Serine activation is the rate limiting step of tRNASer aminoacylation by yeast seryl tRNA synthetase.
Using the quenched flow technique the mechanism of seryl tRNA synthetase action has been investigated with respect to the presteady state kinetics of individual steps. Under conditions where the strong binding sites of the enzyme are nearly saturated and the steady state turnover number is about 1 s-1, rate constants of four different processes have been determined: steps connected with substrate associations are relatively slow (12 s-1 for the entire process); activation of serine is the rate determining step (about 1.2 s-1 in presence of tRNASer); whereas the transfer of serine onto tRNASer (35 s-1) and the dissociation of seryl tRNASer (70 s-1) are fast. Similar kinetic parameter seem to hold also for the steady state reactions. This conclusion is based on a detailed study of the substrate, product, and Mg2+ concentration dependence of the transfer reaction. The results also indicate that a second serine binding site is operative. Since the transfer of serine from a preformed adenylate complex onto tRNASer is fast, seryl adenylate seems to be a kinetically competent intermediate of the aminoacylation reaction although, of course, alternative mechanisms cannot be excluded.


Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein Sex comb on midleg.
Sex comb on midleg (Scm) is a member of the Polycomb group of proteins involved in the maintenance of repression of Hox and other developmental control genes in Drosophila. The two malignant brain tumour (MBT) repeats of Scm form a domain that preferentially binds to monomethylated lysine residues either as a free amino acid or in the context of peptides, while unmodified or di- or trimethylated lysine residues are bound with significantly lower affinity. The crystal structure of a monomethyl-lysine-containing histone tail peptide bound to the MBT repeat domain shows that the methyl-lysine side chain occupies a binding pocket in the second MBT repeat formed by three conserved aromatic residues and one aspartate. Insertion of the monomethylated side chain into this pocket seems to be the main contributor to the binding affinity. Functional analyses in Drosophila show that the MBT domain of Scm and its methyl-lysine-binding activity are required for repression of Hox genes.


Chronic urticaria treated with soft nasal filters.
A 22-year-old boy having two attacks of urticaria per day for the last 5 years and intermittent attacks of sneezing and rhinorrhoea, and without any clues to the causative agent in spite of a detailed history and follow up, showed almost complete relief on wearing an ordinary cloth mask for 3 days. He was subsequently trained to use the soft nasal filters and obtained almost 80% relief in urticaria and complete relief in rhinitis during the next 1 year. Wearing the mask for 2 days again led to complete relief and further training in the proper use of the filters was helpful.


Experimental evaluation of conversion factors for the [h]thymidine incorporation assay of bacterial secondary productivity.
The relationship between bacterial growth and incorporation of [methyl-H]thymidine in oligotrophic lake water cultures was investigated. Prescreening, dilution, and addition of organic and inorganic nutrients were treatments used to prevent bacterivory and stimulate bacterial growth. Growth in unmanipulated samples was estimated through separate measurements of grazing losses. Both bacterial number and biovolume growth responses were measured, and incorporation of [H]thymidine in both total macromolecules and nucleic acids was assayed. The treatments had significant effects on conversion factors used to relate thymidine incorporation to bacterial growth. Cell number-based factors ranged from 1.1 x 10 to 38 x 10 cells mol of total thymidine incorporation and varied with treatment up to 10-fold for the same initial bacterial assemblage. In contrast, cell biovolume-based conversion factors were similar for two treatment groups across a 16-fold range of [H]thymidine incorporation rates: 5.54 x 10 mum mol of total thymidine incorporation and 15.2 x 10 mum mol of nucleic acid incorporation. Much of the variation in cell number-based conversion factors was related to changes in apparent mean cell volume of produced bacteria. Phosphorus addition stimulated [H]thymidine incorporation more than it increased bacterial growth, which resulted in low conversion factors.


Intramedullary spinal epidermoid associated with an intramedullary lipoma.
True intramedullary epidermoids and true intramedullary lipomas of the spinal cord are very rare lesions. To our knowledge, there has been no reported case associated with an intramedullary spinal lipoma. This is the first reported case with the association of these two lesions. In this report a 3-year-old boy with intramedullary spinal lipoma is presented. We discuss the frequency, clinical features, MRI characteristics and limits of surgical treatment of these tumors and review the associated literature.


Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: findings from a linked-data study.
In spite of the mounting interest in the nexus between erectile dysfunction (ED) and cardiovascular (CV) diseases, there is little published information on the role of ED as a predictor for subsequent CV events. This study aimed to investigate the role of ED as a predictor for atherosclerotic CV events subsequent to the manifestation of ED. Method. The investigation involved the retrospective study of data on a cohort of men with ED linked to hospital morbidity data and death registrations. By using the linked data, the incidence rates of atherosclerotic CV events subsequent to the manifestation of ED were estimated in men with ED and no atherosclerotic CV disease reported prior to the manifestation of ED. The risk of subsequent atherosclerotic CV events in men with ED was assessed by comparing these incidence rates with those in the general male population. Standardized incidence rate ratio (SIRR), comparing the incidence of atherosclerotic CV events subsequent to the manifestation of ED in a cohort of 1,660 men with ED to the incidence in the general male population. On the basis of hospital admissions and death registrations, men with ED had a statistically significantly higher incidence of atherosclerotic CV events (SIRR 2.2; 95% confidence interval 1.9, 2.4). There were significantly increased incidence rate ratios in all age groups younger than 70 years, with a statistically highly significant downward trend with increase of age (P < 0.0001) across these age groups. Younger age at first manifestation of ED, cigarette smoking, presence of comorbidities and socioeconomic disadvantage were all associated with higher hazard ratios for subsequent atherosclerotic CV events. The findings show that ED is not only significantly associated with but is also strongly predictive of subsequent atherosclerotic CV events. This is even more striking when ED presents at a younger age.


Out of the blue: A new rain frog species of the genus Pristimantis (Anura: Craugastoridae) from the northern Cordillera Central in Colombia.
Continuous sampling in well studied areas may lead to new amphibian species discoveries, because population dynamics allow rare species to go unnoticed for years. Based on recent sampling of frogs in the northeastern region of Colombia, here we provide genetic, morphological, and bioacoustics evidence to support the description of a new species of the genus Pristimantis. Phylogenetic analysis suggests the new species is a member of the P. lacrimosus species group, a clade of 25 species that is highly diverse in Ecuador and Peru. This new species is more closely related to allopatric species from Peru and Guyana (i.e. P. olivaceus, P. pluvialis, P. pulchridormientes, and an undetermined Pristimantis). The new species has green-yellow coloration and a remarkable brown interocular band, which is unusual in the genus and which inspired the epithet. Pristimantis zorro sp. nov. has only been found at one locality at 1860 m s.a.l., on the eastern flank of the northern Cordillera Central in Department of Antioquia, Colombia. The new species inhabits the ecotone between the humid cloud forest and open areas. Repeated visits to the type locality suggest high variation in population abundance and/or species detection, because we have occasionally observed many individuals in briefs periods of times. In addition, we discuss the biogeographical and systematic implications of our species discovery.


Methods for imaging thick specimens: confocal microscopy, deconvolution, and structured illumination.
When a thick specimen is viewed through a conventional microscope, one sees the sum of a sharp image of an in-focus region plus blurred images of all of the out-of-focus regions. High background, scattering, and aberrations are all problems when viewing thick specimens. Several methods are available to deal with these problems in living samples. These methods can be grouped into three classes: primarily optical (e.g., confocal microscopy, multiphoton microscopy), primarily computational (e.g., deconvolution techniques), and mixed (e.g., structured illumination) approaches. This article describes these techniques, which make it possible to see details within thick specimens (e.g., the interiors of cells within living tissue) by optical sectioning, without the artifacts associated with physically sectioning the specimen.


Method for Assessing Heterogeneity in Turnover Rates within Microbial Communities.
A method is presented for determining both the average turnover rate and the standard deviation of the average turnover rate of the adenine nucleotide (AN) pool within a population of microorganisms. The method requires the calculation of the initial slope and curvature of a plot of AN specific activity versus time following the introduction of [H]adenine. An analysis of noise-corrupted data indicated that the method is capable of detecting a lack of uniformity in the turnover rate when the coefficient of variation of the turnover rate exceeds 39%. An analysis of field data revealed a significant lack of uniformity in the turnover rates of microbial communities in a marine sediment sample and freshwater pond but no significant nonuniformity in the turnover rates of microbial communities in a seawater sample and in a second freshwater pond. Although the method has been applied only to the analysis of AN turnover rates, it is applicable to any intracellular pool for which a suitable radioactive precursor exists.


Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non-small cell lung cancer patients with asymptomatic brain metastases.
The study was designed to investigate the safety of ramucirumab administered in combination with erlotinib or osimertinib for patients with untreated EGFR-mutated non-small cell lung cancer (NSCLC) and asymptomatic brain metastases, a patient subgroup in which these regimens have remained untested. This phase 1b study (RELAY-Brain) consisted of two cohorts with three patients each. Patients with asymptomatic brain metastases received ramucirumab every 2 weeks plus either daily oral erlotinib or osimertinib until disease progression or intolerable toxicity. The primary objective was to assess dose-limiting toxicity (DLT), defined as central nervous system (CNS) hemorrhage of grade ≥ 2. Six patients were enrolled. Neither DLT nor serious or unexpected adverse events were observed. One treatment-related adverse event of grade ≥ 3 (hypertension of grade 3) was apparent. Common adverse events were generally manageable. The median number of ramucirumab administrations was 18.5 (range, 13 to 31), and there were no detected episodes of CNS hemorrhage. Five of the six patients showed an objective systemic response. Although only one patient had a measurable CNS lesion at baseline, a confirmed intracranial partial response was observed. Ramucirumab in combination with erlotinib or osimertinib showed safety for EGFR-mutated NSCLC with brain metastases.


Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells.
Cytotoxic T-lymphocyte-mediated tumor immunity against major histocompatibility antigen class II-negative tumors requires help from CD4(+) T-cells. The major antigen presenting cells for CD4(+) cell activation are dendritic cells. Studies in mice and humans have demonstrated the potent capacity of these cells to induce specific antitumor immunity. To control the growth of a metastasized parathyroid carcinoma, by immunizing a patient with tumor lysate and parathyroid hormone-pulsed dendritic cells. Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. Antigen-loaded dendritic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLH) as a CD4(+) helper antigen. After 10 vaccinations, a specific cellular immune response to tumor lysate was observed. In vitro T-cell proliferation assays revealed a dose-dependent stimulation index of 1.8-5.7 compared with 0.9-1.1 before vaccination. In vivo immune response was demonstrated by positive delayed-type hypersensitivity toward tumor lysate. Intradermal injection of tumor lysate resulted in an erythema and induration, suggesting the efficient generation of tumor lysate-specific memory T-cells. These data indicate that dendritic cell vaccination can induce in vitro and in vivo responses in a highly malignant endocrine carcinoma. Regardless of the clinical outcome of our patient, this approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.


CSF Neurofilament Light Chain but not FLT3 Ligand Discriminates Parkinsonian Disorders.
The differentiation between multiple system atrophy (MSA) and Parkinson's disease (PD) is difficult, particularly in early disease stages. Therefore, we aimed to evaluate the diagnostic value of neurofilament light chain (NFL), fms-like tyrosine kinase ligand (FLT3L), and total tau protein (t-tau) in cerebrospinal fluid (CSF) as biomarkers to discriminate MSA from PD. Using commercially available enzyme-linked immunosorbent assays, we measured CSF levels of NFL, FLT3L, and t-tau in a discovery cohort of 36 PD patients, 27 MSA patients, and 57 non-neurological controls and in a validation cohort of 32 PD patients, 25 MSA patients, 15 PSP patients, 5 CBS patients, and 56 non-neurological controls. Cut-offs obtained from individual assays and binary logistic regression models developed from combinations of biomarkers were assessed. CSF levels of NFL were substantially increased in MSA and discriminated between MSA and PD with a sensitivity of 74% and specificity of 92% (AUC = 0.85) in the discovery cohort and with 80% sensitivity and 97% specificity (AUC = 0.94) in the validation cohort. FLT3L levels in CSF were significantly lower in both PD and MSA compared to controls in the discovery cohort, but not in the validation cohort. t-tau levels were significantly higher in MSA than PD and controls. Addition of either FLT3L or t-tau to NFL did not improve discrimination of PD from MSA above NFL alone. Our findings show that increased levels of NFL in CSF offer clinically relevant, high accuracy discrimination between PD and MSA.


Arthroscopic debridement of the posterior compartment of the knee after total knee arthroplasty.
Arthroscopic debridement of the posterior compartment of the knee after total knee arthroplasty is difficult because it is tough to obtain intercondylar notch views. Herein, we performed arthroscopic debridement of the posterior compartment of an infected knee after total knee arthroplasty by using a transseptal portal in a 62-year-old woman with rheumatoid arthritis. Palpation of anatomical landmarks and posterior capsule protection are important for safe creation of a transseptal portal following to making 2 posterior portals.


Identification of Metabolite Interference Is Necessary for Accurate LC-MS Targeted Metabolomics Analysis.
Targeted metabolomics has been broadly used for metabolite measurement due to its good quantitative linearity and simple metabolite annotation workflow. However, metabolite interference, the phenomenon where one metabolite generates a peak in another metabolite's MRM setting (Q1/Q3) with a close retention time (RT), may lead to inaccurate metabolite annotation and quantification. Besides isomeric metabolites having the same precursor and product ions that may interfere with each other, we found other metabolite interferences as the result of inadequate mass resolution of triple-quadruple mass spectrometry and in-source fragmentation of metabolite ions. Characterizing the targeted metabolomics data using 334 metabolite standards revealed that about 75% of the metabolites generated measurable signals in at least one other metabolite's MRM setting. Different chromatography techniques can resolve 65-85% of these interfering signals among standards. Metabolite interference analysis combined with the manual inspection of cell lysate and serum data suggested that about 10% out of ∼180 annotated metabolites were mis-annotated or mis-quantified. These results highlight that a thorough investigation of metabolite interference is necessary for accurate metabolite measurement in targeted metabolomics.


Attention to overlapping objects: detection and discrimination of luminance changes.
Selective attention to 1 of 2 overlapping objects was assessed in a cuing paradigm. Participants detected or identified targets that appeared in 1 of 6 possible target locations (3 on each object). Significant cuing effects for the simple detection of such targets using both reaction time and sensitivity measures of performance were found. Cuing effects were consistently greater when the participants were required to identify some aspect of the target even when the tasks (detection vs. identification) were equated for overall performance level. These differences in cuing effects between tasks were much reduced if the target locations were no longer grouped into 2 objects. It is suggested that identical stimuli can elicit differing attentional mechanisms depending on task type (rather than task difficulty) and that these mechanisms differ in the nature of the representation of the visual world.


C1q nephropathy: a true immune complex disease or an immunologic epiphenomenon?
We describe a 16-year-old Caucasian boy who presented with steroid-sensitive nephrotic syndrome aged 2 years. His clinical course was one of frequent relapses and severe steroid dependence. To manage this, he was sequentially treated with levamisole, then oral cyclophosphamide before being started on ciclosporin. A renal biopsy performed prior to commencement of ciclosporin confirmed minimal change disease on light microscopy. The immunohistochemistry and electron microscopy findings were in keeping with this. His complement levels were normal and his lupus serology negative. He remained on ciclosporin therapy for 8 years and had two further renal biopsies to detect ciclosporin-induced renal damage. Both biopsies showed evidence of increasing amounts of C1q deposition on immunohistochemistry and the presence of immune deposits on electron microscopy. As he had continued negative lupus serology, this was compatible with a diagnosis of C1q nephropathy. In addition both biopsies had changes compatible with chronic mild ciclosporin nephrotoxicity. This case is the first report describing in detail a paediatric patient with evolving C1q nephropathy who was treated successfully with rituximab. We discuss the role of C1q in this clinicopathological entity and question its significance.


Intertwined Solitons and Impurities in a Quasi-One-Dimensional Charge-Density-Wave System: In/Si(111).
Recent studies on a quasi-one-dimensional (quasi-1D) charge-density-wave (CDW) system, In atomic wires on Si(111), have brought intriguing issues on topological solitons in quasi-1D systems: the existence of few-atom-sized solitons, chirality of solitons, and the realization of logic exploiting the chirality switching. Using scanning tunneling microscopy and first-principles calculations, we show that the previously reported "short" phase-flip defects are In adatoms and thus have nonsolitonic nature, resolving the controversy over the existence of highly localized solitons. The observed "long" phase-flip and phase-slip defects are genuine solitons with and without chirality, respectively. While achiral solitons (phase-slip defects) can exist on the pristine CDW (8×2) surface, chiral solitons (phase-flip defects) cannot due to their breakage of 8×2 ordering. The chiral solitons can exist only when they are trapped by In adatoms and constitute a part of a closed-loop domain wall. The intertwinement of chiral solitons and In adatoms implies the limitations of the previously proposed logic utilizing soliton chirality, but it provides an opportunity to realize this by controlling the In-adatom defect.


Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System.
Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. From a phylogenetic point of view, the human co-evolution between the endocannabinoid system and dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a "clinical endocannabinoid deficiency syndrome". This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm.


Integration of biostatistics and pharmacometrics computing platforms for efficient and reproducible PK/PD analysis: a case study.
Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.


Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States.
IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20–1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01–1.03]) and MT (odds ratio, 1.08 [95% CI,1.05–1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time. Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.


The OsCBL8-OsCIPK17 Module Regulates Seedling Growth and Confers Resistance to Heat and Drought in Rice.
The calcium signaling pathway is critical for plant growth, development, and response to external stimuli. The CBL-CIPK pathway has been well characterized as a calcium-signaling pathway. However, in most reports, only a single function for this module has been described. Here, we examined multiple functions of this module. CIPK showed a similar distribution to that of CBL, and OsCBL and OsCIPK families were retained after experiencing whole genome duplication events through the phylogenetic and synteny analysis. This study found that OsCBL8 negatively regulated rice seed germination and seedling growth by interacting with OsCIPK17 with overexpression and gene editing mutant plants as materials combining plant phenotype, physiological indicators and transcriptome sequencing. This process is likely mediated by OsPP2C77, which is a member of the ABA signaling pathway. In addition, OsCBL mediated the targeting of OsNAC77 and OsJAMYB by OsCIPK17, thus conferring resistance to high temperatures and pathogens in rice. Our work reveals a unique signaling pathway, wherein OsCBL8 interacts with OsCIPK17 and provides rice with multiple resistance while also regulating seedling growth.


Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery systems for cancer treatment.
This review is an attempt to assess the different classes of phytochemicals and some of their members which have been encapsulated into nanocarrier systems for their chemotherapeutic or chemopreventive properties. Given the broad spectrum of nanomedicines currently in clinical trial and clinical use from polymer-protein conjugates, through nanocrystals, nanogels, dendrimers to ethosomes, the focus of this review will be on block copolymer nanomicelles, nanoparticles, polymer-drug conjugates, liposomes and solid lipid nanocarriers (SLNs). The twenty phytochemicals investigated for encapsulation and targeted delivery were selected from a variety of classes intended to encompass the largest possible chemical compositions, namely flavonoids, aromatic acids, xanthones, terpenes, quinones, lignans and alkaloids. To the best of our knowledge, reviews on the nanoencapsulation of these phytochemicals and their delivery are not available. In this review, the issues associated with the limited use of each phytochemical in cancer therapy in humans are reviewed and the advantages of entrapment into nanocarriers are assessed in terms of drug loading efficiency, size of nanocarriers, drug release profiles and in vitro and/or in vivo testing specific to cancer research, e.g., cytotoxicity assay, cell inhibition/viability, scavenging of reactive oxygen species and biodistribution studies (elimination half-life and mean residence time).


Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis.
Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mechanism is still not fully characterized. Here, using a small-molecule functional screening, we identified NADPH oxidase-dependent reactive oxygen species as key regulators of neutrophil chemotactic migration. Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic granulomatous disease (CGD) patients and mice, formed more frequent multiple pseudopodia and lost their directionality as they migrated up a chemoattractant concentration gradient. Knocking down NADPH oxidase in differentiated neutrophil-like HL60 cells also led to defective chemotaxis. Consistent with the in vitro results, adoptively transferred CGD murine neutrophils showed impaired in vivo recruitment to sites of inflammation. Together, these results present a physiological role for reactive oxygen species in regulating neutrophil functions and shed light on the pathogenesis of CGD.


[A Case of Advanced Esophagogastric Junction Cancer Responding to S-1 Neoadjuvant Chemotherapy].
A 56-year-old man was diagnosed with advanced adenocarcinoma of the esophagogastric junction. He received 1 course of neoadjuvant chemotherapy with S-1. After neoadjuvant chemotherapy, the primary tumor showed a remarkable decrease in size. Subtotalesophagectomy, D2 lymph node dissection, and reconstruction with a gastric tube through the posterior mediastinal route were performed. Pathological examination showed that most of the cancer cells had been destroyed, with a part where adenocarcinoma mucosa was seen. We successfully treated a case of advanced adenocarcinoma of the esophagogastric junction, with neoadjuvant S-1 chemotherapy and surgicalresection.


Prediction of Sequential Organelles Localization under Imbalance using A Balanced Deep U-Net.
Assessing the structure and function of organelles in living organisms of the primitive unicellular red algae Cyanidioschyzon merolae on three-dimensional sequential images demands a reliable automated technique in the class imbalance among various cellular structures during mitosis. Existing classification networks with commonly used loss functions were focused on larger numbers of cellular structures that lead to the unreliability of the system. Hence, we proposed a balanced deep regularized weighted compound dice loss (RWCDL) network for better localization of cell organelles. Specifically, we introduced two new loss functions, namely compound dice (CD) and RWCD by implementing multi-class variant dice and weighting mechanism, respectively for maximizing weights of peroxisome and nucleus among five classes as the main contribution of this study. We extended the Unet-like convolution neural network (CNN) architecture for evaluating the ability of our proposed loss functions for improved segmentation. The feasibility of the proposed approach is confirmed with three different large scale mitotic cycle data set with different number of occurrences of cell organelles. In addition, we compared the training behavior of our designed architectures with the ground truth segmentation using various performance measures. The proposed balanced RWCDL network generated the highest area under the curve (AUC) value in elevating the small and obscure peroxisome and nucleus, which is 30% higher than the network with commonly used mean square error (MSE) and dice loss (DL) functions. The experimental results indicated that the proposed approach can efficiently identify the cellular structures, even when the contour between the cells is obscure and thus convinced that the balanced deep RWCDL approach is reliable and can be helpful for biologist to accurately identify the relationship between the cell behavior and structures of cell organelles during mitosis.


Hunting of roe deer and wild boar in Germany: Is non-lead ammunition suitable for hunting?
Non-lead hunting ammunition is an alternative to bullets that contain lead. The use of lead ammunition can result in severe contamination of game meat, thus posing a health risk to consumers. With any kind of ammunition for hunting, the terminal effectiveness of bullets is an animal welfare issue. Doubts about the effectiveness of non-lead bullets for a humane kill of game animals in hunting have been discussed. The length of the escape distance after the shot has been used previously as an indicator for bullet performance. The object of this study was to determine how the bullet material (lead or non-lead) influences the observed escape distances. 1,234 records of the shooting of roe deer (Capreolus capreolus) and 825 records of the shooting of wild boar (Sus scrofa) were evaluated. As the bullet material cannot be regarded as the sole cause of variability of escape distances, interactions of other potential influencing variables like shot placement, shooting distance, were analyzed using conditional regression trees and two-part hurdle models. The length of the escape distance is not influenced by the use of lead or non-lead ammunition with either roe deer or wild boar. With roe deer, the length of the escape distance is influenced significantly by the shot placement and the type of hunting. Increasing shooting distances increased the length of the escape distance. With wild boar, shot placement and the age of the animals were found to be a significant influencing factor on the length of the escape distance. The length of the escape distance can be used as an indicator for adequate bullet effectiveness for humane killings of game animals in hunting.Non-lead bullets already exist which have an equally reliable killing effect as lead bullets.


Study Design, Rationale and Procedures for Human Biomonitoring of Hazardous Chemicals from Foods and Cooking in Korea.
Objectives: A nationwide biomonitoring program identified the long-term trends of environmental exposures to hazardous chemicals in the general population and found geographical locations where body burdens of an exposed group significantly differed from those of the general population. The purpose of this study is to analyze the hazardous compounds associated with foods and cooking in the nationwide general population for evaluation of the environmental exposures and health risk factors and for the establishment of the reference levels at the national level. Methods: During 2009-2010, the National Institute of Food and Drug Safety Evaluation (NIFDS) conducted a nationwide human biomonitoring study, including a questionnaire survey and environmental exposure assessments for specific hazardous compounds from foods and cooking among the general population in South Korea. Results: A total of 2139 individuals voluntarily participated in 98 survey units in South Korea, including 889 (41.6%) men and 1250 women (58.4%). Bio-specimens (serum and urine) and questionnaires were collected from the study population. Acrylamides, heterocyclic amines (HCAs), phenols, and phthalates were analyzed from urine, and perfluorinated compounds (PFCs) and organic chloride pesticides (OCPs) were analyzed from serum samples. The information on exposure pathway and geographical locations for all participants was collected by questionnaire interviews, which included demographic characteristics, socioeconomic status, history of family diseases, conditions of the indoor and outdoor environment, lifestyles, occupational history, and food and dietary information. Conclusion: We describe the design of the study and sampling of human biospecimen procedures including bio-sample repository systems. The resources produced from this nationwide human biomonitoring study and survey will be valuable for use in future biomarkers studies and for the assessment of exposure to hazardous compounds associated with foods and cooking.


Fanconi's aplastic anaemia in two sisters in Trinidad and Tobago.
This report describes two cases of Fanconi's anaemia in Trinidadian sisters of East Indian origin. The cases have been confirmed by chromosomal analysis which showed increased breaks and ring forms. Anorexia was a persistent finding in both cases. One of the sisters also had a poor growth hormone response.


40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?
Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.


The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review.
Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied.


Salary survey of certified athletic trainers in delaware, new jersey, new york, and pennsylvania.
The objective of this study was to obtain salary information from certified athletic trainers in District Two of the National Athletic Trainers' Association (NATA) for use as a reference guide to assist entry-level and experienced ATCs interested in obtaining athletic training positions in Delaware, New Jersey, New York, and Pennsylvania. Mailed survey, sample of convenience. This study was conducted in the Sports Medicine Department of a children's hospital. A survey was sent to all 2,274 certified members of District Two. Of the surveys mailed, 970 (42.7%) were returned. Of the surveys returned, 725 (74.7%) were from full-time athletic trainers, 105 (10.8%) were from part-time athletic trainers, and 140 (14.4%) were unusable. A survey consisting of 15 questions related to salaries and demographics of the athletic trainers' employment settings. Forty-eight percent of the respondents were employed in the clinic or hospital setting, and almost 48% of those responding possessed a master's degree. The state with the highest response rate was Pennsylvania with 45% of the total. The highest rate of response according to experience was 27% from athletic trainers having 4 to 6 years of experience. According to practice setting, the lowest mean salary was $32,928 +/- $10,098 at the college or university level, and the highest was $59,778 +/- $48,803 at the professional sport level. According to education level, the lowest mean salary was $30,132 +/- $9,584 (bachelor's degree), and the highest was $48,070 +/- $12,973 (PT or ATC). The mean salary by state was lowest in Delaware ($32,330 +/- $12,865) and highest in New Jersey ($36,695 +/- $12,593). The highest mean salary by years of experience was $57,308 +/- $30,723 (25 years or more). Further comparative studies in this area need to be conducted to recognize current trends with the intent of establishing national or regional standards of salary compensation for certified athletic trainers.


