Evaluation of biodegradable polymer conduits--poly(L-lactic acid)--for guiding sciatic nerve regeneration in mice.
Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) - PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.


Integrating visuospatial information across distinct experiences.
In two experiments, we examined whether the presence of stable visual information and the confluence of the viewpoints would cause participants to integrate in a single memory representation spatial locations they encoded at different points in time. Participants studied from the same or from different viewpoints two layouts of objects within a common visually cluttered room. Then, they carried out a series of pointing trials that involved objects from either the same or different layouts. Results showed that participants were faster for within- than between-layout judgments when they had studied the two layouts from different viewpoints but were equally fast across the two types of judgment after studying the layouts from the same viewpoint (Experiment 1). This finding suggests that they integrated locations into a single representation only when encoding the layouts from the same viewpoint. However, when participants' memory for the layout studied first was refreshed prior to testing (Experiment 2), no difference in response time was found, suggesting that they had integrated all locations in a single representation before the beginning of testing.


Uncertainty quantification and attention-aware fusion guided multi-modal MR brain tumor segmentation.
Brain tumor is one of the most aggressive cancers in the world, accurate brain tumor segmentation plays a critical role in clinical diagnosis and treatment planning. Although deep learning models have presented remarkable success in medical segmentation, they can only obtain the segmentation map without capturing the segmentation uncertainty. To achieve accurate and safe clinical results, it is necessary to produce extra uncertainty maps to assist the subsequent segmentation revision. To this end, we propose to exploit the uncertainty quantification in the deep learning model and apply it to multi-modal brain tumor segmentation. In addition, we develop an effective attention-aware multi-modal fusion method to learn the complimentary feature information from the multiple MR modalities. First, a multi-encoder-based 3D U-Net is proposed to obtain the initial segmentation results. Then, an estimated Bayesian model is presented to measure the uncertainty of the initial segmentation results. Finally, the obtained uncertainty maps are integrated into a deep learning-based segmentation network, serving as an additional constraint information to further refine the segmentation results. The proposed network is evaluated on publicly available BraTS 2018 and BraTS 2019 datasets. The experimental results demonstrate that the proposed method outperforms the previous state-of-the-art methods on Dice score, Hausdorff distance and Sensitivity metrics. Furthermore, the proposed components could be easily applied to other network architectures and other computer vision fields.


Jasmonate in lepidopteran eggs and neonates.
Jasmonic acid (JA) is a key molecule initiating plant defensive responses to attack by pathogens and herbivores. This phytohormone is produced at sites of insect damage and is ingested by feeding insects, but its subsequent occurrence in insect tissues remains to be studied. We report the presence of JA in eggs and neonates of all nine lepidopteran species that we screened, representing four superfamilies and five families of Lepidoptera. Concentrations of JA in some lepidopteran species far exceeded those found in most plant species. Levels of JA varied significantly among species and between eggs and neonates of the same species. In some cases, eggs contained significantly more JA than neonates, but for at least one species (Lymantria dispar) neonates had more JA than their eggs despite lacking food upon emergence. The presence of JA in eggs and neonates across a wide taxonomic range may indicate that JA has an undescribed function in insects.


Localization of the human progesterone receptor gene to chromosome 11q22-q23.
The human progesterone receptor gene was mapped by in situ hybridization using two cDNA probes corresponding to the 5' and 3' part of the coding sequence. This gene was localized to 11q22-q23.


Directional atherectomy in iliac stent failure: clinical technique and histopathologic correlation.
To assess the feasibility and efficacy of directional atherectomy in the treatment of iliac stent stenosis or occlusion and to evaluate the histologic composition of excised atherectomy specimens. Directional atherectomy of six occluded and 10 severely stenosed iliac stents was undertaken in 12 patients at a mean interval of 28 months (range 3-69 months) after stent insertion for occlusive aortoiliac disease. In cases of stent occlusion, atherectomy was preceded by low-dose thrombolysis. In all patients stent clearance with return of femoral pulses was achieved within 24 hr and there were no significant complications. All excised specimens were sent for histologic examination. Eleven patients (92%) remain symptom free with unlimited walking distance at a mean follow-up interval of 11.5 months (range 3-31 months) after treatment. Histologic examination revealed typical myointimal hyperplasia at three excision sites, intimal fibrosis at three sites, atheroma at four sites and organized thrombus at six sites. Atherectomy offers an effective treatment in iliac stent occlusion and restenosis with no significant adverse effects. Debulking of these lesions seems to offer a more logical approach than simple balloon angioplasty. Clinical and duplex follow-up confirms satisfactory outcome within the first year but longer-term results are not yet known. The histologic data obtained demonstrate that stent restenosis and occlusion are likely to be multifactorial, and challenge the assumption that myointimal hyperplasia is the sole cause of iliac stent occlusion.


Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study.
The FDA has recently endorsed metformin use in patients with T2D and stage 3 CKD (CKD3). However, metformin safety in elderly individuals is unknown. The aim of this study was to identify frequency and risk factors of lactic acid (LA) elevation in ambulatory elderly male US veterans with stable diabetic CKD3 treated with metformin. We studied 92 patients with non-diabetic CKD3 (Group1), diabetic CKD3 not on metformin (Group2) and diabetic CKD3 on metformin (Group 3). Mean LA levels were similar at 1.3 ± 0.3 and 1.3 ± 0.4 mmol/L in Groups 1 and 2, respectively; while, LA was significantly higher in Group 3 (2.1 ± 1.0 mmol/L, P < .001). Only 1 patient in each Groups 1 (4%) and 2 (4%) had hyperlactatemia (LA > 2.0 mmol/L), as compared with 17 (42.5%) patients in Group 3 (P < .05). No differences in age, BMI, eGFR, metformin dosage, and HbA1c were seen in Group 3 patients with and without hyperlactatemia. In the multivariate logistic regression analyses, metformin use was the only factor significantly associated with hyperlactatemia (adjusted OR 25.48, P < .005). In conclusion, metformin therapy is associated with increased risk of hyperlactatemia in elderly men with diabetic CKD3.


Evidence for the involvement of the transcortin carbohydrate moiety in the glycoprotein interaction with the plasma membrane of human placental syncytiotrophoblast.
We have studied the interaction of human transcortin and the pregnancy-associated transcortin variant with the microvesicular membrane fraction derived from the human placental syncytiotrophoblast. Two classes of specific binding sites for these glycoproteins were found in this membrane preparation. One of these displays a relatively high binding capacity, Bmax = 140 +/- 60 fmol transcortin per mg membrane protein, and a significantly higher affinity for transcortin, Kd = (1.6 +/- 0.6).10(-10) mol/l, than for the pregnancy-associated variant, Kd = (4.5 +/- 1.2).10(-9) mol/l. On the contrary, another class of the binding sites, occurring in the membranes at a far lower concentration: Bmax = 3.0 +/- 2.2 fmol transcortin per mg membrane protein, shows a higher affinity for the pregnancy-associated transcortin variant, Kd = (3.3 +/- 2.0).10(-12) mol/l, than for normal transcortin, Kd = (2.5 +/- 0.7).10(-11) mol/l. Since the pregnancy-associated variant differs from normal transcortin with respect to its carbohydrate structures only (Avvakumov, G.V. and Strel'chyonok, O.A. (1987) Biochim. Biophys. Acta 925, 11-16), the results of the present work suggest that the transcortin carbohydrates are directly involved in the specific interaction of this serum hormone-binding globulin with the plasma membrane of the placental syncytiotrophoblast.


Crystallogenesis of adenosine A(2A) receptor-T4 lysozyme fusion protein: a practical route for the structure.
G-protein-coupled receptors (GPCRs) represent a major class of receptors through which a number of signals ranging from photons to large glycoprotein hormones are recognized. Human genome encodes about 800 GPCRs, yet very little structural information is available on this class of receptors. Structural studies provide a wealth of information about not only the activation mechanism of the receptor but also the crucial information about the ligand-binding pocket which could lead to the development of subtype-specific ligands. The crystal structure of human adenosine A(2A) receptor was solved in complex with a high-affinity antagonist ZM241385 at 2.6Å resolution. Here, we describe the methods that were undertaken to solve the fusion protein structure.


[Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling].
The small guanosine triphosphatase Rho and its target, Rho kinase, play important roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein, such as angiotensin II and phenylephrine. Once Rho is activated, it translocates to the cell membrane where it, in turn, activates Rho kinase. Activated Rho kinase phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation,and cell migration. In this way, Rho and Rho kinase activation have important effects on several cardiovascular diseases. Currently available substances that specifically inhibit this signaling pathway could offer clinical benefits in several cardiovascular, as well as noncardiovascular diseases, such as arterial hypertension, pulmonary hypertension, cerebral or coronary spasm, post-angioplasty restenosis, and erectile dysfunction.


Comparative study of the resistance of manual and mechanical sutures in the bronchial stump of dogs submitted to left pneumonectomy.
To compare the resistance of manual suture with that of mechanical suture immediately after the suture of the left bronchial stump of dogs submitted to pneumonectomy. A total of 15 mixed-breed dogs of both genders, each weighing between 8 and 23 kg, were randomly divided into 2 groups. In group I (n = 7), the bronchial stump was sutured manually (the Sweet method) and, in group II (n = 8), it was stapled. Immediately after the closure of the bronchial stump, the intratracheal pressure was progressively increased in a controlled manner. The mean rupture pressure of the bronchial stump suture line was 33.71 mmHg in group I and 89.87 mmHg in group II (p < 0.01). These data allowed us to conclude that mechanical suture of the bronchial stump, submitted to pressure immediately after closure, is more resistant than is manual suture in dogs submitted to pneumonectomy.


