Relationship between maternal sodium intake and blood lead concentration during pregnancy.
Pb is released from bone stores during pregnancy, which constitutes a period of increased bone resorption. A high Na intake has been found to be negatively associated with Ca and adversely associated with bone metabolism. It is possible that a high Na intake during pregnancy increases the blood Pb concentration; however, no previous study has reported on the relationship between Na intake and blood Pb concentration. We thus have investigated this relationship between Na intake and blood Pb concentrations, and examined whether this relationship differs with Ca intake in pregnant Korean women. Blood Pb concentrations were analysed in 1090 pregnant women at mid-pregnancy. Dietary intakes during mid-pregnancy were estimated by a 24 h recall method covering the use of dietary supplements. Blood Pb concentrations in whole-blood samples were analysed using graphite furnace atomic absorption spectrophotometry. Multiple regression analysis performed after adjustment for covariates revealed that maternal Na intake was positively associated with blood Pb concentration during pregnancy, but only when Ca intake was below the estimated average requirement for pregnant Korean women (P= 0·001). The findings of the present study suggest that blood Pb concentration during pregnancy could be minimised by dietary recommendations that include decreased Na and increased Ca intakes.


[Clinical and hygienic aspects of asbestos-induced lung diseases].
The outcomes of 31 operations made in patients with asbestos-induced lung cancer and mesothelioma are considered; the relationships of age, lengths of services, and occupation to the occurrence of diseases are analyzed. A phenomenological concept of development of asbestos-induced cancer diseases is proposed. The functional and morphological features of the course of the disease have been established. Recommendations on the prevention and treatment of abnormalities are given.


Emergence of carbapenem-resistant Klebsiella pneumoniae harbouring bla OXA-48-like genes in China.
Klebsiella pneumoniae strains carrying OXA-48-like carbapenemases are increasingly prevalent across the globe. There is thus an urgent need to better understand the mechanisms that underpin the dissemination of bla OXA-48-like carbapenemases. To this end, four ertapenem-resistant K. pneumoniae isolates producing OXA-48-like carbapenemases were isolated from two patients. Genome sequencing revealed that one sequence type (ST) 17 isolate carried bla OXA-181, whilst three isolates from a single patient, two ST76 and one ST15, carried bla OXA-232. The 50514 bp bla OXA-181-harbouring plasmid, pOXA-181_YML0508, was X3-type with a conjugation frequency to Escherichia coli of 1.94×10-4 transconjugants per donor. The bla OXA-232 gene was located on a 6141 bp ColKP3-type plasmid, pOXA-232_WSD, that was identical in the ST76 and ST15 K. pneumoniae isolates. This plasmid could be transferred from K. pneumoniae to E. coli at low frequency, 8.13×10-6 transconjugants per donor. Comparative analysis revealed that the X3 plasmid acquired the bla OXA-48-like gene via IS3000-mediated co-integration of the ColKP3-type plasmid. Our study highlights how plasmid integration and rearrangements can contribute to the spread of bla OXA-48-like genes, which provides important clues for clinical prevention of the dissemination of K. pneumoniae strains carrying bla OXA-48-like carbapenemases.


Exhaled breath condensate: methodological recommendations and unresolved questions.
Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.


Importance of the dermal-epidermal junction and recent advances.
The zone of human skin between the epidermis and dermis is called the dermal-epidermal junction (DEJ). The importance of the DEJ is outlined and three new areas of research involving the DEJ are reviewed: the intracellular pool of bullous pemphigoid antigen, the interactions between fibronectin and keratinocytes and the epidermolysis bullosa acquisita antigen.


[Pathogenetical features of the acute period of traumatic disease. Traumatic shock as a special manifestation of the acute period].
Clinico-pathogenetical features of the acute period of trauma disease due to a severe combined injury were studied in 644 patients. An analysis of clinical indices was made in 428 of them, clinico-laboratory indices--in 216 patients. The results have shown that the main form of the acute period of the trauma disease are traumatic shock (62.8%), traumatic coma (18.3%), acute respiratory insufficiency (5.7%). Dramatically decreased delivery and consumption of oxygen lower than the metabolic requirements of the tissues accompany the traumatic shock which results in the suppression of tissue metabolism. Pronounced endotoxicosis developing along with the traumatic shock results not from the degree of injured tissues only, but from the centralization of blood circulation. It is also supported by the insufficient detoxicating function of the kidneys. A severe degree of the traumatic shock causes disseminated intravascular coagulation (DIC) of the II-III degree. After helping out from shock the patient has normocoagulation or the I degree DIC. Traumatic shock with marked hypotension and metabolic acidosis is a significant factor of high risk of the development of acute lesion of the lungs.


Detection of novel Bartonella strains and Yersinia pestis in prairie dogs and their fleas (Siphonaptera: Ceratophyllidae and Pulicidae) using multiplex polymerase chain reaction.
We developed a multiplex polymerase chain reaction (PCR) assay that simultaneously detects three types of flea-associated microorganisms. Targets for the assay were sequences encoding portions of the gltA, a 17-kDa antigen, and pla genes of Bartonella spp. Strong et al., Rickettsia spp. da Rocha-Lima, and Yersinia pestis Yersin, respectively. A total of 260 flea samples containing bloodmeal remnants were analyzed from fleas collected from abandoned prairie dog (Cynomys ludovicianus) burrows at the site of an active plague epizootic in Jefferson County, CO. Results indicated that 34 (13.1%) fleas were positive for Bartonella spp., 0 (0%) were positive for Rickettsia spp., and 120 (46.2%) were positive for Y. pestis. Twenty-three (8.8%) of these fleas were coinfected with Bartonella spp. and Y. pestis. A second group of 295 bloodmeal-containing fleas was collected and analyzed from abandoned burrows in Logan County, CO, where a prairie dog die-off had occurred 2-4 mo before the time of sampling. Of these 295 fleas, 7 (2.4%) were positive for Bartonella spp., 0 (0%) were positive for Rickettsia spp., and 46 (15.6%) were positive for Y. pestis. Coinfections were not observed in fleas from the Logan County epizootic site. The multiplex PCR also was used to identify Y. pestis and Bartonella in prairie dog blood and tissues. This report represents the first identification of Bartonella from prairie dogs and their fleas. Prairie dog fleas were tested with PCR, and the Bartonella PCR amplicons produced were sequenced and found to be closely related to similar sequences amplified from Bartonella that had been isolated from prairie dog blood samples. Phylogenetic analyses indicate that the sequences of bartonellae from prairie dogs and prairie dog fleas cluster tightly within a clade that is distinct from those containing other known Bartonella genotypes.


Ontogenetic changes in the fractal geometry of the bronchial tree in Rattus norvegicus.
Respiration and metabolism change dramatically over the course of the development of vertebrates. In mammals these changes may be ascribed to organogenesis and differentiation of structures involved in gas exchange and transport and the increase in size. Since young as well as mature individuals must be well-designed if the species is to survive, the physiological changes during the development should be matched with geometrical or structural adjustments of the respiratory system. The aim of this study was to evaluate changes in the fractal geometry of the bronchial tree during the postnatal development of the rat. The average fractal dimension of the bronchial tree of the rats was 1.587, but that of juveniles was larger than that of the adults. We found a significant negative correlation between age and fractal dimension. This correlation could be considered be misleading because of the difficulty of separating age/body size effects. Nevertheless, because fractal dimensions of the bronchial tree of rabbits and humans are known to be similar, 1.58 and 1.57 respectively, the body size effect may be nil. To our knowledge, this is the first report of ontogenetic changes in the fractal dimension of the bronchial tree in mammals.


Synechococcus: 3 billion years of global dominance.
Cyanobacteria are among the most important primary producers on the Earth. However, the evolutionary forces driving cyanobacterial species diversity remain largely enigmatic due to both their distinction from macro-organisms and an undersampling of sequenced genomes. Thus, we present a new genome of a Synechococcus-like cyanobacterium from a novel evolutionary lineage. Further, we analyse all existing 16S rRNA sequences and genomes of Synechococcus-like cyanobacteria. Chronograms showed extremely polyphyletic relationships in Synechococcus, which has not been observed in any other cyanobacteria. Moreover, most Synechococcus lineages bifurcated after the Great Oxidation Event, including the most abundant marine picoplankton lineage. Quantification of horizontal gene transfer among 70 cyanobacterial genomes revealed significant differences among studied genomes. Horizontal gene transfer levels were not correlated with ecology, genome size or phenotype, but were correlated with the age of divergence. All findings were synthetized into a novel model of cyanobacterial evolution, characterized by serial convergence of the features, that is multicellularity and ecology.


