Antibody-induced mitogenicity mediated by a chimeric CD2-c-fms receptor.
A chimeric receptor composed of the extracellular domain of the human T-cell antigen CD2 (T11) joined to the membrane-spanning segment and the intracellular tyrosine kinase domain of the human colony-stimulating factor 1 receptor (CSF-1R) was expressed in murine NIH 3T3 fibroblasts. Stimulation of these cells with monoclonal antibodies to CD2 induced phosphorylation of the chimeric glycoprotein on tyrosine, receptor downmodulation, and mitogenesis. In contrast, neither human CSF-1R nor the chimeric receptor was able to function in interleukin-2-dependent murine T cells. In fibroblasts, then, CSF-1 per se is not required for activation of the receptor kinase or for a biological response, whereas in T cells, CSF-1R may be unable to engage the downstream signal transduction machinery.


Structure of high alumina content Al2O3-SiO2 composition glasses.
The structure of binary aluminosilicate glasses containing 60-67 mol % Al2O3 were investigated using high-resolution 27Al NMR and X-ray and neutron diffraction. The glasses were made by aerodynamic levitation of molten oxides. The 67% alumina composition required a cooling rate of approximately 1600 degrees C s(1-) to form glass from submillimeter sized samples. NMR results show that the glasses contain aluminum in 4-, 5-, and 6-fold coordination in the approximate ratio 4:5:1. The average Al coordination increases from 4.57 to 4.73 as the fraction of octahedral Al increases with alumina content. The diffraction results on the 67% composition are consistent with a disordered Al framework with Al ions in a range of coordination environments that are substantially different from those found in the equilibrium crystalline phases. Analysis of the neutron and X-ray structure factors yields an average bond angle of 125 +/- 4 degrees between an Al ion and the adjoining cation via a bridging oxygen. We propose that the structure of the glass is a "transition state" between the alumina-rich liquid and the equilibrium mullite phase that are dominated by 4- and 6-coordinated aluminum ions, respectively.


Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening.
To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy. NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated. Six genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile. These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.


Binding of Hoechst 33258 and 4',6'-diamidino-2-phenylindole to self-complementary decadeoxynucleotides with modified exocyclic base substituents.
Fluorescence titrations have been carried out to determine the association constants (Ka) for binding of the dyes Hoechst 33258 and DAPI to the self-complementary decamer d(CTGAATTCAG) and nine duplex derivatives with exocyclic substituent changes in the six central base pairs. Many Ka values are in the range (2-5) x 10(8) (duplex M)-1 at 5.5 degrees C. Replacement of the leftmost adenine by 2-aminopurine in the sequence decreases Ka for Hoechst 33258 by a factor of 170. When the centermost adenine is replaced by 2-aminopurine, Ka for Hoechst 33258 and DAPI is too small to be evaluated. When the centermost adenine is replaced by purine, Ka for both dyes increases, but this very stable duplex-Hoechst 33258 complex is nonfluorescent. The measured affinities are compared to expectations derived from X-ray studies with dodecamer-dye complexes having an identical central binding sequence (Pjura et al., 1987; Teng et al., 1988; Larsen et al., 1989).


Rheological and physical parameters correlations in formulations with pinhão derivatives stability study: building up an analytical route.
This study focuses on the correlation investigation between rheological and physical parameters and how it can contribute to optimize the topical formulations development. A gel and an emulgel containing pinhão derivatives, and their respective controls, were analyzed along six months of storage. A flowchart of analyses was proposed to use in topical formulation development when a benchmark is the goal or when it is necessary to change some raw material. All formulations were stable over the storage time and the formulations containing pinhão starch and coat extract presented similar properties to those of the control formulations. Correlations between rheological and physical data, as moisture content and particle size, were determined using Pearson's correlation coefficient. A moderate positive correlation was verified between particle size distribution and flow index, and a strong positive correlation between particle size and flow index. It was also found that the higher the moisture content, the higher the consistency index, quality factor, and apparent viscosity. The correlation analyses applied in this study contributed to build up an analytical route for topical formulation development, saving time and costs.


Generation of gold nanoclusters encapsulated in an MCM-22 zeolite for the aerobic oxidation of cyclohexane.
In this work, we will report the generation of Au clusters in a purely siliceous MCM-22 zeolite. The catalytic properties of these Au clusters have been tested for the selective oxidation of cyclohexane to cyclohexanol and cyclohexanone (KA-oil). The Au clusters encapsulated in the MCM-22 zeolite are highly active and selective for the oxidation of cyclohexane to KA-oil, which is superior to Au nanoparticles on the same support. These results suggest that Au clusters are highly active for the activation of oxygen to produce radical species.


Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy.
The first redox deracemization of a series of cyclic benzylic ethers, including 6H-benzo[c]chromenes, isochromans, and 1H-isochromenes, is described. An "acetal pool" strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.


Undifferentiated connective tissue disease with pulmonary involvement.
Pulmonary involvement in collagen vascular diseases is extremely common. It is usually seen in the well described dyscollagenoses and in mixed connective tissue diseases (MCTD). However, there is a lesser known entity called Undifferentiated Connective Tissue Disease (UCTD) which can also involve the lung. We herein present a case of a young man who was detected to have lung involvement secondary to UCTD.


Quantitative Appearance Inspection for Film Coated Tablets.
The decision criteria for the physical appearance of pharmaceutical products are subjective and qualitative means of evaluation that are based entirely on human interpretation. In this study, we have developed a comprehensive method for the quantitative analysis of the physical appearance of film coated tablets. Three different kinds of film coated tablets with considerable differences in their physical appearances were manufactured as models, and their surface roughness, contact angle, color measurements and physicochemical properties were investigated as potential characteristics for the quantitative analysis of their physical appearance. All of these characteristics were useful for the quantitative evaluation of the physical appearances of the tablets, and could potentially be used to establish decision criteria to assess the quality of tablets. In particular, the analysis of the surface roughness and film coating properties of the tablets by terahertz spectroscopy allowed for an effective evaluation of the tablets' properties. These results indicated the possibility of inspecting the appearance of tablets during the film coating process.


All-Direction Random Routing for Source-Location Privacy Protecting against Parasitic Sensor Networks.
Wireless sensor networks are deployed to monitor the surrounding physical environments and they also act as the physical environments of parasitic sensor networks, whose purpose is analyzing the contextual privacy and obtaining valuable information from the original wireless sensor networks. Recently, contextual privacy issues associated with wireless communication in open spaces have not been thoroughly addressed and one of the most important challenges is protecting the source locations of the valuable packages. In this paper, we design an all-direction random routing algorithm (ARR) for source-location protecting against parasitic sensor networks. For each package, the routing process of ARR is divided into three stages, i.e., selecting a proper agent node, delivering the package to the agent node from the source node, and sending it to the final destination from the agent node. In ARR, the agent nodes are randomly chosen in all directions by the source nodes using only local decisions, rather than knowing the whole topology of the networks. ARR can control the distributions of the routing paths in a very flexible way and it can guarantee that the routing paths with the same source and destination are totally different from each other. Therefore, it is extremely difficult for the parasitic sensor nodes to trace the packages back to the source nodes. Simulation results illustrate that ARR perfectly confuses the parasitic nodes and obviously outperforms traditional routing-based schemes in protecting source-location privacy, with a marginal increase in the communication overhead and energy consumption. In addition, ARR also requires much less energy than the cloud-based source-location privacy protection schemes.


The association of grandmaternal and maternal factors with maternal adult stature.
Stature is an important determinant of several reproductive and non-reproductive health problems. Documentation of secular trends in stature has been based primarily on cross-sectional studies of special populations, primarily of men. The objective of this study is to determine how growth and socio-economic status (SES) factors relate to stature changes among lineal female relatives, maternal grandmothers to mothers. The study base was derived from a population-based intergenerational cohort which linked several statewide databases to data from the mothers' own birth certificates: the Washington State Intergenerational Cohort. Mothers in these ethnic groups were separately studied: non-Hispanic Whites, African Americans, Native Americans, Hispanics. We generated simple, partial, and multiple correlation coefficients to investigate the association between stature and other growth and SES factors. A mother's stature is determined partly by her own mother's stature and partly by her birthweight. These two measures are individually stronger predictors of stature than are several available SES factors considered in combination-grandmother's age, parity, marital status, and mother's age. The maximal multiple correlation models yielded R2 values from 18% to 28%. Growth measures are stronger predictors of intergenerational changes in stature than are the several available socio-economic factors. However, socio-economic factors are partly responsible for the level of achieved prenatal and postnatal growth. Since grandmother's stature is a determinant of mother's birthweight, which in turn is a determinant of infant birthweight, some environmentally influenced determinants of some birth outcomes are already established before a prospective mother is conceived or born.


Prevalence of cardiovascular diseases among alpine skiers and hikers in the Austrian Alps.
Mountain sports, especially hiking and alpine skiing, are very popular. It is speculated that a high percentage of hikers and skiers are older and have cardiovascular diseases, but little is known about the real frequency of cardiovascular diseases in mountaineers and skiers. The goal of this study was to provide data on the prevalence of cardiovascular diseases (coronary artery disease with and without myocardial infarction, hypertension, and arrhythmias) of a representative sample of hikers and skiers in the Austrian Alps. Questionnaire results of 1431 hikers and 1043 skiers were included in the evaluation. Regarding the whole sample, 12.7% (11.0 to 14.4) of the hikers and 11.2% (9.3 to 13.1) of the skiers are afflicted with at least one type of cardiovascular disease. The frequency of cardiovascular diseases is age dependent and more pronounced in men, but only small differences were detected between hikers and skiers. It can be assumed that 4 to 5 million hikers and skiers with known cardiovascular diseases are active in the Alps annually. Scientific research should provide the basis of an optimal risk management for this large group of persons.