Haemodynamic responses to laryngoscopy and tracheal intubation in geriatric patients: effects of fentanyl, lidocaine and thiopentone.
The haemodynamic responses to laryngoscopy and intubation after induction of anaesthesia with thiopentone alone or in combination with 1.5 mg.kg-1 lidocaine and/or 1.5 or 3.0 microgram.kg-1 fentanyl were measured in 150 patients over 64 years of age to determine whether lidocaine, fentanyl or both lidocaine and fentanyl attenuated the pressor response. Fentanyl reduced the rises in systolic, diastolic and mean arterial pressures, heart rate, and rate pressure product and lidocaine decreased the rises in arterial blood pressure and rate pressure product (P less than 0.05). Fentanyl decreased the incidence of marked fluctuations in haemodynamic variables, often seen in geriatric patients (P less than 0.05). The haemodynamic effects of lidocaine and fentanyl were independent of each other. Complications occurred in all groups. Lidocaine-treated patients had fewer cardiac dysrhythmias (P less than 0.05) and 34 per cent of them had tinnitus. Fentanyl-treated patients had a higher incidence of hypotension (P less than 0.05). Respiratory depression developed in only one per cent of the fentanyl-treated patients. Both lidocaine and fentanyl are recommended adjuncts to induction of anaesthesia with thiopentone in geriatric patients.


Epidermal growth factor differentially regulates low density lipoprotein receptor-related protein gene expression in neoplastic and fetal human astrocytes.
Low density lipoprotein receptor-related protein (LRP) is a multifunctional endocytotic receptor that may modify the biological activity of reactive astrocytes in neuroplasticity and neurodegeneration and of malignant astrocytes in brain invasion. In this study, the regulation of LRP by epidermal growth factor receptor (EGFR) ligands in both cultured human fetal astrocytes and astrocytic tumor cell lines (U-251 MG and U-1242 MG) was investigated. All astrocytic cell types expressed LRP, as determined by the binding of activated alpha2-macroglobulin (alpha2M*) on intact cells and by Western and Northern blot analyses of cell extracts. Primary cultured astrocytes expressed the highest levels of alpha2M*-binding capacity (Bmax = 30 fmol/mg protein). This was twofold higher than for the U-1242 MG astrocytoma cells (Bmax = 15 fmol/mg protein) and fourfold greater than for the glioblastoma U-251 MG cells (7.0 fmol/mg protein). Receptor affinity (K(D)) ranged from 0.25 to 0.6 nM in all the astroglial cell types. Functional LRP at the surface was down-regulated by EGF, compared with controls, as indicated by a reduction of both Bmax and LRP-mediated endocytosis by approximately 50% and 60%, respectively. In comparison, EGF treatment of primary astrocytes did not down-regulate LRP expression or LRP-mediated endocytosis. Treatment of the tumor cells with EGF or TGFalpha (25 ng/ml) significantly down-regulated total cellular LRP. Receptor-associated protein (RAP) mRNA expression was not affected by EGF in either tumor cells or primary astrocytes. The reduction of LRP in the tumor cells resulted from a specific decrease in LRP mRNA transcription, as determined by Northern blot and nuclear run-on experiments. These data suggest that EGF mediates a functional down-regulation of LRP endocytotic activity in astrocytic tumor cells and that LRP expression is differentially regulated in neoplastic and non-neoplastic astrocytes.


Evaluation of clinical named entity recognition methods for Serbian electronic health records.
The importance of clinical natural language processing (NLP) has increased with the adoption of electronic health records (EHRs). One of the critical tasks in clinical NLP is named entity recognition (NER). Clinical NER in the Serbian language is a severely under-researched area. The few approaches that have been proposed so far are based on rules or machine-learning models with hand-crafted features, while current state-of-the-art models have not been explored. The objective of this paper is to assess the performance of state-of-the-art NER methods on clinical narratives in the Serbian language. We designed an experimental setup for a comprehensive evaluation of state-of-the-art NER models. The gold standard corpus we used for the evaluation is comprised of discharge summaries from the Clinic for Nephrology at the University Clinical Center of Serbia. The following models were evaluated: conditional random fields (CRF), multilingual transformers (BERT Multilingual and XLM RoBERTa), and long short-term memory (LSTM) recurrent neural networks, and their ensembles. In addition, we investigated the necessity of the pretraining task of transformer based models and the use of pretrained word embeddings with LSTM model. Our results show that individually CRF had the best precision, the pretrained BERT Multilingual model had the best recall values, and the LSTM model had the best F1 score. The best performance was achieved by combining the existing models in a majority voting ensemble with an F1 score of 0.892. The presented results are similar to the inter annotator agreement on our gold standard corpus and are comparable to existing state-of-the-art results for clinical NER reported in literature. Existing state-of-the-art models can provide viable results for clinical named entity recognition when applied to languages with the complexity of the Serbian language without major modifications.


Electrophoretic separation of purified myelin: a method to improve the protein pattern resolving.
Myelin sheath is a lipid-rich membrane, consisting of 70% lipid and 30% proteins, that is involved in physiological and pathological processes. For this reason its protein composition has been often investigated, principally by two-dimensional electrophoresis; however, the consistent lipid content makes it difficult to obtain good proteins separation. To improve the resolution of myelin proteins in a denaturing monodimensional gel electrophoresis, we examined several mixtures for the denaturation of the sample, utilizing different detergents and reducing agents. The definition of the protein pattern was analyzed by both "Blue Silver" Coomassie staining and Western Blot analysis against myelin basic protein, one of the most represented myelin proteins. The best resolution is observed when the sample was incubated with a mixture containing 1.25% dithiothreitol, 4 M urea, and 1% dodecyl maltoside or 1 % 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, prior to addition of denaturing agents. In conclusion, this work describes a novel method to improve the separation of myelin proteins in a monodimensional gel electrophoresis. It may be also useful for investigating other lipid-rich samples.


Maternal mortality. A report of the KMA Maternal Mortality Study Committee.
This maternal mortality report delineates the course of a myocardial infarction subsequent to a cesarean section. A brief discussion of this entity is presented.


Disruptive patterns of eating behaviors and associated lifestyles in males with ADHD.
Attention deficit hyperactivity disorder (ADHD) is a neurological/behavioral disorder characterized by inattention or hyperactivity and impulsivity, or combined symptomatology. Children with ADHD are predisposed to irregular and/or impulsive eating patterns often leading to compromised physical condition. The goal of the present study was to statistically evaluate parental scoring of patterned eating behaviors and associated lifestyles within a cohort of 100 boys diagnosed with ADHD in comparison to age-matched male controls. The study population consisted of 100 boys aged 6-10 years diagnosed with mixed type ADHD by DSM-IV criteria and 100 aged-matched healthy male control subjects. Patterns of eating behaviors and associated lifestyles were scored by structured parental interviews using a nominal rating scale. Interview scores indicated statistically significant differences in patterned eating behaviors in subjects with ADHD in comparison to healthy controls. Notably, subjects diagnosed with ADHD exhibited markedly diminished adherence to a traditional breakfast, lunch, and dinner schedule, which was linked to a significantly higher frequency (>5/day) of irregular eating times. In the ADHD cohort, disruptive patterns of eating behaviors were associated with diminished nutritional value of ingested food (expressed as lowered content of fruits and vegetables) and increased consumption of sweetened beverages. Disruptive patterns of eating behaviors, metabolically unfavorable nutritional status, and diminished physical activities of male children diagnosed with ADHD are linked to compromised growth and development and appearance of metabolic diseases in adulthood.


Evolution of prokaryotic genomes.
Molecular genetics, which has its roots mainly in the development of microbial genetics in the middle of this century, not only greatly facilitates investigations of essential cellular functions, but also offers a means to better understand evolutionary progress. Spontaneous mutagenesis, the driving force of biological evolution, depends on a multitude of mechanistically distinct processes, many of which are already quite well understood. Often, enzymes act as variation generators, and natural gene vectors help to spread functional domains, entire genes and groups of genes across natural isolation barriers. In this overview, particular attention is given to comparing three selected natural strategies for the generation of genetic diversity: nucleotide substitution, DNA rearrangements, and gene acquisition. All of these mechanisms, as well as many others, appear to fulfill their specific roles in microbial evolution. Rather than being the result of an accumulation of errors, biological evolution may depend on a multitude of specific biological functions, as well as on a certain degree of intrinsic structural flexibility of biological molecules.


Histopathology of pineal germ cell tumors.
Germ cell tumors (GCTs) classically occur in gonads. However, they are the most frequent neoplasms in the pineal region. The pineal location of GCTs may be caused by the neoplastic transformation of a primordial germ cell that has mismigrated. The World Health Organization (WHO) recognizes 5 histological types of intracranial GCTs: germinoma and non-germinomatous tumors including embryonal carcinoma, yolk sac tumor, choriocarcinoma and mature or immature teratoma. Germinomas and teratomas are frequently encountered as pure tumors whereas the other types are mostly part of mixed GCTs. In this situation, the neuropathologist has to be able to identify each component of a GCT. When diagnosis is difficult, use of recent immunohistochemical markers such as OCT(octamer-binding transcription factor)3/4, Glypican 3, SALL(sal-like protein)4 may be required. OCT3/4 is helpful in the diagnosis of germinomas, Glypican 3 in the diagnosis of yolk sac tumors and SALL4 in the diagnosis of the germ cell nature of an intracranial tumor. When the germ cell nature of a pineal tumor is doubtful, the finding of an isochromosome 12p suggests the diagnosis of GCT. The final pathological report should always be confronted with the clinical data, especially the serum or cerebrospinal fluid levels of β-human chorionic gonadotropin (HCG) and alpha-fetoprotein.