Baseline and long-term gamma-glutamyltransferase, heart failure and cardiac arrhythmias in middle-aged Finnish men: Prospective study and pooled analysis of published evidence.
To assess the associations of baseline and long-term gamma-glutamyltransferase (GGT) activity with risk of heart failure (HF), ventricular arrhythmias (VAs) and atrial fibrillation (AF). GGT measurements were made in a prospective cohort of 1780 men free of HF and cardiac arrhythmias at baseline. Correction for within-person variability was made using data from repeat measurements taken several years apart. During an average follow-up of 22 years, 222 HF, 56 VA and 336 AF events occurred. The regression dilution ratio of loge GGT was 0.68 (95% confidence interval (CI): 0.61-0.74). Serum GGT was log-linearly associated with risk of HF, VAs and AF. In analyses adjusted for established risk factors, the hazard ratios (HRs) (95% CIs) for HF, VAs and AF per 1 SD higher baseline loge GGT values were 1.25 (1.07-1.45), 1.37 (1.04-1.80) and 1.04 (0.92-1.18), respectively. After correction for within-person variability, the corresponding HRs were 1.38 (1.11-1.73), 1.58 (1.06-2.37) and 1.06 (0.88-1.27), respectively. These findings remained consistent in analyses accounting for incident coronary heart disease and the development of impaired renal function. In a meta-analysis of five population-based studies, the fully adjusted relative risks for HF per 1 SD higher baseline and long-term GGT values were 1.28 (1.20-1.35) and 1.43 (1.31-1.56), respectively. In a pooled analysis of two studies, the corresponding risks for AF were 1.09 (1.02-1.16) and 1.14 (1.03-1.25), respectively. GGT is positively and log-linearly associated with future risk of HF, VAs and AF. Further research is needed in order to assess the causal relevance of these findings.


Hyperthermia, teratogenesis and the heat shock response in mammalian embryos in culture.
Hyperthermia is a recognized teratogen in animals and there is strong evidence that it also causes significant damage to human embryos. Studies with induced hyperthermia in pregnant animals defined the defects which are produced, the susceptible stages of development, and threshold doses of heat required to cause defects. The in vivo experiments lacked precision because of variability of embryonic development at a given conceptual age, varying maternal responses to agents causing temperature elevations, the difficulty in measuring embryonic temperature and the possibility that defects were caused by toxic changes in maternal metabolism. These variables were eliminated by the use of postimplantation whole rat and mouse embryo cultures, which were exposed to various doses of heat at closely defined stages of development. The studies showed that heat acts directly on embryos and that elevations of 2 degrees C and greater sustained over early rat organogenesis cause defects mainly by causing apoptotic cell death especially in the developing central nervous system. A moderate, non damaging exposure is followed within 15 min by protection for up to 8 h against a more severe and otherwise teratogenic exposure. The protective heat shock response is accompanied by a reduction of normal protein synthesis and concurrent synthesis of heat shock proteins (HSP90, 71, 47, 27). Most HSP in these families are also present constitutively in embryos, probably having important roles in protecting newly synthesized proteins from aggregation and facilitating folding into their normal functional configurations. The appearance of induced HSP and hsp mRNA at known sites of thermal damage suggests a protective role. Heat induced cell death by apoptosis is a feature of teratogenic damage to the developing brain. Apoptosis could be a by-product of a damaging heat exposure because of a priority favoring induction of the heat shock response over the normal gene program for organogenesis, survival being achieved at the expense of normal development.


Polysaccharides isolated from Echinacea purpurea herba cell cultures to counteract undesired effects of chemotherapy--a pilot study.
In an open prospective study with matched historical controls we aimed to evaluate whether a polysaccharide fraction isolated from the herb Echinacea purpurea could counteract the undesired effects of chemotherapy. Fifteen patients with advanced gastric cancer undergoing palliative chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) received for 10 days (beginning 3 days before chemotherapy) daily i.v. injections of 2 mg of a polysaccharide fraction isolated from Echinacea purpurea herb cell cultures (EPS-EPO VIIa). The median number of leukocytes 14-16 days after chemotherapy was 3630/microL (range 1470-5770) in the patients receiving EPS-EPO VIIa compared with 2370/microL (870-3950) in the patients of the historical control group (p = 0.015). EPS-EPO VIIa had no clinically relevant effects on phagocytic activity of granulocytes or on lymphocyte subpopulations. Sixty-eight adverse events including two deaths were observed, most likely due to chemotherapy and the general condition of the patients. However, an association with the test intervention cannot be ruled out completely. The results of this pilot study suggest that EPS-EPO VIIa might be effective in reducing chemotherapy-induced leukopenia. The efficacy and safety should be investigated in further studies.


Frondoside A Inhibits an MYC-Driven Medulloblastoma Model Derived from Human-Induced Pluripotent Stem Cells.
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MYC-driven MBs, commonly found in the group 3 MB, are aggressive and metastatic with the worst prognosis. Modeling MYC-driven MB is the foundation of therapeutic development. Here, we applied a synthetic mRNA-driven strategy to generate neuronal precursors from human-induced pluripotent stem cells (iPSCs). These neuronal precursors were transformed by the MYC oncogene combined with p53 loss of function to establish an MYC-driven MB model recapitulating the histologic and transcriptomic hallmarks of group 3 MB. We further show that the marine compound Frondoside A (FA) effectively inhibits this MYC-driven MB model without affecting isogenic neuronal precursors with undetectable MYC expression. Consistent results from a panel of MB models support that MYC levels are positively correlated with FA's antitumor potency. Next, we show that FA suppresses MYC expression and its downstream gene targets in MB cells, suggesting a potential mechanism underlying FA's inhibitory effects on MYC-driven cancers. In orthotopic xenografts of MYC-driven MB, intratumoral FA administration potently induces cytotoxicity in tumor xenografts, significantly extends the survival of tumor-bearing animals, and enhances the recruitment of microglia/macrophages and cytotoxic T lymphocytes to tumors. Moreover, we show that MYC levels also predict FA potency in glioblastoma and non-small cell lung cancer cells. Taken together, this study provides an efficient human iPSC-based strategy for personalizable cancer modeling, widely applicable to mechanistic studies (e.g., genetic predisposition to cancer) and drug discovery. Our preclinical results justify the clinical translation of FA in treating MYC-driven MB and other human cancers.


Autologous fat grafting in onco-plastic breast reconstruction: A systematic review on oncological and radiological safety, complications, volume retention and patient/surgeon satisfaction.
This study presents an up-to-date overview of the literature on autologous fat grafting (AFG) in onco-plastic breast reconstruction, with respect to complications, oncological and radiological safety, volume retention and patient/surgeon satisfaction. Although AFG is increasingly being applied in onco-plastic breast reconstruction, a comprehensive overview of the available evidence for this procedure is still lacking. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was conducted. Case series, cohort studies and randomized controlled trials (RCTs) reporting on relevant outcomes of breast reconstruction with supplemental AFG were included. In total, 43 studies were included reporting on 6260 patients with a follow-up period ranging from 12 to 136 months. The average locoregional and distant oncological recurrence rates after breast reconstruction with AFG were 2.5% (95% confidence interval (CI) 1.7-3.7) and 2.0% (95% CI 1.1-3.5), respectively. Fewer cysts and calcifications were seen on radiological images for this procedure than for other types of breast surgery. However, more biopsies were performed based on radiological findings (3.7% vs. 1.6%), and more cases of fat necrosis (9.0% vs 4.7%) were seen after treatment with AFG. The total complication rate of 8.4% (95% CI 7.6-9.1) is lower than those reported following other reconstructive breast procedures. The mean volume retention was 76.8% (range 44.7-82.6%) with a satisfaction rate of 93.4% for patients and 90.1% for surgeons. AFG in breast reconstruction is a promising technique. Safety is not compromised as cancer recurrence and complications are not observed. Whether AFG interferes with radiological follow-up remains to be elucidated. Randomized trials with sound methodology are needed to confirm these conclusions.


Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.
Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool. The review was registered within the Prospero database (CRD42021275256). Search strategies were created and input into the PubMed database, where three authors completed all screening. Risk of bias assessments were completed using the Scottish Intercollegiate Guideline Network and Methodological Index for Non-Randomized Studies. A total of 128 articles were identified; however, only seven satisfied all inclusion criteria. The studies ranged from 2012 to 2021 and included sample sizes of 21 to 81 participants, albeit only ∼14% of the included athletes were females. The studies displayed low-to-high levels of bias due to the small sample sizes and preliminary nature of most investigations. Although heterogeneous methods, tasks, and analytical techniques were used, 86% of the studies found differences compared with control athletes, in both the symptomatic and asymptomatic phases of SRC. One study used raw EEG data as a diagnostic indicator demonstrating promise; however, more research and standardization are a necessity. Collectively, the findings highlight the utility of EEG in assessing adolescent SRC; however, future studies should consider important covariates including biological sex, maturation status, and development.


