclusion and show that a global conformation change occurs in ER when bound to the different ER binding sites. Models for these interactions are discussed, together with a hit-and-run mechanism that HMGB proteins may utilize to produce these effects.


A family of microRNAs present in plants and animals.
Although many miRNAs are deeply conserved within each kingdom, none are known to be conserved between plants and animals. We identified Arabidopsis thaliana miR854 and miR855, two microRNAs (miRNAs) with multiple binding sites in the 3' untranslated region (3'UTR) of OLIGOURIDYLATE binding PROTEIN1b (At UBP1b), forming miRNA:mRNA interactions similar to those that cause translational repression/mRNA cleavage in animals. At UBP1b encodes a member of a heterogeneous nuclear RNA binding protein (hnRNP) family. The 3'UTR of At UBP1b is sufficient to repress reporter protein expression in tissues expressing miR854 or miR855 (rosette leaves and flowers, respectively) but not where both miRNAs are absent (cauline leaves). Intergenic regions containing sequences closely resembling miR854 are predicted to fold into stable miRNA precursors in animals, and members of the miR854 family are expressed in Caenorhabditis elegans, Mus musculus, and Homo sapiens, all with imperfect binding sites in the 3'UTR of genes encoding the T cell Intracellular Antigen-Related protein, an hnRNP of the UBP1 family. Potential binding sites for miR854 are absent from UBP1-like genes in fungi lacking the miRNA biogenetic machinery. Our results indicate that plants and animals share miRNAs of the miR854 family, suggesting a common origin of these miRNAs as regulators of basal transcriptional mechanisms.


Phospholipase Dδ negatively regulates plant thermotolerance by destabilizing cortical microtubules in Arabidopsis.
The pattern of cortical microtubule arrays plays an important role in plant growth and adaptation in response to hormonal and environmental changes. Cortical microtubules are connected with the plasma membrane (PM); however, how the membrane affects cortical microtubule organization is not well understood. Here, we showed that phospholipase Dδ (PLDδ) was associated with the PM and co-localized with microtubules in cells. In vitro analysis revealed that PLDδ bound to microtubules, resulting in microtubule disorganization. Site-specific mutations that decreased PLDδ enzymatic activity impaired its effects on destabilizing microtubule organization. Heat shock transiently activated PLDδ, without any change of its PM localization, triggering microtubule dissociation from PM and depolymerization and seedling death in Arabidopsis, but these effects were alleviated in pldδ knockout mutants. Complementation of pldδ with wild-type PLDδ, but not mutated PLDδ, restored the phenotypes of microtubules and seedling survival to those of wild-type Arabidopsis. Thus, we conclude that the PM-associated PLDδ negatively regulates plant thermotolerance via destabilizing cortical microtubules, in an activity-dependent manner, rather than its subcellular translocation.


Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma.
To define the maximum-tolerated dose (MTD) of liposome-encapsulated doxorubicin (LED) when used every 2 weeks with granulocyte colony-stimulating factor (G-CSF) in patients with advanced soft tissue sarcoma. Doxorubicin encapsulated in egg phosphatidylcholine/cholesterol liposomes was given to patients with sarcoma in a disease-specific phase I trial. The initial dose was 75 mg/m2 with G-CSF 5 micrograms/kg. The MTD was defined as the highest dose that could be given every 2 weeks. Twenty-nine patients participated in this study. Major toxicities included myelosuppression, nausea and vomiting, fatigue, and mucositis. Eight patients were hospitalized for nadir fever. No cardiotoxicity was seen. The MTD was LED 105 mg/m2 with G-CSF 5 micrograms/kg. LED 120 mg/m2 resulted in tolerable, albeit prominent, acute toxicity, but did not permit recycling of therapy on day 15. Among 26 patients with soft tissue sarcoma, 23 had measurable disease, of whom three achieved a partial response (13%; 95% confidence interval, 2% to 34%). LED can be administered every 2 weeks at a dose of 105 mg/m2 with G-CSF support, which provides a dose-intensity of 52.5 mg/m2/wk. To exceed this intensity, the dose of LED that would have to be administered every 3 weeks would be greater than 157.5 mg/m2. A formal phase II trial is needed to estimate better the true response rate.


[Influence of risk factors on the angiographic findings of occlusive cerebrovascular disease (author's transl)].
The angiographic findings in 69 patients suffering from ischaemic stroke or transient ischaemic attacks were compared with the clinical data. The incidence of extracranial stenoses increases with age and is higher in patients with hypertriglyceridaemia and with occlusive arterial disease of the heart or the limbs. Hypertensive patients show extracranial stenoses less frequently, but a greater number is without any visible stenoses in the vessels supplying the affected part of the brain. The influence of the diastolic blood pressure on the distribution of the angiographic findings is greater than that of the systolic pressure, but if the diastolic pressure exceeds 105 mm Hg, the incidence of the different angiographic findings is equalized. Among female patients there are more without visible stenoses in the vessels supplying the affected part of the brain. Blood glucose and cholesterol showed no influence on the distribution of the angiographic findings and the incidence of intracranial stenoses was independent of any of the investigated factors. These results support the hypothesis that different risk factors cause different forms of arterial occlusive disease.


Functional Roles of Astrocyte Calcium Elevations: From Synapses to Behavior.
Astrocytes are fundamental players in the regulation of synaptic transmission and plasticity. They display unique morphological and phenotypical features that allow to monitor and to dynamically respond to changes. One of the hallmarks of the astrocytic response is the generation of calcium elevations, which further affect downstream cellular processes. Technical advances in the field have allowed to spatially and to temporally quantify and qualify these elevations. However, the impact on brain function remains poorly understood. In this review, we discuss evidences of the functional impact of heterogeneous astrocytic calcium events in several brain regions, and their consequences in synapses, circuits, and behavior.


The Functions of Mitochondrial 2',3'-Cyclic Nucleotide-3'-Phosphodiesterase and Prospects for Its Future.
2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) is a myelin-associated enzyme that catalyzes the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides. However, its presence is also found in unmyelinated cells and other cellular structures. Understanding of its specific physiological functions, particularly in unmyelinated cells, is still incomplete. This review concentrates on the role of mitochondrial CNPase (mtCNPase), independent of myelin. mtCNPase is able to regulate the functioning of the mitochondrial permeability transition pore (mPTP), and thus is involved in the mechanisms of cell death, both apoptosis and necrosis. Its participation in the development of various diseases and pathological conditions, such as aging, heart disease and alcohol dependence, is also reviewed. As such, mtCNPase can be considered as a potential target for the development of therapeutic strategies in the treatment of mitochondria-related diseases.


Molecular Structure Related to an S = 5/2 High-Spin S2 State Manganese Cluster of Photosystem II Investigated by Q-Band Pulse EPR Spectroscopy.
The high-spin S2 state of the photosynthetic oxygen-evolving cluster Mn4CaO5, corresponding to the g = 4.1 signal for X-band electron paramagnetic resonance (EPR), was investigated using Q-band pulsed EPR, which detected a main peak at g = 3.10 and satellite peaks at 5.25, 4.55, and 2.80. We evaluated the spin state as the zero-field splitting of D = 0.465 cm-1 and E/D = 0.245 with S = 5/2. The temperature dependence of the T1 relaxation time revealed that the excited-state energy was 28.7 cm-1 higher than that of the S = 5/2 ground state. By comparing present quantum mechanical (QM) calculation models, a closed-cubane structure with the protonation state of two oxygens, W1 (= OH-) and W2 (= H2O), was the most probable structure for the S = 5/2 state. The three-pulse electron spin-echo envelope modulation (ESEEM) detected the nuclear signal, which was assigned to nitrogen as His332 ligated to the Mn1 ion. The obtained hyperfine constant for the nitrogen signal was significantly reduced from that in the S = 1/2 low-spin state. These results indicate that the S = 5/2 spin state arises from the closed-cubane structure.