A review of methylmercury and child development.
Methylmercury (MeHg) is a neurotoxin present in both fresh and saltwater fish throughout the world. Increased levels of MeHg can be found in individuals who regularly consume fish. The developing brain is very sensitive to the deleterious effects of MeHg, and prenatal exposure can occur when the mother has a diet high in fish. If the level of MeHg exposure achieved by eating fish adversely affects the fetus or child's neurological development it could have far reaching public health implications. Studies of human prenatal MeHg poisoning in Iraq suggest that MeHg levels achieved by eating fish may affect neurological development even when the fish MeHg levels are not elevated by obvious pollution. Studies in fish eating populations have identified adverse neurological and developmental outcomes, but these findings have not been consistent. Additional studies are presently underway to determine whether consistent adverse outcomes can be identified using more sensitive testing methods and examining children older than in previous studies. This review examines studies of human prenatal and postnatal MeHg exposure. Studies of poisoning episodes where children are symptomatic and studies of fish eating populations where no symptoms are apparent will be addressed. Individuals around the world depend on fish as a protein source and increasing evidence suggests that regular fish consumption has cardiovascular benefits. It is not presently clear whether MeHg exposures from a high fish diet adversely affect children's neurological development, but it is an important question to answer.


Localization of the central pressor action of bradykinin to the cerebral third ventricle.
Bradykinin injected into the lateral ventricle produces a rise in blood pressure. Cream plugs selectively localized to discrete regions of the ventricular system were used to block drug access to periventricular sites. Third ventricular plugs blocked the pressor response to lateral ventricular injections of 5 micrograms bradykinin (27 +/- 5 before vs. 5 +/- 5 mmHg after plug, n = 7) and 100 ng angiotensin II (22 +/- 3 before vs. 4 +/- 2 mmHg after plug, n = 5). Third ventricular plugs also suppressed the drinking response to angiotensin II (3.7 +/- 0.6 before vs. 0.9 +/- 0.6 ml after plug, n = 5). However, plugs that occluded the fourth ventricle failed to suppress the central bradykinin pressor response (27 +/- 8 before vs. 35 +/- 9 mmHg after plug, n = 5). The data suggest that the central bradykinin pressor response has a site of action similar to that of angiotensin II in the ventral third ventricle.


Covariation of amino acid positions in HIV-1 protease.
We have examined patterns of sequence variability for evidence of linked sequence changes in HIV-1 subtype B protease using translated sequences from protease inhibitor (PI) treated and untreated subjects downloaded from the Stanford HIV RT and Protease Sequence Database (http://hivdb.stanford.edu). The final data set size was 648 sequences from untreated subjects (notx) and 531 for PI-treated subjects (tx). Each subject was uniquely represented by a single sequence. Mutual information was calculated for all pairwise comparisons of positions with nonconsensus amino acids in at least 5% of sequences; significance of pairwise association was assessed using permutation tests. In addition pairs of positions were assessed for linkage by comparing the observed occurrences of amino acid combinations to expected values. The mutual information statistic indicated linkage between nine pairs of sites in the untreated data set (10:93, 12:19, 35:38, 37:41, 62:71, 63:64, 71:77, 71:93, 77:93). Strong statistical support for linkage in the treated data set was seen for 32 pairs, eight involving position 10:7 involving position 71, with the rest being 12:19, 15:77, 20:36, 30:88, 35:36, 35:37, 36:62, 36:77, 46:82, 46:84, 48:54, 48:82, 54:82, 63:64, 63:90, 73:90, 77:93, and 84:90. Most associations were positive, although negative associations were seen for five pairs of interactions. Structural proximity suggests that numerous pairs may interact within a local environment. These interactions include two distinct clusters around 36/77 and 71/93. While some of these interactions may reflect fortuitous linkage in heavily treated subjects with many resistance mutations, others will likely represent important cooperative interactions that are amenable to experimental validation.


Correlation for volumetric mass transfer coefficient in mechanically agitated aerated vessel for oxygen absorption in aqueous electrolyte solutions.
Empirical equations used so for for computing k(l)a in mechanically agitated aerated vessels agree well with the measured dependence of K(l)a on the power input of the stirrer and the superficial velocity of the gas. However, they do not fit the dependence of K(l)a on the physical properties of the liquid batch. From the data published so far it can be deduced that the equations suitable for the description of the dependence of k(mol)a on the liquid physical properties must include some independent variable, which characterizes the rate of coalescence of the bubbles. About 400 experimental values of K(l)a were compared with those calculated from different relations. This comparison shows that the rate of coalescence for the aqueous electrolyte solutions is well described on the basis of the Gibbs theory of adsorption of the solute in the surface layer of the solution.


Evaluating a clinical practice intervention to promote delivery of salbutamol by metered-dose inhalers with holding chambers in a pediatric emergency department.
The primary objective of this study was to quantify the impact of a clinical practice intervention to promote the delivery of salbutamol by metered-dose inhaler (MDI) in a pediatric emergency department (PED). A secondary objective was to retrospectively document the components of the intervention. PED inventory data for salbutamol inhalation solution (nebules), MDIs, and holding chambers were obtained from the pharmacy department. Patient data were obtained from the hospital's decision support unit. Interrupted time series analysis was used to evaluate trends in salbutamol inventory data, patient triage acuity, and hospital admissions from January 1, 2003, to May 31, 2010. Interviews and administrative documents were used to identify components of the intervention, which began in 2006. There was a 1,215% increase in the proportion of salbutamol delivered as MDIs compared to total inhaled salbutamol (MDI plus nebulization solution) following the intervention (95% CI 1,032% to 1,396%, p < 0.001). Increases in salbutamol MDI use were associated with the implementation of an institution-specific asthma care map. A relative decrease of 32% in the hospital admission rate (absolute -7.25%: 95% CI -8.31 to -6.19, p < 0.001) was associated with the change in salbutamol MDI use and the use of the asthma care map. A multifaceted intervention, designed and implemented by local PED clinical leaders, resulted in a pronounced change in salbutamol inhalation practice, with an associated decrease in admission rates. This intervention demonstrated many of the criteria for successful health system change. Findings from this research may be contextualized to inform change elsewhere.


Emphysematous gastritis in a cat.
To describe the presentation, diagnosis, treatment, and outcome of a case of emphysematous gastritis (EG) in a cat. A 15-year-old female neutered domestic short-hair cat presented for a 4-month history of weight loss and intermittent vomiting. Clinicopathologic and imaging findings suggested an underlying primary gastrointestinal (GI) disease, as well as possible hepatobiliary disease. Two days following exploratory laparotomy to obtain GI and liver biopsies, the patient became septic and intracellular bacteria were present on cytology of peritoneal effusion. On radiographs, the stomach was markedly distended with fluid and contained a thin gas opacity surrounding the stomach wall. The patient was taken back to surgery to identify a source of sepsis. At surgery, the patient's stomach was firm and emphysematous on palpation but grossly appeared normal. There were no signs of dehiscence of the previous biopsy sites. Stomach biopsy confirmed the presence of intralesional Gram-positive rods, consistent with microbial EG, and a light growth of a Clostridium sp. was cultured from abdominal fluid, consistent with clostridial peritonitis. During a third surgery for suspected septic peritonitis, a jejunostomy tube was placed for postgastric enteral feeding. The patient ultimately survived to discharge and is clinically stable 10 months later. EG is a rare but potentially fatal clinical entity in the human and veterinary literature with only 1 other case reported in cats. Though clostridial organisms have been reported in EG in people, this is the first implication of EG secondary to a Clostridium sp. in the cat. This is also the first report to document the use of a jejunostomy tube for postgastric enteral nutrition to treat EG in the veterinary literature.


Deodorizing effects of tea catechins on amines and ammonia.
Deodorizing effects of tea catechins on amines were examined under alkaline conditions to eliminate the neutralization reaction. They showed deodorizing activity on ethylamine, but none on dimethylamine or trimethylamine. Deodorizing activity on ethylamine was found to be in the order of (-)-epigallocatechin gallate > gallic acid > (-)-epigallocatechin (EGC) > (-)-epicatechin gallate > ethyl gallate >> (+)-catechin = (-)-epicatechin. Further, reaction products of EGC with methylamine, ethylamine, and ammonia were detected by HPLC, indicating that a deodorizing reaction other than neutralization occurs. From structural analysis of the reaction product with the methylamine isolated as a peracetylated derivative, the product was presumed to be methylamine substituted EGC, in which the hydroxyl group of EGC at the 4' position is replaced by the methylamino group. The same replacement reaction took place in the case of ethylamine and ammonia.


Synergistic action of E74B and ecdysteroid receptor in activating a 20-hydroxyecdysone effector gene.
A number of insect effector genes activated by the steroid hormone 20-hydroxyecdysone (20E) are dually controlled by the ecdysteroid receptor (EcR/USP) and products of ecdysteroid early responsive genes (E74, E75, and Broad). However, the molecular mechanism of this dual action is poorly understood. Here we examined transcriptional activation of the vitellogenin (Vg) gene in the yellow fever mosquito, Aedes aegypti, by EcR/USP and E74 in response to an elevation of 20E titers. There are two isoforms of the Aedes E74 gene, AaE74A and AaE74B, which have a common C-terminal Ets DNA-binding domain and isoform-specific N termini in the female mosquito. Inhibiting expression of AaE74B but not AaE74A by RNA interference led to substantial reduction in the Vg gene expression. AaE74B and the ecdysteroid receptor synergistically enhanced 20E-induced transcription of the Vg promoter. This action required the E74-binding sites and the ecdysone response elements in the Vg 5' regulatory region. Two-hybrid assays and coimmunoprecipitation analyses demonstrated direct interaction between AaE74B and AaEcR/AaUSP. Moreover, disruption of this interaction by a dominant negative E74 mutant abolished the enhanced activation of Vg. Therefore, the cooperative interaction between AaE74B and the ecdysteroid receptor is required for high-level expression of the Vg gene in vivo. The synergistic activation is accomplished through their 20E-dependent protein-protein interaction on the gene promoter. This study reveals how the 20E direct-indirect regulation of an effector gene is achieved at the molecular level.