Statistical recommendations for the Global Burden of Disease studies.
Studies Global Burden of Disease (GBD) presents an all-encompassing portrayal of mortality and disability, considering various countries, time periods, age groups, and sex. This article presents statistical recommendations for GBD studies.


Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.
Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex.


Three-dimensional rotational spinal angiography in the evaluation and treatment of vascular malformations.
Conventional spinal angiography, although useful in providing angioarchitectural details of spinal vascular disease, has limitations. The advent of 3D angiography has provided a better comprehension of angioarchitectural detail when evaluating the intracranial circulation. The purpose of this study was to evaluate the usefulness of 3D angiography in the diagnosis and treatment of vascular malformations of the spine. This retrospective analysis included 17 3D spinal angiograms acquired in 14 consecutive patients examined at our institution for a spinal vascular lesion, which included nine spinal cord arteriovenous malformations (AVMs), one perimedullary arteriovenous fistula (AVF), three spinal dural AVFs, and one nerve root AVM. 3D angiography was obtained with apnea under general anesthesia by using a 14-second acquisition and 200 degrees rotation of the gantry during injection of 300 mg I/mL nonionic contrast material at a rate of 0.5-3.5 mL/s. Multiple reconstructed images were obtained with or without opacification of the surrounding structures. These images were then evaluated by the interventionalists at the time of the procedure and compared with findings obtained by conventional subtraction angiography. 3D angiography was useful in differentiating intramedullary lesions from perimedullary surface lesions; detecting arterial, nidal, or venous aneurysms; and evaluating the 3D structure of the lesion as well as the relationship between the malformation and its draining veins or surrounding bony structures. In specific situations, it obviated the need for contrast-enhanced conventional or 3D CT, as well as for lateral or oblique angiographic views, which are sometimes difficult to obtain with good quality. No 3D angiography-related complications were experienced. Some limitations in the definition of small vessel anatomy in the reconstructed images were noted. In this small series of patients, 3D angiography was safe and useful for evaluation of the 3D vascular anatomy of spinal vascular malformations.


[The treatment of metastasic testicular pure mature teratoma].
Given the low frequency of testicular teratoma in relation to the rest of germ cell testicular tumors and the various treatment options for advanced stages, we report one case of advanced testicular mature teratoma with retroperitoneal adenopathy in which orchyectomy was performed after retroperitoneal lymphadenectomy, with the some pathology found in the primary tumor. We do an update on the treatment for these stages with the possibility of beginning with chemotherapy leaving lymphadenectomy for residual masses, or the contrary, being most cases treated in a mixed way. Without clear evidence for guidelines in these tumors, it is recommended to individualize the treatment for each patient, accordingly to tumor characteristics, probability of relapse and follow-up.


Identifying concepts in medical knowledge.
The barrier word method of identifying nominal phrases in text, using a very long barrier word list, was evaluated in two different sets of text. In a sample of 10 paragraphs from the Medical Knowledge Self-Assessment Program of the American College of Physicians, the yield of nominal phrases as a percent of total chunks isolated was 66%. Some 500,000 chunks were isolated from Principles and Practice of Oncology (PPO). 38% of these chunk-occurrences were of chunks which matched to 10,000 concept names in Meta-1.4, the most recent version of the UMLS Metathesaurus. 50 paragraphs from PPO were chosen at random. Co-occurrences of concepts in those paragraphs were reviewed. 42 of the paragraphs had unique or infrequently occurring co-occurrences which described closely the major thrust of the paragraph.


[Antiviral activity of extracts of transgenic cichory and lettuce plants with the human interferon alpha-2b gene].
Biological activity of protein extracts from transgenic plants of chicory Cichorium intybus L. and lettuce Lactuca sativa L. with human interferon alpha2b gene was investigated against vesicular stomatitis virus. It was shown that the extracts from the hairy roots of chicory and lettuce transformed by A. rhizogenes possess the antiviral activity 1620...5400 IU/g weight, and the extracts from leaves of the plants transformed by A. tumefaciens--till 9375 IU/g weight. Dependence of plant extract biological activity on the transformation vector was shown.


In vitro IgE-secreting cells in man. I. Mitogen-independent and -dependent subpopulations.
In vitro IgE secretion by atopic and normal peripheral-blood lymphocytes was examined in culture with pokeweed mitogen or Staphylococcus aureus strain Cowan-I (StaCw) or without mitogen. IgE secreted in culture supernatants was measured with double antibody radioimmunoassay. Enumeration of IgE-secreting cells was made by a protein-A plaque assay. IgE was detected in increasing quantities in supernatants of cultured lymphocytes without mitogen up to the 12th day. IgE-plaque-forming cells were formed by the lymphocytes in large numbers on days 4-7 in cultures with mitogen. These results suggest that not only mitogen-independent but also mitogen-dependent subpopulations may exist in the IgE-secreting cells.


Stability and change of personality across the life course: the impact of age and major life events on mean-level and rank-order stability of the Big Five.
Does personality change across the entire life course, and are those changes due to intrinsic maturation or major life experiences? This longitudinal study investigated changes in the mean levels and rank order of the Big Five personality traits in a heterogeneous sample of 14,718 Germans across all of adulthood. Latent change and latent moderated regression models provided 4 main findings: First, age had a complex curvilinear influence on mean levels of personality. Second, the rank-order stability of Emotional Stability, Extraversion, Openness, and Agreeableness all followed an inverted U-shaped function, reaching a peak between the ages of 40 and 60 and decreasing afterward, whereas Conscientiousness showed a continuously increasing rank-order stability across adulthood. Third, personality predicted the occurrence of several objective major life events (selection effects) and changed in reaction to experiencing these events (socialization effects), suggesting that personality can change due to factors other than intrinsic maturation. Fourth, when events were clustered according to their valence, as is commonly done, effects of the environment on changes in personality were either overlooked or overgeneralized. In sum, our analyses show that personality changes throughout the life span, but with more pronounced changes in young and old ages, and that this change is partly attributable to social demands and experiences.


Kinetic study of Na+-K+ pump in erythrocytes from essential hypertensive patients.
The interaction of the Na+-K+ pump with internal Na+ was investigated in erythrocytes from 38 normotensive control subjects and 49 essential hypertensive patients. In six of the hypertensive patients, the Na+-K+ pump exhibited an apparent dissociation constant for internal Na+ (KNa) above an upper normal limit of 7 mmol/l cells. Four of these six hypertensives showed an increase in the maximal rate of ouabain-sensitive Na+ efflux (Vmax), above an upper normal limit of 11 mmol X l cells-1 X h-1. These abnormalities were stable in repeated determinations over 1-3 yr. A kinetic study of other erythrocyte Na+ transport pathways showed that 16 hypertensives had a low apparent affinity of the Na+-K+ cotransport system for internal Na+, 10 hypertensives exhibited increased Na+-Li+ countertransport fluxes, and 11 hypertensives had increased Na+ leak. None of these three abnormalities were observed in the six hypertensives with abnormal pump fluxes. We thus propose to denominate them as Pump (-) hypertensives. Interestingly, four Pump (-) hypertensives exhibited an increased maximal rate of outward Na+-K+ cotransport. Basal erythrocyte Na+ content of Pump (-) hypertensives was within normal range. This suggests that the increased maximal rates of the Na+-K+ pump and Na+-K+ cotransport system compensate the low pump affinity for internal Na+.


Pulmonary sequestration with elevated serum level of progastrin-releasing peptide.
A 74-year-old woman with rheumatoid arthritis was referred for a mass incidentally noted on chest radiograph. Chest CT scan showed cystic lesions in the right lower lobe. The lesion was evaluated as bronchiectasis, and she was followed up. Three years after the initial presentation, the appearance of the lesion had changed significantly and an elevated air-fluid level in the cystic structures was shown on chest CT scan. The preoperative serum progastrin-releasing peptide (proGRP) level was elevated (108.0 pg/ml; normal: <50 pg/ml). Histopathological specimen obtained by standard lower lobectomy confirmed that the lesion was an intralobar pulmonary sequestration. In the resected lobe, there was no malignant finding, but there were neuroendocrine tumorlet cells, which were positive for proGRP. One month after the resection, the serum proGRP level returned to normal. No pulmonary sequestration with high levels of proGRP has been reported, and this is the first case with elevated serum levels of proGRP.