Dissemination of heart health promotion in the Ontario Public Health System: 1989-1999.
This paper reports the results of an analysis of the dissemination of community-based heart health promotion strategies. The research draws on diffusion and socio-ecological theories to study the first 10 years of heart health promotion in the public health system in Ontario, Canada. Using case description and interpretive analysis, the study describes developments in five stages of dissemination, and examines the interplay of factors operating in the internal organizational setting and the external environment in order to explain these developments. Findings demonstrate that dissemination of health promotion is a long-term, iterative process involving multiple stages. Dissemination is influenced by a complex interplay of factors operating within the public health system (especially traditional public health practice and champions) and factors in the environment in which the public health system operates (especially research, practice information and health policies). Implications are that policy makers should take a long-term view of dissemination, identify intermediate and long-term goals consistent with dissemination stages, and capitalize on internal and external forces supporting dissemination goals. Similar case-study research in other public health systems and time periods, and in more advanced stages of dissemination, will add further insight into the dissemination process.


Immunomodulation by LongoVital in patients with recurrent aphthous ulceration.
LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during 6 months' daily LV intake in a double-blind, randomized, crossover 1-year study. Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6 months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (P less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.


Ability of monoclonal antibodies to the thyrotropin receptor to increase collagen synthesis in human fibroblasts: an assay which appears to measure exophthalmogenic immunoglobulins in Graves' sera.
Immunoglobulin G (IgG) preparations from 17 of 20 hyperthyroid patients with Graves' ophthalmopathy stimulated collagen biosynthesis in human fibroblasts, as measured by [3H]proline incorporation. This activity was not associated with thyroid-stimulating antibody (TSAb) activity in a thyroid cell cAMP assay in 50% of the IgG preparations, and it was not found in IgGs from 12 normal subjects, 7 of 8 patients with Graves' hyperthyroidism but no ophthalmopathy, 4 patients with Hashimoto's disease, 7 patients with nontoxic goiter, or 4 hypothyroid patients. In the same assay, 11E8, 22A6, and 13D11, 3 mouse monoclonal antibodies to the bovine TSH receptor, and 307H6, a human monoclonal antibody to the TSH receptor of the thyroid from a Graves' patient with ophthalmopathy, also stimulated [3H]proline incorporation into collagen and were active at more than 1,000- to 10,000-fold lower IgG concentrations (0.1-0.5 microgram/ml as opposed to greater than 1 mg/ml). 11E8 and 13D11 are TSH binding inhibitory antibodies (TBIAbs); 22A6 and 307H6 are TSAbs in cAMP assays. Two other mouse anti-TSH receptor monoclonal antibodies, both TBIAbs, as well as 8 human monoclonal antibodies to the TSH receptor from Graves' patients with or without ophthalmopathy (2 TBIAbs and 6 TSAbs) were negative or significantly less potent (greater than 50 fold) in the assay. The fibroblast activity of the monoclonal antibodies was lost if the antibodies were preincubated with thyroid membranes, was significantly decreased when fibroblasts were exposed to mild trypsin treatment before the assay, was not inhibited by human asialoagalacto-thyroglobulin, and required more than a TSH receptor determinant, since TSH alone neither duplicated nor inhibited the antibody activity. In summary, an assay for measuring the activity of autoantibodies active in causing ophthalmopathy is described, and some but not all TSH receptor monoclonal antibodies have been found to duplicate the action of the autoimmune IgGs from the ophthalmopathy patients.


[Tumour illnesses and nutrition].
It is very important for contemporary medicine to create new effective cytotoxic compounds of platinum with better clinical tolerance. Harmful elements which exist in food delivered to a human organism may either get inactive or activate complex processes which may to lead to illnesses such as tumors. One of these elements are. Undoubtedly, free radicals. They destroy, among other things, the DNA, causing changes in the genetic code and its mutations. More recently came the publication of speaking a lot about the capabilities of the organism to defend against the above-mentioned factors. Eating adequate amounts of fruits and vegetables contain antioxidants in its composition contributes positively to our body and reduces the risk of cancer.


Postnatal Evaluation of Congenital Chest Pathologies Using a Low-Dose Computed Tomography (CT) Protocol - a Pictorial Review.
Computed tomography with its excellent spatial and temporal resolution remains a valuable diagnostic modality in pediatrics. On the other hand an increasing attention has been placed on the radiation risks associated with CT imaging, especially in children. In recent years, many advances in CT hardware and software, for example, automatic exposure control tools and iterative reconstruction techniques, have allowed for a reduction of applied radiation doses while maintaining image quality. The purpose of this paper is to present our protocol for chest CT imaging in the youngest age group, together with a pictorial review of congenital pathologies of the chest, and to emphasize factors that optimize postnatal CT imaging in infants. In our opinion, modern CT imaging with the use of dose reduction techniques and iterative reconstructions allows for a proper visualization of chest pathologies in small children, which has no influence on observer performance. The presented review of low-dose diagnostic images of a wide spectrum of congenital pathologies may serve as an example of routine utilization of the current concepts in pediatric CT optimization.


The effect of H1 and H2 receptor blockers on immunological and nonspecific histamine release from isolated target cells.
The investigations were carried out on isolated peritoneal rat mast cells and human basophils. Cell histamine release was induced by a specific antigen, anti-IgE and by compound 48/80. Mepyramine and Diphenhydramine were used as H1 receptor blockers and Cimetidine as H2 receptor blocker. It was shown that effect of H1 and H2 receptor blockers on histamine release depends on concentration of drugs used in experiments, on the presence of exogenous histamine in the medium, on the kind of histamine liberators and also on the type of investigated target cells. The results obtained seem to indicate the presence of H2 receptors not only on basophils but also on mast cells.


Impact of whole-canopy and systemic insecticidal treatments on Callirhytis cornigera (Hymenoptera: Cynipidae) and associated parasitoids on pin oak.
The gall wasp Callirhytis cornigera (Osten Sacken) is a cynipid with alternating generations that produce large, woody stem galls and tiny blister-like leaf galls on pin oak, Quercus palustris Muenchhausen, in the United States. We tested 3 approaches to control the leaf-galling generation, and determined their impact on associated parasitoids and effectiveness in reducing numbers of new stem galls. First, trees were sprayed with bifenthrin or chlorpyrifos in late March to kill females emerging from stem galls before they oviposited into buds. Second, concentrated solutions of abamectin, imidacloprid, or bidrin were injected from pressurized containers into tree sapwood to control larvae developing in young leaf galls. Finally, systemic insecticides (acephate, abamectin, dimethoate, or imidacloprid) were sprayed at early leaf expansion (2 May) or to young, expanded leaves (17 May) to target larvae in leaf galls. Parasitoids, mostly eulophids, accounted for approximately 70% mortality of leaf-galling C. cornigera larvae on untreated trees. Whole-canopy sprays during C. cornigera emergence from stem galls reduced overall numbers of galled leaves and leaf galls. Trunk injections of bidrin or abamectin resulted in significant mortality of gall inhabitants, including parasitoids. However, neither of the aforementioned approaches significantly reduced numbers of new stem galls. Sprays of abamectin, dimethoate, or imidacloprid applied on 2 May caused high mortality of all gall inhabitants. There was no net benefit, however, because parasitism caused a similar reduction in C. cornigera survival on unsprayed shoots. Sprays applied later in leaf expansion had little impact on gall inhabitants. Of the treatments tested, bifenthrin sprays at bud break provided the greatest reduction in new leaf galls, whereas bidrin injections provided the greatest reduction in gall wasps emerging from galled leaves. This study suggests that gall wasp outbreaks are unlikely to be controlled by a single treatment, regardless of application method.


Synthesis of novel antibacterial and antifungal quinoxaline derivatives.
A series of quinoxaline derivatives were designed, synthesized and evaluated as antimicrobial agents against plant pathogenic bacteria and fungi. Some of these compounds exhibited significant antibacterial and antifungal activities in vitro. Compound 5k displayed good antibacterial activity against Acidovorax citrulli (Ac). Compounds 5j and 5t exhibited the most potent anti-RS (Rhizoctonia solani) activity, with the corresponding EC50 values of 8.54 and 12.01 μg mL-1, respectively, which are superior to that of the commercial azoxystrobin (26.17 μg mL-1). Further, the scanning electron microscopy results proved that compound 5j had certain effects on the cell morphology of RS. Moreover, an in vivo bioassay also demonstrated that the anti-RS activity of compound 5j could effectively control rice sheath blight. These results indicate that quinoxaline derivatives could be promising agricultural bactericides and fungicides.