[Identification of the degradation compounds of cefathiamidine by liquid chromatography-tandam mass spectrometry].
To identify the degradation compounds of cefathiamidine by a liquid chromatography-tandam mass spectrometry (LC-MS). According to the accelerated storage condition, two main degradation compounds of cefathiamindine were its hydrolytic products. Cefathiamidine was separated on a C18 column, with 1% acetate solution-acetonitrile (85 : 15) as mobile phase. The mass spectra and MS/MS spectra were obtained with set at the positive ion mode. Combined the UV spectra and the chromatography behavior, the structures of two degradation compounds were identified. The method can be used for the separation of the degradation compounds of cefathiamindine. The two major degradation compounds were desacetylcefathiamidine and cefathiamidine lactone. The method is rapid, sensitive and specific, and it is suitable for the identification of the degradation compounds of cephalosporin.


Development and validation of a fluorescence polarization-based competitive peptide-binding assay for HLA-A*0201--a new tool for epitope discovery.
Various approaches are currently proposed to successfully develop therapies for the prevention and treatment of infectious diseases and cancer. One of the most promising approaches is the development of vaccines that elicit cytotoxic T lymphocyte (CTL) responses. Consequently, identification and exact definition of molecular parameters involved in peptide-MHC class-I interactions of putative CTL epitopes are of prime importance for the development of immunomodulating compounds. To better facilitate epitope discovery, we developed and validated a novel state-of-the-art biochemical HLA-A0201 assay, which is comprised of technologically advanced cutting edge reagents. The technique is based on competition and uses a FITC-labeled reference peptide and highly purified soluble HLA-A0201 molecules to quantitatively measure the binding capacity of nonlabeled peptide candidates. Detection by fluorescence polarization allows real-time measurement of binding ratios without separation steps. During standardization, the problem of assay parameter variation is discussed, showing the dramatic influence of HLA and reference peptide concentrations as well as the choice of the reference peptide itself on IC(50) determinations. For validation, a panel of 15 well-defined HLA-A0201 ligands from various sources covering a broad range of binding affinities was tested. Binding data were used to compare against pre-existing quantitative assay systems. The results obtained demonstrated significant correlation among assay procedures, suggesting that the application of fluorescence polarization in combination with recombinant sHLA molecules is highly advantageous for the accurate assessment of peptide binding. Furthermore, the assay also features high-throughput screening capacity, providing uniquely efficient means of identifying and evaluating immune target molecules.


Quantitative studies of lymphocytes and other cell populations in the bone marrow of neonatally thymectomized C3H mice.
The effects of neonatal thymectomy on the development of the lymphoid, erythroid and granulocytic cell populations in mouse bone marrow have been assessed by quantitative techniques. The numbers per unit volume of bone marrow of 17 cell types were determined in neonatally thymectomized and sham thymectomized C3H mice at two, four and eight weeks of age, and compared with those of normal C3H mice. After neonatal thymectomy the numbers of small lymphocytes, large and medium-sized lymphoid cells, and erythroid cells reached normal levels at two weeks but fell progressively to 18%, 22% and 42% of normal, respectively, by eight weeks. In sham thymectomized mice these cell populations did not differ significantly from normal. Immature and mature granulocytes were elevated in numbers two weeks after either neonatal thymectomy or sham thymectomy, suggesting a transient non-specific stimulation of granulocytopoiesis. During continuous infusion of 3H-thymidine for ten days in neonatally thymectomized mice aged four weeks and eight weeks many bone marrow small lymphocytes remained unlabeled. The results demonstrate that early postnatal development of bone marrow lymphoid and erythroid cells proceeds normally in the absence of the thymus, in accord with the concept of the bone marrow as a primary site of lymphocyte production and differentiation. In addition, some slowly-renewing small lymphocytes in bone marrow appear to be thymus-independent cells.


Oligomeric structure of the alpha1b-adrenoceptor: comparisons with rhodopsin.
The structural basis of the quaternary organization of rhodopsin has recently been explored and modeled. Because information obtained from studying rhodopsin has frequently been directly applicable to other G protein-coupled receptors we wished to ascertain if dimeric and/or oligomeric forms of the alpha(1b)-adrenoceptor could be observed and if so whether rhodopsin might provide insights into the quaternary structure of this receptor. Co-immunoprecipitation and both conventional and time-resolved fluorescence resonance energy transfer studies demonstrated quaternary structure of the alpha(1b)-adrenoceptor and, in concert with the reconstitution of fragments of this receptor, provided information on the molecular basis of these interactions. Development of three color fluorescence resonance energy transfer (FRET) allowed the imaging of alpha(1b)-adrenoceptor oligomers in single living cells. Mutation of hydrophobic residues in transmembrane domains I and IV of the receptor resulted in marked reduction in three color FRET suggesting an alteration in oligomeric organization and potential similarities with rhodopsin. The mutated alpha(1b)-adrenoceptor was unable to reach the cell surface, did not become terminally N-glycosylated and was unable to signal.


Dianthracene-cyclen conjugate: the first equal-equivalent responding fluorescent chemosensor for Pb2+ in aqueous solution.
A dianthracene-cyclen conjugate was synthesized via 'click' chemistry, which could serve as an equal-equivalent responding chemosensor for Pb(2+) in aqueous solution. Moreover, it could be successfully applied in the detection of Pb(2+) in living cells and fetal calf serum.


Sensors and sensory processing for airborne vibrations in silk moths and honeybees.
Insects use airborne vibrations caused by their own movements to control their behaviors and produce airborne vibrations to communicate with conspecific mates. In this review, I use two examples to introduce how insects use airborne vibrations to accurately control behavior or for communication. The first example is vibration-sensitive sensilla along the wing margin that stabilize wingbeat frequency. There are two specialized sensors along the wing margin for detecting the airborne vibration caused by wingbeats. The response properties of these sensors suggest that each sensor plays a different role in the control of wingbeats. The second example is Johnston's organ that contributes to regulating flying speed and perceiving vector information about food sources to hive-mates. There are parallel vibration processing pathways in the central nervous system related with these behaviors, flight and communication. Both examples indicate that the frequency of airborne vibration are filtered on the sensory level and that on the central nervous system level, the extracted vibration signals are integrated with other sensory signals for executing quick adaptive motor response.


Intravascular large B-cell lymphoma involving large blood vessels, three autopsy cases.
Although intravascular large B-cell lymphoma (IVLBCL) is an extranodal lymphoma characterized by the selective growth of lymphoma cells within the lumina of small vessels, we here report three autopsy cases of IVLBCL characterized by the proliferation within large blood vessels. These three cases were diagnosed as IVLBCL of the bone marrow or skin biopsy. Two cases died suddenly before treatment, whereas the other died during treatment. Autopsies showed a large embolus of dense lymphoma cells extending from the truncus pulmonalis to the pulmonary arteries in Case 1, emboli of lymphoma cells in the aorta and carotis in Case 2, and a mass of lymphoma cells blocking the lumen of the aortic arch in Case 3. This is the first report of IVLBCL involving large blood vessels, and it is essential to note that this type of IVLBCL might cause sudden death because of tumor emboli within large blood vessels.