Perceived physical strain in paid and unpaid work and the work-home interface: the associations with musculoskeletal pain and fatigue among public employees.
The aim of the present study was to analyze the association between number of working hours, the level of perceived physical strain, work-home interface and musculoskeletal pain and fatigue among women and men employed in the public sector. Cross-sectional data from 1,180 employees (86% women) in 49 public workplaces in 2002-2003 were analyzed. Odds ratios (OR) with 95% confidence intervals (CIs) were used as measures of the associations. The analyses showed differences as well as similarities between women and men. Overall the women reported higher levels of perceived physical strain relative to total workload. A high level of physical strain was strongly associated with musculoskeletal pain and fatigue. Nevertheless, no detrimental effects were observed on health of high total working hours which indicates that a large number of total working hours might be balanced by accompanying multiple roles or many responsibilities and therefore not be generally regarded as risk factors for ill health.


Iron stress-induced changes in root epidermal cell fate are regulated independently from physiological responses to low iron availability.
Iron-overaccumulating mutants were investigated with respect to changes in epidermal cell patterning and root reductase activity in response to iron starvation. In all mutants under investigation, ferric chelate reductase activity was up-regulated both in the presence and absence of iron in the growth medium. The induction of transfer cells in the rhizodermis appeared to be iron regulated in the pea (Pisum sativum L. cv Dippes Gelbe Viktoria and cv Sparkle) mutants bronze and degenerated leaflets, but not in roots of the tomato (Lycopersicon esculentum Mill. cv Bonner Beste) mutant chloronerva, suggesting that in chloronerva iron cannot be recognized by putative sensor proteins. Experiments with split-root plants supports the hypothesis that Fe(III) chelate reductase is regulated by a shoot-borne signal molecule, communicating the iron status of the shoot to the roots. In contrast, the formation of transfer cells was dependent on the local concentration of iron, implying that this shoot signal does not affect their formation. Different repression curves of the two responses imply that the induction of transfer cells occurs after the enhancement of electron transfer across the plasma membrane rather than being causally linked. Similar to transfer cells, the formation of extra root hairs in the Arabidopsis mutant man1 was regulated by the iron concentration of the growth medium and was unaffected by interorgan signaling.


Measurement of percentage depth dose and lateral beam profile for kilovoltage x-ray therapy beams.
In this work, nine commonly used dosimetry detectors have been investigated to determine suitable relative dosimeters for kilovoltage x-ray beams. By comparison with the Monte Carlo calculated data, it was determined that for the detectors studied the PTW N23342, Markus and NACP parallel-plate chambers are more suitable for the measurement of percentage depth dose (PDD) data for this beam quality range with an uncertainty of about 3%. A diode detector may be used to measure the PDD for the 100 kVp beam, but it is not suitable for higher energies (300 kVp). The Capintec parallel-plate chamber may be adequate for medium-energy photons, but it has a slightly higher uncertainty for low-energy x-rays (100 kVp). For the measurement of beam profiles, diode and film yield incorrect profile tails, which can be corrected using the RK ionization chamber.


Serum hormone profiles, pregnancy rates, and offspring performance of Rambouillet ewes treated with recombinant bovine somatotropin before breeding.
An experiment was conducted to examine effects of bovine ST (bST) on serum hormone concentrations, pregnancy rates, and offspring performance. Before initiation of a fall breeding period, 75 Rambouillet ewes (68.8 ± 1.5 kg) received an intravaginal insert containing 0.3 g of progesterone (P4) to synchronize onset of estrus. After 12 d, inserts were removed (d 0), and ewes (stratified by BW and age) received either 0 (control, n = 37) or 250 (n = 38) mg of recombinant bST (Posilac, Monsanto, St. Louis, MO, subcutaneously). Ewes were joined with fertile rams 24 h after insert removal. Blood samples were collected from 12 ewes in each treatment group daily from d 0 to 20 after insert removal. Serum IGF-I concentrations were 315 and 437 (± 58) ng/mL in control and bST-treated ewes 2 d after receiving bST (P = 0.02) and remained increased (P < 0.03) in bST-treated ewes throughout the 13-d period (P < 0.05). Serum prolactin (P > 0.10) and estradiol (P = 0.65) were similar between treatments. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were similar (P > 0.20) between treatments from d 0 through 8. Controls had greater (P < 0.04) serum T3 and T4 concentrations than treated ewes did until d 18. Serum P4 was similar (P > 0.10) in control and bST-treated ewes from d 0 through 3 but was increased (P < 0.05) from d 4 to 8 in control ewes. Serum P4 was again similar (P > 0.10) between treatments from d 9 to 20. Serum insulin concentrations were 0.44 and 1.74 (± 0.19) ng/mL in control and bST-treated ewes, respectively, 1 d after receiving bST (P < 0.001) and remained increased (P < 0.03) in bST-treated ewes through d 9 (P < 0.03). Serum glucose was increased (P = 0.003) from d 0 to 10 in bST-treated ewes compared with controls. Thirty-three of 37 (89%) control ewes were pregnant, whereas 27 of 38 (71%) bST-treated ewes were pregnant (P = 0.05). As a percentage of ewes lambing, 61% and 39% of control ewes produced single and twin lambs, respectively, compared with 41% and 59% of bST-treated ewes (P = 0.12). Lamb 60-d adjusted weaning weights were 23.0 and 21.2 (± 0.65) kg for offspring produced by control and bST-treated dams, respectively (P = 0.04). In conclusion, serum IGF-I, insulin, and glucose were greater whereas serum T3, T4, and P4 were less in bST-treated ewes than in controls. Pregnancy rates and offspring adjusted weaning weights were decreased by bST treatment immediately before breeding.


HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions.
The assessment of human epidermal growth factor receptor 2 (HER2) status in gastric cancer is crucial in selecting patients who may benefit from targeted therapy, yet heterogeneous expression could represent an important drawback for HER2 testing. We aimed to analyze (i) HER2 heterogeneity in primary gastric cancers, pre-neoplastic and metastatic lesions and (ii) HER2 prognostic role. We studied 292 surgically resected primary gastric carcinomas and constructed 21 tissue microarrays including tumor tissue cores, invasive front, paired lymph node metastasis, low- and high-grade dysplasia. Microarrays were immunohistochemically stained with HER2 antibody and digitally scanned. Novel digital analysis algorithms were developed to score HER2 expression. Fluorescence in situ hybridization was performed on equivocal cases. HER2-positive cases were 13% and heterogeneous HER2 expression was observed in 71% of positive samples. Analysis of HER2 status in tumor and tumor invasive front demonstrate concordance in 177 cases (88%). Comparison of HER2 expression in primary cancer and synchronous lymph node metastasis exhibited discordant status in 14% of cases. Dysplastic epithelium surrounding the tumor showed immunohistochemical score 2 or 3 in 19% of high-grade and in 9% of low-grade dysplastic samples. HER2 status was significantly associated with intestinal-type carcinomas (P=0.018) and prognosis since patients with primary HER2-positive tumor showed decreased overall survival (P=0.006). Intratumoral HER2 expression heterogeneity and variable lymph node metastases status strongly suggest evaluating more than one sample and, if available, metastatic foci for routinely HER2 testing.


Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome.
Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.


Hybrid Silsesquioxane/Benzoate Cu7-Complexes: Synthesis, Unique Cage Structure, and Catalytic Activity.
A series of phenylsilsesquioxane-benzoate heptacopper complexes 1-3 were synthesized and characterized by X-ray crystallography. Two parallel routes of toluene spontaneous oxidation (into benzyl alcohol and benzoate) assisted the formation of the cagelike structure 1. A unique multi-ligation of copper ions (from (i) silsesquioxane, (ii) benzoate, (iii) benzyl alcohol, (iv) pyridine, (v) dimethyl-formamide and (vi) water ligands) was found in 1. Directed self-assembly using benzoic acid as a reactant afforded complexes 2-3 with the same main structural features as for 1, namely heptanuclear core coordinated by (i) two distorted pentameric cyclic silsesquioxane and (ii) four benzoate ligands, but featuring other solvate surroundings. Complex 3 was evaluated as a catalyst for the oxidation of alkanes to alkyl hydroperoxides and alcohols to ketones with hydrogen peroxide and tert-butyl hydroperoxide, respectively, at 50 °C in acetonitrile. The maximum yield of cyclohexane oxidation products as high as 32% was attained. The oxidation reaction results in a mixture of cyclohexyl hydroperoxide, cyclohexanol, and cyclohexanone. Upon the addition of triphenylphosphine, the cyclohexyl hydroperoxide is completely converted to cyclohexanol. The specific regio- and chemoselectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicate the involvement of of hydroxyl radicals. Complex 3 exhibits a high activity in the oxidation of alcohols.