Subcellular localization and in vivo oxidation-reduction kinetics of thiol peroxidase in Escherichia coli.
Peroxiredoxins are a class of peroxide-scavenging enzymes having a conserved cysteine residue(s) in their active centers. Thiol peroxidase (Tpx) is one of the peroxiredoxins identified in Escherichia coli. Despite the absence of the N-terminal signal sequence for transport across the membrane, it has been characterized as a periplasmic protein. Reanalysis of Tpx localization, using active site cysteine mutants of thioredoxin 1 (Trx1), demonstrated that Tpx forms a mixed-disulfide complex with cytoplasmic Trx1, indicating that Tpx localizes in the cytoplasm.


Massive reflux and aspiration after radiographically inserted gastrostomy tube placement.
To the authors' knowledge, fatal postgastrostomy aspiration within 2 days of enteral nutrition has not been reported. The authors report consecutive cases of severe postgastrotomy aspiration with one being fatal for a 26-yr-old with Duchenne muscular dystrophy 2 days after initiation of gastrostomy feedings. Previous to these consecutive radiographically inserted gastrostomies, all gastrotomies at the institution were percutaneous endoscopic gastrostomies or open gastrostomies. Radiographically inserted gastrostomy tubes have an increased likelihood of being oriented toward the esophagus as opposed to the duodenum, which may increase the risk for reflux. Elimination of invasive airway tubes should be delayed until after gastrostomy feedings are documented to be well tolerated. Oximetry and repeated measurements of vital capacity can suggest changes in the status of airway clearance.


Clinical value of manual fusion of PET and CT images in patients with suspected recurrent colorectal cancer.
The purpose of this study was to compare the diagnostic performance of manually fused PET images obtained using 18F-FDG and CT images with that of CT alone, PET alone, and conventional side-by-side review of PET images and CT images (hereafter referred to as "PET + CT") in patients with suspected recurrent colorectal cancer. Ethics committee approval and informed consent were obtained. Sixty-three patients with suspected recurrent colorectal cancer underwent whole-body 18F-FDG PET followed by diagnostic CT. The acquired PET and CT images were merged on a workstation on a pixel-to-pixel basis. CT, PET, PET + CT, and fused images were evaluated separately in terms of the presence or absence of recurrence, new metastases, or both using a 5-point grading scale (0 = definitely negative, 1 = probably negative, 2 = equivocal, 3 = probably positive, and 4 = definitely positive). Lesions determined to be grade 3 or 4 were considered positive, and diagnostic accuracy and certainty were evaluated with statistical analysis using the chi-square test for independence. Of 119 pathologically or clinically confirmed lesions in 36 patients, evaluation of CT, PET, PET + CT, and fused images resulted in the detection of 75 (63%), 84 (71%), 91 (76%), and 111 (93%) lesions, respectively (p < 0.01) with the number of grade 4 lesions detected being 59 (50%), 72 (61%), 84 (71%), and 108 (91%), respectively (p < 0.01). Overall, the diagnostic accuracy of CT, PET, PET + CT, and fused images according to patient were 78%, 79%, 84%, and 92%, respectively (p = 0.13). Interpreting fused images provided more accurate diagnoses than interpreting CT, PET, or PET + CT images. This method of manually fusing separately obtained PET and CT images increased the diagnostic certainty for detecting colorectal cancer recurrence and decreased the number of equivocal cases.


Current knowledge of thrombocytopenia in sepsis and COVID-19.
Thrombocytopenia, characterized by a decrease in platelet count, is commonly observed in sepsis and COVID-19. In sepsis, thrombocytopenia can result from various mechanisms, including impaired platelet production in the bone marrow, accelerated platelet destruction due to increased inflammation, sequestration of platelets in the spleen, immune-mediated platelet destruction, or dysregulated host responses. Similarly, thrombocytopenia has been reported in COVID-19 patients, but the immune-related mechanisms underlying this association remain unclear. Notably, interventions targeting thrombocytopenia have shown potential for improving outcomes in both sepsis and COVID-19 patients. Understanding these mechanisms is crucial for developing effective treatments.


Spectroscopic study of J aggregates of amphiphilic merocyanine dyes formed in their pure Langmuir films.
It is known that an amphiphilic merocyanine dye, 3-carboxymethyl-5-[2-(3-octadecyl-2(3H)- benzothiazolylidene)ethylidene]-2-thioxo-4-thiazolidinone (DS) and its derivatives DSe and 6MeDS form J aggregates under the presence of metallic cations, although the dyes' static dipole moments must be favorable for H aggregates. A metal-free J aggregate of 6MeDS has been generated in its pure Langmuir films and transferred onto CaF2 substrates to investigate the molecular environment around the carboxylic group born by the dye. Combining visible and infrared spectroscopy, geometrical consideration based on ab initio calculations, and simulation of the excitation energy, a structural model of this J aggregate has been proposed. With this model, formation of intermolecular carboxyl-keto hydrogen bonds, which can compensate the electrostatic disadvantage of the J aggregate under the presence of water, has been suggested. As for another derivative of DS, DO, similar discussion has been made for its Mg2+ -containing J aggregate, which is found in this work. In addition, the proposed structural model can tell the cause of the difference in the tendency to J aggregate among 6MeDS, DSe, DS, and DO.


Large functional variability in cockroach photoreceptors: optimization to low light levels.
The compound eyes of insects contain photoreceptors in small eyelets, ommatidia. The photoreceptors generally vary very little from ommatidium to ommatidium. However, in the large compound eyes of the cockroach (Periplaneta americana), previous studies have shown large differences in the optical structure between the ommatidia. The anatomy suggests pooling of 6-20 photoreceptor signals into one second-order cell in the first synapse. Here, we show and characterize an unexpectedly large and seemingly random functional variability in the cockroach photoreceptors in terms of sensitivity, adaptation speed, angular sensitivity, and signal-to-noise ratio. We also investigate the implications of action potentials, triggered by the light-induced membrane depolarization in the photoreceptor axons. The combination of the functional features reported here is unique among the compound eyes. Recordings from the proximal parts of the thin and long photoreceptor axons or small and distant second-order neurons are not practical with the present methods. To alleviate this lack of data, we used computer simulations mimicking the functional variability, spike coding, and pooling of 12 photoreceptor signals, on the basis of our recordings from the photoreceptor somata and distal axons. The predicted responses of a simulated second-order cell follow surprisingly reliably the simulated light stimuli when compared with a simulation of functionally identical photoreceptors. We hypothesize that cockroach photoreceptors use action potential coding and a kind of population coding scheme for making sense of the inherently unreliable light signals at low luminance and for optimization of vision in its mainly dim living conditions.


Don't stand so close to me: a behavioral and ERP study of preferred interpersonal distance.
The space between people, or interpersonal distance, creates and defines the dynamics of social interactions. Given that invasion of one's interpersonal space may trigger threat and anxiety, a critical question is if high vulnerability to social anxiety (SA) is associated with avoidance and attentional biases when anticipating invasion to one's interpersonal space. Therefore, the current study sought to examine the behavioral mechanisms, time course and neural correlates underlying the threat of interpersonal distance invasion with a focus on different SA levels, using both a behavioral and an ERP experiment. Preferred interpersonal distance was assessed using a paradigm that involves responding to different virtual protagonists (friend or stranger) approaching the participant by indicating where one would like the protagonist to stop. In addition, participants' level of social anxiety was measured. The behavioral experiment indicated that levels of SA predicted one's preferred interpersonal distance such that higher SA individuals preferred further distance from a stranger. At the neural level, across groups, early (N1) but not late (LPP) differences were found between stranger and friend conditions. Importantly, SA individuals were characterized by attenuated early ERP responses, suggesting less attentional resources allocated to social stimuli. The results suggest that high SA individuals feel discomfort earlier than others in social engagement, which may lead them to stand further away, thus creating less communicative social interactions.


First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years.
In March 2016, an outbreak of Rift Valley fever (RVF) was identified in Kabale district, southwestern Uganda. A comprehensive outbreak investigation was initiated, including human, livestock, and mosquito vector investigations. Overall, four cases of acute, nonfatal human disease were identified, three by RVF virus (RVFV) reverse transcriptase polymerase chain reaction (RT-PCR), and one by IgM and IgG serology. Investigations of cattle, sheep, and goat samples from homes and villages of confirmed and probable RVF cases and the Kabale central abattoir found that eight of 83 (10%) animals were positive for RVFV by IgG serology; one goat from the home of a confirmed case tested positive by RT-PCR. Whole genome sequencing from three clinical specimens was performed and phylogenetic analysis inferred the relatedness of 2016 RVFV with the 2006-2007 Kenya-2 clade, suggesting previous introduction of RVFV into southwestern Uganda. An entomological survey identified three of 298 pools (1%) of Aedes and Coquillettidia species that were RVFV positive by RT-PCR. This was the first identification of RVFV in Uganda in 48 years and the 10th independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010.