The effect of prior surgery on blood oxygen level-dependent functional MR imaging in the preoperative assessment of brain tumors.
Blood oxygen level-dependent functional MR imaging (BOLD fMRI) is a clinically useful technique for preoperative mapping of eloquent cortices in patients with brain tumors. The purpose of this study was to determine the effect on BOLD fMRI accuracy of susceptibility artifacts caused by prior surgery by comparing volumes of activation in the primary motor cortex (PMC) of patients with and without prior brain surgery. The volumes of fMRI activation of the PMC were measured for the tumor and nontumor sides in patients with (n = 13) and without (n = 30) prior neurosurgery. Statistical comparisons of the volumes were performed by using paired t tests and linear regression analysis. The location and degree of susceptibility artifact were subjectively assessed. No significant difference was found between the mean tumor and nontumor volumes of fMRI activations in patients without prior surgery (P = .51). In patients who had prior surgery, the volume of activation was significantly smaller on the side of the prior operation when compared with the contralateral side (P = .001). The volume of activation on the side of the tumor was also significantly smaller in the patients with prior surgery compared with those without prior surgery (P < .001). Nevertheless, the PMC was identified in all cases, and its location was confirmed intraoperatively. Prior surgery is associated with a decrease in the volume of fMRI activation in patients with prior surgery; however, by examining the T2 images, an astute radiologist can recognize this phenomenon, draw the appropriate conclusions, and correctly identify the PMC.


Ganglioneuroblastoma in a cat: a rare neoplasm treated with electrochemotherapy.
An 8-year-old male castrated cat was referred for sudden onset of lameness. Physical examination revealed a 1x2x1cm mass originating from a footpad of the right hind leg. A diagnosis of ganglioneuroblastoma was suggested by the tumour appearance following histopathological staining with haematoxylin and eosin and haematoxylin/van Gieson. Immunohistochemical staining for glial fibrillary acidic protein (GFAP), vimentin, neuron-specific enolase (NSE), neurofilament and S100 further confirmed the diagnosis. The staging process did not indicate metastatic spread. The cat was treated with three sessions of electrochemotherapy (ECT) 1 week apart, following local injection of bleomycin. The tumour had completely regressed within 1 week of the third ECT application and remained in remission for 402 days at which time a small recurrence was noted. The animal was given a further session of ECT using intra-lesional cisplatin and again went into remission. It remained tumour free at 450 days. Electrochemotherapy is considered a safe and effective treatment for localised neoplasms of cats and dogs and warrants further investigation.


Mn(II) Oxidation by the Multicopper Oxidase Complex Mnx: A Coordinated Two-Stage Mn(II)/(III) and Mn(III)/(IV) Mechanism.
The bacterial manganese oxidase MnxG of the Mnx protein complex is unique among multicopper oxidases (MCOs) in carrying out a two-electron metal oxidation, converting Mn(II) to MnO2 nanoparticles. The reaction occurs in two stages: Mn(II) → Mn(III) and Mn(III) → MnO2. In a companion study , we show that the electron transfer from Mn(II) to the low-potential type 1 Cu of MnxG requires an activation step, likely forming a hydroxide bridge at a dinuclear Mn(II) site. Here we study the second oxidation step, using pyrophosphate (PP) as a Mn(III) trap. PP chelates Mn(III) produced by the enzyme and subsequently allows it to become a substrate for the second stage of the reaction. EPR spectroscopy confirms the presence of Mn(III) bound to the enzyme. The Mn(III) oxidation step does not involve direct electron transfer to the enzyme from Mn(III), which is shown by kinetic measurements to be excluded from the Mn(II) binding site. Instead, Mn(III) is proposed to disproportionate at an adjacent polynuclear site, thereby allowing indirect oxidation to Mn(IV) and recycling of Mn(II). PP plays a multifaceted role, slowing the reaction by complexing both Mn(II) and Mn(III) in solution, and also inhibiting catalysis, likely through binding at or near the active site. An overall mechanism for Mnx-catalyzed MnO2 production from Mn(II) is presented.


Comparative study of receptor discordance between primary and corresponding metastatic lesions in breast cancer.
It is well-known that tumor phenotype may change during the progression of breast cancer (BC). The purpose in this study was to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary and recurrent/metastatic lesions (RML) and also to evaluate the prognostic significance of change in tumor phenotype on survival in patients with metastatic BC. The medical records of 6638 patients with BC from two breast centers treated between 1992 and 2015 were retrospectively analyzed. Of the 6638 patients, 549 cases in whom recurrence was histologically proven by biopsy or by surgical resection were enrolled into this study. Our presentation 13.5% of the patients had metastatic disease. Biopsy on recurrence was obtained from distant metastasis sites in 250 (63.6%) patients or from locoregional soft tissues/lymph-nodes in 143 (36.4%). Receptor discordance in ER, PgR and HER2 expressions between primary and RML were 27.2% (p=0.32), 38.6% (p<0.001) and 14.4% (p=0.007), respectively. Subsequent gain of ER and PgR showed significantly higher overall survival (OS) and post-recurrence survival (PRS) compared to the corresponding concordant-negative patients (119 vs 57 months, p=0.001 and 56 vs 31 months, p=0.03 for ER, 148 vs 58 months, p=0.003 and 64 vs 31 months, p=0.01 for PgR, respectively), hormone receptor (HR) loss was associated with worse OS. Similarly, HER2-loss cases experienced poorer PRS and OS outcomes, compared with those having stable HER2 expression (median 26 vs 60 months, p=0.009 for PRS and median 60 vs 111 months, p=0.06 for OS, respectively). This study confirmed the receptor discordance in ER/PgR and HER2 receptor expressions between primary and RML in patients with metastatic BC. As the loss of receptor expression is the most responsible factor for the discordance, treatments of recurrent/metastatic tumors should be individualized on the basis of molecular and genomic properties.


Use of everolimus as a rescue immunosuppressive therapy in liver transplant patients with neoplasms.
Everolimus is a new immunosuppressant with antitumoral properties and few side effects, but limited use in liver transplantation. The aim of the present study was to evaluate the effect on survival and safety of everolimus in post liver transplantation neoplasms in a single center. Ten liver transplant recipients with a posttransplant diagnosis of neoplasm received everolimus during a median of 12.7 (5.5-27.5) months; median survival was 21.3 (7.5-40.5) months. The probability of survival of everolimus group was significantly greater than the observed in a historical cohort of 14 liver recipients with comparable tumors who did not receive everolimus (100%, 90%, 72% vs. 50%, 29%, 14%) at 6, 12, and 24 months, respectively (HR=4.6, 95% confidence interval: 1.3-16.4; P=0.008). During everolimus therapy no patients showed rejection. Renal function improved in three patients. Furthermore, severe adverse effects and infections were infrequent. In summary, everolimus seems safe for liver transplant recipients with cancer and may improve short-term survival, but further studies are needed to determine long-term benefits and safety.


Status of adjuvant chemotherapy in patients with breast cancer.
The clinical behavior of breast cancer in the human female is characterized by inconsistency. Without question, however, the clinical management of this disease in all stages has resulted in the improved quality and quantity of life. The histologic evidence of axillary lymph node involvement correlates well in a number of series with ultimate prognosis. The ability to characterize high-risk groups for recurrent disease set the stage for surgical adjuvant clinical trials in humans. As the chemotherapeutic management of advanced breast cancer patients improved as well, it seemed logical to attempt to treat patients with evidence of lymph node involvement with an adjuvant program in addition to surgical extirpation. The early results of a number of clinical trials in the surgical adjuvant setting has clearly shown that this concept was worth testing; a biologic effect has been observed with the most pronounced effect in younger women. Improved disease-free intervals occurred and ultimate survival seems to have been affected. The ultimate cure for the majority of females with operable but prognostically unfavorable breast cancer has not as yet been reached however. Thus, in an appropriately highly charged research atmosphere the "routine" management of this disease has as yet to be demonstrated.