The height of the pituitary in preterm infants during the first 2 years of life: an MRI study.
Pituitary secretory activity is different in premature and full-term infants. The height of the pituitary is a marker of its secretory activity. Our purpose was to use MRI to measure height of the pituitary of premature infants and to compare it with full-term controls. The height was measured on a midline sagittal T1-weighted image in 86 premature infants (gestational age 26-36.9 weeks, mean 32.3+/-2.85 weeks, corrected age 0.33-2 years, mean 0.76+/-0.42 years) and in 70 age- and sex-matched full-term controls. The children were was divided into four age groups: A: > or =0.5 years; B: 0.51-1.0 year; C: 1.01-1.5 years; and D: 1.51-2.00 years. The gland was significantly (P<0.01) higher in the preterm infants than in the controls (3.88+/-0.61 vs 3.31+/-0.64 mm). In the preterm group no significant difference was found between children small or appropriate for gestational age or between those with and without periventricular leukomalacia. Pituitary height by age group was: A: 3.71+/-0.57, B: 3.81+/-0.56, C: 4.09+/-0.68; and D:4.45+/-0.57 mm; statistically significant (P<0.01) differences were found between groups A and D and B and D. The pituitary is thus higher in premature than in full-term controls and shows a trend to increase after the first year of corrected-age life.


Effectiveness of a Prudhoe Bay crude oil and its aliphatic, aromatic and heterocyclic fractions in inducing mortality and aryl hydrocarbon hydroxylase in chick embryo in ovo.
Prudhoe Bay crude oil (PBCO) and its aliphatic, aromatic and heterocyclic fractions were tested on the developing chick embryo for (i) embryotoxicity (ii) their ability to induce hepatic and renal cytochrome P450 levels as well as hepatic, renal and pulmonary aryl hydrocarbon hydroxylase activities. On the basis of its concentration in PBCO, the aromatic fraction was responsible for most of the embryotoxicity as well as for the enzyme inducing ability. The NOS fraction constituted less than 7% (w/v) of PBCO but, on a weight equivalent basis, was roughly as potent as the aromatic fraction in causing embryotoxicity and in inducing cytochrome P450 levels and aryl hydrocarbon hydroxylase. The aliphatic fraction was found to be essentially inactive. The results are consistent with the concept that elevation of aryl hydrocarbon hydroxylase levels by certain components of PBCO may lead to increased embryotoxicity.


The role of clonal hematopoiesis as driver of therapy-related myeloid neoplasms after autologous stem cell transplantation.
Therapy-related myeloid neoplasm (t-MN) is a threatening complication of autologous stem cell transplantation (ASCT). Detecting clonal hematopoiesis (CH) mutations in cryopreserved cells before ASCT has been associated with a higher risk of t-MN, but the evolution of molecular abnormalities from pre-ASCT to t-MN, within the same patient, remains to be elucidated. We evaluated the mutational profile of 19 lymphoma/myeloma patients, at both pre-ASCT and t-MN diagnosis, using a targeted NGS approach; 26 non-developing t-MN control patients were also studied pre-ASCT. At ASCT, we found a higher frequency of CH in patients developing t-MN (58%) than in those who did not (23%) (P = 0.029); mutations in epigenetic (DNMT3A, TET2, and ASXL1) and DNA repair genes (PPM1D, RAD21, TP53, and STAG2) were the most represented. At t-MN, CH increased to 82% of patients. Cumulative mutational burden and variant allele frequency (VAF) also increased at t-MN. CH clones detected at ASCT were found at t-MN in eight out of 16 patients, mainly with stable VAF. Among the new driver mutations appeared at t-MN, TP53 increased from one to 13 mutations, in nine patients; being associated with complex karyotype. Mutations in transcription factor (RUNX1, CEBPA) and intracellular signaling genes (FLT3, RAS genes) also increased from three to 17 mutations in eight patients, presenting with a normal karyotype. Overall, we found that preexisting CH at ASCT rarely causes t-MN directly, but may rather facilitate the appearance of new mutations, especially those involving TP53, RUNX1, and RAS, that can drive the evolution to t-MN of at least two distinct types.


Positive and negative health behaviors used to ensure compliance with the U.S. Army's weight control standards by a reserve component unit.
This paper describes the results of a nonexperimental descriptive research study in which specific positive and negative health behaviors used by soldiers in a medical reserve unit to ensure compliance with the Army Weight Control standards were surveyed using a questionnaire. The findings of the survey, particularly the prevalent use of negative health behaviors to control or maintain weight, were startling. The authors offer their conclusions and propose solutions relative to changing the emphasis of the program from having a single focus, i.e., weight control, to a comprehensive focus, i.e., physical fitness and wellness.


Morphological distribution and internal enhancement architecture of contrast-enhanced magnetic resonance imaging in the diagnosis of non-mass-like breast lesions: a meta-analysis.
The aim of this study is to assess the diagnostic performance of contrast-enhanced magnetic resonance (MR) imaging in patients with non-mass-like breast lesions in a meta-analysis. Literature study was performed on PubMed data base on the diagnostic performance of MR imaging in patients with non-mass-like breast lesions. Details of the relevant studies were reviewed and a meta-analysis was performed to estimate the overall sensitivity and specificity of contrast-enhanced MR imaging of non-mass-like breast lesions. A summary receiver operating characteristic curve (sROC) was developed to explore the threshold effect by ROC space. Spearman correlation coefficient was calculated using Meta-Disc version 1.4 to analyze the heterogeneity between studies. A total of 858 non-mass-like lesions from 15 studies were included in the meta-analysis (sample size range: 27-131). Pooled weighted estimates of sensitivity and specificity were 50% (95% CI: 46%, 53%) and 80% (95% CI: 77%, 83%), respectively. The heterogeneity among studies was caused by other factors other than threshold effect. The findings were influenced by cancer prevalence (p = 0.0359). Subgroup analyses indicated that the sensitivity and specificity in studies with combined diagnostic criterion was higher than that in studies with single diagnostic criterion. In evaluation of non-mass-like breast lesions, contrast-enhanced MRI has high specificity and relatively lower sensitivity.


On the art of stealing chloroplasts.
Sea slugs increase the longevity of the chloroplasts they steal from algae by limiting the harmful side-effects of photosynthesis.


Correction: Phylogenetic Analysis Reveals a Cryptic Species Blastomyces gilchristii, sp. nov. within the Human Pathogenic Fungus Blastomyces dermatitidis.
[This corrects the article DOI: 10.1371/journal.pone.0059237.].


Uptake, distribution and elimination of chemicals in fish - Which physiological parameters are the most relevant for toxicokinetics?
Bioconcentration and toxicity studies are regularly conducted for the risk assessment of chemicals. If such tests yield different results for different fish species, this can either be due to differences in toxicokinetics or to differences in toxicodynamics. Here we investigate which physiological parameters could cause major differences in the toxicokinetics in fish. To this end it is important to distinguish physiological parameters that affect the sorption capacity of the fish from those that affect kinetic processes. Variability in the lipid content of a fish is the most influential parameter for the sorption capacity of fish and therefore most relevant for the total concentration in fish under steady-state conditions when metabolism is not relevant. In terms of kinetics, ventilation rate, uptake efficiency from food and metabolism are the most influential factors. While ventilation rate can roughly be estimated from allometric scaling equations, little general information is available on the uptake efficiency from food. The metabolism rate constant appears to be the single most influential toxicokinetic factor. This information cannot be estimated but must be determined experimentally, preferably from in vitro experiments.


Effect of ultraviolet irradiation on postharvest quality and composition of tomatoes: a review.
Ultraviolet (UV) irradiation has recently emerged as a possible alternative to currently used postharvest phytosanitary treatments. Research has also highlighted other benefits associated with UV irradiation in postharvest technology. This review presents the effects of UV irradiation on postharvest and nutritional quality of tomatoes. The application of UV irradiation on tomatoes is discussed including its effect on biological (respiration rate, ethylene production and microbial growth), physico-chemical (firmness, colour, total soluble solids and titratable acidity) and nutritional (vitamins, carotenoids, phenolic and antioxidants) quality. UV-treated tomatoes have shown resistance to microbial growth and decay. Although UV irradiation reduces the loss of vitamin C during storage, the loss of vitamin E remains a concern. UV treatments lead to higher antioxidant capacity, flavonoids and phenolic content. UV irradiation significantly reduced carotenoids in certain cultivars. Based on the literature reviewed, the success of UV irradiation treatments is cultivar-dependent. While improved retention of phytochemicals has been reported in UV-C treated fruit, increased losses have been reported in certain cultivars. Research efforts on the development of cultivar-specific UV irradiation protocols are warranted. The effect of harvest maturity and seasonal differences in the efficacy of UV treatments is required to be investigated.


Can maximal aerobic running speed be predicted from submaximal cycle ergometry in soccer players? The effects of age, anthropometry and positional roles.
Considering maximal aerobic running speed (MAS) as a useful tool to evaluate aerobic capacity and monitor training load in soccer, there is an increasing need to develop indirect assessment methods of MAS, e.g., submaximal tests. The aim of this study was to examine the prediction of MAS from the physical working capacity (PWC) in heart rate (HR) 170 beat/min test (PWC170). This cross-sectional study was done on adolescent (n = 67) and adult soccer players (n = 82) were examined for anthropometric characteristics, PWC170 and performed Conconi test to assess MAS. Midfielders scored higher than goalkeepers (GKs) and defenders in MAS while GKs scored lower than all the other playing positions. Although this trend was also observed in PWC170, statistical difference was only observed between midfielders and GKs. Players with higher MAS had also higher PWC170 in both age groups (P < 0.05). The odds ratio of a player of the best PWC170 group to belong also to the best MAS group was 3.96 (95% confidence interval 2.00; 7.84). That is players with high-performance in the PWC170 were about 4 times more likely than those with low PWC170 to achieve a high score in MAS. Regression analysis suggested body fat (BF) percentage, PWC170, maximal HR and age as predictors of MAS (R = 0.61, R (2) = 0.37 and standard error of estimate [SEE] =1.3 km/h, in total; R = 0.74, R (2) = 0.55 and SEE = 1.2 km/h, in adolescents; R = 0.55, R (2) = 0.30 and SEE = 1.3 km/h, in adults). While there was only moderate correlation between MAS and PWC170, the former can be predicted from the latter when BF, HRmax, and age are considered (large to very large multiple correlation coefficients).