The Role of Big Data in the Development and Evaluation of US Dialysis Care.
Rapid growth in electronic communications and digitalization, combined with advances in data management, analysis, and storage, have led to an era of "Big Data." The Social Security Amendments of 1972 turned end-stage renal disease (ESRD) care into a single-payer system for most patients requiring dialysis in the United States. As a result, there are few areas of medicine that have been as influenced by Big Data as dialysis care, for which Medicare's large administrative data sets have had a central role in the evaluation and development of public policy for several decades. In the 1970/1980s, Medicare data helped identify concerning trends in costs, access to dialysis care, and quality of care delivered. As the research community and policymakers made Medicare's administrative data increasingly accessible for investigation, analyses of Medicare claims have had a large role in facilitating policy synthesis and refinement. Efforts to address the skyrocketing cost of injectable drugs in the 1990s and 2000s exemplify this expanded role of Big Data. Although there are opportunities for large government and nongovernmental administrative data sets to continue serving a critical role in the evaluation and development of ESRD policies, it is important to understand challenges and limitations associated with their use.


Enhanced Alcohol Preference and Anxiolytic Alcohol Effects in Niemann-Pick Disease Model in Mice.
Major depression and alcohol use disorder are severe psychiatric diseases affecting the world's population with high comorbidity level. However, the pathogenesis of this comorbidity remains unclear, and no selective treatment for this condition is available. A pathogenic pathway and a possible therapeutic target for the treatment of depression-alcoholism comorbidity based on the hyperfunction of acid sphingomyelinase (Asm) were recently suggested. Here we analyzed the effects of alcohol on the depression/anxiety state of homozygous Asm-knockout mice (Asm - /-), which can be considered as a model of an early stage of Niemann-Pick disease, as well as their drinking pattern under normal and stress conditions. It was observed that forced treatment with alcohol (2 g/kg, i.p.) reduces the anxiety level of Asm-/- mice as measured in the elevated plus maze (EPM) test, but enhances the depression level in the forced swim test (FST). The analysis of drinking pattern of these animals in a free-choice alcohol drinking paradigm revealed higher alcohol intake and preference in Asm-/- mice compared to wild type (wt) littermates. However, this difference was overwritten by the stress exposure. Stronger sedating effects of alcohol were observed in Asm-/- mice compared to wt animals in the loss of righting reflex test after single and repeated alcohol injections (3 g/kg, i.p.). Altogether, the present findings might indicate an Asm involvement in the mechanisms of comorbidity between alcoholism and anxiety/depression.


Nickel-catalyzed intermolecular [2 + 2] cycloaddition of conjugated enynes with alkenes.
A nickel-catalyzed intermolecular [2 + 2] cycloaddition of conjugated enynes with alkenes has been developed. A variety of electron-deficient alkenes as well as electronically neutral norbornene and 1-decene were applicable to this reaction. The use of conjugated enynes circumvented possible side rections, such as oligomerizations and cyclotrimerizations. The isolation of reaction intermediate complexes revealed that the η(3)-butadienyl coordination is the key for the selective formation of cyclobutene.


Is IIIG9 a New Protein with Exclusive Ciliary Function? Analysis of Its Potential Role in Cancer and Other Pathologies.
The identification of new proteins that regulate the function of one of the main cellular phosphatases, protein phosphatase 1 (PP1), is essential to find possible pharmacological targets to alter phosphatase function in various cellular processes, including the initiation and development of multiple diseases. IIIG9 is a regulatory subunit of PP1 initially identified in highly polarized ciliated cells. In addition to its ciliary location in ependymal cells, we recently showed that IIIG9 has extraciliary functions that regulate the integrity of adherens junctions. In this review, we perform a detailed analysis of the expression, localization, and function of IIIG9 in adult and developing normal brains. In addition, we provide a 3D model of IIIG9 protein structure for the first time, verifying that the classic structural and conformational characteristics of the PP1 regulatory subunits are maintained. Our review is especially focused on finding evidence linking IIIG9 dysfunction with the course of some pathologies, such as ciliopathies, drug dependence, diseases based on neurological development, and the development of specific high-malignancy and -frequency brain tumors in the pediatric population. Finally, we propose that IIIG9 is a relevant regulator of PP1 function in physiological and pathological processes in the CNS.


The significance of Atlanto-axial instability in Down's syndrome.
Atlanto-axial instability has been a cause for concern amongst those with Down's syndrome who take part in 'high risk' sports. The authors recommend radiological screening of people with Down's syndrome to help identify those with unstable and symptomatic Atlanto-axial joints and suggest advice on management.


Flow-by induced hypoventilation in high spinal cord lesions--report of two cases.
Flow triggering in ventilators is an alternative to pressure triggering. Differences between these two trigger mechanisms may not be clinically significant in most patients. We report two patients with high spinal cord lesions in whom the use of flow triggering was unsuccessful. Severe muscle weakness in these patients made them sensitive to small changes in ventilator trigger characteristics.


Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing.
Diabetic foot ulcers (DFUs) are a threat to human health and can lead to amputation and even death. Recently neurotensin (NT), an inflammatory modulator in wound healing, was found to be beneficial for diabetic wound healing. As we demonstrated previously, polylactide-polyglycolide (PLGA) and cellulose nanocrystals (CNCs) (PLGA/CNC) nanofiber membranes show good cytocompatibility and facilitate fibroblast adhesion, spreading and proliferation. PLGA/CNC nanofiber membranes are novel materials that have not been used previously as NT carriers in diabetic wounds. This study aims to explore the therapeutic efficacy and possible mechanisms of NT-loaded PLGA/CNC nanofiber membranes in full-thickness skin wounds in spontaneously diabetic mice. The results showed that NT could be sustained released from NT-loaded PLGA/CNC composite nanofiber membranes for 2 weeks. NT-loaded PLGA/CNC composite nanofiber membranes induced more rapid healing than other control groups. After NT exposure, the histological scores of the epidermal and dermal regeneration and the ratios of the fibrotic area to the whole area were increased. NT-loaded PLGA/CNC composite nanofiber membranes also decreased the expressions of the inflammatory cytokines IL-1β and IL-6. These results suggest that NT-loaded PLGA/CNC composite nanofiber membranes for sustained delivery of NT should effectively promote tissue regeneration for the treatment of DFUs.


[Toxicological significance of biological markers].
Biological monitoring or, simply, biomonitoring (BM), refers to the periodic measurement of biological markers, or biomarkers (BMKs), in human fluids and tissues to assess the interaction (absorption, early health effects, susceptibility) between physical, chemical or biological agents and the human organism. The primary aim of BM in the workplace is to integrate environmental monitoring data and detect early, reversible biochemical or functional changes in workers exposed to chemicals before they become clinically relevant. BM also contributes to the assessment of chemical risk to workers, as individuals or as a group. Biomarkers are generally divided into three main types: biomarkers of exposure (BME), response/effect (BMR), and susceptibility (BMS). Other, more specific types of biomarkers are those of internal dose (BID), those of biologically effective dose (BED) and early biomarkers of disease (EBD). It is not always easy, however, to allocate a given BMK--such as the measurement of cytochrome P450 phenotype in subjects exposed to organic solvents--to one or the other type. Biomonitoring provides several advantages over environmental monitoring or health surveillance. For example, it allows an estimate of inter- and intra-individual variability in the absorption, distribution and excretion of chemicals. It also allows the detection of reversible changes before the appearance of a clinically relevant occupational impairment or disease. For these reasons, BM has become a routine procedure in occupational health practice throughout the world. Even the widely acknowledged, recently updated Code of Ethics for Occupational Health Professionals, a milestone in occupational health practice, only provides the basic ethical principles associated with biological monitoring. The aim of the present paper is to survey the various types of BMK available today with two main objectives: to discuss their toxicological significance and highlight the substantial differences that exist between their use in the practice of occupational health and in medical research. The development of new, more valid and reliable BMKs is strongly dependent on the understanding not only of the toxicokinetic and toxicodinamic mechanisms of chemicals, but also of the various susceptibility factors involved, whether genetic or environmental. It is hoped that the concurrent use of BMKs of different types may improve chemical risk assessment in workers, both individually and as a group.


Synthesis of 3,5-Disubstituted BODIPYs Bearing N-Containing Five-Membered Heteroaryl Groups via Nucleophilic C-N Bond Formation.
Aromatic substitution reactions were applied to the divergent synthesis of a series of symmetrically and unsymmetrically 3,5-disubstituted BODIPYs bearing N-heteroaryl groups. Furthermore, the effect of N-heteroaryl substituents at the 3- and 5-positions on the optical and photophysical properties of the BODIPY π-electron system was elucidated.


Are chest radiographs routinely indicated after chest tube removal following cardiac surgery?
The purpose of this prospective study was to determine the incidence and clinical significance of pneumothoraces detected on routine radiography after chest tube removal following cardiac surgery and correlate those findings with an immediate postprocedure assessment of the likelihood of new pneumothorax. Routine portable chest radiographs obtained after chest tube removal in 400 consecutive cardiac surgery patients were assessed by a radiologist to determine the incidence and grade of pneumothoraces and were correlated with the clinical estimation of the likelihood of this complication, and whether the radiographic finding changed medical management or led to surgical intervention. Of 9.3% of cases (37/400) of new pneumothoraces after chest tube removal, 70.3% were tiny (barely perceptible), 27.0% were small (< 1 cm from the pleural line to the apex of the hemithorax), and 2.7% were medium (6-10 cm from the pleural line to the apex of the hemithorax). The incidences of small and medium pneumothoraces were substantially greater in patients with higher levels of clinical suspicion. All tiny pneumothoraces had no clinical importance. Not obtaining routine chest radiographs after chest tube removal in the 345 patients (86.3%) with the lowest level of clinical suspicion would have resulted in missing six small pneumothoraces (1.7%), none of which led to medical or surgical intervention or a delay in discharge. Chest radiography performed after chest tube removal following cardiac surgery is necessary only if the patient has respiratory or hemodynamic changes or if there are problems with the technical aspect of chest tube removal. Following this guideline in our patient population could have eliminated 86.3% of radiographs without missing any clinically significant pneumothoraces.