Prescriptions for Bedtime Sedatives After the Introduction of a General Admission Order Set at an Academic Health Center: The Potential and Pitfalls of Order Sets.
This study describes the impact of modifications to a general admission order set on physician prescribing of 2 as-needed or pro re nata (PRN) bedtime sedatives. The hospitalists at our institution have used a general medical admission order set since 2005. Zolpidem was the only as-needed (PRN) bedtime sedative option on the order set until trazodone was added in December 2008. Trazodone is preferred over zolpidem in the geriatric population. We identified patients admitted by the hospitalists between January 2007 and August 2013 who were prescribed with either zolpidem or trazodone as a PRN sedative. Patient demographics, date and time of the order, and number of sedative doses administered during the hospitalization were recorded. Orders placed within 12 hours of admission were attributed to admission orders. Between 2007 and 2013, the number of patients admitted by the hospitalists with an order for PRN trazodone on admission increased by 18-fold. During the same period, the number of admissions by the hospitalists increased by 2.3 times. Zolpidem orders exceeded those for trazodone in all age groups until 2008. After the addition of trazodone, its use exceeded that of zolpidem. Almost half (48%) of all patients did not have a dose of the PRN trazodone administered. Although order sets can be leveraged to align practitioners with established guidelines, the expediency of using medications on an order set may overcome physicians' clinical judgment. The content of an order set therefore deserves careful scrutiny before implementation.


Moderator effect of sex in the clustering of treatment-seeking patients with gambling problems.
There are no studies based on a person-centered approach addressing sex-related differences in the characteristics of treatment-seeking patients with gambling disorder (GD). The main objective of the current study is to identify empirical clusters of GD based on several measures of the severity of gambling behavior, and considering the potential role of patient sex as a moderator. An agglomerative hierarchical clustering method was applied to an adult sample of 512 treatment-seeking patients (473 men and 39 women) by using a combination of the Schwarz Bayesian Information Criterion and log-likelihood function. Three clusters were identified in the subsample of men: cluster M1 (low-mild gambling severity level, 9.1%), cluster M2 (moderate level, 60.9%), and cluster M3 (severe level, 30.0%). In the women subsample, two clusters emerged: cluster W1 (mild-moderate level, 64.1%), and cluster W2 (severe level, 35.9%). The most severe GD profiles were related to being single, multiple gambling preference for nonstrategic plus strategic games, early onset of the gambling activity, higher impulsivity levels, higher dysfunctional scores in the personality traits of harm avoidance, and self-directedness, and higher number of lifespan stressful life events (SLE). Differences between the empirical men and women clusters were found in different sociodemographic and clinical measurements. Men and women have distinct profiles regarding gambling severity that can be identified by a clustering approach. The sociodemographic and clinical characterization of each cluster by sex may help to establish specific preventive and treatment interventions.


What determines arthritogenicity of bacterial cell wall? A study on Eubacterium cell wall-induced arthritis.
To study what determines the arthritogenicity of the bacterial cell wall (CW) using Eubacterium CW-induced arthritis in the rat. Eubacterium aerofaciens, previously reported as arthritogenic, and E. limosum and E. alactolyticum, known as non-arthritogenic, were used. Gas chromatography-mass spectrometry (GC-MS) was applied to analyse the chemical composition of the bacterial cell wall. Cellular immune response was measured by concanavalin A (Con A) stimulation and FACScan analysis. Also, serum antibodies against the injected cell wall were determined. Unexpectedly, from the two strains of E. aerofaciens used only one proved to be arthritogenic (with a CW inducing chronic arthritis after a single intraperitoneal injection), even though these two strains were 100% identical by 16S rDNA analysis. CW of the other E. aerofaciens strain induced only transient acute arthritis; CW of E. limosum and E. alactolyticum induced weak signs of acute arthritis. Based on the GC-MS analysis and on the results published previously, putative structures of peptidoglycan (PG) in the four CW preparations are presented. It is apparent that the presence of lysine in position 3 of the PG stem peptide contributes to arthritogenicity but is alone not decisive. Both strains of E. aerofaciens were immunosuppressive, when tested by Con A response at 2 weeks after CW injection. Such an immunosuppression was not observed after injection of CW from E. limosum or E. alactolyticum. FACScan analysis for six T cell markers and studies on serum antibody responses did not reveal any differences in the effect of the four bacterial strains used. The results obtained suggest that the chemical structure of PG present in the bacterial CW is decisive in determining arthritogenicity/non-arthritogenicity. Therefore, from two bacterial strains belonging to normal human intestinal flora and 100% identical by 16S rDNA analysis, one proved to be arthritogenic and the other non-arthritogenic.


Kuwait oil fires: correction.
In our article "Airborne studies of the smoke from the Kuwait oil fires" (15 May, p. 987) (1), we stated that the depletions of sulfur dioxide (SO(2)) and nitrogen oxides (NO(x)) in the smoke plume from the Kuwait oil fires were 50 and 60% per hour, respectively. These values were derived from measurements made aboard a Convair C-131 aircraft, and measurements of CO(2) were used as a conserved tracer. Subsequent comparisons of these measurements of CO(2) (which were obtained from a continuous analyzer) with independent measurements of CO(2) (obtained from "grab" samples) revealed that the continuous CO(2) measurements were occasionally contaminated by cabin air. Recalculation of the depletion rates of SO(2) and NO(x), with the use of uncontaminated measurements of CO(2) from the "grab" sampler aboard the aircraft yielded values of 6 and 22%, respectively (2). Our conclusions with regard to the climatic effects of the Kuwait oil fires are unchanged.


Prognostic value of lymphocyte-to-monocyte ratio in gastric cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint inhibitor (ICI) therapy. Nevertheless, the existing findings remain contentious. A comprehensive search of literature was conducted in databases including PubMed, Embase, Web of Science, and the Cochrane Library, spanning from the inception of each database to August 30, 2023 to collect studies exploring the interplay between LMR and clinical outcomes. Eligible studies were selected following predefined inclusion and exclusion criteria. Primary outcomes encompassed progression-free survival (PFS) and overall survival (OS), which were estimated using hazard ratios (HR) and corresponding 95% confidence intervals (CI). Our analysis incorporated eight cohort studies, involving 815 patients. Aggregate data revealed associations between an elevated LMR at baseline and prolonged PFS (HR=0.58; 95% CI: 0.47-0.71, p<0.00001) and improved OS (HR=0.51, 95% CI: 0.33-0.79; p=0.003). Furthermore, LMR exhibited a favorable association with PFS after treatment (HR=0.48; 95% CI: 0.29-0.79; p= 0.004), while such a correlation was not evident in the OS analysis. Importantly, a high level of LMR was associated with prolonged PFS across varying sample sizes, follow-up duration, treatment combinations, line of therapy, and cut-off values. A high pre-treatment LMR is associated with improved OS and PFS in GC patients treated with ICIs. LMR emerges as a potent biomarker for prognostic assessment in these patients, offering valuable insights for informed treatment decisions within the domain of GC immunotherapy. PROSPERO, identifier CRD42021228512.


Performance monitoring and the medial prefrontal cortex: a review of individual differences and context effects as a window on self-regulation.
The medial prefrontal cortex (MPFC) is central to self-regulation and has been implicated in generating a cluster of event-related potential components, collectively referred to as medial frontal negativities (MFNs). These MFNs are elicited while individuals monitor behavioral and environmental consequences, and include the error-related negativity, Nogo N2, and the feedback-related negativity. A growing cognitive and affective neuroscience literature indicates that the activation of the anterior cingulate cortex (ACC) and surrounding medial prefrontal regions during performance monitoring is not only influenced by task context, but that these patterns of activity also vary as a function of individual differences (e.g., personality, temperament, clinical and non-clinical symptomatology, socio-political orientation, and genetic polymorphisms), as well as interactions between individual differences and task context. In this review we survey the neuroscience literature on the relations between performance monitoring, personality, task context, and brain functioning with a focus on the MPFC. We relate these issues to the role of affect in the paradigms used to elicit performance-monitoring neural responses and highlight some of the theoretical and clinical implications of this research. We conclude with a discussion of the complexity of these issues and how some of the basic assumptions required for their interpretation may be clarified with future research.