[Craniocervical amyloid tumor with destructive spondyloarthropathy and myelocompression as a rare complication of long-term dialysis].
Dialysis-associated amyloidosis has become a frequent and sometimes disabling complication in long-term dialysis patients. The main protein implicated in amyloidosis is beta 2 microglobulin, which accumulates in patients with renal insufficiency. We report on a 47-year-old patient, who was on haemodialysis treatment for 17 years. After a period of 15 years on dialysis treatment he underwent surgery for a carpal tunnel syndrome. Two years later he developed destructive spondyloarthropathy of the cervical region and destruction of the occipital bone. He lost stability of his neck necessitating his remaining mainly in the lying position. Since the type of dialysis membrane may play an important role in the pathogenesis of dialysis-associated amyloidosis, a dialysator with a polysulfone membrane, which is assume to have a beneficial effect on the progression of amyloidosis, was established.


Microsomal epoxide hydrolase in different rat strains.
Epoxide hydrolase activity was determined in hepatic microsomes of adult males of 22 rat strains. The specific activity varied between 4.3 and 12.7 nmole styrene glycol/mg protein per min. The enzyme in F344, DA and Sprague--Dawley rats, strains with low, high and intermediate activity, respectively, was studied in more detail. No differences in substrate specificity and pH-dependence of the activity were observed between the strains with high and low activity, and immunoprecipitation by antibodies raised against microsomal epoxide hydrolase purified from Sprague--Dawley rats showed that the amounts of enzyme protein in microsomes from DA and F344 rats correlated with the activities. These results indicate quantitative rather than qualitative differences in epoxide hydrolase. The enzyme activity was inherited in an autosomal and codominant manner. The hepatic activity in females (about 78% of that in males) and, with the limitation that only few situations were studied, the trans-stilbene oxide-induced activity were under the same genetic control as the basal hepatic activity in males. In contrast, some extrahepatic tissues showed strain differences in epoxide hydrolase activity which contrasted with those found in liver. Hence, the enzyme activity in one tissue cannot serve as a reliable guide to the relative activity in another tissue, unless a specific correlation between the two tissues has been established. Although the strain differences in activity were not very large in themselves, in combination with inter-individual variation, sex differences and effects of the enzyme inducer transstilbene oxide they led to a 20-fold variation in hepatic epoxide hydrolase activity among the rats investigated in the present study.


Brief psychological interventions for borderline personality disorder. A systematic review and meta-analysis of randomised controlled trials.
People with Borderline Personality Disorder (BPD) have limited access to long term psychological therapies. Briefer interventions have been developed but trial evidence to support their use has not been reviewed. To examine whether psychological interventions for adults with BPD of six months duration or less improve symptoms, mood, self-harm, suicidal behaviour, and service use. The protocol was prospectively registered (PROSPERO CRD42017063777). Database searches were conducted up to April 2020. Inclusion, data extraction and risk of bias were assessed in duplicate. We identified 27 randomised controlled trials. We conducted random-effects meta-analyses sub-grouping data into delivery method, additional support, and comparison type. High levels of bias were found for attrition and reporting. Heterogeneity was high in some pooled data. Borderline symptom reductions were greatest for interventions including additional support (SMD. -1.23, 95% C.I. -2.13, -0.33). Planned generic support may be as effective as specialist interventions for borderline symptoms (SMD = -0.11, 95% C.I. -0.51, 0.29) and social functioning (SMD = -0.16., 95% C.I. -0.65, 0.33). Follow-up was limited and direct comparison with post-intervention results was unreliable. Short-term interventions may be effective. Access to additional support has an impact on outcomes. It is unclear if symptomatic change is sustained.


Breed, age, and social environment are associated with personality traits in dogs.
Personality in pets and other domesticated animals is important for their well-being and it can also influence human-animal relationships. Genetic and environmental factors influencing unwanted behavior in dogs are somewhat well known, but the factors influencing dog personality remain understudied. Here we examined environmental and demographic factors associated with seven broad personality traits in a survey of over 11,000 dogs. We utilized linear models and extensive model validation to examine the factors that have the most significant influences on personality and calculated effect sizes to assess the importance of these variables. Breed and age had the strongest associations with dog personality traits. Some environmental factors, especially puppyhood socialization, were also associated with personality. All factors had small effect sizes, highlighting that a lot of variation in personality remains unexplained. Our results indicate that personality traits are complex and strikingly similar in dogs, humans, and other nonhuman animals.


Magnetic resonance image-guided focal laser ablation in clinically localized prostate cancer: safety and efficacy.
To evaluate the safety and efficacy of focal laser ablation (FLA) in low-intermediate risk prostate cancer. Inclusion criteria were men aged 50-75 years, prostate-specific antigen (PSA) ≤15 ng/mL, clinical stage T1c-T2a, one or two lesions (PI-RADS ≥3) on magnetic resonance imaging (MRI), and Gleason score 6 (>3 mm) or Gleason 7 on targeted biopsy. Treatment success was defined as no clinically significant cancer in ablated areas. The study is prospective. Under MRI guidance, laser ablation was applied to the visible lesion(s). International Prostate Symptoms Score, Sexual Health Inventory in Men score and PSA levels were assessed at baseline and repeated at 1, 3, 6, 12 and 18 months. MRI was repeated at 3 and 12 months. Cancer control was assessed at 6 months using targeted and systematic biopsies. FLA was performed in 49 patients. Gleason scores were 3 + 3 in 13 patients (26.5%), 3 + 4 in 29 (59.2%) and 4 + 3 in 7 (14.3%). No significant complications were noticed. International Prostate Symptoms Score measurements up to 18 months were not different from baseline (all P > 0.05). Sexual Health Inventory in Men scores dropped in the first year (all P < 0.05), but were not different from baseline levels at 18 months (P = 0.097). PSA levels dropped significantly at 3-18 months (all P < 0.05). Treatment was successful in 39 patients (79.6%). Persistent cancer in treated areas was found in 10 patients (20.4%). FLA is safe with no impact on urinary and sexual functions at 18 months follow-up. Oncologic control is encouraging. Larger scale studies and longer follow-up are required.


Impaired face discrimination in acquired prosopagnosia is associated with abnormal response to individual faces in the right middle fusiform gyrus.
The middle fusiform gyrus (MFG) and the inferior occipital gyrus (IOG) are activated by both detection and identification of faces. Paradoxically, patients with acquired prosopagnosia following lesions to either of these regions in the right hemisphere cannot identify faces, but can still detect faces. Here we acquired functional magnetic resonance imaging (fMRI) data during face processing in a patient presenting a specific deficit in individual face recognition, following lesions encompassing the right IOG. Using an adaptation paradigm we show that the fMRI signal in the rMFG of the patient, while being larger in response to faces as compared to objects, does not differ between conditions presenting identical and distinct faces, in contrast to the larger response to distinct faces observed in controls. These results suggest that individual discrimination of faces critically depends on the integrity of both the rMFG and the rIOG, which may interact through re-entrant cortical connections in the normal brain.


Diagnostic and prognostic problems in early gastric cancer.
Although common in Japan, early gastric cancer is rarely seen in Western countries and generally accounts for only 7 to 10 percent of all gastric malignancies. Eleven patients with early gastric cancer seen over a 10 year period have been reviewed for clinical and pathologic features, method of diagnosis, treatment, and prognosis. The symptoms usually consisted of vague epigastric pain or dyspepsia, but anorexia, weight loss, anemia, and hypoalbuminemia were not commonly seen. Barium meal examination was not helpful in the diagnosis in 50 percent of the patients. The diagnosis was made by endoscopic biopsy of abnormal areas of the stomach, although in 6 of 11 patients, there was no macroscopic suspicion of malignancy. All patients were treated by surgical resection. The tumor was confined to the mucosa in five patients and had infiltrated the submucosa in six patients. The lymph nodes were free of tumor in every patient. At last follow-up, seven patients had survived more than 5 years after operation and were well, although recurrent tumors developed in two patients 3 and 4 years postoperatively but were detected early by endoscopic surveillance. Early gastric cancer has a good prognosis after surgical resection, but the symptoms are vague and the diagnostic tests can be misleading. A vigorous approach to investigation, treatment, and follow-up is necessary to achieve satisfactory results.


Genistein suppresses ox-LDL-elicited oxidative stress and senescence in HUVECs through the SIRT1-p66shc-Foxo3a pathways.
The anti-senescence function of genistein is related to inhibiting oxidative stress, however, the mechanism has not been clarified. The present study aimed to explore the effects of genistein on oxidized low-density lipoprotein (ox-LDL)-induced endothelial senescence and the role of the sirtuin-1 (SIRT1)-66-kDa Src homology 2 domain-containing protein (p66Shc)-forkhead box protein O3 (Foxo3a) pathways in the process. In this paper, human umbilical vein endothelial cells were pretreated with 1000 nM genistein for 30 min and then incubated with 50 mg/L ox-LDL for another 12 h; meanwhile, the functions of adenovirus-mediated overexpression of p66shc and small interfering RNA-mediated silencing of SIRT1 were investigated. Results showed that genistein pretreatment alleviated ox-LDL-induced mitochondrial reactive oxygen species, the levels of oxidatively modified DNA (8-OHdG) and pai-1, and the activity of SA-β-gal, which was associated with mitigating p66shc. Further studies indicated the inhibitory effect of genistein on p66shc was correlated with suppressing the acetylation and phosphorylation of p66shc, and ameliorating its mitochondrial translocation by activating SIRT1. Moreover, the inactivated p66shc could enhance the activity of Foxo3a via restraining the phosphorylation and triggering nucleus accumulation. The study demonstrates genistein could prevent ox-LDL-induced mitochondrial oxidative stress and senescence through the SIRT1-p66shc-Foxo3a pathways.