Peripheral lymphedema: new advances in microsurgical treatment and long-term outcome.
We report on the modern surgical management of peripheral lymphedema. An adequate diagnostic route is essential: it has to include patient history and clinical examination, an isotopic lymphography, an accurate study of the venous circulation, and in cases of angiodysplasia, an accurate study of the artery circulation. Based on over 25 years of clinical experience (more than 1,000 patients), the role of derivative and (in those cases where a venous disease is associated with lymphostatic pathology) reconstructive lymphatic microsurgery is particularly underlined, in comparison with conservative medico-physical treatment, to which it is complementary. "Debulking" surgery can be used just in properly selected patients for minor operations with only cosmethic-reductive purposes. With a follow-up even over 15 years after surgery, positive results from lymphatic microsurgery can be achieved in more than 80% of cases, especially in patients at precocious stages.


Effects of chemical amendments on aquatic floc structure, settling and strength.
Using a shear-cell/flow-cell combination integrated with an inverted microscope, the behaviour of Hamilton Harbour sediments was studied mixed with three different amendments: alum, chitosan (both coagulants) and a polyacrylamide (a flocculant). Samples from the shear cell were drawn into the flow cell, where floc structure and size were assessed throughout the floc formation and breakage stages using computer image analysis. Settling velocity, density and porosity were also assessed, with results suggesting that amendment addition may be an effective method for the management of high-turbidity environments, provided there are no toxicological effects. In an assessment of performance, it was found that the polyacrylamide flocculant showed the greatest promise in reducing turbidity levels as it produced the largest flocs with the highest settling velocity. Although more prone to break-up, these flocs still remained larger than those formed with alum or chitosan at the same shear. All flocs, regardless of amendment, broke up due to a fracture mechanism rather than by microscale erosion. By improving our understanding of how these amendments may influence floc properties and behaviours, more effective management tools may be developed for the remediation and control of high-turbidity aquatic environments.


Racial differences in corneocytes. A comparison between black, white and oriental skin.
It is well known that spontaneous desquamation and corneocyte size can reflect respectively stratum corneum cohesiveness and epidermal cell proliferation. The influence of skin pigmentation on these parameters has been investigated on the upper-outer arm of black, white and oriental volunteers, using the detergent scrub method. We found no difference between race in corneocyte surface area, a mean size of 900 microns 2 agreeing closely with that generally encountered in Whites on the upper-outer arm. By contrast, spontaneous desquamation is increased in black vis-à-vis white and oriental skin (factor 2.5, p less than 0.001). Taking into account the importance of the intercellular cement for the cohesion between corneocytes, racial differences in epidermal lipid composition should be investigated.


Transfer factor in the treatment of chronic mucocutaneous candidiasis: a controlled study.
A controlled cross-over study with transfer factor was carried out on 7 patients suffering from chronic mucocutaneous candidiasis. Only one patient showed clinical improvement, which started during a period of pretreatment with 5-fluorocytosine given orally 14 days before the patient entered this trial. No conversion to a positive skin test with Candida antigen or PPD was demonstrated following TF in the 6 patients who were anergic to either of these antigens. Variations in the cell-mediated immune response as revealed by lymphocyte transformation were observed in most patients, especially when studied over a long period of time. However, no pronounced efficacy of TF vis-à-vis placebo in normalizing the cell-mediated immune response could be demonstrated in the 5 patients who completed the clinical trial. Systemic side effects were not observed.


Traditional versus modern values, self-perceived interpersonal factors, and posttraumatic stress in Chinese and German crime victims.
The influence of cultural factors on mental health is not disputed in general - but elaborated research approaches are still lacking. We investigate cultural influences not only by nationality but also by value orientation (modern vs. traditional). A cross-cultural comparison with Chinese and German crime victims included an assessment of value orientation according to Schwartz's theory (Schwartz, 1994) of personal values. Chinese and German adult crime victims were assessed. By means of structural equation multi-sample analysis, data of the two groups were compared. Traditional (conformity, benevolence, customs orientation) and modern values (achievement, hedonism, stimulation), traumatic exposure, posttraumatic stress (PTS), and two self-perceived interpersonal mediator processes (disclosure intentions, social acknowledgement as a victim) were assessed by self-report measures in 130 Chinese and 151 German crime victims. The two patterns of prediction for PTS differed between the countries: In the German sample both value types but in the Chinese sample only traditional values were directly or indirectly predictive of PTS. Traditional values inhibited social acknowledgement as a victim in China and Germany. In Germany, traditional values were related to increased PTS severity. Modern values predicted social acknowledgement as well as lower symptoms in Germany, but not in China. The study shows cultural and interpersonal factors that may contribute to the development of PTSD that are under-researched in contemporary psychology and psychotherapy.


Evaluation of the European Union Programme of Community Action on Health Promotion, Information, Education and Training 1996-2000.
The Programme of Community Action on Health Promotion, Information, Education and Training 1996-2000 was administered by the European Commission's Services in DGV Luxembourg. The programme was a consequence of a decision of the European Parliament and the Council of the European Union in March 1996. Middlesex University Health Research Centre won the tender to evaluate this programme. In this paper the evaluation team disseminate some of the findings that are pertinent to the international health promotion community. Key findings include significant differences in number of applications and in acceptance rates for different Member States. The expert assessors' opinions of the programme suggest a number of problems with its administration. Some projects were awarded commendably high ratings and others were very weak. The most serious weakness of many of the supported projects is lack of any internal evaluation. In order to broaden the scope of the second phase of the evaluation of this programme, more open communication and dialogue will be needed between all of the stakeholders. This implies a change in the culture of the European Commission's Services which, in the case of the units involved with this evaluation, are lacking in efficiency, openness and transparency.


The expression of Fc receptors for immunoglobulin G in human rectal epithelium.
The rectal mucosa is one of the routes of transmission of the HIV virus, although the mechanism of transmission is unknown. We carried out an immunohistological investigation of human rectal epithelium to detect CD4 glycoprotein and Fc receptors (FcR) for immunoglobulin G which may be involved in HIV infection. CD4 was not detected by monoclonal antibodies (MAb) in normal rectal epithelial cells, although CD4+ mononuclear cells were found in the lamina propria of the rectum. FcR3 and FcR2 were, however, detected in surface or crypt epithelial cells of rectal mucosa, using MAb to CD16 and CD32, respectively. In addition, CD16 messenger RNA (mRNA) was found in surface and crypt epithelial cells by in situ hybridization using an RNA probe. FcR3 and FcR2 were also detected in fetal recto-colonic tissue by immunohistology, suggesting that these are constitutive receptors. FcR3 and FcR2 gene transcripts were then demonstrated in fetal recto-colonic tissue using the polymerase chain reaction to amplify a portion of FcR3 and FcR2 coding sequences in complementary DNA (cDNA) prepared from fetal RNA. These findings suggest the possibility that rectal transmission of HIV-antibody complexes might be facilitated by the expression of FcR3 and FcR2 in rectal epithelial cells.


Effect of temporal stimulus properties on the nociceptive detection probability using intra-epidermal electrical stimulation.
Chronic pain disorders can be initiated and maintained by malfunctioning of one or several mechanisms underlying the nociceptive function. Although several quantitative sensory testing methods exist to characterize the nociceptive function, it remains difficult to distinguish the contributions of individual mechanisms. Intra-epidermal electrical stimulation of nociceptive fibers allows defining stimuli with temporal properties within the timescale of these mechanisms. Here, we studied the effect of stimulus properties on the psychophysical detection probability. A psychophysical detection experiment was conducted including 30 healthy human participants. Participants were presented with electrical stimuli having various temporal properties. The pulse-width was varied for single pulse stimuli (either 420 or 840 μs), and the inter-pulse interval for double pulse stimuli (10, 50, or 100 ms). Generalized linear mixed models were used to obtain estimates of thresholds and slopes of the psychophysical function. The 840-μs single pulse resulted in a lower threshold and steeper slope of the psychophysical function than the 420-μs single pulse. Moreover, a double-pulse stimulus resulted in a lower threshold and steeper slope than single pulse stimuli. The slopes were similar between the double pulse stimuli, but thresholds slightly increased with increasing inter-pulse intervals. In the present study, it was demonstrated that varying the temporal properties of intra-epidermal electrical stimuli results in variations in nociceptive processing. The estimated thresholds and slopes corresponding to the selection of temporal properties suggest that contributions of peripheral and central nociceptive mechanisms can be reflected in psychophysical functions.


Enhanced stability of low fouling zwitterionic polymer brushes in seawater with diblock architecture.
The successful implementation of zwitterionic polymeric brushes as antifouling materials for marine applications is conditioned by the stability of the polymer chain and the brush-anchoring segment in seawater. Here we demonstrate that robust, antifouling, hydrophilic polysulfobetaine-based brushes with diblock architecture can be fabricated by atom-transfer radical polymerization (ATRP) using initiator-modified surfaces. Sequential living-type polymerization of hydrophobic styrene or methyl methacrylate and commercially available hydrophilic sulfobetaine methacrylamide (SBMAm) monomer is employed. Stability enhancement is accomplished by protecting the siloxane anchoring bond of brushes on the substrate, grafted from silicon oxide surfaces. The degradation of unprotected PSBMAm brushes is clearly evident after a 3 month immersion challenge in sterilized artificial seawater. Ellipsometry and atomic force microscopy (AFM) measurements are used to follow changes in coating thickness and surface morphology. Comparative stability results indicate that surface-tethered poly(methyl methacrylate) and polystyrene hydrophobic blocks substantially improve the stability of zwitterionic brushes in an artificial marine environment. In addition, differences between the hydration of zwitterionic brushes in fresh and salt water are discussed to provide a better understanding of hydration and degradation processes with the benefit of improved design of polyzwitterionic coatings.