Prone Dispatch-Directed CPR in Out-of-Hospital Cardiac Arrest: Two Successful Cases.
Historically, dispatch-directed cardiopulmonary resuscitation (CPR) protocols only allow chest compression instructions to be delivered for patients able to be placed in the traditional supine position. For patients who are unable to be positioned supine, the telecommunicator and caller have no option except to continue attempts to position supine, which may result in delayed or no chest compressions being delivered prior to emergency medical services arrival. Any delay or lack of bystander chest compressions may result in worsening clinical outcomes of out-of-hospital cardiac arrest (OHCA) victims. We present the first two cases, to the best of our knowledge, of successfully delivered, bystander-administered, prone CPR instructions by a trained telecommunicator for two OHCA victims unable to be positioned supine.


[Laparoscopic appendectomy. State of the art].
The authors present the results of a fact-finding survey on the state of the art of laparoscopic appendectomy in North-Eastern Italy. Over the period from 1991 to 2000 a total of 10,451 laparoscopic procedures were performed. Despite the extensive and increasing use of minimally invasive surgery, only 58% of the surgeons surveyed adopt laparoscopy in the management of suspected acute appendiceal disease. Thirty-six percent of surgeons indicate laparoscopy for all patients, while 60% reserve laparoscopic appendectomy for female patients. Forty-seven point one percent of procedures are performed in an emergency setting (within 6 hours of admission to hospital). The mean conversion rate is 4.9% and is mainly due to the aftermath of inflammation. Major intraoperative complications are of the order of 0.08%, while major postoperative morbidity is 0.6%. Wound infections are reported in 2% of patients. The mean hospital stay is 3 days. The majority of surgeons remove the appendix even in the absence of macroscopic inflammation and convert the procedure in the presence of suspected neoplastic disease found incidentally at surgery. The high diagnostic potential of the laparoscopic approach may well explain the infrequent use of preoperative imaging techniques.


Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.
Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.


[Musculoskeletal rehabilitation and bone. Prevention of fall-related fractures in elderly].
Fall-related fracture in elderly is one of the big issues in our aging society. A major cause of fractures in elderly is fall. Therefore, the prevention of falls is essential for the prevention of fractures in elderly. Various risk factors of falls such as physical fragility, cognitive decline and visual problem have been reported. The effective way for prevention of falls is the modification of the risk factors for falls. Especially, exercise has been known effective. In addition to prevention of falls, we should explore the appropriate approach to modify fall direction, defensive reaction, local shock absorption, which are closely related to fall-related fracture risk.


Effective palliation for inoperable esophageal cancer using intensive intracavitary radiation.
In a pilot study between May 1988 and May 1989, ten consecutive patients with advanced esophageal cancer were treated with a short intensive course of intraluminal curietherapy without external beam irradiation at the Kaiser Permanente-Los Angeles Medical Center. Nine of ten patients achieved effective palliation comparable to that of standard external beam teletherapy from other series. Most patients had already failed other palliative modalities including chemotherapy, laser debridement, dilation, and electrocautery. The duration of response was generally longer than with these techniques. All patients completed therapy, and tolerance was excellent. Intraluminal irradiation is an attractive, effectual therapeutic alternative, especially in patients with advanced local or distant disease unlikely to tolerate 5 to 7 weeks of external beam therapy.


New Approach to Cryopreservation of Primary Noncultivated Human Umbilical Vein Endothelium in Biobanking.
It is widely accepted that endothelial dysfunction (ED) is a common feature and a risk factor for cardiovascular diseases and metabolic disorders. Cultures of human umbilical vein endothelial cells (HUVECs) are routinely used in cell-based models to study in vitro molecular and cellular mechanisms of development of different aspects of ED. The methods of the HUVEC extraction and expansion are well developed and standardized. However, when large collections of samples are needed for certain projects, or when samples from a rare population of patients should be collected for future experimental use, HUVEC samples should be transferred to a biobank to be saved in liquid nitrogen for a long period of time until the required collection is completed. This scenario is not always convenient since it requires a lot of effort, a large quantity of expensive culture reagents with limited expiration periods, and sometimes special facilities and well-trained cell biologists among the biobank staff. In this project, we evaluated a method of HUVEC cryopreservation, where the stage of cell culturing and expansion before the transfer of samples to the biobank is eliminated. A total of 55 samples of umbilical cord (UC) were obtained from women immediately after delivery. A primary endothelium pellet derived from 17 UC samples was isolated, frozen, and placed in long-term storage in a liquid nitrogen freezer. Other samples were used to obtain HUVEC cultures. We have demonstrated that cryopreservation of primary endothelium pellets from UC veins without culturing and expansion steps does not affect the physiological features of HUVECs. This new approach would improve the efficiency of biobanking logistics, especially in the case of banking of large collections of endothelial samples.


Mechanism of action of spiramycin and other macrolides.
Macrolide antibiotics constitute a group of 12 to 16-membered lactone rings substituted with one or more sugar residues, some of which may be amino sugars. They inhibit bacterial protein synthesis both in vivo and in vitro with varying potencies. Macrolides are generally bacteriostatic, although some of these drugs may be bactericidal at very high concentrations. The mechanism of action of macrolides has been a matter of controversy for some time. Spiramycin, a 16-membered macrolide, inhibits translocation by binding to bacterial 50S ribosomal subunits with an apparent 1:1 stoichiometry. This antibiotic is a potent inhibitor of the binding to the ribosome of both donor and acceptor substrates. Spiramycin induces rapid breakdown of polyribosomes, an effect which has formerly been interpreted as occurring by normal ribosomal run-off followed by an antibiotic-induced block at or shortly after initiation of a new peptide. However, there is now convincing evidence that spiramycin, and probably all macrolides, act primarily by stimulating the dissociation of peptidyl-tRNA from ribosomes during translocation. Although the ribosomes of both Gram-positive and Gram-negative organisms are susceptible to macrolides, these antibiotics are mainly used against Gram-positive bacteria since they are unable to enter the porins of Gram-negative bacteria. Resistance to macrolides in clinical isolates is most frequently due to post-transcriptional methylation of an adenine residue of 23S ribosomal RNA, which leads to co-resistance to macrolides, lincosamides and streptogramins type B (the so-called MLSB phenotype). Other mechanisms of resistance involving cell impermeability or drug inactivation have been detected in Staphylococcus spp. and Escherichia coli. These strains are resistant to 14-membered macrolides (erythromycin and oleandomycin) but remain susceptible to spiramycin.