Epidermal growth factor enhances glomerular mesangial cell soluble phospholipase A2 activity.
We have previously characterized a hormonally regulated soluble form of phospholipase A2 (PLA2) in the cultured renal mesangial cell which is similar and possibly identical to the major form in rat kidney. In an attempt to further characterize the mechanisms of regulation of this enzyme we have used epidermal growth factor (EGF), which does not activate polyphosphoinositide-specific phospholipase C in these cells. EGF-enhanced PLA2 activity as assayed by the ability of the soluble extracts of cells to cleave arachidonic acid from the sn-2 position of phosphatidylcholine and phosphatidylethanolamine. This represents a direct demonstration of EGF-induced PLA2 activation which is preserved in a cell-free extract. Phorbol myristate acetate (PMA), as well as 1-oleoyl-2-acetylglycerol, also enhanced PLA2 activity. By contrast, the calcium ionophore A23187 had no effect on extract PLA2 activity. The EGF- and PMA-induced enhanced activity was recovered following fractionation by Mono-Q anion exchange chromatography. The peak of activity comigrated for both agonists, suggesting that both EGF and PMA stimulated the same form of the enzyme. Down-regulation of protein kinase C by pretreatment with PMA resulted in loss of the PMA-induced, but not the EGF-induced, enhancement in PLA2 activity. 8-Bromo-cAMP had no effect upon the PLA2 activity, and did not modulate the EGF effect. Pertussis toxin induced G protein ADP-ribosylation but had no effect upon PLA2 activity, and did not alter the EGF effect. In summary, EGF results in a stable modification of PLA2 activity in glomerular mesangial cells. This enhanced activity is independent of polyphosphoinositide hydrolysis, insensitive to protein kinase C down-regulation, and is not affected by cAMP or pertussis toxin pretreatment of the cells.


Peroxiredoxin VI oxidation in cerebrospinal fluid correlates with traumatic brain injury outcome.
Traumatic brain injury (TBI) patients would benefit from the identification of reliable biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant stress-mediated damage progression after hospital admission and subsequent ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner glutathione S-transferase Pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) in TBI. Furthermore, significant and progressive oxidation of "buried" protein thiols in CSF of TBI patients (compared to those of nontrauma controls) was detected over a 24-h period after hospital admission, with increased oxidation correlating with severity of trauma. Conversely, recovery of Prdx6 activity after 24h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a biomarker for TBI outcome and a future indicator of therapeutic efficacy.


Including the Nordic hamstring exercise in injury prevention programmes halves the rate of hamstring injuries: a systematic review and meta-analysis of 8459 athletes.
Does the Nordic hamstring exercise (NHE) prevent hamstring injuries when included as part of an injury prevention intervention? Systematic review and meta-analysis. We considered the population to be any athletes participating in any sporting activity, the intervention to be the NHE, the comparison to be usual training or other prevention programmes, which did not include the NHE, and the outcome to be the incidence or rate of hamstring injuries. The effect of including the NHE in injury prevention programmes compared with controls on hamstring injuries was assessed in 15 studies that reported the incidence across different sports and age groups in both women and men. MEDLINE via PubMed, CINAHL via Ebsco, and OpenGrey. There is a reduction in the overall injury risk ratio of 0.49 (95% CI 0.32 to 0.74, p=0.0008) in favour of programmes including the NHE. Secondary analyses when pooling the eight randomised control studies demonstrated a small increase in the overall injury risk ratio 0.52 (95% CI 0.32 to 0.85, p=0.0008), still in favour of the NHE. Additionally, when studies with a high risk of bias were removed (n=8), there is an increase of 0.06 in the risk ratio to 0.55 (95% CI 0.34 to 0.89, p=0.006). Programmes that include the NHE reduce hamstring injuries by up to 51%. The NHE essentially halves the rate of hamstring injuries across multiple sports in different athletes. PROSPERO CRD42018106150.


Development of high-voltage and high-energy membrane-free nonaqueous lithium-based organic redox flow batteries.
Lithium-based nonaqueous redox flow batteries (LRFBs) are alternative systems to conventional aqueous redox flow batteries because of their higher operating voltage and theoretical energy density. However, the use of ion-selective membranes limits the large-scale applicability of LRFBs. Here, we report high-voltage membrane-free LRFBs based on an all-organic biphasic system that uses Li metal anode and 2,4,6-tri-(1-cyclohexyloxy-4-imino-2,2,6,6-tetramethylpiperidine)-1,3,5-triazine (Tri-TEMPO), N-propyl phenothiazine (C3-PTZ), and tris(dialkylamino)cyclopropenium (CP) cathodes. Under static conditions, the Li||Tri-TEMPO, Li||C3-PTZ, and Li||CP batteries with 0.5 M redox-active material deliver capacity retentions of 98%, 98%, and 92%, respectively, for 100 cycles over ~55 days at the current density of 1 mA/cm2 and a temperature of 27 °C. Moreover, the Li||Tri-TEMPO (0.5 M) flow battery delivers an initial average cell discharge voltage of 3.45 V and an energy density of ~33 Wh/L. This flow battery also demonstrates 81% of capacity for 100 cycles over ~45 days with average Coulombic efficiency of 96% and energy efficiency of 82% at the current density of 1.5 mA/cm2 and at a temperature of 27 °C.


Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins.
The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.


Investigation of the survival viability of cervical cancer cells (HeLa) under visible light induced photo-catalysis with facile synthesized WO3/ZnO nanocomposite.
The photo catalytic degradation, a proven chemical process used for the decontamination of organic/inorganic pollutants and microorganisms in water was implemented. In this work for the selective killing of cervical cancer cells (HeLa cells) by using nano-composite of ZnO (Zinc Oxcide), WO3 (tungsten oxide) and (n-WO3/ZnO) as a photo-catalyst under the irradiation of visible light. All the three nanostructured semiconducting materials (WO3, ZnO and n-WO3/ZnO) were synthesized by facile chemical precipitation method and their morphological and optical characterization studies were carried out to elucidate the observed enhancement in the photo-catalytic killing of HeLa cancer cells with n-WO3/ZnO as a photo-catalyst. After 60 min of photo-catalytic reaction with n-WO3/ZnO as a photo-catalyst, a survival viability of HeLa cancer cells as low as 15% was achieved (nearly 85% of killing), as compared to 65% of HeLa cancer cell survival viability (nearly 35% of killing) with individual use of WO3 and ZnO as photo-catalysts under the same irradiation and experimental conditions. This improved photo-catalytic killing of HeLa cancer cells using n-WO3/ZnO in the visible spectral region is attributed to the enhanced visible light absorption and reduced electron hole recombination, characteristically brought about in the n-WO3/ZnO composite material. As photo-catalytic killing of the cancer cells can be selective, localized and reasonably efficient, in principle, this method can be considered as a non-invasive targeted treatment option for killing any type of cancer cells. HeLa cells, in particular are the cervical cancer cell and the tumors in and around cervix, containing HeLa cells can be non-surgically accessed and photo-catalytically treated with appropriate photo-catalyst and light source.


The extracellular matrix between the optic vesicle and presumptive lens during lens morphogenesis in an anophthalmic strain of mice.
Extracellular matrix material present during early lens morphogenesis in anophthalmic strain ZRDCT-Ch mice was studied histochemically by the Alcian blue 8GX pH 2.5, Alcian blue 8GX pH 2.5/periodic acid-Schiff combined, high iron diamine, and Van Gieson methods. Observed staining patterns were compared with results from an analysis of a normal strain of mice (E.H. Webster, Jr., A.F. Silver, and N.I. Gonsalves, 1983, Develop. Biol. 100, 147-157). No differences in constituents were found between the strains in staining patterns of the ectodermal basal lamina. However, the optic vesicle basal lamina in the anophthalmic strain was found to have a relatively lower staining intensity for sulfated glycosaminoglycan associated with it than was observed in the normal strain, although these mutant optic vesicles were morphologically normal. Results from this and the earlier study on normal mice indicate that one function of sulfated glycosaminoglycan in early lens morphogenesis may be to serve as a cementing medium between the optic and lens rudiments. This sulfated glycosaminoglycan deficiency on the anophthalmic optic vesicle basal lamina is temporally correlated with and may be causally related to precocious lens cup formation and frequently observed separation of the normally adherent eye rudiments. Conclusions drawn from this study are consistent with the speculation of H.B. Chase and E.B. Chase (1941, J. Morphol. 68, 279-301) that there may be abnormal contact between the optic vesicle and presumptive lens ectoderm in the mutant strain, although there is a differing view on the cause of the abnormal contact.


The development of monoaminergic brainstem-spinal systems in the North American opossum.
Evidence is presented for an early appearance of monoaminergic neurites within the spinal cord of the developing opossum. They are present within the marginal zone before hindlimb movements begin (stage I) and they start to grow into the intermediate zone by the time hindlimb movements are first observed (stage II). Monoaminergic neurites grow first into the dorsolateral intermediate zone and the intermediolateral cell column where they can be found by the beginning of stage II. Shortly thereafter, fluorescent varicosities can be traced into the area dorsal to the central canal presumed to become lamina X. Fluorescent processes extend in to the ventral intermediate zone (ventral horn) somewhat later in development. Monoaminergic axons have grown into all of the areas they occupy in the adult animal, except for laminae I and II, by the time immature hindlimb movements can be altered by cutting all brainstem projections to the lumbosacral cord (stage III). Monoaminergic innervation of laminae I and II is the last to develope, but it is present by the time thoracic transection produces complete spinal shock.