Impacts of artificial reservoirs on floristic diversity and plant functional traits in dry forests after 15 years.
Dams are of paramount importance to a wide variety of human services and many of their environmental problems are known; however, there are few studies in the world addressing the impacts on the native vegetation previously distant from water bodies which became close to the lakeshore created by a dam. Thus, this paper aims to analyze the responses of a dry forest to a dam after 15 years. For this, 20 random samples of 40 trees were made, 10 close to the lakeshore and 10 distant from it, by applying the central square point method. Close to the dam, we found higher values regarding basal area, number of trees, number of evergreen trees, and zoochoric syndrome, but there were lower values of Shannon's diversity index. Therefore, the impacts of the dam after 15 years caused several changes to the tree community. The greater basal area close to the dam suggests that water deficit during the dry season was decreased and plants have thicker trunks. On the other hand, this sector had much more zoochoric syndrome and a larger number of evergreen trees than plots which are distant from water, suggesting changes with regard to the community's ecological functions. Furthermore, structural floristic data shows that the sector close to the dam is less similar to other deciduous forests within the same geographical region than the sector distant from water, thus providing evidence of the impacts of dams on the tree community.


Nutritional care of cancer patients: a survey on patients' needs and medical care in reality.
Cancer patients represent a patient group with a wide-range of nutrition related problems which are often under-recognized and undertreated. In order to assess the status quo of nutritional care in Germany, we conducted a survey among patients with different types of cancer. A standardized questionnaire was distributed online by two national umbrella organizations for self-help groups. 1335 participants completed the questionnaire. 69 % of the participants reported having received information on nutrition and/or specific nutrition-related symptoms. Most often this information was derived from print media (68.5 %) or from within self-help groups (58.7 %). 57.0 % of participants reported having had questions concerning nutrition and/or problems with food intake. most frequently named topics of interest were "healthy diet" (35.0 %) weakness/fatigue (24.3 %), dietary supplements (21.3 %) and taste changes (19.8 %). Nutrition information was most often provided by dietitians (38.7 %) followed by physicians (9.8 %). Women reported receiving nutrition counseling in the hospital nearly twice as often as men (12.5 % versus 5.7 %; p < 0.001). A quarter of the patients (24.1 %) reported using dietary supplements and patients who had received some sort of nutrition information more often reported using supplements (p < 0.001). Nutrition is an essential element in cancer care and patients report a high interest and need: Yet, many patients do not have access to high quality nutrition therapy during and after cancer therapy. With respect to survival and quality of life, increasing the availability and resources for provision of evidence based nutrition information seems mandatory.


Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study.
Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.


Feasibility and Preliminary Effectiveness of Behavioral Activation for Patients with Cancer and Depression in Japan.
Though the effectiveness of behavioral activation (BA) for patients with cancer and depression were reported, there is no evidence in Japan. This study aimed at examining the feasibility and preliminary effectiveness of BA for patients with cancer and depression in Japan. This pre-post study without a control group was conducted in patients with cancer and depression in Japan. The program completion rate was compared with those of previous studies to examine feasibility. To examine the preliminary effectiveness, outcomes were evaluated four times: before and immediately after the program, and two weeks and three months after the program ended. The primary outcome was the remission rate of depression using the 17-item version of the GRID Hamilton Rating Scale for Depression (HAMD17). Secondary outcomes were self-reported depression, anxiety, quality of life, changes in behavior, values, and perceived reward of activity and environmental factors. Pre- and post-program data were compared using paired-samples t-tests, and data obtained at four time points were analyzed using one-way repeated-measures analysis of variance. Of the 68 patients recruited from February 2018 to January 2022, 32 were registered. The completion rate was 75% (24/32), which was similar to previous studies. The total HAMD17 score significantly improved after the program. The remission rate of depression was 62.5% (20/32), which was above the defined threshold value (30%). All but two secondary outcomes significantly improved after the program (p < 0.05). The feasibility and preliminary effectiveness of BA for patients with cancer and depression in Japan were suggested. The Clinical Trial Registration number: UMIN 000036104.


Inhibition of carbonic anhydrases IX/XII by SLC-0111 boosts cisplatin effects in hampering head and neck squamous carcinoma cell growth and invasion.
Hypoxic tumor microenvironment (TME) contributes to the onset of many aspects of the cancer biology associated to the resistance to conventional therapies. Hypoxia is a common characteristic and negative prognostic factor in the head and neck squamous carcinomas (HNSCC) and is correlated with aggressive and invasive phenotype as well as with failure to chemo- and radio-therapies. The carbonic anhydrase isoenzymes IX and XII (CA IX/XII), regulators of extra and intracellular pH, are overexpressed in TME and are involved in adaptative changes occurring in cancer cells to survive at low O2. In this study, we aim to investigate in HNSCC cells and murine models the possibility to target CA IX/XII by the specific inhibitor SLC-0111 to potentiate the effects of cisplatin in hampering cell growth, migration and invasion. Furthermore, we analyzed the signal pathways cooperating in acquisition of a more aggressive phenotype including stemness, epithelial-mesenchymal transition and apoptotic markers. The effects of cisplatin, CA IX/XII specific inhibitor SLC-0111, and the combinatorial treatment were tested on proliferation, migration, invasion of HNSCC cells grown in 2D and 3D models. Main signal pathways and the expression of stemness, mesenchymal and apoptotic markers were analyzed by western blotting. Molecular imaging using NIR-Annexin V and NIR-Prosense was performed in HNSCC xenografts to detect tumor growth and metastatic spread. HNSCC cells grown in 2D and 3D models under hypoxic conditions showed increased levels of CA IX/XII and greater resistance to cisplatin than cells grown under normoxic conditions. The addition of CA IX/XII inhibitor SLC-0111 to cisplatin sensitized HNSCC cells to the chemotherapeutic agent and caused a reduction of proliferation, migration and invasiveness. Furthermore, the combination therapy hampered activation of STAT3, AKT, ERK, and EMT program, whereas it induced apoptosis. In HNSCC xenografts the treatment with cisplatin plus SLC-0111 caused an inhibition of tumor growth and an induction of apoptosis as well as a reduction of metastatic spread at a higher extent than single agents. Our results highlight the ability of SLC-0111 to sensitize HNSCC to cisplatin by hindering hypoxia-induced signaling network that are shared among mechanisms involved in therapy resistance and metastasis.


[A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode/Leigh overlap syndrome].
We experienced a case in which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was identified as complications following the onset of Leigh syndrome along with a 10191 T>C mutation of the mitochondrial gene. The case pertains to a 26-year-old woman. The disease appeared when she was 11 years old due to divergent strabismus, at which point a diagnosis of juvenile Leigh syndrome was made. Many infraction images not conforming to the vessel region were observed upon a brain MRI which was performed at 26 years of age, thus leading to her being diagnosed with MELAS as a complication. Upoon bibliographical consideration, it was speculated that the clinical features of MELAS/Leigh overlap syndrome clearly differ from Leigh syndrome in terms of age of onset, symptoms, and prognosis. Pleiotropic genetic factors including heteroplasmy were presumed to be involved in the diverse phenotype of overlap syndrome.


On the formation of bromhexine impurity E and its chromatographic behaviour.
An unknown bromhexine hydrochloride (BRH) degradation product in BRH oral solutions (finished products) was potentially related to the purity of this API. Several degradation experiments were conducted and its identity and formation were investigated using LC-DAD and LC-DAD-MS/MS. Using the LC method described in the Ph.Eur monograph BRH the degradation product was observed at RRTBRH 0.1 and the specified impurities A-D were ruled out as candidates. Impurity E was initially not considered as a candidate as EDQM reported an expected RRTBRH of 1.8. Still, the LC-DAD-MS/MS results were consistent with the M+ ion for impurity E and its expected fragment ions. Therefore, standard addition was carried out using the Ph. Eur. method which confirmed that the degradation product at RRT 0.1 was impurity E. Upon changing the column type to a column described in the knowledge database, impurity E eluted at an RRT of 1.5. Nevertheless, both columns met all of the criteria in the monograph. The formation of impurity E was even observed in BRH solutions without added reagents. As the conversion from BRH to impurity E requires a source of carbon, we suggest that one BRH molecule degrades through a radical mechanism to a reactive species which subsequently is quenched by another BRH molecule producing impurity E. We suggest the transparency list for BRH to be more explicit on the formation of impurity E, its RRT and the permissible LC columns.


[Immobilization of lipase by chemical modification of chitosan].
Lipase (EC220.127.116.11) from Candida sp. 99-125 was immobilized on chitosan by chemical covalence. Lipase was first immobilized to chitosan beads by activating its hydroxyl groups with carbodiimide followed by cross-linking more lipase to the amino groups with glutaraldehyde. In this article, different factors that influenced the immobilization were investigated, and the optimum conditions were ascertained. Comparative studies of organic solvent and thermal stability between free lipase and immobilized lipase were conducted. Immobilization enhanced the lipase stability against changes of temperature and organic solvent. Immobilization lipase can be reused in the synthesis system of palmitate hexadecyl. Operational stability tests indicated that the immobilized lipase occurs after 16 consecutive batches, the conversion rate remained 85%. Such results revealed good potential for recycling under esterification system.


[Analysis of medical records as an element of quality control and safety of medical activities].
Studying the issue of quality control and safety of medical activities. The analysis of domestic literature on the quality of filling out medical documentation has been carried out. A dental patient's medical record (ICSD) is not only the most important legal document, but also a certain indicator of the level of professional competence of a dentist. To find out all sorts of reasons that led to professional errors and adverse consequences after the provision of dental care, a thorough study and general analysis of medical documentation is of great importance, the maintenance and correct execution of which is also necessary for solving a number of other, including legal issues. The most common drawbacks in the design of a dental patient's medical record have been identified, which indicates a decrease in the quality of medical care provided to patients. At the moment, there are still unresolved issues related to complete completion of medical documentation. When analyzing the literature, we did not find a purposeful study of the medical history of a dental patient during surgical treatment, which requires further research.