Diagnostic criteria for apical ballooning derived from quantitative analysis of left ventricular angiograms.
The aim of this study was to evaluate diagnostic criteria for apical ballooning (AB) derived from quantitative analysis of left ventricular angiograms. AB is an unusual cause of left ventricular dysfunction mimicking acute transmural ischemia (STEMI). This study compared the systolic and diastolic linear measures of left ventricle (LV) of ten consecutive patients with AB to those obtained in a control group of STEMI patients. These measures allowed the calculation of the systolic shortening of the long and short axis of the LV. Systolic short axis and long axis shortening are significantly different in the two groups, so that both the systolic and diastolic sphericity indexes (SI) were much lower in AB patients (diastolic SI: 1.62+/-0.18 vs. 1.81+/-0.16; P=0.026 and systolic SI: 1.58+/-0.22 and 2.48+/-0.54 P<0.001). Moreover, a long axis shortening >0.6 cm was 100% sensitive and specific for AB. This study demonstrated that AB can be differentiated from STEMI by means of imple parameters of LV motion with a high degree of sensitivity and specificity.


Models, standards and structures of nursing documentation in European countries.
The use of standardized nursing languages varies between and even within different European countries. Standardization of a nursing language is a demanding process which requires substantial methodological and technological knowledge as well as cultural experience in terminology development work. A survey was carried out to describe the current state of art of the use of models, standards and structures in nursing documentation. A web-based questionnaire was targeted to members of the Association for Common European Nursing Diagnoses, Interventions and Outcomes (ACENDIO). Replies were received from 17 countries in Europe. Results show that the nursing process is the model most often used to structure nursing documentation in Europe. Many standardized nursing terminologies are used in Europe but general use in nursing is still lacking which makes access to nursing data an obstacle. In more than 60% of the institutions in the countries that replied were nursing data not stored and could therefore not be retrieved. These results should be a major concern to nurses in Europe. This relates to the lack of use of standards in use of nursing terminologies and information systems. Standardization activities in existing and evolving networks in Europe, as well as in other parts of the world, need to be enhanced. As a European platform, ACENDIO can play a role in these standardization activities and should develop its role accordingly.


Kinetically induced irreversibility in electro-oxidation and reduction of Pt surface.
A mean field kinetic model was developed for electrochemical oxidations and reductions of Pt(111) on the basis of density functional theory calculations, and the reaction mechanisms were analyzed. The model reasonably describes asymmetric shapes of cyclic voltammograms and small Tafel slopes of relevant redox reactions observed in experiments without assuming any unphysical forms of rate equations. Simulations using the model indicate that the oxidation of Pt(111) proceeds via an electrochemical oxidation from Pt to PtOH and a disproportionation reaction from PtOH to PtO and Pt, while its reduction proceeds via two electrochemical reductions from PtO to PtOH and from PtOH to Pt.


Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques.
Although BCG vaccine protects infants from tuberculosis (TB), it has limited efficacy in adults against pulmonary TB. Further, HIV coinfection significantly increases the risk of developing active TB. In the lack of defined correlates of protection in TB disease, it is essential to explore immune responses beyond conventional CD4 T cells to gain a better understanding of the mechanisms of TB immunity. Here, we evaluated unconventional lipid-reactive T cell responses in cynomolgus macaques following aerosol BCG inoculation and examined the impact of subsequent SIV infection on these responses. Immune responses to cellular lipids of M. bovis and M. tuberculosis were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL). Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ responses to mycobacterial lipids in peripheral blood and BAL, suggesting the induction of systemic and local Th1-type response in lipid-reactive T cells. Subsequent SIV infection resulted in a significant loss of IL-7R expression on blood and BAL γδT cells. Additionally, IFN-γ responses of mycobacterial lipid-reactive T cells in BAL fluid were significantly lower in SIV-infected macaques, while perforin production was maintained through chronic SIV infection. Overall, these data suggest that despite SIV-induced decline in IL-7R expression and IFN-γ production by mycobacterial lipid-reactive T cells, their cytolytic potential is maintained. A deeper understanding of anti-mycobacterial lipid-reactive T cell functions may inform novel approaches to enhance TB control in individuals with or without HIV infection.


Dermatopathology 101: Part 1 - Inflammatory skin diseases.
Dermatopathology is an indispensable tool in the diagnostic workup of inflammatory and neoplastic lesions. For the dermatologist in everyday clinical practice, basic knowledge of dermatopathology is highly valuable, as it allows for proper classification and interpretation of histological findings, as well as their correlation with the clinical picture (especially in case of inflammatory skin diseases). Such basic understanding is also important with regard to selecting the appropriate biopsy technique, thus increasing the overall diagnostic quality. The present article describes the diagnostic approaches taken by dermatopathologists in the histological workup of inflammatory skin diseases. The basic principles of this workup are highlighted on the basis of key histological patterns. Published in an upcoming issue, the second part of this article will address the histological characteristics of the most common skin tumors.


Estimated Long-Term (1981-2016) Concentrations of Ambient Fine Particulate Matter across North America from Chemical Transport Modeling, Satellite Remote Sensing, and Ground-Based Measurements.
Accurate data concerning historical fine particulate matter (PM2.5) concentrations are needed to assess long-term changes in exposure and associated health risks. We estimated historical PM2.5 concentrations over North America from 1981 to 2016 for the first time by combining chemical transport modeling, satellite remote sensing, and ground-based measurements. We constrained and evaluated our estimates with direct ground-based PM2.5 measurements when available and otherwise with historical estimates of PM2.5 from PM10 measurements or total suspended particle (TSP) measurements. The estimated PM2.5 concentrations were generally consistent with direct ground-based PM2.5 measurements over their duration from 1988 onward ( R2 = 0.6 to 0.85) and to a lesser extent with PM2.5 inferred from PM10 measurements from 1985 to 1998 ( R2 = 0.5 to 0.6). The collocated comparison of the trends of population-weighted annual average PM2.5 from our estimates and ground-based measurements was highly consistent (RMSD = 0.66 μg m-3). The population-weighted annual average PM2.5 over North America decreased from 22 ± 6.4 μg m-3 in 1981, to 12 ± 3.2 μg m-3 in 1998, and to 7.9 ± 2.1 μg m-3 in 2016, with an overall trend of -0.33 μg m-3 yr-1 (95% CI: -0.35, -0.31).


Autophagy in innate and adaptive immunity against intracellular pathogens.
Autophagy delivers cytoplasmic constituents for lysosomal degradation. Recent studies have demonstrated that this pathway mediates resistance to pathogens and is targeted for immune evasion by viruses and bacteria. Lysosomal degradation products, including pathogenic determinants, are then surveyed by the adaptive immune system to elicit antigen-specific T cell responses. CD4(+) T helper cells have been shown to recognize nuclear and cytosolic antigens via presentation by major histocompatibility complex (MHC) class II molecules after autophagy. Furthermore, some sources of natural MHC class II ligands display characteristics of autophagy substrates, and autophagosomes fuse with late endosomes, in which MHC class II loading is thought to occur. Although MHC class II antigen processing via autophagy has so far mainly been described for professional antigen-presenting cells like B cells, macrophages, and dendritic cells, it might be even more important for cells with less endocytic potential, like epithelial cells, when these express MHC class II at sites of inflammation. Therefore, autophagy might contribute to immune surveillance of intracellular pathogens via MHC class II presentation of intracellular pathogen-derived peptides.


Lysosomal acid lipase deficiency allograft recurrence and liver failure- clinical outcomes of 18 liver transplantation patients.
Lysosomal acid lipase deficiency (LAL-D) results in progressive microvesicular hepatosteatosis, fibrosis, cirrhosis, dyslipidemia, and vascular disease. Interventions available prior to enzyme replacement therapy development, including lipid lowering medications, splenectomy, hematopoietic stem cell and liver transplantation were unsuccessful at preventing multi-systemic disease progression, and were associated with significant morbidity and mortality. We report two sisters, diagnosed in infancy, who succumbed to LAL-D with accelerated disease progression following splenectomy and liver transplantation. The index patient died one year after hematopoietic stem cell transplant and liver transplantation. Her younger sister survived five years post liver-transplantation, complicated by intermittent, acute rejection. Typical LAL-D hepatopathology, including progressive, microvesicular steatosis, foamy macrophage aggregates, vacuolated Kupffer cells, advanced fibrosis and micronodular cirrhosis recurred in the liver allograft. She died before a second liver transplant could occur for decompensated liver failure. Neither patient received sebelipase alfa enzyme replacement therapy, human, recombinant, lysosomal acid lipase enzyme, FDA approved in 2015. Here are reviewed 18 LAL-D post-liver transplantation cases described in the literature. Multi-systemic LAL-D progression occurred in 11 patients (61%) and death in six (33%). These reports demonstrate that liver transplantation may be necessary for LAL-D-associated liver failure, but is not sufficient to prevent disease progression, or liver disease recurrence, since the pathophysiology is predominantly mediated by deficient enzyme activity in bone marrow-derived monocyte-macrophages. Enzyme replacement therapy addresses systemic disease and hepatopathology, potentially improving liver-transplantation outcomes. This is the first systematic review of liver transplantation for LAL-D, and the first account of liver allograft LAL-D-associated hepatopathology recurrence.