Lower Extremity Revascularization for Chronic Limb-Threatening Ischemia among Patients at the Extremes of Age.
Patients with chronic limb-threatening ischemia (CLTI) at the extremes of age are thought to have distinct risk factor profiles and poor outcomes after lower extremity revascularization (LER). The aim of this study is to examine the relationships among age, risk factor profiles, and outcomes of LER in patients with CLTI in a large database focusing on the extreme age groups. Patients undergoing LER for CLTI in the Vascular Quality Initiative suprainguinal bypass, infrainguinal bypass, and peripheral vascular intervention files were reviewed through 2019. Patients were stratified into 3 groups: premature peripheral artery disease (PAD) (≤50 years old), 51-84 years old, and elderly (≥85 years old). Trends in major amputation and mortality by age group were analyzed. There were 156,513 patients who underwent LER for CLTI. Of these, 9,063 (5.79%) patients had premature PAD, 131,694 (84.14%) patients were 51-84 years old, and 15,756 (10.07%) were elderly. Patients with premature PAD were more likely to have insulin-dependent diabetes, be dialysis-dependent, and be active smokers compared to patients 51-84 years old and the elderly. Elderly patients were more likely to undergo an endovascular procedure for tissue loss compared to younger groups. Perioperative and 1-year major amputation rates were highest among patients with premature PAD and decreased with increasing age (P < 0.001), while perioperative and 1-year mortality increased with age (P < 0.001). On multivariable analysis, premature PAD was associated with an increased risk of major amputation (odds ratio, OR = 1.41 [1.22-1.62]), while elderly age was associated with decreased odds of major amputation compared to patients 51-84 years old (OR = 0.61 [0.51-0.73]). Patients at the extremes of age have significantly different outcomes after LER for CLTI. Although mortality increases with age, the risk of major amputation decreases. Patients with premature PAD constitute a group of patients with a high risk of perioperative and 1-year major amputation.


Label-free peptide nucleic acid biosensor for visual detection of multiple strains of influenza A virus suitable for field applications.
Accurate and rapid diagnosis of Influenza A viruses (IAVs) is challenging because of multiple strains circulating in humans and animal populations, and the emergence of new strains. In this study, we demonstrate a simple and rapid strategy for visual detection of multiple strains of IAVs (H1 to H16 subtypes) using peptide nucleic acid (PNA) as a biosensor and unmodified gold nanoparticles (AuNPs) as a reporter. The design principle of the assay is based on the color change on account of free PNA-induced aggregation of AuNPs in the presence of non-complementary viral RNA sequence and vice-versa. The assay could detect IAV RNA with a visual limit of detection of 2.3 ng. The quantification of RNA with a considerable accuracy on a simple spectrophotometer was achieved on plotting the PNA-induced colorimetric changes (absorption ratio of A640/A520) in the presence of a varying concentration of complementary RNA. As a proof-of-concept, the visual assay was validated on 419 avian clinical samples and receiver operating characteristic (ROC) curve analysis showed a high diagnostic specificity (96.46%, 95% CI = 93.8 to 98.2) and sensitivity (82.41%, 95% CI = 73.9 to 89.1) when RT-qPCR was used as reference test. Hence, the simplicity, rapidity, and universality of this strategy make it a potential candidate visual assay for clinical diagnosis and surveillance of IAVs, especially in the resource-limited settings. The proposed strategy establishes new avenues for developing a simple and rapid diagnostic system for viral infections and biomolecules.


Possible existence of hybrid glycosyltransferase in heterozygous blood group AB subjects.
The human blood group glycosyltransferases A and B have a dimeric structure, i.e., the A enzyme is an aa dimer and the B enzyme is a bb dimer. Considering the fact that the ABO blood group determinant are not x-linked, i.e. both A and/or B genes are expressed in a given cell, a hybrid enzyme (ab dimer) may exist in heterozygous A1B subjects. Because the A enzyme, but not the B enzyme, adsorbs with Sepharose 4-B, the adsorption characteristics of the A and B enzymes from plasma fo various phenotypes were examined to look for this hybrid enzyme. The A enzyme activity from A1 plasma and from a mixture of AU and B plasma was completely adsorbed to Sepharose 4-B, while 25-50% of A enzyme activity from heterozygous A1B plasma was not adsorbed. The results indicated that heterozygous A1B plasma contains an additional enzyme component which does not exist in a mixture of A1 and B plasma, suggesting the existence of a hybrid heterodimer (ab) in heterozygous A1B subjects.


Prediction methods for B-cell epitopes.
In this chapter, two prediction servers of linear B-cell epiotpes have been described; (i) BcePred, based on physico-chemical properties that include hydrophilicity, flexibility/mobility, accessibility, polarity, exposed surface, turns, and antigenicity and ii) ABCpred, based on recurrent neural network. Both of the servers assist in locating linear epitope regions in a protein.


In situ mineralization of nitorgen and phosphorus of arctic soils after perturbations simulating climate change.
Seasonal net nitrogen (N) and phosphorus (P) mineralization was investigated at Abisko, Swedish Lapland in soils of a subarctic heath and in soils of a colder (by about 4° C), high altitude fellfield by (a) using in situ soil incubation in soils which had been shaded or subjected to two levels of increased temperature, combined with (b) reciprocal transplantation of soils between the two sites. Proportionally large and significant net seasonal mineralization of N, in contrast to non-significant P mineralization, was found in untransplanted and transplanted fellfield soil. In contrast, P was mineralized in proportionally large amounts, in contrast to low N mineralization, in the transplanted and untransplanted heath soil. The differences indicate that P was strongly immobilized in relation to N at the fellfield and that N was more strongly immobilized than P in the heath soil. The immobilization in both soils remained high even after a temperature change of 4-5° C experienced by transplanted soils. Air temperature increases of up to 4-5° C in greenhouses resulted in a soil temperature increase of 1-2° C and did not cause any extra increase of net N and P mineralization. The results suggest that soil temperature increases of up to 2° C, which are likely to occur by the end of the next century as an effect of a predicted 4-5° C rise in air temperature, have only small effects on net mineralization in at least two characteristic tundra soils. These effects are probably smaller than the natural fluctuation of plant available nutrients from site to site, even within the same plant community. A further soil temperature increase of up to 4-5° C may enhance decomposition and gross mineralization, but the rate of net mineralization, and hence the change of nutrient availability to the plants, depends on the extent of microbial immobilization of the extra nutrients released.


Guardians of the ERAD Galaxy.
The endoplasmic reticulum-associated degradation (ERAD) pathway facilitates the disposal of terminally misfolded proteins in the early secretory pathway yet spares folding intermediates from being destroyed. Zhang et al. report on a protein complex that acts as a guardian to protect these folding intermediates from being targeted for ERAD.


Non organ based laboratory markers in systemic sclerosis.
Candidate markers for endothelial cell, lymphocyte and fibroblast function in systemic sclerosis have been reviewed. Autoantibody measurement and general inflammatory markers were considered the minimum requirements, with other markers needing further evaluation.


Integrated organic-aqueous biocatalysis and product recovery for quinaldine hydroxylation catalyzed by living recombinant Pseudomonas putida.
In an earlier study, biocatalytic carbon oxyfunctionalization with water serving as oxygen donor, e.g., the bioconversion of quinaldine to 4-hydroxyquinaldine, was successfully achieved using resting cells of recombinant Pseudomonas putida, containing the molybdenum-enzyme quinaldine 4-oxidase, in a two-liquid phase (2LP) system (Ütkür et al. J Ind Microbiol Biotechnol 38:1067-1077, 2011). In the study reported here, key parameters determining process performance were investigated and an efficient and easy method for product recovery was established. The performance of the whole-cell biocatalyst was shown not to be limited by the availability of the inducer benzoate (also serving as growth substrate) during the growth of recombinant P. putida cells. Furthermore, catalyst performance during 2LP biotransformations was not limited by the availability of glucose, the energy source to maintain metabolic activity in resting cells, and molecular oxygen, a possible final electron acceptor during quinaldine oxidation. The product and the organic solvent (1-dodecanol) were identified as the most critical factors affecting biocatalyst performance, to a large extent on the enzyme level (inhibition), whereas substrate effects were negligible. However, none of the 13 alternative solvents tested surpassed 1-dodecanol in terms of toxicity, substrate/product solubility, and partitioning. The use of supercritical carbon dioxide for phase separation and an easy and efficient liquid-liquid extraction step enabled 4-hydroxyquinaldine to be isolated at a purity of >99.9% with recoveries of 57 and 84%, respectively. This study constitutes the first proof of concept on an integrated process for the oxyfunctionalization of toxic substrates with a water-incorporating hydroxylase.


MDR1-P-glycoprotein (ABCB1)-mediated disposition of amyloid-β peptides: implications for the pathogenesis and therapy of Alzheimer's disease.
The accumulation of neurotoxic amyloid-β (Aβ) peptides within the brain represents a hallmark of Alzheimer's disease (AD). It is proposed to be partly due to reduced elimination of Aβ from the brain into the blood. Diverse mechanisms of Aβ clearance out of the brain have been suggested. As discussed here, several lines of evidence suggest a significant role of the MDR1-P-glycoprotein (ABCB1), which is a major component of the blood-brain barrier (BBB).


Sleep Consolidates Motor Learning of Complex Movement Sequences in Mice.
Sleep-dependent consolidation of motor learning has been extensively studied in humans, but it remains unclear why some, but not all, learned skills benefit from sleep. Here, we compared 2 different motor tasks, both requiring the mice to run on an accelerating device. In the rotarod task, mice learn to maintain balance while running on a small rod, while in the complex wheel task, mice run on an accelerating wheel with an irregular rung pattern. In the rotarod task, performance improved to the same extent after sleep or after sleep deprivation (SD). Overall, using 7 different experimental protocols (41 sleep deprived mice, 26 sleeping controls), we found large interindividual differences in the learning and consolidation of the rotarod task, but sleep before/after training did not account for this variability. By contrast, using the complex wheel, we found that sleep after training, relative to SD, led to better performance from the beginning of the retest session, and longer sleep was correlated with greater subsequent performance. As in humans, the effects of sleep showed large interindividual variability and varied between fast and slow learners, with sleep favoring the preservation of learned skills in fast learners and leading to a net offline gain in the performance in slow learners. Using Fos expression as a proxy for neuronal activation, we also found that complex wheel training engaged motor cortex and hippocampus more than the rotarod training. Sleep specifically consolidates a motor skill that requires complex movement sequences and strongly engages both motor cortex and hippocampus.