Change in human chorionic gonadotropin in gestational trophoblastic disease observed during the course of chemotherapy.
This study investigates the physicochemical characteristics of human chorionic gonadotropin (hCG) in gestational trophoblastic disease (GTD), with special reference to the clinical course of chemotherapy and prognosis. In gel high performance liquid chromatography (HPLC), the hCG molecules from normal pregnancy and from the hydatidiform mole had the same molecular form as standard purified hCG, whereas hCG from choriocarcinoma was inconsistent in molecular form, containing molecules which are smaller, the same or larger than those of standard purified hCG. In two fatal choriocarcinoma patients, large hCG and large hCG alpha were found in the urine samples collected within one month prior to death. In a chromatofocusing study, the chromatofocusing pattern of hCG from GTD was acidic and similar to that of early pregnancy. The chromatofocusing patterns did not alter or were altered only slightly during the course of chemotherapy. In a Concanavalin A-Sepharose (Con A) chromatography study, the Con A binding shifted from low to high binding in patients with GTD who were responsive to chemotherapy. In summary, the molecular form, electric charge and Con A binding of hydatidiform mole hCG are similar to those of early pregnancy hCG and standard purified hCG, whereas the molecular form and Con A binding of choriocarcinoma are different from those of early pregnancy hCG and standard purified hCG. The presence of smaller or larger molecular forms of hCG may be an ominous sign, whereas the presence of high Con A binding may be a favorable sign. The chromatofocusing pattern seems to be unrelated to the clinical course of chemotherapy.


Deep Learning-Based Survival Analysis Identified Associations Between Molecular Subtype and Optimal Adjuvant Treatment of Patients With Gastric Cancer.
Gastric cancer (GC) is the third-leading cause of cancer-related deaths. Several pivotal clinical trials of adjuvant treatments were performed during the previous decade; however, the optimal regimen for adjuvant treatment of GC remains controversial. We developed a novel deep learning-based survival model (survival recurrent network [SRN]) in patients with GC by including all available clinical and pathologic data and treatment regimens. This model uses time-sequential data only in the training step, and upon being trained, it receives the initial data from the first visit and then sequentially predicts the outcome at each time point until it reaches 5 years. In total, 1,190 patients from three cohorts (the Asian Cancer Research Group cohort, n = 300; the fluorouracil, leucovorin, and radiotherapy cohort, n = 432; and the Adjuvant Chemoradiation Therapy in Stomach Cancer cohort, n = 458) were included in the analysis. In addition, we added Asian Cancer Research Group molecular classifications into the prediction model. SRN simulated the sequential learning process of clinicians in the outpatient clinic using a recurrent neural network and time-sequential outcome data. The mean area under the receiver operating characteristics curve was 0.92 ± 0.049 at the fifth year. The SRN demonstrated that GC with a mesenchymal subtype should elicit a more risk-adapted postoperative treatment strategy as a result of its high recurrence rate. In addition, the SRN found that GCs with microsatellite instability and GCs of the papillary type exhibited significantly more favorable survival outcomes after capecitabine plus cisplatin chemotherapy alone. Our SRN predicted survival at a high rate, reaching 92% at postoperative year 5. Our findings suggest that SRN-based clinical trials or risk-adapted adjuvant trials could be considered for patients with GC to investigate more individualized adjuvant treatments after curative gastrectomy.


Severe obscure gastrointestinal bleeding successfully treated with idarucizumab.
Idarucizumab is a monoclonal antibody that rapidly reverses the anticoagulant effect of dabigatran. The experience with this drug in the setting of gastrointestinal bleeding is scarce. We present the case of an 84-year-old male with known history of non-valvular atrial fibrillation anticoagulated with dabigatran who presented to the emergency room with melena. During his stay in the emergency department he suddenly worsened with hemodynamic derangement and massive melena so idarucizumab was administered. Gastroscopy and colonoscopy were performed without identifying a bleeding source. After the administration of idarucizumab, the patient did not presented signs of ongoing bleeding. Anticoagulation was resumed on the sixth day and no rebleeding or thromboembolic events have been recorded after six months of follow-up. This case and the limited information available in the literature suggest that idarucizumab can be useful and safe in cases of severe gastrointestinal bleeding with recent intake of dabigatran.


Crystal and molecular structure of 4,6-bis(nitroimino)-1,3,5-triazinan-2-one: theoretical and X-ray studies.
This paper provides an overview of recent progress on structural data on the title compound. Theoretical work based on quantum mechanical calculations was performed to gain some understanding on the heterocyclic tautomerism potentially exhibited by the compound. The computational studies encompassed a wide range of tautomers/conformers, allowing the determination of the most probable molecular structure. In the gas phase, the nitroimine tautomers are computed to be substantially more stable than the nitramine tautomers. Among three plausible nitroimine forms, special attention was given to 4,6-bis(nitroimino)-1,3,5-triazinan-2-one, whose crystal structure was unequivocally solved by X-ray diffraction. The crystals are orthorhombic, space group Pnma with a = 6.187(2)A, b = 13.252(5)A, c = 8.802(4)A, and Z = 4. The structure was solved by direct methods and refined to a final R = 0.0326. The molecule has an approximate mirror plane relating the two symmetry related halves. The nitroimine groups are positioned in a syn-syn conformation. The least-squares (LS) plane of the heterocyclic ring and the nitroimine ([double bond]N-NO2) substituent LS plane make an angle of 10.05(11) degrees. The crystal structure is held together via hydrogen bonds that assemble the molecules in chains running along the b-axis. Every H-atom is involved in bifurcated hydrogen bonds.


Variability in mineral and trace element content of dairy cattle feeds.
Trace element content of feeds is extremely variable compared to total digestible nutrients or protein. Differences are wide between low and high values for many trace elements within a given type of feed. Coefficients of variation for forages range from 42 to 100%. Summary data are given for both major and trace elements. Problems in supplementation are discussed. Amounts for some elements are skewed with relatively few samples around the mean and over 60% below the mean. Suggested mineral allowances for dairy cows are listed. Under current supplementation, zinc is the trace element most likely to be limiting and manganese the least likely. Iron, copper, cobalt, and iodine may be limiting in some cases. Needs of research and applied nutrition are presented.


A net water production model for ultrafiltration including flow direction reversal and chemically assisted backwashing.
Flow direction reversal (FDR) was proposed as a novel method to increase net water production (NWP) during cross-flow ultrafiltration. The design of the pilot-plant study allowed measurement of specific flux recovery after each chemically assisted backwash (BW) combined with FDR and after each FDR at the midpoint of each BW/FDR cycle. The percent recovery of specific flux was higher following FDR (55%) than combined BW and FDR (53%) at lower chemical dosages; however, the percent increase in specific flux recovery by FDR was much lower (20%) when the chemical dose was doubled. A mathematical model was developed to predict the NWP achieved by any combination ofBW/ FDR and FDR frequency. For example, the advantage of introducing FDR was demonstrated at the lower chlorine dose, whereby the percent increase in NWP by alternating 15-minute intervals of BW/FDR with FDR over BW/ FDR alone was 10% for 30-minute BW/FDR intervals and 2% for 15-minute BW/FDR intervals.


An update on adjunctive treatment options for bipolar disorder.
Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes. Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature. A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery. Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder.


Comparative transcription analysis of different Antirrhinum phyllotaxy nodes identifies major signal networks involved in vegetative-reproductive transition.
Vegetative-reproductive phase change is an indispensable event which guarantees several aspects of successful meristem behaviour and organ development. Antirrhinum majus undergoes drastic changes of shoot architecture during the phase change, including phyllotactic change and leaf type alteration from opposite decussate to spiral. However, the regulation mechanism in both of phyllotactic morphology changes is still unclear. Here, the Solexa/Illumina RNA-seq high-throughput sequencing was used to evaluate the global changes of transcriptome levels among four node regions during phyllotactic development. More than 86,315,782 high quality reads were sequenced and assembled into 58,509 unigenes. These differentially expressed genes (DEGs) were classified into 118 pathways described in the KEGG database. Based on the heat-map analysis, a large number of DEGs were overwhelmingly distributed in the hormone signal pathway as well as the carbohydrate biosynthesis and metabolism. The quantitative real time (qRT)-PCR results indicated that most of DEGs were highly up-regulated in the swapping regions of phyllotactic morphology. Moreover, transcriptions factors (TFs) with high transcripts were also identified, controlling the phyllotactic morphology by the regulation of hormone and sugar-metabolism signal pathways. A number of DEGs did not align with any databases and might be novel genes involved in the phyllotactic development. These genes will serve as an invaluable genetic resource for understanding the molecular mechanism of the phyllotactic development.


Changing concepts in skeletal physiology: Wolff's Law, the Mechanostat, and the "Utah Paradigm".
According to the Utah paradigm of skeletal physiology: (1) mechanical forces on skeletons generate signals in skeletal organs that control the biologic mechanisms that determine the architecture and strength of those organs, (2) these occur in ways that let the organs endure their voluntary mechanical usage for life without hurting or breaking, (3) to work properly, these mechanisms need nonmechanical factors (hormones, vitamins, calcium, genes, cytokines, etc.), (4) only mechanical factors can guide those mechanisms in time and anatomical space, (5) this arrangement determines skeletal health and disorders can cause or help to cause numerous disorders of skeletal and extraskeletal organs (the collagenous tissue in ligaments and tendons also forms a part of extraskeletal organs). Accumulated evidence now strongly supports these features of the Utah paradigm, which supplements a 1960 paradigm. It incites reassessment of some former ideas about skeletal physiology and disease. Some controversies ensue that will take time to resolve. After they are resolved, skeletal science, medicine, and surgery should be significantly better than before and different in unforeseeable respects as well. Am. J. Hum. Biol. 10:599-605, 1998. © 1998 Wiley-Liss, Inc.