Streptococcal vertebral osteomyelitis: multiple faces of the same disease.
The role of Streptococcus species as an aetiological microorganism of vertebral osteomyelitis (VO) is considered to be of little relevance. We aimed to describe a large number of cases of streptococcal vertebral osteomyelitis (SVO), to analyze the clinical features associated with different Streptococcus species, and to compare them with a cohort of patients with VO caused by Staphylococcus aureus. An incidence study and a retrospective, multicenter, observational clinical study of cases of SVO (1991-2011) were performed. Statistical comparison of SVO by different species and between them and staphylococcal VO was carried out. Over the whole period there was an increasing incidence in the number of VOs and SVOs per year (p <0.05). Among 58 cases of SVO, those caused by non-viridans streptococcus (Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus pyogenes; n = 26) mimicked VO by S. aureus, and presented with more fever, neurological symptoms and paravertebral abscesses in comparison with those caused by the viridans group (remaining species). In contrast, the latter have a sub-acute clinical picture and were associated with the presence of endocarditis (p <0.05). Among non-viridans SVOs, concomitant infection was specifically related to S. pneumoniae (p <0.05). In conclusion, SVO presents a wide range of clinical patterns. The relationship between VO and diagnosis of endocarditis was established with SVO caused by the viridans group. Whereas non-viridans SVO mimics acute characteristics of VO caused by S. aureus, cases of viridans SVO are significantly more likely to have a sub-acute clinical presentation. The increased incidence of SVO during the last decades could support a new epidemiological scenario.


Dysglycemia and a history of reproductive risk factors.
The purpose of this study was to identify reproductive risk factors associated with dysglycemia (diabetes, impaired glucose tolerance, and impaired fasting glucose) in a contemporary multiethnic population. We studied 14,661 women screened with an oral glucose tolerance test for the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial. Reproductive risk factors were compared in normoglycemic and dysglycemic women. Dysglycemia was significantly associated with the number of children born (odds ratio 1.03 per child [95% CI 1.01-1.05]), age (1.05 per year [1.04-1.05]), non-European ancestry (1.09 [1.01-1.17]), preeclampsia/eclampsia (1.14 [1.02-1.27]), irregular periods (1.21 [1.07-1.36]), and gestational diabetes mellitus (GDM) (1.53 [1.35-1.74]). The relationship between GDM and dysglycemia did not differ across BMI tertiles (P = 0.84) nor did the relationships of other risk factors. Reproductive factors, particularly GDM, are associated with dysglycemia in middle-aged women from many ethnicities. Reproductive factors can be used to counsel young women about their future risk of dysglycemia, whereas in middle age they may help screen for dysglycemia.


The IMEx Coronavirus interactome: an evolving map of Coronaviridae-Host molecular interactions.
The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website ( www.ebi.ac.uk/intact ), and will be continuously updated as research on COVID-19 progresses.


[Non-nutritious sucking in preterm babies: bibliographic study].
This is a bibliographic study on non-nutritive sucking in pre-term infants. To characterize and analyze the scientific production on non-nutritive sucking in pre-term infants and identify how the transition from gastric to oral feeding takes place as well as how it begins and develops by considering the stimulation of non-nutritive sucking. Review of secondary sources (MEDLINE and LILACS). Pre-term infants presented a stable clinical condition, without cardiorespiratory, neurological or gastro-intestinal alterations. Gestational age varied from 30 to 35 weeks and the weight from 1,400 to 1,800 g. The stimulus for non-nutritive sucking used was a pacifier or bottle nipple. The time and frequency of stimulus application varied. As a result of the stimulation programs, there were early hospital discharges and greater weight gain. Literature on this subject, particularly that of national authorship, is scarce and the articles do not address a detailed description of the transition from gastric to oral feeding, thus leaving a gap that deserves to be further studied.


The relationships of spiritual health, pregnancy worries and stress and perceived social support with childbirth fear and experience: A path analysis.
Given maternal health is a major health indicator, the present research aimed at determining the causal relationships of spiritual health, worries, stress and perceived social support with the fear and experience of childbirth in pregnant women. The present longitudinal prospective research recruited 352 pregnant women presenting to selected health centers in Qazvin, Iran in 2021. The data were collected using the Childbirth Experience Questionnaire-2 (CEQ-2), the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), the Multidimensional Scale of Perceived Social Support (MSPSS), the Persian version of the Pregnancy Worries and Stress Questionnaire (PWSQ), the Spiritual Health Questionnaire, the Socioeconomic Status (SES) questionnaire and a sociodemographic checklist, and were analyzed in SPSS-25 and Lisrel-8.8. The mean age of the participants was 28.1±6.8 years. According to the results of the path analysis, among the variables related to fear of childbirth, childbirth experience (B = -0.37, CI:-0.44;-0.22) in the direct path and perceived social support (B = -0.51, CI:-0.58;-0.43) in both direct and indirect paths demonstrated the most significant negative relationship. Among the variables related to childbirth experience, pregnancy worries and stress had a negative causal relationship (B = -0.06, CI:-0.079;-0.043) in the direct path, spiritual health showed the highest significant positive relationship (B = 0.01, CI: 0.008; 0.012) in the indirect path, and perceived social support (B = 0.112, CI: 0.092; 0.131) and the number of children (B = 0.32,CI: 0.30; 0.34) demonstrated the highest significant positive relationship in both direct and indirect paths. In other words, childbirth experience becomes more desirable as spiritual health, social support, and the number of children increases, and it becomes less desirable as pregnancy worries and stress rise. According to the present findings, various psychological, social, and spiritual factors are associated with childbirth fear and experience. It is thus necessary to utilize appropriate methods and promote training and support to reduce the adverse outcomes of childbirth.


Static gain saturation in quantum dot semiconductor optical amplifiers.
Measurements of saturated amplified spontaneous emission-spectra of quantum dot semiconductor optical amplifiers demonstrate efficient replenishment of the quantum-dot ground state population from excited states. This saturation behavior is perfectly modeled by a rate equation model. We examined experimentally the dependence of saturation on the drive current and the saturating optical pump power as well as on the pump wavelength. A coherent noise spectral hole is observed with which we assess dynamical properties and propose optimization of the SOA operating parameters for high speed applications.


Shell-vial assay: evaluation of a new technique for determining antibiotic susceptibility, tested in 13 isolates of Coxiella burnetii.
Coxiella burnetii is a strictly intracellular bacterium. Bacteriostatic effects have been described previously on a few isolates in embryonated eggs (A. J. Spicer, M. G. Peacock, and J. C. Williams, p. 375-383, in W. Burgdorfer and R. L. Anacker, ed., Rickettsiae and rickettsial diseases, 1981). We used the shell-vial technique (D. Raoult, G. Vestris, and M. Enea, J. Clin. Microbiol. 28:2482-2484, 1990) to determine the susceptibility of C. burnetii to amoxicillin, amikacin, erythromycin, co-trimoxazole, pefloxacin, ofloxacin, ciprofloxacin, chloramphenicol, tetracycline, doxycycline, minocycline, and rifampin antibiotics at a single dilution. Human embryonic lung fibroblast monolayers in shell vials were seeded with 13 different C. burnetii isolates, including 3 reference strains (Nine Mile, Q212, and Priscilla) and 10 new isolates, in order to obtain 30% infected cells 6 days later. After inoculation, antibiotics were added, shell vials were incubated for 7 days, and immunofluorescence was revealed and compared with that of the positive controls. Strain Nine Mile was more susceptible than strains Q212 and Priscilla were. The heterogeneity of susceptibility to fluoroquinolones, chloramphenicol, and erythromycin was noted among the strains; all were resistant to amoxicillin and amikacin, and all were susceptible to rifampin, co-trimoxazole, tetracycline, and tetracycline analogs.


Inequality in social rank and adult nutritional status: evidence from a small-scale society in the Bolivian Amazon.
Research on the social determinants of health has highlighted (a) the adverse effects of social inequality on individual health and (b) the association between individual social rank and health. In this paper, we contribute to the growing literature on the health consequences of social inequalities by assessing the association between village level inequality in social rank, a form of non-material inequality, and indicators of nutritional status. We use quantitative survey information from 289 men (18+ years of age) from a society of forager-farmers in the Bolivian Amazon (Tsimane'). We construct village level measures of non-material inequality by using individual measures of men's positions in the village hierarchy according to prestige (or freely conferred deference) and dominance (or social rank obtained through power). We find that village inequality in dominance, but not village inequality in prestige, is associated with short-term indices of individual nutritional status. Doubling the coefficient of variation of dominance in a village would be associated to a 6.7% lower BMI, a 7.9% smaller mid-arm circumference, and a 27.1% smaller sum of four skin folds of men in the village. We also find that once we decouple individual social rank based on dominance from individual social rank based on prestige, only prestige-based social rank is associated with nutritional status. Potential explanations for our findings relate to the differential forms of resource access derived from the two forms of social hierarchies and to the social and psychological benefits associated with prestige versus the social costs and psychological stress generated by dominance.