Engineering potent long-acting variants of the Wnt inhibitor DKK2.
Wnt signaling pathways are required for a wide variety of biological processes ranging from embryonic development to tissue repair and regeneration. Dickkopf-2 (DKK2) is classically defined as a canonical Wnt inhibitor, though it may play a role in activating non-canonical Wnt pathways in the context of endothelial network formation after acute injury. Here we report the discovery of a fusion partner for a DKK2 polypeptide that significantly improves the expression, biochemical properties and pharmacokinetics (PK) of the DKK2 polypeptide. Specifically, human serum albumin (HSA) was identified as a highly effective fusion partner. Substitution of selected amino acid residues in DKK2 designed to decrease heparan sulfate binding by HSA-DKK2 variants, further improved the PK properties of the molecule in rodents. The HSA-DKK2 variants were monomeric, as thermally stable as wild type, and active as measured by their ability to bind to and prevent phosphorylation of the Wnt coreceptor LRP6. Our engineering efforts resulted in potent long-lived variants of the canonical Wnt inhibitor DKK2, applicable for Wnt pathway manipulation either by systematic delivery or focused administration at sites of tissue injury.


[Analysis of the results of 6 months of activities in an emergency medical clinic].
In our country emergency medicine expertise programmes have 6-year post yet. The second university emergency medicine department, S.U.T.F. Emergency Medicine Department and clinic, which was founded in 1995, has come a long way in 5 years. 934 patients who have been followed in observation and intensive care units had stayed in emergency medicine clinic for 45.53 hours on an average, after this time %53 had discharged from hospital, %42.25 had been sent to other connected clinics, %4 died in S.U.T.F emergency medicine clinic in 6 months. The results of this article can be summarized as the emergency medicine clinic is as successful as other clinics, reduced waiting on transport problems and prevented the complications because of unwilling behaviours to emergency patients. Becoming widespread of emergency medicine expertise programmes and emergency medicine clinics can be solution for reducing the delay in help, identification and treatment of patients.


Primary Mediastinal Seminoma Achieved by Transbronchial Mediastinal Cryobiopsy.
Mediastinal biopsy is essential for the clinical diagnosis of mediastinal disease. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established approach for obtaining diagnostic samples from mediastinal masses or enlarged lymph nodes which is proven to be minimally invasive and effective. However, the insufficiency of intact samples acquired might restrict the diagnostic efficacy of EBUS-TBNA for mediastinal lesions such as rare malignancy and granulomatous disorder. We here present an EBUS-guided approach for the cryobiopsy of mediastinal diseases that is capable of providing larger amounts of intact tissue with few observed complications.


Glycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulence.
Pel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, Pel is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic and mucolytic treatments. While genes encoding glycoside hydrolases have long been linked to biofilm exopolysaccharide biosynthesis, their physiological role in biofilm development is unclear. Here we demonstrate that the glycoside hydrolase activity of P. aeruginosa PelA decreases adherent biofilm biomass and is responsible for generating the low molecular weight secreted form of the Pel exopolysaccharide. We show that the generation of secreted Pel contributes to the biomechanical properties of the biofilm and decreases the virulence of P. aeruginosa in Caenorhabditis elegans and Drosophila melanogaster. Our results reveal that glycoside hydrolases found in exopolysaccharide biosynthetic systems can help shape the soft matter attributes of a biofilm and propose that secreted matrix components be referred to as matrix associated to better reflect their influence.


A Randomized Study Comparing the Sniffing Position with Simple Head Extension for Glottis Visualization and Difficulty in Intubation during Direct Laryngoscopy.
Proper positioning of the head and neck is important for an optimal laryngeal visualization. Traditionally, sniffing position (SP) is recommended to provide a superior glottic visualization, during direct laryngoscopy, enhancing the ease of intubation. Various studies in the last decade of this belief have challenged the need for sniffing position during intubation. We conducted a prospective study comparing the sniffing head position with simple head extension to study the laryngoscopic view and intubation difficulty during direct laryngoscopy. Five-hundred patients were included in this study and randomly distributed to SP or simple head extension. In the sniffing group, an incompressible head ring was placed under the head to raise its height by 7 cm from the neutral plane followed by maximal extension of the head. In the simple extension group, no headrest was placed under the head; however, maximal head extension was given at the time of laryngoscopy. Various factors as ability to mask ventilate, laryngoscopic visualization, intubation difficulty, and posture of the anesthesiologist during laryngoscopy and tracheal intubation were noted. In the incidence of difficult laryngoscopy (Cormack Grade III and IV), Intubation Difficulty Scale (IDS score) was compared between the two groups. There was no significant difference between two groups in Cormack grades. The IDS score differed significantly between sniffing group and simple extension group (P = 0.000) with an increased difficulty during intubation in the simple head extension. Patients with simple head extension needed more lifting force, increased use of external laryngeal manipulation, and an increased use of alternate techniques during intubation when compared to SP. We conclude that compared to the simple head extension position, the SP should be used as a standard head position for intubation attempts under general anesthesia.


Early precursors and enabling skills of reading acquisition.
Research on early linguistic precursors and enabling skills of reading acquisition among young children is reviewed. Language development starts early in infancy when the child learns to categorize the speech sounds according to the pattern typical of the mother tongue. Equipped with these sound categories the child is ready to learn to segment words from the sound stream and to understand and to use words. The precise phonological representation of words will facilitate the important development of phonological awareness, a basic prerequisite for reading acquisition. This paper reviews some of my longitudinal research and training studies indicating the causal direction of the relation between phonological awareness and reading and includes some ongoing studies, where gender differences, socio-economic factors, dose-response-effects and motivational factors are explored. Preventive and remedial implications of the findings are pointed out. Finally, the complexity of the causal relationships between different aspects of early language development, including genetic influences and later reading is pointed out.


Genome-Wide Identification and Expression Analysis of Cytokinin Response Regulator (RR) Genes in the Woody Plant Jatropha curcas and Functional Analysis of JcRR12 in Arabidopsis.
The cytokinin (CK) response regulator (RR) gene family plays a pivotal role in regulating the developmental and environmental responses of plants. Axillary bud outgrowth in the perennial woody plant Jatropha curcas is regulated by the crosstalk between CK and gibberellins (GA). In this study, we first analyzed the effects of gibberellin A3 (GA3), lovastatin (a CK synthesis inhibitor), decapitation, and their interaction, on the outgrowth of axillary buds. The results indicate that lovastatin completely inhibited GA-promoted axillary bud outgrowth and partially weakened the decapitation-promoted axillary bud outgrowth. To further characterize and understand the role of CK signaling in promoting the development of female flowers and branches, we performed bioinformatics and expression analyses to characterize the CK RR gene (JcRR) family in J. curcas. A total of 14 members of the JcRR family were identified; these genes were distributed on 10 chromosomes. Phylogenetic analysis indicated that the corresponding RR proteins are evolutionarily conserved across different plant species, and the Myb-like DNA-binding domain divides the 14 members of the JcRR family into type-A and type-B proteins. Further analysis of cis-acting elements in the promoter regions of JcRRs suggests that JcRRs are expressed in response to phytohormones, light, and abiotic stress factors; thus, JcRRs may be involved in some plant development processes. Genomic sequence comparison revealed that segmental duplication may have played crucial roles in the expansion of the JcRR gene family, and five pairs of duplicated genes were all subjected to purifying selection. By analyzing RNA sequencing (RNA-seq) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data, we characterized that the temporospatial expression patterns of JcRRs during the development of various tissues and the response of these genes to phytohormones and abiotic stress. The JcRRs were mainly expressed in the roots, while they also exhibited differential expression patterns in other tissues. The expression levels of all six type-A and one type-B JcRRs increased in response to 6-benzylaminopurine (6-BA), while the four type-B JcRRs levels decreased. The expression levels of two type-B JcRRs increased in response to exogenous GA3 treatment, while those of three type-A and three type-B JcRRs decreased. We found that type-A JcRRs may play a positive role in the continuous growth of axillary buds, while the role of type-B JcRRs might be the opposite. In response to abiotic stress, the expression levels of two type-A and three type-B JcRRs strongly increased. The overexpression of JcRR12 in Arabidopsis thaliana slightly increased the numbers of rosette branches after decapitation, but not under normal conditions. In conclusion, our results provide detailed knowledge of JcRRs for further analysis of CK signaling and JcRR functions in J. curcas.


Pituitary adenoma: a cephalometric finding.
A case of a young girl with an abnormally shaped sella turcica is reported. A routine lateral cephalograph of the skull was taken for orthodontic purposes. The cephalograph revealed that the sella turcica was abnormally shaped. Magnetic resonance imaging of the patient confirmed the presence of a pituitary adenoma in the sellar region. This article reports and discusses the incidental finding of a pituitary adenoma and also emphasizes the orthodontist's important role in the initial diagnosis of such cases.