Surgical treatment of vasculo-Behçet's disease. A review of patients with concomitant multiple aneurysms and venous lesions.
Vascular complications can be seen in patients with Behçet's disease. Arterial and venous complications may be found separately or concomitantly in patients. Out of 29 patients with vasculo-Behçet's disease 7 patients with multiple aneurysms and venous lesions were documented over a period of 20 years. All patients were male, ranging in age from 24 to 52 years. The mean duration of the disease was 6 +/- 2 years. The aneurysms were found in the following locations: one pulmonary artery, two abdominal aorta, four iliac, five femoral, and two popliteal artery. Both aneurysmal and occlusive lesions were present in three patients. In the venous lesions associated with the aneurysms there were three deep and three superficial venous thrombosis. Two patients had caval involvement-superior and inferior vena caval syndromes. We performed seven interposition grafting by polytetrafloroethylene, one Y-grafting, one aneurysmorrhaphy, one lobectomy. Re-anastomosis was performed in two patients who had anastomotic aneurysms and graft occlusion without disabling ischemia. Venous pathologies were treated by medical therapy. The patients were followed up between 1 to 8 years. One of the patients with iliac artery aneurysm died due to gastrointestinal bleeding 15 months after the operation. In conclusion, when an aneurysm has been found in a patient with Behçet's disease, the patient should be scanned for possible multiple aneurysms and venous lesions since they might be found together. Surgical treatment, when feasible, should be performed in cases with Behçet aneurysms because of a high risk of rupture. However, the possibility of an anastomotic aneurysm developing after surgery should also be kept in mind.


Late presentation of haemorrhagic disease of the newborn.
A 9 week old infant presented with bleeding due to vitamin K deficiency. He had not been given vitamin K after birth but there was no associated risk factor for deficiency and he had not bled from circumcision performed at 8 days of age.


Stimulant-induced enhanced sexual desire as a potential contributing factor in HIV transmission.
Stimulant abuse is associated with an increased risk of contracting human immunodeficiency virus (HIV). Although sharing of contaminated needles is one of the routes by which HIV is spread, noninjection abusers are also at high risk. The authors investigated the effect of the stimulant drug methylphenidate (given intravenously) on sexual desire as a possible contributing factor to risky sexual behavior associated with the contraction of HIV. The effects of intravenous methylphenidate (0.5 mg/kg) on self-reports of sexual desire (rated from 0-10) were evaluated in 39 comparison subjects and 39 cocaine abusers. Intravenous methylphenidate significantly increased self-reports of sexual desire in comparison subjects (1.4 versus 3.7) and cocaine abusers (2.8 versus 4.8). Stimulant-induced enhancement of sexual desire could be one mechanism by which stimulant drugs such as cocaine and methamphetamine increase the risk for HIV transmission even when they are not injected.


Differential attraction of Heliothis subflexa males to synthetic pheromone lures in Eastern US and Western Mexico.
The mate attraction signal of Heliothis subflexa (Hs) females consists of a multicomponent sex pheromone blend. In this study, we assessed the intraspecific importance of three groups of compounds found in Hs pheromone glands: three acetate esters (Z7-16:OAc, Z9-16:OAc, and Z11-16:OAc), two 14-carbon aldehydes (14:Ald and Z9-14:Ald), and one 16-carbon alcohol (Z11-16:OH). Because the relative importance of pheromone components may vary in different regions, we conducted experiments in Eastern US (North Carolina) and Western Mexico (Jalisco). Our experiments in Eastern US showed that when the acetates were omitted from a 7-component blend in rubber septa, fewer males were caught in cone traps. Subsequent experiments conducted both in Eastern US and Western Mexico indicated that the addition of Z9-16:OAc alone does not increase attraction of male Hs, while Z11-16:OAc does. The Hs male response to Z7-16:OAc differed between the two regions. In Eastern US, significantly more males were attracted to a minimal three-component blend to which Z7-16:OAc was added, but this was not the case in Western Mexico. The two 14-carbon aldehydes also showed differential attraction between the two regions. 14:Ald and Z9-14:Ald appeared not to play any role in the sexual communication of Hs in Eastern US, but reduced trap catches in Western Mexico. The alcohol Z11-16:OH was tested in two concurrent dose-response studies with Hs males in Western Mexico, one using a minimal blend and one using a complete blend. The minimal three-component blend provided a more discriminating tool for delineating dose-response effects of Z11-16:OH than the seven-component blend. In the minimal blend, the optimal dose of Z11-16:OH was 1%, while in the complete blend similar numbers of males were caught when the alcohol ranged from 1 to 25%.


In vivo detection of hESC-RPE cells via confocal near-infrared fundus reflectance.
To investigate whether the confocal near-infrared reflectance (NIR) imaging modality could detect the in vivo presence of retinal pigment epithelium cells derived from embryonic human stem cells (hESC-RPE) implanted into the subretinal space of the Royal College of Surgeons (RCS) rat. Monthly NIR images were obtained from RCS rats implanted with either hESC-RPE seeded on a parylene membrane (n = 14) or parylene membrane without cells (n = 14). Two independent, masked investigators graded the images. Histology and immunohistochemistry were performed at different time points (150, 210, and 270 postnatal days of age). NIR images revealed that an average of 20.53% of the parylene membrane area was covered by hESC-RPE. RPE-65 and TRA-1-85 confirmed the presence of human-specific RPE cells in those animals. No areas corresponding to cells were found in the group implanted with membrane only. Intergrader agreement was high (r = 0.89-0.92). The NIR mode was suitable to detect the presence of hESC-RPE seeded on a membrane and implanted into the subretinal space of the RCS rat.


Sensitization as a mechanism for multiple chemical sensitivity: relationship to evolutionary theory.
Multiple chemical sensitivity (MCS) is a disorder in humans attributed to prior chemical exposure. Sensitization is an amplification of neuronal responsiveness that elicits increased behavioral responding to stimuli, and occurs in a recently developed rat model of MCS. Rats were exposed to repeated formaldehyde (Form) and their response in three behavioral tests, including locomotor activity after a cocaine challenge, conditioned fear, and behavioral avoidance of Form, was assessed. In all three tests, rats demonstrated sensitized behaviors, implicating amplified responding within specific limbic brain regions. Evolutionary theory in the context of MCS specifies how the behavioral strategies of those with MCS are consistent with the notion that their self-perceived sense of survival and reproductive fitness may be threatened by chemical exposures. This behavior may be mediated by the same limbic brain regions that become sensitized after repeated chemical exposure in animals.


The efficacy of a semirigid ankle stabilizer to reduce acute ankle injuries in basketball. A randomized clinical study at West Point.
This randomized clinical study was designed to prospectively determine the efficacy of a semirigid ankle stabilizer in reducing the frequency and severity of acute ankle injuries in basketball. Athletic shoe, playing surface, athlete-exposure, ankle injury history, and brace assignment were either statistically or experimentally controlled. Participants in the study were 1601 United States Military Academy cadets with no preparticipation, clinical, functional, or radiographic evidence of ankle instability. Subjects experienced a total of 13,430 athlete-exposures in the 1990 and 1991 intramural basketball seasons. Ankle injury was defined as acute trauma to the ankle ligaments that resulted in an athlete's inability to participate in basketball 1 day after the injury. Use of ankle stabilizers significantly reduced the frequency of ankle injuries. Reduction in ankle injuries, however, depended on the nature of injury (fewer contact injuries occurred among those who wore braces). Injury severity was not statistically reduced, and wearing the ankle stabilizer did not affect the frequency of knee injuries. Attitude toward ankle stabilizer use improved as use of the stabilizer increased.


[Isolation and purification of specific proteins, forming during endometrium differentiation into decidual tissue].
Using analytical PAAG-electrophoresis two specific proteins, D1 and D2, were found in decidual tissue of pregnant women (6-12 weeks). These proteins were isolated and purified by means of ammonium sulfate saturation, chromatography on Sepharose 6B and ion exchange chromatography on DEAE 52 cellulose. The degree of purification of both D1 and D2 proteins was 100% and 81%, respectively. The both proteins were free of DNA, RNA and polysaccharides. The pI values of D1 and D2 proteins were at pH 5.6-6.0. According to gel electrophoresis on PAA-SDS-Na and gel filtration on Sepharose 6B, molecular weight of D1 protein was about 50,000-55,000 and of D2 protein--150,000-160,000 and 300,000-320,000, respectively. The specific decidual proteins D1 and D2 appear to be distinct from the so-called "pregnancy proteins" described previously.


Triboelectric Nanogenerators Based on Fluid Medium: From Fundamental Mechanisms toward Multifunctional Applications.
Fluid-based triboelectric nanogenerators (FB-TENGs) are at the forefront of promising energy technologies, demonstrating the ability to generate electricity through the dynamic interaction between two dissimilar materials, wherein at least one is a fluidic medium (such as gas or liquid). By capitalizing on the dynamic and continuous properties of fluids and their interface interactions, FB-TENGs exhibit a larger effective contact area and a longer-lasting triboelectric effect in comparison to their solid-based counterparts, thereby affording longer-term energy harvesting and higher-precision self-powered sensors in harsh conditions. In this review, various fluid-based mechanical energy harvesters, including liquid-solid, gas-solid, liquid-liquid, and gas-liquid TENGs, have been systematically summarized. Their working mechanism, optimization strategies, respective advantages and applications, theoretical and simulation analysis, as well as the existing challenges, have also been comprehensively discussed, which provide prospective directions for device design and mechanism understanding of FB-TENGs.