Identification of a biochemical marker for endothelial dysfunction using Raman spectroscopy.
In the present work, we propose the spectroscopic approach to identify biochemical alterations in endothelial dysfunction. The method is based on the quantification of the ratio of phenylalanine (Phe) to tyrosine (Tyr) contents in the endothelium. The synthesis of Tyr from Phe requires the presence of tetrahydrobiopterin (BH4) as a cofactor of phenylalanine hydroxylase (PAH). Limitation of BH4 availability in the endothelium is a hallmark endothelial nitric oxide synthase (eNOS) dysfunction that may also lead to PAH dysfunction and a fall in Tyr contents. Using Raman spectra, the ratio of marker bands of Tyr to Phe was calculated and the pathological state of the endothelium was detected. We provide evidence that Phe/Tyr ratio analysis by Raman spectroscopy discriminate endothelial dysfunction in ApoE/LDLR(-/-) mice as compared to control mice.


3D collagen scaffolds coated with multiwalled carbon nanotubes: initial cell attachment to internal surface.
The cell adhesion in a multiwalled carbon nanotube-coated collagen sponge (MWCNT-coated sponge) was investigated. Immediately after seeding, the cells adhered to the inner surface of the MWCNT-coated sponge and a significantly larger number of cells were observed there than for a pure collagen sponge used as control. On the MWCNT-coated sponge, the cells appeared favorable adhesion and spread in the early stages in the center part of the sponge which cells rarely attached without MWCNT-coating. It was suggested that the physical structure of MWCNTs was effective for initial adhesion of cells from the result of serum-free culture. MWCNT-coating makes the material a suitable three-dimensional scaffold for cell culturing, as opposed to other scaffold systems where such an effect is not seen.


The impact of driver distraction on road safety: results from a representative survey in two Australian states.
To quantify the prevalence and effects of distracting activities while driving. Cross sectional driver survey. New South Wales and Western Australia, Australia. 1347 licensed drivers aged between 18 and 65 years. Data were weighted to reflect the corresponding driving population. Prevalence of distracting activities while driving; perceived risks and adverse outcomes due to distractions. The most common distracting activities during the most recent driving trip were lack of concentration (weighted percentage (standard error, SE) 71.8% (1.4%) of drivers); adjusting in-vehicle equipment (68.7% (1.5%)); outside people, objects or events (57.8% (1.6%)); and talking to passengers (39.8% (1.6%)). On average, a driver engaged in a distracting activity once every six minutes. One in five crashes (21%) during the last three years, involving one in 20 drivers (5.0% (0.7%)), was attributed to driver distraction based on self-report. In the population under study, this equated to 242,188 (SE 34,417) drivers. Younger drivers (18-30 years) were significantly more likely to report distracting activities, to perceive distracting activities as less dangerous, and to have crashed as a result. Distracting activities while driving are common and can result in driving errors. Driver distraction is an important cause of crashes. Further research is needed to estimate the risk conferred by different distracting activities and the circumstances during which activities pose greatest risk. These results suggest that a strategy to minimize distracting activities while driving, with a focus on young drivers, is indicated.


"Benign" early repolarization versus malignant early abnormalities: clinical-electrocardiographic distinction and genetic basis.
In the great majority of cases the ECG pattern of early repolarization (ERP) is a benign phenomenon observed predominantly in teenagers, young adults, male athletes and the black race. The universally accepted criterion for its diagnosis is the presence, in at least two adjoining leads, of ≥ 1 mm or 0.1 mV ST segment elevation. In benign ERP reciprocal ST segment changes are possible only in lead aVR. In contrast, reciprocal ST segment changes can be observed in several leads in idiopathic ventricular fibrillation (IVF) and acute coronary syndrome. In benign ERP the ST segment and T wave patterns have a relative temporal stability. IVF is an entity with low prevalence, possibly familiar, and characterized by the occurrence of VF events in a young person. More frequently this occurs in male subjects without structural heart disease and with otherwise with normal ECG even using high right accessory leads and/or after ajmaline injection. Several clinical entities cause ST segment elevation include asthenic habitus, acute pericarditis, ST segment elevation myocardial infarction, Brugada syndrome, congenital short QT syndrome, and idiopathic VF. In these circumstances clinical and ECG data are most important for differential diagnosis. In IVF the modifications could be dramatic and predominantly at night during vagotonic predominance when J waves > 2 mm in amplitude. The ST/T abnormalities are dynamic, inconstant, and reversed with isoproterenol. Convex upward J waves, with horizontal/descending ST segments or "lambda-wave" ST shape are suggestive of IVF with early repolarization abnormalities. Premature ventricular contractions with very short coupling and "R on T" phenomenon are characteristics with two pattern: When originate from right ventricular outflow tract left bundle branch block morphology and from peripheral Purkinje network, left bundle branch block pattern. The inherited-familial forms are not frequent in IVF; however mutations were identified in the genes KCNJ8, DPP6, SCN5A, SCN3B, CACNA1C, CACNB2, and CACNA2D1. The management of IVF has class I indication for ICD implantation. Ablation therapy is considered additional to ICD implantation in those patients with repetitive ventricular arrhythmia. Quinidine is a highly efficient drug that prevents recurrence.


[Nature of inhibition of the activity of macromolecular antibodies].
The presence in the organism of an inhibitory factor expressing its activity under conditions of increased macromolecular globulins production (of M-immunoglobulins in particular) was established experimentally. The inhibitory factor depressed the avidity of the macromolecular antibodies; its appearance preceded reduction of the macromolecular protein level in the blood serum. The inhibitory effect of the blood serum in blood letting and vaccination with bacterial antigen is connected with the blood serum albumins, and with increased cystein and sulfhydryl groups concentration.


Experimental investigations on nonlinear dynamics in supercontinuum generation with feedback.
A system for supercontinuum generation by using a photonic crystal fiber within a synchronously pumped ring cavity is presented. The feedback led to an interaction of the generated supercontinuum with the following femtosecond laser pulses and thus to the formation of a nonlinear oscillator. The nonlinear dynamical behavior of this system was investigated experimentally and compared with numerical simulations. Steady state, period doubling and higher order multiplication of the repetition rate as well as limit cycle and chaotic behavior were observed in the supercontinuum generating system.


The effect of the intracervical application of follicle-stimulating hormone or luteinizing hormone on the pattern of expression of gonadotrophin receptors in the cervix of non-pregnant ewes.
During the periovulatory period, the cervix relaxes in response to changes in circulating concentrations of reproductive hormones. The present study investigated the role of gonadotrophins in cervical function by examining the expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) and their mRNAs following intracervical treatment with either FSH or LH. Eighteen ewes were assigned to four groups, and they were then treated with progestagen sponges and PMSG to synchronize their oestrous cycles. Intracervical treatments were given 24 h after sponge removal as follows: Group 1: FSH 2 mg; Group 2: LH 2 mg; Group 3: Vehicle and Group 4: Control. Cervices were collected 54 h after sponge removal and then divided into three regions. The expression of FSHR and LHR was determined by immunohistochemistry and FSHR mRNA and LH mRNA by in situ hybridization. The expression of LHR, FSHR and their respective mRNAs was compared in six tissue layers (luminal epithelium, subepithelial stroma, circular, longitudinal and transverse muscle and serosa) and in three cervical regions (vaginal, mid and uterine). The results showed that FSH increased transcription of the FSHR gene and the levels of its receptor, but only in subepithelial stroma of the cervix. FSH also increased the levels of LHR in the cervix, but only in the muscle layers. LH had no effect on the levels of FSHR despite the fact that it did increase the level of transcription of the FSHR gene and LH also increased the levels of its own receptor in the cervix, but only in the muscle layers, and this action was independent of increased levels of transcription of the LHR gene. These findings suggest multiple levels of regulation of cervical LH and FSH receptors and that the gonadotrophins may have a role in relaxation of the cervix during oestrus by regulating their own receptors.