Pulmonary antrum radial-linear ablation for paroxysmal atrial fibrillation: interim analysis of a multicenter trial.
Substrate abnormality in pulmonary vein (PV) antrum plays a critical role in mechanism of atrial fibrillation (AF). The present study compares the strategy of PV antrum radial-linear (PAR) ablation to encircling PV isolation for paroxysmal AF. A total of 86 patients with paroxysmal AF were randomly assigned to PAR ablation group or PV isolation group. The average procedure time was 161±21 minutes in PAR ablation group and 199±39 minutes in PV isolation group (P<0.01). The average fluoroscopy time was 25±5 minutes in PAR ablation group and 32±9 minutes in PV isolation group (P<0.001). At 14 (15-12) months of follow-up after single procedure, 31 of 42 (74%) patients in PAR ablation group and 22 of 44 patients (50%) in PV isolation group had no recurrence of AF off antiarrhythmic drug (P=0.0249); and 36 of 42 patients (86%) in PAR ablation group and 26 of 44 patients (59%) in PV isolation group had no recurrence of AF with antiarrhythmic drug (P=0.006). In addition, PAR ablation resulted in greater reduction of left atrial diameter than encircling PV isolation. Multivariable Cox regression analysis showed that only ablation strategy was independently associated with AF recurrence (hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P=0.013). No major adverse event related to the procedures occurred. This study suggests that PAR ablation is a potentially effective strategy for treatment of paroxysmal AF warranting further investigation. URL: http://www.chictr.org; Unique identifier: ChiCTR-TRC-11001191.


Role of visceral proteins in detecting malnutrition in the elderly.
In the clinical practice, visceral proteins are used as indirect markers of protein energy malnutrition (PEM), but their reliability could be reduced with advancing age. The aim of this work is to investigate the reliability of albumin, prealbumin, retinol-binding protein (RBP) and transferrin in evaluating nutritional status in old patients and their relationship with fat-free mass (FFM). Cross-sectional study. Padua, Italy. In 44 underweight (body mass index < 20 kg/m(2)) (66-97 years) and 69 normal weight or overweight elderly subjects (62-98 years), albumin, prealbumin, transferrin and RBP were determined in the plasma. Body composition and particularly FFM was obtained by dual X-ray absorptiometry. FFM was also expressed as FFM index (FFMI) calculated as FFM divided by height squared. Subjects affected by acute illnesses and inflammatory states were excluded. Albumin, prealbumin and RBP mean values were significantly lower in underweight subjects. No differences between two groups were found for transferrin. Albumin prealbumin and RBP resulted under the normal range in 55, 25 and 54% of underweight subjects, respectively. Transferrin's values were low in about 40% of underweight and normal weight subjects, respectively. In all subjects, FFMI shows a significant correlation with albumin (r: 0.52), prealbumin (r: 0.64) and RBP (r: 0.57). No correlation between FFMI and transferrin was found. Visceral proteins, except for transferrin, seem to be useful indexes in detecting malnutrition in the elderly; low values still in the normal range should also be carefully evaluated because they could suggest a poor nutritional status.


Effects of probiotics on non-alcoholic fatty liver disease: a review of human clinical trials.
Non-alcoholic fatty liver disease (NAFLD) is a global public health issue, of which the prevalence is about 25% worldwide. The incidence of NAFLD is increasing in patients with obesity, type 2 diabetes (T2DM) and the metabolic syndrome. The crosstalk between gut microbiota and metabolism-related diseases has been raised great concern. Patients with NAPLD were observed with disruption of gut microbiota. Several researches showed that gut microbiota was the determination in the progression of NAFLD by the experiments using fecal microbiota transplants. The application of probiotics, as one of the most important strategies for the regulation of gut microbiota disorder, have been explored whether it is beneficial to gut-related diseases of intestine-distal organs. Some probiotics were showed to improve the liver parameters and phenotype in patients with NAFLD. The oral intake of them might become the effective management for the prevention and treatment of NAFLD. In this review, we summarized the human clinical trials focusing on the effects of probiotics on NAFLD to give some evidential reference for the administration of NAFLD.


Genetic susceptibility testing and prophylactic oophorectomy.
About 10% of ovarian cancer cases are thought to have a hereditary basis and family history is the strongest risk factor for the development of this disease. In the past, prophylactic oophorectomy has been advocated for women with two or more affected first-degree relatives. More recently, with the identification of the genes responsible for most hereditary ovarian cancers (BRCA1, BRCA2), oophorectomy can now be offered specifically to women who are mutation carriers. Conversely, non-carriers in these families can be reassured that their risk of ovarian cancer is not increased. The value of oophorectomy in mutation carriers has not yet been proven, however, and there are concerns that the benefit may be less than intuitively expected. First, although the lifetime risk of ovarian cancer initially was reported to be as high as 60%, more recent studies have reported risks in the range of 15-30%. A better understanding of the genetic and/or environmental basis of variable penetrance is needed to augment our ability to counsel women regarding their risk. In addition, peritoneal papillary serous carcinoma indistinguishable from ovarian cancer occurs in some women following oophorectomy. Studies that better define how often this occurs also are needed to establish more firmly the value of prophylactic oophorectomy. In view of the uncertainty regarding the efficacy of prophylactic oophorectomy, chemopreventive and early detection approaches also deserve consideration as strategies for decreasing ovarian cancer mortality in women who carry mutations in ovarian cancer susceptibility genes.


[Complete cytogenetic remission of chronic myeloid leukemia with low-dose interferon alfa-2b and monthly high-dose busulfan].
Two patients with chronic myelogenous leukaemia were treated according to an original regimen consisting of the association of alpha-2b interferon, three days a week, plus hydroxyurea during ten months, followed by interferon (same doses) and intermittent high doses of busulphan (50 mg, one dose per month, up to 6 doses). Both patients achieved minor cytogenetic remission in the first stage (50% and 80% of Ph'-positive metaphases, respectively). Upon concluding the second phase, one patient attained complete cytogenetic remission and the other showed major cytogenetic remission (3% Ph'-positive metaphases); complete remission was achieved in the second patient after 4 more doses of busulphan. Both patients remain in complete cytogenetic remission after 4 and 2 years, respectively, with three weekly doses of interferon as maintenance therapy. This protocol is quite different to others applied so far and might represent a good choice for patients unsuitable for bone marrow transplantation.


[The effects of acute large dose of gamma-irradiation on immune function of mice].
To observe the effects of large dose of gamma-irradiation on immune function of mice. 225 cleaning-grad C57 mice, weighing(20+/-2.0) g, were randomly divided into 6 groups, and treated with 0, 6, 9, 12, 15 and 20 Gy gamma-irradiation. At different times after irradiation, lymphocytes were collected and lymphocytic apoptosis and T cell subsets were analyzed by TUNEL, May-Grunwald Giemsa (MGG) staining and flow cytometry. (1)At early stage(1-14) d after radiation, the apoptotic rate of peripheral blood lymphocytes increased significantly and 12 Gy radiation resulted in the highest apoptotic rate. The number of T lymphocytes and T cell subsets decreased continuously in a dose-dependent manner. CD8(+) T cells were the most sensitive in T cell subsets to irradiation. These results suggested that early severe injury might be one of the important features of immune injury caused by acute radiation. (2) One month after radiation, the apoptotic rate of lymphocytes began to decrease and T lymphocytes and their subsets recovered gradually. However, neither the lymphocytic apoptotic rate nor the number of CD3(+) T cells and CD8(+) T cells, recovered to normal level, indicating that large dose of radiation had severe remote effects on immune function. Apoptosis of a large number of peripheral blood lymphocytes in early stage after radiation may result in sharp reduction of T cell number and late immune function depression.