Haemoglobin synthesis by fetal erythroid cells in an adult environment.
Although the developmental switch from fetal to adult haemoglobin production has been well characterized in terms of protein synthesis, very little is known about its control at the cellular level. In order to determine whether the switch is controlled by environmental factors or programmed into the haemopoietic cell population, we have studied the effects of transplantation of fetal and adult haemopoietic cells into lethally irradiated lambs on haemoglobin synthesis by the transplanted cells. In two lambs which were irradiated but not transplanted, two lambs which were grafted with autologous marrow, and one lamb which was grafted from an allogenic twin, haemoglobin synthesis showed an adult pattern following transplantation, with gamma-chain synthesis never exceeding 7% of non-alpha chain production. Of 11 lambs transplanted with fetal haemopoietic cells, only two showed evidence of engraftment. During the 24-26 d that these animals survived, haemoglobin synthesis showed a predominantly fetal pattern, though there was a gradual increase in beta-chain production of donor origin. This increase occurred earlier than would be expected from the gestational age of the transplanted cells, but more slowly than might be expected if environmental factors were entirely responsible for expression of adult or fetal haemoglobin synthesis.


Purification and characterization of two alpha-keto ester reductases from Streptomyces thermocyaneoviolaceus IFO 14271.
Two NADPH-dependent alpha-keto ester reductases (Streptomyces thermocyaneoviolaceus keto ester reductase, STKER-II and -III) were purified from S. thermocyaneoviolaceus IFO 14271, one of thermophilic actinomycetes. The molecular masses of native STKER-II and -III were estimated to be 60 kDa and 70 kDa by gel filtration chromatography, respectively. These enzymes were both homodimers, with 29-kDa and 30-kDa subunit molecular masses based on SDS polyacrylamide gel electrophoresis. STKER-II and -III were stable from pH 7.0 to 10.0 and pH 5.5 to 9.0, respectively. Ethyl 3-methyl-2-oxobutanoate was reduced by both enzymes isolated to the corresponding (R)-hydroxy ester with excellent enantiomeric excess. STKER-III showed high stereoselectivity for the reduction of bulky substrates, while the selectivity of the STKER-II-catalyzed reduction was low except for ethyl 3-methyl-2-hydrox-ybutanoate. Both enzymes had small Km values toward aliphatic keto esters having a long alkyl chain.


Regulation of the NMDA receptor: implications for neuropsychological development.
Recent work has shown that zinc is involved in the developmental regulation of neurotrophins and N-methyl-D-aspartate (NMDA) receptors, controlling use of glutamate as a neurotransmitter in the central nervous system (CNS). This is particularly important in the hippocampus, a region of the brain involved in learning and memory, and is an intriguing link to the role of zinc in neuropsychological development.


Incantations in the dark: Medicaid, managed care, and maternity care.
Public program reforms in the 1980s have substantially increased the numbers of poor pregnant women potentially eligible for Medicaid coverage. Structural deficiencies in the Medicaid program, together with inadequate arrangements in managed-care plans, however, have not led to generally acceptable levels of maternity care. Demonstration projects indicate that Medicaid can be modified cost effectively to underwrite early, continuous, and comprehensive care delivery. Recommendations are suggested for eligibility guarantees, enrollment safeguards, benefit and treatment protocols, provider recruitment, quality control, and sufficient payment rates to overcome barriers to adequate levels of material health care.


Analysis of all-optical temporal integrator employing phased-shifted DFB-SOA.
All-optical temporal integrator using phase-shifted distributed-feedback semiconductor optical amplifier (DFB-SOA) is investigated. The influences of system parameters on its energy transmittance and integration error are explored in detail. The numerical analysis shows that, enhanced energy transmittance and integration time window can be simultaneously achieved by increased injected current in the vicinity of lasing threshold. We find that the range of input pulse-width with lower integration error is highly sensitive to the injected optical power, due to gain saturation and induced detuning deviation mechanism. The initial frequency detuning should also be carefully chosen to suppress the integration deviation with ideal waveform output.


Four buildings and a flush: Lessons from degraded water quality and recommendations on building water management.
A reduction in building occupancy can lead to stagnant water in plumbing, and the potential consequences for water quality have gained increasing attention. To investigate this, a study was conducted during the COVID-19 pandemic, focusing on water quality in four institutional buildings. Two of these buildings were old (>58 years) and large (>19,000 m2), while the other two were new (>13 years) and small (<11,000 m2). The study revealed significant decreases in water usage in the small buildings, whereas usage remained unchanged in the large buildings. Initial analysis found that residual chlorine was rarely detectable in cold/drinking water samples. Furthermore, the pH, dissolved oxygen, total organic carbon, and total cell count levels in the first draw of cold water samples were similar across all buildings. However, the ranges of heavy metal concentrations in large buildings were greater than observed in small buildings. Copper (Cu), lead (Pb), and manganese (Mn) sporadically exceeded drinking water limits at cold water fixtures, with maximum concentrations of 2.7 mg Cu L-1, 45.4 μg Pb L-1, 1.9 mg Mn L-1. Flushing the plumbing for 5 min resulted in detectable residual at fixtures in three buildings, but even after 125 min of flushing in largest and oldest building, no residual chlorine was detected at the fixture closest to the building's point of entry. During the pandemic, the building owner conducted fixture flushing, where one to a few fixtures were operated per visit in buildings with hundreds of fixtures and multiple floors. However, further research is needed to understand the fundamental processes that control faucet water quality from the service line to the faucet. In the absence of this knowledge, building owners should create and use as-built drawings to develop flushing plans and conduct periodic water testing.


The life-saving emergency thoracic endovascular aorta repair management on suspected aortoesophageal foreign body injury.
Fatal aortic rupture caused by esophageal foreign body (EFB), is associated with a high mortality, but can be prevented by thoracic endovascular aorta repair (TEVAR) that performed increasingly as technology improves. This study aims to investigate the cause, management and prognosis of suspected penetrating aortoesophageal foreign body injury. Twelve cases who met the criteria were enrolled in this study. The demographic and clinical data were reviewed for evaluating the characteristics of EFB. Among 12 cases enrolled, 7 were males and 5 were females, with an age 27-86 years. The distance of EFB from aorta (DFA) of 7 cases were less than or equal to 0 mm, 5 cases were 0-2 mm. Eleven cases were managed with TEVAR, only one case was with open surgery standby but finally treated by flexible endoscopy (FE) successfully, without TEVAR. In group with TEVAR, EFB of 7 cases were successfully removed by rigid endoscopy (RE), and one of them was failed at the first RE treatment. EFB of 2 cases were successfully removed by open surgery with TEVAR, and other 9 cases were managed by endoscopies with TEVAR. The mean length of stay of hospitalization (LOS) and length of ICU stay of patients treated by open surgery with TEVAR (18.50±2.12 days and 5.50±0.71 days) was significantly longer than those of patients treated by endoscopy with TEVAR (7.00±2.74 days and 1.33±1.12 days, P<0.001 and P=0.001, respectively). Five cases had severe complications. Rational application of TEVAR can be a life-saving management for aortoesophageal foreign body injury, and jointed with endoscopy is safe and effective with a shorter length of ICU or total hospital stay.


Development of Personalized Signature Based on the Immune Landscape to Predict the Prognosis of Osteosarcoma and the Response to Immunotherapy and Targeted Therapy.
As a heterogeneous and aggressive disease, osteosarcoma (OS) faces great challenges to prognosis and individualized treatment. Hence, we explore the role of immune-related genes in predicting prognosis and responsiveness to immunotherapy and targeted therapies in patients with OS based on the immunological landscape of osteosarcoma. Based on the database of the Therapeutical Applicable Research to Generate Effective Treatments (TARGET), single-sample gene set enrichment analysis (ssGSEA) was used to obtain the enrichment scores of 29 immune characteristics. A series of bioinformatics methods were performed to construct the immune-related prognostic signature (IRPS). Gene set enrichment analysis and gene set variation analysis were used to explore the biological functions of IRPS. We also analyzed the relationship between IRPS and tumor microenvironment. Lastly, the reactivity of IRPS to immune checkpoint therapy and targeted drugs was explored. The ssGSEA algorithm was used to define two immune subtypes, namely Immunity_High and Immunity_Low. Immunity_High was associated with a good prognosis and was an independent prognostic factor of OS. The IRPS containing 7 genes was constructed by the least absolute shrinkage and selection operator Cox regression. The IRPS can divide patients into low- and high-risk patients. Compared with high-risk patients, low-risk patients had a better prognosis and were positively correlated with immune cell infiltration and immune function. Low-risk patients benefited more from immunotherapy, and the sensitivity of targeted drugs in high- and low-risk groups was determined. IRPS can be used to predict the prognosis of OS patients, and provide therapeutic responsiveness to immunotherapy and targeted therapy.


Early stage of development in testicular choriocarcinomas.
Choriocarcinoma is the most malignant among germ cell tumors in the testis. However little is known about the early stage of its development. To understand the development of testicular choriocarcinomas, twenty cases of testicular choriocarcinoma were studied histologically and immunohistochemically. It was found that in the early stage of development, choriocarcinomas imitate the morphologic or functional differentiation of normal trophoblasts. It was also found that some choriocarcinomas regress spontaneously in the early stage. The majority of choriocarcinomas seemed to develop by first going through the embryonal carcinoma phase. However, there were some choriocarcinomas that showed no relationship with embryonal carcinoma.


[Late results of total colectomies for inflammatory colitis].
A retrospective study of 41 patients colectomized for inflammatory colitis has been conducted with a mean follow-up of 90 months. The results of rectum preservation and of ileo-rectal anastomoses were disappointing, with a respective success rate of 15% and 44%. 15% of patients had a change of diagnosis after colectomy, all in favour of undetected Crohn's disease. The results of mucosal proctectomy with ileoanal anastomosis are highly encouraging. An attempt is made to specify the indications for each type of surgery.