Changes of tension and [Ca2+]i during beta-adrenoceptor activation of single, intact fibres from mouse skeletal muscle.
beta-Adrenergic agonists increase tension production in fast-twitch skeletal muscle, but the underlying mechanism is unknown. In the present study we have exposed intact, single fibres from a mouse muscle to the beta 2-adrenergic agonist terbutaline. Fibres were stimulated to produce 350-ms tetani at 20-100 Hz while measuring the myoplasmic Ca2+ concentration ([Ca2+]i) and tension. The fluorescent indicator Indo-1 was used to measure [Ca2+]i. Application of terbutaline resulted in marked increases of both tetanic [Ca2+]i and tension. Terbutaline had no significant effect on myofibrillar function as judged from normal Ca2+ sensitivity and tension production at saturating [Ca2+]i. The rate of [Ca2+]i and tension decline during relaxation was not affected by terbutaline, thus indicating a normal function of the sarcoplasmic reticulum (SR) Ca2+ pumps. The effect of terbutaline developed gradually over 5-10 min when fibres were stimulated each minute; the full effect of terbutaline was also obtained after a 10-min rest period in terbutaline. The [Ca2+]i at rest was not affected by terbutaline. In conclusion, beta-adrenergic stimulation increases tetanic tension by enhancing SR Ca2+ release.


Methods for in situ detection and characterization of extracellular polymers in biofilms by electron microscopy.
Electron microscopy of biofilms and the localization of extracellular polymers at high resolution require the adaptation of conventional electron microscopic preparation and imaging techniques. A method developed for in situ fixation and embedding of biofilms, imaging of unstained thick sections with electron spectroscopic imaging and the application of lectin or antibody-based marker systems allowed interpretation of extracellular polymer distribution at micrometer scale. By this way, it is possible to discriminate in situ between extracellular polymers produced by different organisms.


A metal-organic framework supported iridium catalyst for the gas phase hydrogenation of ethylene.
The mutable structures of metal-organic frameworks (MOFs) allow their use as novel supports for transition metal catalysts. Herein we prepare an iridium bis(ethylene) catalyst bound to the neutral N-donors of a MOF structure and show that the compound is a stable gas phase ethylene hydrogenation catalyst. The data illustrate the need to carefully consider the inner sphere (support) and outer sphere (anion) chemistry.


Brief Report: Supporting Access to HIV Care for Children and Youth During the COVID-19 Pandemic With Telemedicine and Rideshare.
In response to the COVID-19 pandemic, we scaled up telemedicine and rideshare services for clinic and laboratory visits for pediatric and adolescent patients with HIV. HIV subspecialty program for patients aged 0-24 years at Children's National Hospital, Washington, DC. Using the χ2 and Wilcoxon rank sum tests, we compared demographics, visit and laboratory data, and rideshare usage among patients who scheduled telemedicine at least once (telemedicine) versus those who never scheduled telemedicine (no-telemedicine) during the pandemic (April-September 2020). We compared the number and proportion of scheduled and completed clinic visits before the pandemic (April-September 2019) with those during the pandemic. We analyzed 178 pediatric and adolescent patients with HIV (median age 17.9 years, 89.3% Black, 48.9% male patients, 78.7% perinatally infected), of whom 70.2% and 28.6% used telemedicine and rideshare, respectively. Telemedicine patients scheduled more visits (236 vs 179, P < 0.0001) and completed a similar proportion of visits (81.8% vs 86.0%, P = 0.3805) compared with no-telemedicine patients. Laboratory testing rates (81.3% versus 98.5%, P = 0.0005) were lower in telemedicine patients compared with no-telemedicine patients. Rideshare usage (12.4% versus 26.5%, P = 0.0068) was lower in telemedicine versus no-telemedicine patients. During the pandemic, most of the patients (81.0%) had HIV RNA <200 copies/mL. The total number of completed visits and the proportion of visits completed were similar before and during the pandemic. Most of the pediatric and adolescent patients with HIV used telemedicine and maintained HIV RNA <200 copies/mL during the pandemic. Despite rideshare usage, laboratory testing rates were lower with telemedicine compared with in-person visits.


[Delays related to maternal mortality in the department of Santander from 2012 to 2015].
To characterize maternal deaths in the department of Santander, Colombia, and the delays that contributed to these deaths during the period 2012-2015, through a systematic review of health care, in order to offer an input that allows proposing actions that contribute to reduce these fatal outcomes. Descriptive, retrospective, cross-sectional study that determines the characteristics of maternal mortality in pregnant or postpartum women who were administered complete analysis units and whose death was not caused by external or violent causes. The most frequent delay in the 49 cases of maternal deaths was type IV, which refers to the delay in receiving adequate and timely medical treatment (87.8%), mainly due to deficiencies in promotion and prevention strategies (63.2%). The majority of the deaths were avoidable (61.2%) in the puerperium (84%), and in users of the subsidized insurance scheme (57.1%). Although 98% of mothers were affiliated to the health system (subsidized, contributory, special or exceptional schemes), it was possible to demonstrate that women who were affiliated to the subsidized regime showed a greater frequency of the event, which reflects that there are important opportunities for improvement in the care provided to pregnant women in this type of scheme.


Correlation between airway inflammation and loss of deep-inhalation bronchoprotection in asthma.
One of the characteristic features of the hyperresponsive airway smooth muscle in asthma is the loss of deep-inhalation bronchoprotection and bronchodilation. The airway of individuals with asthma is also characterized by inflammation. To evaluate whether the loss of deep-inhalation bronchoprotection is correlated with the degree of inflammation in the asthmatic airway. Eighteen study participants performed 2 methacholine challenges (identical doses), 1 with deep inhalations and 1 without, separated by at least 24 hours. Airway inflammation was evaluated by measurement of fraction of exhaled nitric oxide (FE(NO)) and induced sputum eosinophils. A significant negative correlation was found between the degree of deep-inhalation bronchoprotection and airway inflammation when measured by FE(NO) (P = .02, r = .54, n = 18) and by percentage of eosinophils (P = .002, r = .76, n = 12). A significant positive correlation was also found between the FE(NO) and percentage of eosinophils (P = .009, r = .68, n = 12). Deep-inhalation bronchoprotection was significantly impaired in individuals with greater airway inflammation. This finding suggests that therapy directed at decreasing airway inflammation may promote the recovery of normal deep-inhalation bronchoprotection.


Optoelectronic parametric oscillator.
Oscillators are one of the key elements in various applications as a signal source to generate periodic oscillations. Among them, an optical parametric oscillator (OPO) is a driven harmonic oscillator based on parametric frequency conversion in an optical cavity, which has been widely investigated as a coherent light source with an extremely wide wavelength tuning range. However, steady oscillation in an OPO is confined by the cavity delay, which leads to difficulty in frequency tuning, and the frequency tuning is discrete with the minimum tuning step determined by the cavity delay. Here, we propose and demonstrate a counterpart of an OPO in the optoelectronic domain, i.e., an optoelectronic parametric oscillator (OEPO) based on parametric frequency conversion in an optoelectronic cavity to generate microwave signals. Owing to the unique energy-transition process in the optoelectronic cavity, the phase evolution in the OEPO is not linear, leading to steady single-mode oscillation or multimode oscillation that is not bounded by the cavity delay. Furthermore, the multimode oscillation in the OEPO is stable and easy to realize owing to the phase control of the parametric frequency-conversion process in the optoelectronic cavity, while stable multimode oscillation is difficult to achieve in conventional oscillators such as an optoelectronic oscillator (OEO) or an OPO due to the mode-hopping and mode-competition effect. The proposed OEPO has great potential in applications such as microwave signal generation, oscillator-based computation, and radio-frequency phase-stable transfer.


Effect of double-application of all-in-one adhesives on dentin bonding.
To evaluate the effect of double-application of all-in-one adhesives using the micro-shear bond test. The occlusal surfaces of extracted human third molars were ground perpendicular to the long axis of each tooth to expose a flat dentin surface. Three commercially available and one experimental bonding system were used in this study: Adper Prompt L-Pop (APL, 3M ESPE), REACTMER BOND (RB, Shofu), XENO III (Xeno, Dentsply-Sankin) and newly developed OBF-2 (OB2, Tokuyama Dental). These adhesives were applied on the dentin surfaces by either the manufacturers' instructions or by an experimental method (single-application or double-application). Resin composite was then placed and light-cured for 40s. After 24h immersion in water, a micro-shear bond test was carried out and the fractured dentin surfaces were observed microscopically. The data were analyzed by one-way ANOVA and Tukey's HSD tests (p<0.05). The mean bond strengths of APL, RB, Xeno and OB2 with single-application were 22.7, 28.3, 30.3 and 34.6MPa, respectively. The mean bond strengths of APL, RB, Xeno and OB2 with double-application were 29.5, 27.2, 29.6 and 32.5MPa, respectively. There were no statistically significant differences in micro-shear bond strengths between the single- and double-application methods for each adhesive system (p>0.05). The morphological observation of the fractured dentin surfaces revealed differences between the single- and double-application groups especially for APL and OB2. Micro-shear bond strengths of all-in-one adhesives in this study showed no statistically significant differences between the single-application and the double-application method.


Maximal cardiopulmonary exercise testing in laryngectomised patients using different heat and moisture exchangers - feasibility and exercise responses.
After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded. All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample.