Activity regulation and physiological impacts of maize C(4)-specific phosphoenolpyruvate carboxylase overproduced in transgenic rice plants.
Phosphoenolpyruvate carboxylase (PEPC) was overproduced in the leaves of rice plants by introducing the intact maize C(4)-specific PEPC gene. Maize PEPC in transgenic rice leaves underwent activity regulation through protein phosphorylation in a manner similar to endogenous rice PEPC but contrary to that occurring in maize leaves, being downregulated in the light and upregulated in the dark. Compared with untransformed rice, the level of the substrate for PEPC (phosphoenolpyruvate) was slightly lower and the product (oxaloacetate) was slightly higher in transgenic rice, suggesting that maize PEPC was functioning even though it remained dephosphorylated and less active in the light. (14)CO(2) labeling experiments indicated that maize PEPC did not contribute significantly to the photosynthetic CO(2) fixation of transgenic rice plants. Rather, it slightly lowered the CO(2) assimilation rate. This effect was ascribable to the stimulation of respiration in the light, which was more marked at lower O(2) concentrations. It was concluded that overproduction of PEPC does not directly affect photosynthesis significantly but it suppresses photosynthesis indirectly by stimulating respiration in the light. We also found that while the steady-state stomatal aperture remained unaffected over a wide range of humidity, the stomatal opening under non-steady-state conditions was destabilized in transgenic rice.


Symptomatic Discoid Meniscus in Children and Adolescents: A Review of 470 Cases.
Discoid meniscus is a congenital variant, typically involving the lateral meniscus, that comprises a spectrum of meniscal shapes and degrees of instability in an estimated 1% to 15% of the population. The purpose of this study was to describe the clinical and operative course of a large cohort of children and adolescents patients with symptomatic lateral discoid meniscus. Medical records of 470 knees with symptomatic lateral discoid meniscus in 401 patients ages 18 years or younger diagnosed at a single institution between 1991 and 2016 were reviewed retrospectively for patient characteristics, treatment course (nonoperative and/or operative), and complications. Surgical reports were reviewed in the operative group. The series included 401 patients of mean age 11.6 years (range: 1 mo-18.9 y), of which 222 (55%) were female, and 69 (17%) had bilateral involvement. Of 470 knees, 83 (18%) were initially managed nonoperatively. Of these, 32 knees (39%) failed nonoperative management and were converted to surgical treatment at a median of 7.9 months (interquartile range: 4.0-15.1). In total, 419 knees were managed surgically with saucerization (partial meniscectomy) with or without meniscal repair/stabilization; 84 knees (20%) required at least one concurrent nonmeniscal procedure. Discoid meniscus tears were reported in 264/419 knees (63%) intraoperatively; horizontal cleavage tears were most common. Reoperation was required for 66/379 cases (17%) with clinical follow-up, at a median of 19.6 months (range: 9.2-34.9) after index saucerization; 60/379 cases (16%) had ongoing pain and/or mechanical symptoms at final follow-up. With a failure rate of 39% (32/83 knees), nonoperative management for discoid lateral meniscus frequently convert to surgical treatment. During surgery, meniscus tearing and instability are common and should be anticipated. Postoperatively, 33% (126/379) of knees with clinical follow-up underwent either reoperation, or had ongoing symptoms of the knee at final follow-up. Discoid mensical retear is the most common complication (94%, 62/66) prompting repeat surgery, and should be discussed with families before the index operation. Level IV-descriptive case series.


Continuous infusion low-dose CDDP/5-FU plus radiation in inoperable or recurrent non-small-cell lung cancer: preliminary experience.
The combination therapy of continuous infusion low-dose cisplatin plus 5-fluorouracil (5-FU) with radiation for non-small-cell lung cancer (NSCLC) was performed to assess its effectiveness and any adverse reactions. During the period from April 1994 to December 1998, 18 patients with inoperable or recurrent NSCLC at Aichi Cancer Center Hospital had been treated by chemoradiation with continuous infusion of low-dose cisplatin/5-FU. The median total radiation dose was 66 Gy (range: 60-74.4 Gy). The daily doses of cisplatin and 5-FU ranged from 3 to 6 mg/m2, and from 170 to 250 mg/m2, respectively. In 18 total patients, a complete response was achieved in 4 patients (22%), and a partial response was observed in 12 patients (67%). Grade III toxicity was limited to leukopenia (14.3%). The 1-year and 2-year survival rate in 14 previously untreated patients were 77.4% and 53.1%, respectively. This combination therapy is a well-tolerated regimen. In the future, a study protocol should be designed with a dose-escalation component to further define the optimal doses and schedule for this regimen.


Multiple Natural Polymers in Drug and Gene Delivery Systems.
Natural polymers are organic compounds produced by living organisms. In nature, they exist in three main forms, including proteins, polysaccharides and nucleic acids. In recent years, with the continuous research on drug and gene delivery systems, scholars have found that natural polymers have promising applications in drug and gene delivery systems due to their excellent properties such as biocompatibility, biodegradability, low immunogenicity and easy modification. However, since the structure, physicochemical properties, pharmacological properties and biological characteristics of biopolymer molecules have not yet been entirely understood, further studies are required before large-scale clinical application. This review focuses on recent advances in the representative natural polymers such as proteins (albumin, collagen, elastin), polysaccharides (chitosan, alginate, cellulose) and nucleic acids. We introduce the characteristics of various types of natural polymers, and further outline the characterization methods and delivery forms of these natural polymers. Finally, we discuss possible challenges for natural polymers in subsequent experimental studies and clinical applications. It provides an important strategy for the clinical application of natural polymers in drug and gene delivery systems.


Moonlighting glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells.
Prokaryotic pathogens establish infection in mammals by capturing the proteolytic enzyme plasminogen (Plg) onto their surface to digest host extracellular matrix (ECM). One of the bacterial surface Plg receptors is the multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In a defensive response, the host mounts an inflammatory response, which involves infiltration of leukocytes to sites of inflammation. This requires macrophage exit from the blood and migration across basement membranes, a phenomenon dependent on proteolytic remodeling of the ECM utilizing Plg. The ability of Plg to facilitate inflammatory cell recruitment critically depends on receptors on the surface of phagocyte cells. Utilizing a combination of biochemical, cellular, knockdown, and in vivo approaches, we demonstrated that upon inflammation, macrophages recruit GAPDH onto their surface to carry out the same task of capturing Plg to digest ECM to aid rapid phagocyte migration and combat the invading pathogens. We propose that GAPDH is an ancient, evolutionarily conserved receptor that plays a key role in the Plg-dependent regulation of macrophage recruitment in the inflammatory response to microbial aggression, thus pitting prokaryotic GAPDH against mammalian GAPDH, with both involved in a conserved role of Plg activation on the surface of their respective cells, to conflicting ends.-Chauhan, A. S., Kumar, M., Chaudhary, S., Patidar, A., Dhiman, A., Sheokand, N., Malhotra, H., Raje, C. I., Raje, M. Moonlighting glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells.