Phase II trial of 5-FU administered Ip to patients with refractory ovarian cancer.
A phase II study of ip 5-FU was performed in 14 patients with ovarian cancer who were refractory to systemic chemotherapy including prior iv 5-FU in 12 of the patients. 5-FU was administered via a semipermanent Tenckhoff peritoneal dialysis catheter. The starting concentration of 5-FU in the dialysate was 4 mM. The patients received eight consecutive 2-L exchanges, each of 4-hour duration, for a total of 36 hours including time for instillation and drainage. Treatment courses were repeated every 2 weeks for six cycles or until disease progression occurred. A total of 69 cycles of ip 5-FU were administered to 14 patients. There was one complete response to therapy documented by second-look laparotomy. While the response rate was only 7%, in seven of eight (88%) patients with small volume disease (tumor masses less than 2.0 cm in diameter), there was no evidence for disease progression while receiving ip 5-FU therapy. In this phase II trial, the major toxic effect of ip 5-FU was abdominal pain. While there were no cases of documented bacterial peritonitis, all of the patients experienced some degree of abdominal discomfort while receiving therapy. Fifty percent of the patients had severe abdominal pain with at least one cycle of therapy. Other toxic effects included myelosuppression, mucositis, nausea and vomiting, and skin rash. The results of this study indicate that ip 5-FU should be further evaluated in patients with ovarian cancer who have a small volume of disease and who have not had prior therapy with 5-FU.


Enhanced growth and bioconversion of isoflavones in prebiotic-soymilk fermented by UV-treated lactobacilli and bifidobacteria.
The aim of this study was to evaluate the effects of ultraviolet (UV) radiation (ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC) at 30-90 J/m²) on the membrane properties of lactobacilli and bifidobacteria, and their bioconversion of isoflavones in prebiotic-soymilk. UV treatment caused membrane permeabilization and alteration at the acyl chain, polar head and interface region of membrane bilayers via lipid peroxidation. Such alteration subsequently led to decreased (p < 0.05) viability of lactobacilli and bifidobacteria immediately after the treatment. However, the effect was transient where cells treated with UV, particularly UVA, grew better in prebiotic-soymilk than the control upon fermentation at 37°C for 24 h (p < 0.05). In addition, UV treatment also increased (p < 0.05) the intracellular and extracellular β-glucosidase activity of lactobacilli and bifidobacteria. This was accompanied by an increased (p < 0.05) bioconversion of glucosides to bioactive aglycones in prebiotic-soymilk. Our present study illustrated that treatment of lactobacilli and bifidobacteria with UV could develop a fermented prebiotic-soymilk with enhanced bioactivity.


Epidemiology of thrombotic risk factors: the difficulty in using clinical trials to develop a risk assessment model.
There is a paucity of data assessing the risks and prevention of venous thromboembolism in critical care settings. Consequently, it is difficult to estimate the risk of venous thromboembolism for a typical patient, on an individual basis, and this difficulty leads to underuse of thromboprophylaxis, especially in intensive care unit patients. Thrombosis is a multifactorial disease and patients may present multiple risk factors simultaneously. The problem in quantifying risk factors is to combine these risk factors even when they are not detected in the same multivariate analysis. A model for predicting the risk of venous thromboembolism in hospitalized medical patients has yet to be developed and validated. Meanwhile, other approaches have been proposed to replace the ideal study utilizing a large prospective cohort of hospitalized medical patients. In this context, several scoring systems based on risk assessment models have been proposed, some including the use of computerized electronic prompts, to help physicians prescribe appropriate prophylaxis. This article reviews evidence on the risk of venous thromboembolism associated with different medical conditions and risk factors, and presents a tentative risk-assessment model for risk stratification in hospitalized medical patients.


Outcome of severe acute pancreatitis: is there a role for conservative management of infected pancreatic necrosis?
Infected pancreatic necrosis is associated with high morbidity and mortality and is mandatory for surgical or radiological intervention. A selected group of patients with CT evidence of infected pancreatic necrosis and a comparatively lower APACHE score may be clinically stable throughout the course of their illness. Case records of 52 patients with severe acute pancreatitis admitted from October 2000 to September 2005 were retrospectively analysed to assess the feasibility of conservative management of infected pancreatic necrosis. CT evidence of retroperitoneal air pockets, deteriorated clinical condition, sepsis and positive blood culture were used to diagnose infected pancreatic necrosis. In the 52 male patients reviewed, 24 patients had infected pancreatic necrosis. Eighteen patients who had progressively deteriorated clinical conditions required surgical intervention; five patients of whom (27.8%) died. Six patients with transient end organ dysfunction and stable clinical conditions were treated with prolonged administration of antibiotics and ICU support. All these patients recovered and discharged from the hospital, and no symptoms or readmission happened during follow-up of 6-44 months. Selected patients with infected pancreatic necrosis who are clinically stable with transient end organ dysfunction can be treated conservatively with a favourable outcome. Necrosectomy associated with high morbidity and mortality in these patients can be avoided. The need for intervention should be individualized and based on clinical conditions of the patients.


tert-Butyl N-(4-hy-droxy-benz-yl)-N-[4-(prop-2-yn-yloxy)benz-yl]carbamate.
In the crystal structure of the title compound, C(22)H(25)NO(4), inter-molecular O-H⋯O hydrogen bonds involving the hy-droxy group of the 4-(amimometh-yl)phenol fragment and the C=O group connect the mol-ecules into infinite chains along the c axis. Two C atoms of the propyne group are disordered over two sites with occupancy factors of 0.53 (2) and 0.47 (2).


Level of neighborhood environmental factors related to noncommunicable diseases in selected wards of urban Puducherry, South India.
Noncommunicable diseases (NCDs) are the leading causes of mortality worldwide. Environmental factors play an important role in development of risk factors. Hence, the study was done to assess the neighborhood environmental factors related to NCDs in urban area. This community-based cross-sectional study was carried out among three selected wards of urban Puducherry. All shops/establishments related to the risk of NCDs within the study area were study units. Information regarding tobacco, alcohol, diet, and physical activity-related establishments was assessed using pretested semi-structured pro forma. Shops/establishments were labeled either as "favorable" (prevents the risk of NCDs) or "unfavorable" (increases the risk of NCDs). Among 655 establishments, 372 (56.8%) belonged to favorable and 283 (43.2%) to unfavorable category, respectively. Tobacco-related establishments amount to 15.1% (95% confidence interval: 12.6-18.1) of the total establishments. Among these tobacco establishments, almost one-third were selling tobacco to minor and located within 100 m of school. Fruits and vegetable markets contributed to 21.8% of the total establishments. About 22% of the establishments were fast-food outlets. Public health sports facilities were only 6.8% of the total establishments. The current study reported almost equal distribution of favorable and unfavorable establishments. However, among unfavorable establishments, tobacco establishments raised concern as one-third of those were selling tobacco to minors. Healthy diet and physical activity related establishments were also found to be less. Hence, corrective measures are to be implemented which will reduce the burden of behavioral risk factors.


Specific nuclear elimination in polyploid plasmodia of the slime mold Physarum polycephalum.
In growing plasmodia of the myxomycete Physarum polycephalum (G2-phase), three distinct classes of nuclei with a relative DNA content of 1x, 2x, and 4x are observed in the presumed haploid strain CL. The 2x and 4x species comprise up to 35% and 5% of the nuclei. Quantitative cytofluorometric studies of nuclei isolated in either G2- or S-phase or after FUDR treatment (G1 arrest) show that the three nuclear populations undergo a synchronous mitotic cycle and that the relative DNA content of the nuclear fractions in G-2 phase reflects the 2c, 4c, and 8c state. The heterogeneity of the nuclear population does, however, seem to be restricted to the growth phase. During a starvation period of 4 days that always preceeds sporulation (and also meiosis), the 4c nuclear population is reduced to 7%, 8c nuclei are no longer detected. These results suggest that a mechanism exists in Physarum for the selective detection and elimination of polyploid nuclei.


[Operative results of distal aortic arch aneurysms--approaching methods, bypass techniques and complications].
Ten patients underwent repair of aneurysms of the distal aortic arch from 1985 to 1989. There were 8 men and 2 women: aged 58 to 77 (average age 67 years). Seven patients had sacciform aneurysms which were closed by graft patch aortoplasty, and three patients had fusiform aneurysms which were corrected by inserting tube grafts. Seven aneurysms operated since 1988 were approached through median sternotomy continued with left anterior thoracotomy, so called door open method. This approach presented good view of the diseased aorta, and effective for preventing recurrent and phrenic nerve palsy. We used temporary bypass for 4 patients, cardiopulmonary bypass for 4 patients (separate carotid artery perfusion for 2 patients) and centrifugal pump for 2 patients during aortic cross clamping. One patient died intraoperatively from intractable bleeding and two patients died postoperatively from brain damage due to embolic episodes during the operations. These patients showed the severely irregular intima in the aortic arch and were complicated with rupture of the aneurysm or dissections arising from the aneurysms. It should be noticed that careless manipulation of the aortic arch and the brachiocephalic vessels cause cerebral complications in such cases.