Antidotal therapy of severe acute organophosphate poisoning: a multihospital study.
Out of 859 consecutive cases treated for exposure to organophosphate (PO) insecticides, 53 were included in the study. Criteria for inclusion were severe OP poisoning necessitating artificial ventilation, intensive care monitoring and treatment according to a standard protocol. The protocol was based on relatively high doses of obidoxime, relatively low doses of atropine and overriding with a pacemaker in cases of ventricular arrhythmias and prolonged Q-T interval. Seven patients died during hospitalization. Thirty-two patients (60%) had major central nervous system (CNS) involvement. Five (9.4%) presented severe psychiatric sequelae. Twenty-two patients (41.5%) presented cardiac arrhythmias. Five (9.4%) had liver dysfunction. High frequency of cardiac arrhythmias was observed in patients who received high cumulative doses of atropine and obidoxime; impairment of liver functions was significantly higher in patients who received high cumulative doses of obidoxime. We conclude that each drug should be titrated separately: atropine dosage should be adjusted to the severity of tracheobronchial secretions and bronchospasm, while full doses of obidoxime are justified for the period before "aging" sets in.


Responses of an African graminoid (Themeda triandra Forsk.) to frequent defoliation, nitrogen, and water: a limit of adaptation to herbivory.
Themeda triandra Forsk., a medium height perennial grass common in semi-arid Africa, was collected from Serengeti National Park in Tanzania, propagated vegetatively and grown in controlled environments simulating native conditions. The experiment demonstrated mechanisms that result in inability to withstand frequent defoliation, and thus how plant-herbivore interactions are affected by plant morpho-physiology. Clipping reduced most plant yield components. After two months leaf elongation rate was greater in clipped plants, but over the whole experiment aboveground yield was unaffected by clipping. Since clipping did not stimulate growth, residual leaf area was less in clipped plants. Tillering was not stimulated by clipping so there was no mechanism to increase leaf area below the clipping height. The resulting reduced leaf area accounted for reduced root and crown production by clipped plants.


Development of peptidyl alpha-keto-beta-aldehydes as new inhibitors of cathepsin L--comparisons of potency and selectivity profiles with cathepsin B.
We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl alpha-keto-beta-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki 0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.


Application of ITC in foods: A powerful tool for understanding the gastrointestinal fate of lipophilic compounds.
Isothermal titration calorimetry (ITC) is a biophysical technique widely used to study molecular interactions in biological and non-biological systems. It can provide important information about molecular interactions (such as binding constant, number of binding sites, free energy, enthalpy, and entropy) simply by measuring the heat absorbed or released during an interaction between two liquid solutions. In this review, we present an overview of ITC applications in food science, with particular focus on understanding the fate of lipids within the human gastrointestinal tract. In this area, ITC can be used to study micellization of bile salts, inclusion complex formation, the interaction of surface-active molecules with proteins, carbohydrates and lipids, and the interactions of lipid droplets. ITC is an extremely powerful tool for measuring molecular interactions in food systems, and can provide valuable information about many types of interactions involving food components such as proteins, carbohydrates, lipids, surfactants, and minerals. For systems at equilibrium, ITC can provide fundamental thermodynamic parameters that can be used to establish the physiochemical origin of molecular interactions. It is expected that ITC will continue to be utilized as a means of providing fundamental information about complex materials such as those found in foods. This knowledge may be used to create functional foods designed to behave in the gastrointestinal tract in a manner that will improve human health and well-being.


Transesophageal echocardiographically detected atherosclerotic aortic debris in a patient with systemic embolism following coronary angiography.
Transesophageal echocardiography (TEE) has enabled detection of the cardiac source of systemic emboli. We report the case of a patient who manifested systemic, multiple embolization in the kidney, skin, and upper gastrointestinal tract following coronary angiography. TEE allowed visualization of the atherosclerotic debris in the thoracic aorta. The clinical picture of the patient was consistent with that of cholesterol embolism. We recommend that patients with extensive atherosclerotic disease should undergo TEE before cardiac catheterization or other invasive procedures involving the aorta are carried out.


Heparin potentiates in vivo neutrophil migration induced by IL-8.
Chemokine IL-8 attracts neutrophils by a haptotactic gradient, made possible by its interaction with proteoglycans of the extracellular matrix. Heparan sulfate, but not heparin, potentiates the attraction exerted in vitro by IL-8. In the present study we first confirmed this in vitro phenomenon, observing that IL-8 activity was potentiated 100% by heparan sulfate, but not by heparin. Then, we evaluated the interference of heparan sulfate or heparin on in vivo neutrophil migration induced by IL-8. The activity of rat IL-8 (3.5 microg/animal) preincubated with heparan sulfate (50 microg/animal) or heparin (77 microg/animal) was assayed on the rat dorsal air pouch. Contrary to in vitro experiments, heparin, but not heparan sulfate, potentiated the in vivo IL-8 activity two-fold. We investigated the relationship between this observation and that reported by others, that IL-8-induced migration depends on the presence of mast cells, which contain heparin-rich granules. We studied the neutrophil migration induced by IL-8 (3.5 microg/animal) into the rat peritoneal cavity depleted of mast cells. Neutrophil migration was reduced by 32% when compared to that observed in normal animals. The response of depleted rats was reconstituted by preincubation of IL-8 with heparin (77 microg/animal). These data suggest that heparin released from cytoplasmic granules may be the contribution of mast cells to IL-8-induced neutrophil migration.


A rheumatoid factor from a normal individual encoded by VH2 and V kappa II gene segments.
To gain insight into the immunoglobulin variable-region repertoire of anti-IgG antibodies (rheumatoid factors [RF]), we characterized the VH and V kappa gene segments utilized in an IgM-RF-secreting lymphoblastoid cell line (SSH23) isolated from a normal individual. The cell line SSH23 was established by Epstein-Barr virus transformation of peripheral blood non-T mononuclear cells. First-strand complementary DNA (cDNA) was generated and used for polymerase chain reaction amplification of the heavy and light chain variable domains. The amplified variable domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. The VH sequence was found to be identical to a previously described fetal VH2 incomplete cDNA and to differ by only 3 nucleotides from a JH proximal germline VH2 gene segment. To our knowledge, this is the first example of a VH2 rheumatoid factor. The V kappa 2-J kappa 4 light chain contains an uncommon 10-amino acid third complementarity-determining region (CDR 3). Utilization of preimmune fetal VH gene segments and unusual light chain junctional diversity appear to be features shared by many physiologic and pathologic rheumatoid factors.


Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis.
Patients with clinically suspect arthralgia (CSA) have, according to their rheumatologists, an increased risk of rheumatoid arthritis (RA), but their actual outcome is unexplored. This longitudinal study investigated (1) progression from CSA to clinically detectable arthritis and (2) associations of clinical factors, serological factors (among which are anticitrullinated peptide antibodies (ACPAs)) and MRI-detected subclinical inflammation with arthritis development. 150 patients with CSA were followed for ≥6 months. At baseline, clinical and serological data were collected and unilateral 1.5 T-MRI of metacarpophalangeal (MCP), wrist and metatarsophalangeal (MTP) joints was made. MRI scoring was done according to the RA MRI scoring system. Subclinical MRI inflammation was defined based on MRI results of 193 symptom-free persons. During follow-up (median=75 weeks, IQR=41-106 weeks), 30 patients developed clinical arthritis; 87% did so <20 weeks after inclusion. In multivariable analyses, age, localisation of initial symptoms in small and large joints (compared with small joints only), C-reactive protein level, ACPA-positivity and subclinical MRI inflammation significantly associated with arthritis development; ACPA and MRI inflammation were most strongly associated (HR (95% CI) respectively, 6.43 (2.57 to 16.05) and 5.07 (1.77 to 14.50)). After 1-year follow-up, 31% of the patients with MRI inflammation and 71% of the ACPA-positive patients with MRI inflammation had progressed to arthritis. Forty-three per cent of the patients that developed arthritis within 1 year were ACPA-negative; 78% of them had subclinical MRI inflammation at baseline. When MRI inflammation was absent arthritis development was infrequent (6% in all patients with CSA and 3% in ACPA-negative patients with CSA). Subclinical MRI inflammation precedes clinical arthritis with a few months. Subclinical MRI inflammation is, independent of other factors such as ACPA, associated with arthritis development.


Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression.
Endometrial cancer (EC) is a common gynaecological cancer worldwide. Exosomes, secreted by living cells and detected in various body fluids, can exchange information between organs and compartments to affect cellular functions, such as proliferation, apoptosis, migration and angiogenesis. We hypothesise that plasma exosomal contents are altered during cancer progression and promote cancer growth and angiogenesis by delivering biomolecules to cancer and vascular endothelial cells. In this study, circulating exosomes derived from EC patients and age-matched healthy people were acquired by commercial kits. Cell counting kit-8, Transwell and Matrigel tube formation assays showed that circulating exosomes from EC patients promote EC cell growth and human umbilical vein endothelial cell (HUVEC) angiogenesis. Next, proteomic analysis and ELISA revealed that plasma exosomal lectin galactoside-binding soluble 3 binding protein (LGALS3BP) increased during EC progression. Moreover, to explore the function of exosomal LGALS3BP, we acquired exosomes containing high levels of LGALS3BP by overexpressing LGALS3BP in human embryonic kidney 293 cells, and we demonstrated that highly contained exosomal LGALS3BP contributed to EC cell proliferation and migration and HUVEC functions via the activation of the PI3K/AKT/VEGFA signalling pathway both in vitro and in vivo. Finally, high LGALS3BP expression was observed in human EC tissue, which indicated a poor prognosis. In addition, immunohistochemical analysis of human EC tissues revealed that LGALS3BP expression was correlated with VEGFA expression and blood vessel density. Hence, we proposed that plasma exosomes containing LGALS3BP contributed to EC growth and angiogenesis during EC progression, which also provided a novel perspective on EC diagnosis and prognosis.