In Vitro Anti-Leishmanial Assessment of Some Medicinal Plants Collected from Al Qassim, Saudi Arabia.
In the present work, a group of nine medicinal plants (Sonchus oleraceus, Echinops spinosissimus, Trichodesma africana, Pergularia tomentosa, Teucrium oliverianum, Blepharis ciliaris, Citrllus colocynthis, Cleome amblyocarpa and Aerva javanica) from eight different families were investigated for their in vitro anti-leishmanial activity against the promastigote and amastigote stages of Leishmania major. L. major is the causative agent of cutaneous leishmaniasis (CL) which is one of the major health problems in Saudi Arabia and neighboring countries such as Iraq and Iran. However, the commonly available commercial therapeutics still come with multiple unwanted side effects in addition to parasite resistance, so medicinal plants have attracted attention due to their affordability and beneficial effects. The selected plants were collected from Al Qassim region in the middle of Saudi Arabia, and then extracts were prepared with methanol using overnight soaking for the whole plants. RPMI 1640 was used to culture L. major to obtain promastigotes and intramacrophage amastigotes, which were used later for evaluation of extract activity in vitro via spectrophotometric and microscopic techniques. The MTT assay was used for cytotoxic evaluation of plant extracts against macrophage cells. Data were expressed in mean ± SD. Linear regression was used for IC50 and CC50 calculation. T test was used for significant differences at P ≤ 0.05. All the plants revealed anti-leishmanial activity against the L. major amastigote stage with IC50 values less than 91 µg/mL. The three most potent were T. oliverianum, P. tomentosa and C. amblyocarpa with IC50 values of 7.8, 13.7 and 21.5 µg/mL, respectively. The L. major promastigote stage was more tolerant, so only T. oliverianum extract showed an IC50 less than 30 (26.6 µg/mL). P. tomentosa is the most toxic plant with CC50 3.1 µg/mL followed by T. africana CC50 9.5 µg/mL, the other plants possess CC50 over 40 µg/mL. The best SI values were obtained from the C. amblyocarpa and T. oliverianum extracts against the L. major amastigote stages with 5.7 and 5.3, respectively. We can conclude that T. oliverianum, P. tomentosa and C. amblyocarpa are the best anti-leishmanial plants, so further phytochemical studies for isolation of active ingredients are highly recommended.


Steroid therapy: still a need for answers.
Various methods of steroid administration are reviewed, with emphasis on single dose alternate-day oral administration as compared with daily administration. Alternate-day therapy produces less adrenal and pituitary gland suppression and a reduced frequency of cushingoid features. Furthermore, the ability to resist infection is evidently better preserved. However, an overall therapeutic advantage cannot be claimed as there are few clinical trials with which to make a direct comparison. The numerous studies dealing with this form of therapy lack the rigorous control needed to answer the question of whether alternate-day steroid therapy should be substituted for daily therapy in certain diseases.


The effects of nicotine use during adolescence and young adulthood on gray matter cerebral blood flow estimates.
Nicotine and tobacco product (NTP) use remains prevalent in adolescence/young adulthood. The effects of NTPs on markers of brain health during this vulnerable neurodevelopmental period remain largely unknown. This report investigates associations between NTP use and gray matter cerebral blood flow (CBF) in adolescents/young adults. Adolescent/young adult (16-22 years-old) nicotine users (NTP; N = 99; 40 women) and non-users (non-NTP; N = 95; 56 women) underwent neuroimaging sessions including anatomical and optimized pseudo-continuous arterial spin labeling scans. Groups were compared on whole-brain gray matter CBF estimates and their relation to age and sex at birth. Follow-up analyses assessed correlations between identified CBF clusters and NTP recency and dependence measures. Controlling for age and sex, the NTP vs. non-NTP contrast revealed a single cluster that survived thresholding which included portions of bilateral precuneus (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥7 contiguous voxels). An interaction between NTP group contrast and age was observed in two clusters including regions of the left posterior cingulate (PCC)/lingual gyrus and right anterior cingulate cortex (ACC): non-NTP exhibited positive correlations between CBF and age in these clusters, whereas NTP exhibited negative correlations between CBF and age. Lower CBF from these three clusters correlated with urine cotinine (rs=-0.21 - - 0.16; ps < 0.04) and nicotine dependence severity (rs=-0.16 - - 0.13; ps < 0.07). This is the first investigation of gray matter CBF in adolescent/young adult users of NTPs. The results are consistent with literature on adults showing age- and nicotine-related declines in CBF and identify the precuneus/PCC and ACC as potential key regions subserving the development of nicotine dependence.


New model for bone resorption study in vitro: human osteoclast-like cells from giant cell tumors of bone.
Cells harvested from 12 human giant cell tumors of bone and kept in culture for several passages were characterized for bone-resorbing capability, total and tartrate-resistant acid phosphatase activity, response to the calciotropic hormone calcitonin, cell proliferation, multinucleation after passages, and presence of calcium sensing. Cells obtained from three tumors presented a complete panel of osteoclast characteristics and maintained their multinuclearity after several passages. Cells from four other tumors increased their cAMP levels after treatment with calcitonin, and the other five apparently consisted of cells of stromal origin. These human cell populations with osteoclast characteristics may provide valid in vitro models for the investigation of osteoclastic differentiation and activity.


Long-Term Follow-Up Study of COVID-19: Evaluation on Thin-Slice CT.
To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge. A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher's exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0. There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe-critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient's condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%). The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients' age and disease conditions were positively correlated with residual lesions.


Effect of dietary alpha-linolenate/linoleate balance on endotoxin-induced hepatitis in mice.
Mice were fed diets with three different ratios of alpha-linolenate (18:3n-3) to linoleate (18:2n-6), and the severity of hepatitis during endotoxic shock was compared. Dietary enrichment with alpha-linolenate increased the severity of hepatitis and the mortality induced by lipopolysaccharide (LPS) in combination with D-galactosamine (GalN). Differences in the dietary alpha-linolenate/linoleate balance were mainly reflected in the levels of arachidonate and eicosapenatenoate in liver phospholipids. Pretreatment of mice with indomethacin was found to also enhance the severity of GalN/LPS-hepatitis. This indicated that cyclooxygenase products of arachidonate may suppress the development of GalN/LPS-hepatitis. The enhancement by high alpha-linolenate diets was not observed when a lethal dose of LPS in the absence of GalN was given. Our results indicate that there are pathophysiological conditions of endotoxin-induced hepatitis under which cyclooxygenase products of arachidonate play protective roles.


Microbial interactions with phosphorus containing glasses representative of vitrified radioactive waste.
The presence of phosphorus in borosilicate glass (at 0.1 - 1.3 mol% P2O5) and in iron-phosphate glass (at 53 mol% P2O5) stimulated the growth and metabolic activity of anaerobic bacteria in model systems. Dissolution of these phosphorus containing glasses was either inhibited or accelerated by microbial metabolic activity, depending on the solution chemistry and the glass composition. The breakdown of organic carbon to volatile fatty acids increased glass dissolution. The interaction of microbially reduced Fe(II) with phosphorus-containing glass under anoxic conditions decreased dissolution rates, whereas the interaction of Fe(III) with phosphorus-containing glass under oxic conditions increased glass dissolution. Phosphorus addition to borosilicate glasses did not significantly affect the microbial species present, however, the diversity of the microbial community was enhanced on the surface of the iron phosphate glass. Results demonstrate the potential for microbes to influence the geochemistry of radioactive waste disposal environments with implication for wasteform durability.


Effects of the Chemical Structure, Surface, and Micropore Properties of Activated and Oxidized Black Carbon on the Sorption and Desorption of Phenanthrene.
The effects of the chemical structure, surface properties, and micropore of modified black carbon samples (BCs) on the sorption mechanism of hydrophobic organic contaminants (HOCs) are discussed. Activated and oxidized BCs were produced from a shale kerogen at 250-500 °C by chemical activation regents (KOH and ZnCl2) and then by oxidative regents (H2O2 and NaClO). The surface properties (water contact angel, Boehm titration, and cation exchange capacity, CEC), structural properties (advanced solid-state 13C NMR), micropore properties (CO2 adsorption), mesopore properties (N2 adsorption), and sorption and desorption properties of phenanthrene were obtained. The results showed that ZnCl2-activated BCs had higher basic surface groups, CEC values, aromatic carbon contents, micropore volumes, and adsorption volumes but exhibited lower acidic surface groups than the KOH-activated BCs did. Micropore modeling and sorption irreversibility indicated that the micropore filling was the main sorption mechanism of phenanthrene. In addition, ZnCl2 activated and NaClO oxidized BCs showed a nice regression equation between adsorption volumes and micropore volumes (CO2- V0) as follows: Q0' = 0.495 V0 + 6.28( R2 = 0.98, p < 0.001). Moreover, the contents of nonprotonated aromatic carbon, micropore volumes, and micropore sizes are the critical factors to micropore filling mechanism of phenanthrene on BCs. The size of fused aromatic rings was estimated from the recoupled 1H-13C dipolar dephasing, and the BC structural models at temperatures ranging from 300 to 500 were proposed. This finding improves our understanding of the sorption mechanism of HOCs from the perspectives of chemical structure and micropore properties.


Effects of carbon monoxide inhalation during experimental endotoxemia in humans.
Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO may act as an antiinflammatory agent in human endotoxemia. The aim of this trial was to study the effects of CO inhalation on cytokine production during experimental human endotoxemia. The main study was a randomized, double-blinded, placebo-controlled, two-way cross-over trial in healthy volunteers. Each volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95% confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an approximately 200-fold increase). These LPS-induced changes were not influenced by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in rodents.


Recent Advances in THz Detection of Water.
The frequency range of terahertz waves (THz waves) is between 0.1 and 10 THz and they have properties such as low energy, penetration, transients, and spectral fingerprints, which are especially sensitive to water. Terahertz, as a frontier technology, have great potential in interpreting the structure of water molecules and detecting biological water conditions, and the use of terahertz technology for water detection is currently frontier research, which is of great significance. Firstly, this paper introduces the theory of terahertz technology and summarizes the current terahertz systems used for water detection. Secondly, an overview of theoretical approaches, such as the relaxation model and effective medium theory related to water detection, the relationship between water molecular networks and terahertz spectra, and the research progress of the terahertz detection of water content and water distribution visualization, are elaborated. Finally, the challenge and outlook of applications related to the terahertz wave detection of water are discussed. The purpose of this paper is to explore the research domains on water and its related applications using terahertz technology, as well as provide a reference for innovative applications of terahertz technology in moisture detection.


MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular Endothelial Cells in Hepatopulmonary Syndrome.
Pulmonary microvascular endothelial cell (PMVEC) proliferation and angiogenesis contribute to the development of hepatopulmonary syndrome (HPS). MicroRNA-199a-5p (miR-199a-5p) has emerged as a potent regulator of angiogenesis, and its expression levels significantly decrease in the serum of patients with hepatopathy. However, it has not been reported about whether miR-199a-5p might control PMVEC proliferation. Here, we described the miR-199a-5p governing PMVEC proliferation in HPS. PMVECs were treated with rat serum from common bile duct ligation (CBDL) or sham. MiR-199a-5p mimic or inhibitor was used to change the miR-199a-5p expression. Knockdown of caveolin-1 (Cav-1) was performed using siRNA. NSC-23766 was used to inhibit Rac1 activity. Gene and protein expressions were quantified by qRT-PCR and western blot. Cell proliferation was analyzed by 3H-TdR incorporation and CCK-8 assays. Stress fibers were detected by immunofluorescence. CBDL rat serum induced the down-regulation of miR-199a-5p. Delivery of miR-199a-5p suppressed the CBDL rat serum-induced PMVEC proliferation whereas knockdown of miR-199a-5p promoted PMVEC proliferation. This was accompanied by a decrease and an increase in Cav-1 expression, respectively. Cav-1 siRNA abolished the enhancement of PMVEC proliferation induced by the miR-199a-5p inhibition. Although stress fibers were disrupted in Cav-1 deficient cells, NSC-23766 increased stress fibers and contributed to cell proliferation. CBDL rat serum induced down-regulation of miR-199a-5p in PMVECs, which led to an increase of Cav-1 gene expression. Increased Cav-1 expression, by inhibiting Rac1 activity, led to the formation of stress fibers, which contribute to PMVEC proliferation and thus the pathogenesis of HPS.


Pyreniporphyrins: Porphyrin Analogues That Incorporate a Polycyclic Aromatic Hydrocarbon Subunit within the Macrocyclic Framework.
The first examples of porphyrin analogues incorporating pyrene units are reported. Acid-catalyzed condensation of a pyrene dialdehyde with a tripyrrane, followed by oxidation with DDQ, afforded a polycyclic aromatic hydrocarbon (PAH)-porphyrin hybrid in 38% yield. Pyreniporphyrin proved to be devoid of global aromatic character, but upon protonation aromatic mono- and dicationic species were generated. In the proton NMR spectrum for the dication, the internal CH was shifted upfield to approximately +3 ppm. NICS calculations and ACID plots confirmed the diatropic nature of these structures. Pyreniporphyrin reacted with palladium(II) acetate to give excellent yields of a palladium(II) complex that showed weakly diatropic properties. Treatment of the pyrene dialdehyde with phenylmagnesium bromide generated a dicarbinol that reacted with excess pyrrole in the presence of boron trifluoride etherate to give a tripyrrane analogue. Lewis acid catalyzed ring closure with a thiophene dialcohol in 2% ethanol-dichloromethane afforded a tetraphenylthiapyreniporphyrin in 31% yield. This porphyrinoid was nonaromatic in the free-base form but showed significant diatropicity upon protonation. These results demonstrate that PAH-porphyrin hybrids are easily accessible, and this strategy may allow the incorporation of even larger aromatic subunits.


Behavioral Psychedelics: Integrating Mind and Behavior to Improve Health and Resilience.
One of the most recent and potentially promising advancements in the health sciences has involved the attempted use of psychedelics for treating mental and behavioral health problems, such as anxiety, depression, posttraumatic stress disorder, and addiction. Despite surging scientific and public interest in this work, however, we presently have no standard of care or consensus regarding how best to combine psychotherapy and psychedelics or to assess effectiveness. We discuss these timely issues here through the lens of behavioral psychedelics, which we define as the study of psychedelics to foster intentional changes in habits and behaviors to improve health and resilience. Psychedelics may have the potential to reduce chronic disease risk caused by mental and behavioral rigidity. To fully realize this potential, though, we believe the field must establish best practices and guidelines that include how to induce lasting changes in behavior.


c-Fos facilitates the acquisition and extinction of cocaine-induced persistent changes.
Development of drug addiction involves persistent neurobiological changes. The dopamine D1 receptor is involved in mediating cocaine-induced neuroadaptation, yet the underlying intracellular mechanisms remain unclear. We examined a potential role of the immediate early gene Fos, which is robustly and rapidly induced by cocaine via D1 receptors, in mediating cocaine-induced persistent neurobiological changes by creating and analyzing a mouse in which Fos is primarily disrupted in D1 receptor-expressing neurons in the brain. We show that the expression levels of several transcription factors, neurotransmitter receptors, and intracellular signaling molecules induced by repeated cocaine administration are altered in Fos-deficient brains. Dendritic remodeling of medium spiny neurons induced by repeated exposure to cocaine is blunted in the mutant mice. The mutant mice exhibit attenuated behavioral sensitization after repeated exposure to cocaine and more persistent memory of cocaine-induced conditioned place preference. Our findings indicate that c-Fos produced in D1 receptor-expressing neurons integrates mechanisms to facilitate both the acquisition and extinction of cocaine-induced persistent changes.