Voice features of Parkinson's disease patients with subthalamic nucleus deep brain stimulation.
Voice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients; however, their characteristics remain unclear. We performed a comprehensive voice evaluation including the multi-dimensional voice program for acoustic analysis, the GRBAS scale for perceptual analysis, and the evaluation of the voice handicap index (VHI) for psychosocial analysis. In total, 68 patients who had undergone STN-DBS (37 assessed in the on- and off-stimulation conditions) and 40 who had been treated with medical therapy alone were evaluated. Further, we performed laryngoscopic examinations in 13 STN-DBS and 19 medical-therapy-alone patients. The STN-DBS group, especially females, showed widespread impairment of voice parameters and significantly poorer VHI scores than the medical-therapy-alone group. The degree of voiceless (DUV) and strained voice were the most impaired factors in the STN-DBS group; and DUV significantly improved after stopping stimulation. Furthermore strained voice, breathiness, and asthenia improved after stopping stimulation. Laryngoscopic examination showed that abnormal laryngeal muscle contraction and incomplete glottal closure were more prominent in the STN-DBS group than in the medical-therapy-alone group. We demonstrated that (1) more widespread voice impairment in females, (2) poorer voice-related QOL, (3) worse DUV and strained voice, and (4) abnormal laryngeal muscle contraction were the characteristic voice and laryngeal findings in the STN-DBS group compared with those in the medical-therapy-alone group.


Complete Genome Sequence of Staphylococcus epidermidis CSF41498.
Staphylococcus epidermidis CSF41498 is amenable to genetic manipulation and has been used to study mechanisms of biofilm formation. We report here the whole-genome sequence of this strain, which contains 2,427 protein-coding genes and 82 RNAs within its 2,481,008-bp-long genome, as well as three plasmids.


Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response.
To show whether intra-articular steroid injections are effective in osteoarthritis; to determine factors that predict response; and to determine whether injection has a beneficial effect on muscle strength. Double blind, placebo controlled, crossover study in 59 patients with symptomatic osteoarthritis of the knee. Outcome measure-Primary outcome measure: change in visual analogue score for pain at three weeks. Predictors of response analysed using logistic regression with a 15% decrease in pain score at three weeks defining response. Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline (median change -2.0 mm, interquartile range -16.25 to 4.0) and placebo (median 0.0 mm, interquartile range -9.0 to 6.25). No clinical predictors of response could be identified. Muscle strength was not significantly improved in the short term by intra-articular injection. Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible. There may be a place for their more widespread use.


The ACOUCOU platform: Online acoustic education developed by an interdisciplinary team.
The ACOUCOU platform is a web-based, interactive, acoustics training platform that includes a set of free educational materials in various technical fields of acoustics. Educational materials are designed to serve as a modern self-development tool for students and engineers, as well as a comprehensive solution for professional education in the work environment. On the other hand, the provided materials of the platform can be a useful tool, supporting teachers, company researchers, and academic lecturers in the process of teaching acoustics. The ACOUCOU platform is a part of a strategic plan for expanding and strengthening acoustic knowledge web-based tools and supporting the development of innovative teaching methods based on attractive and effective delivery of digital content, and best practices at national and international levels. It addresses the challenge of a lack of experts in the acoustics field and the growing needs of the market.


The relationship between electrical auditory brainstem responses and perceptual thresholds in Digisonic® SP cochlear implant users.
Determining the electrical stimulation levels is often a difficult and time-consuming task because they are normally determined behaviorally - a particular challenge when dealing with pediatric patients. The evoked stapedius reflex threshold and the evoked compound action potential have already been shown to provide reasonable estimates of the C- and T-levels, although these estimates tend to overestimate the C- and T-levels. The aim of this study was to investigate whether the evoked auditory brainstem response (eABR) can also be used to reliably estimate a patient's C- and T-levels. The correlation between eABR detection thresholds and behaviorally measured perceptual thresholds was statistically significant (r = 0.71; P < 0.001). In addition, eABR Wave-V amplitude increased with increasing stimulation level for the three loudness levels tested. These results show that the eABR detection threshold can be used to estimate a patient's T-levels. In addition, Wave-V amplitude could provide a method for estimating C-levels in the future. The eABR objective measure may provide a useful cochlear implant fitting method - particularly for pediatric patients.


Binding of inhibitors to the monomeric and dimeric SARS-CoV-2 Mpro.
SARS-CoV-2 rapidly infects millions of people worldwide since December 2019. There is still no effective treatment for the virus, resulting in the death of more than one million patients. Inhibiting the activity of SARS-CoV-2 main protease (Mpro), 3C-like protease (3CLP), is able to block the viral replication and proliferation. In this context, our study has revealed that in silico screening for inhibitors of SARS-CoV-2 Mpro can be reliably done using the monomeric structure of the Mpro instead of the dimeric one. Docking and fast pulling of ligand (FPL) simulations for both monomeric and dimeric forms correlate well with the corresponding experimental binding affinity data of 24 compounds. The obtained results were also confirmed via binding pose and noncovalent contact analyses. Our study results show that it is possible to speed up computer-aided drug design for SARS-CoV-2 Mpro by focusing on the monomeric form instead of the larger dimeric one.


Genetic factors influence cataract formation in alpha 3 connexin knockout mice.
Connexin alpha 3 (Cx46 or Gja3) gene targeted null mice developed lens nuclear cataracts shortly after birth. A large variance in the cataracts was observed in alpha 3 null sibs on a mixed 129SvJae X C57BL/6J F3 background. This suggested that the genetic background might influence the cataract phenotype. Therefore, we placed the alpha 3 null mutation into a 129SvJae background, and also backcrossed the mutation for six generations into 129SvJ and C57BL/6J backgrounds. While alpha 3 nulls on the two 129 backgrounds contained severe cataracts associated with gamma crystallin cleavage, alpha 3 nulls on the C57B16 background had far milder cataracts with no detectable gamma crystallin cleavage. These findings suggest that a genetic modifier exists that influences gamma crystallin stability, and that gamma crystallin breakdown is associated with severe nuclear cataracts.


Review: Immunogenetics of human placentation.
Natural killer (NK) cells are a population of lymphocytes that function in both immune defense and reproduction. Diversifying NK cell phenotype and function are interactions between NK cell receptors and major histocompatibility complex (MHC) class I ligands. As a consequence of strong and variable selection these ligand-receptor systems are polymorphic, rapidly evolving, and considerably species-specific. Counterparts to the human system of HLA class I ligands and killer cell immunoglobulin-like receptors (KIR) are present only in apes and Old World monkeys. HLA-C, the dominant ligand for human KIR and the only polymorphic HLA class I expressed by trophoblast, is further restricted to humans and great apes. Even then, the human system appears qualitatively different from that of chimpanzees, in that it has evolved a genetic balance between particular groups of receptors and ligands that favor reproductive success and other groups of receptors and ligands that have been correlated with disordered placentation. Human populations that have survived successive episodes of epidemic disease and population bottlenecks maintain a breadth of diversity for KIR and HLA class I, implying that loss of such diversity disfavors long-term survival of a human population.


Efficient, ordered bulk heterojunction nanocrystalline solar cells by annealing of ultrathin squaraine thin films.
Spin-cast 2,4-bis[4-(N,N-diisobutylamino)-2,6-dihydroxyphenyl]squaraine (SQ) thin films only 62 A thick are converted from amorphous to polycrystalline via postannealing at elevated temperatures. The surface roughness of the SQ films increases by a factor of 2, while selected area electron diffraction spectra indicate an increase in the extent of postannealed film crystallinity. Dichloromethane solvent annealing is also demonstrated to increase the exciton diffusion length of SQ by a factor of 3 over thermally annealed SQ films as a result of further enhancement in crystalline order. We find that the roughened surface features have a length scale on the order of the exciton diffusion length. Hence, coating the donor SQ with the acceptor, C(60), results in a nearly optimum controlled bulk heterojunction solar cell structure. Optimized SQ/C(60) photovoltaic cells have a power conversion efficiency of eta(p) = 4.6 +/- 0.1% (correcting for solar mismatch) at 1 sun (AM1.5G) simulated solar intensity, and a corresponding peak external quantum efficiency of EQE = 43 +/- 1% even for the very thin SQ layers employed.


6-Acetylmethylenepenicillanic acid (Ro 15-1903), a potent beta-lactamase inhibitor. II. Antibacterial properties.
The beta-lactamase inhibitor Ro 15-1903 showed low affinity for penicillin binding proteins (PBPs) of Escherichia coli. When used as a single compound, it displayed no substantial antibacterial activity but in combination with ampicillin, it was similar to clavulanic acid in conferring activity against ampicillin-resistant strains. Some synergy between Ro 15-1903 and piperacillin was found against high inocula of Pseudomonas aeruginosa. Ro 15-1903 markedly enhanced the activity of ceftriaxone against Bacteroides fragilis. In keeping with the in vitro findings, the combination Ro 15-1903 and ampicillin protected mice against systemic infections with beta-lactamase-producing strains of Staphylococcus aureus, Klebsiella pneumoniae and Proteus sp. but not against those with Enterobacter cloacae, Serratia marcescens, and E. coli producing either chromosomally mediated beta-lactamase of type I or plasmid-mediated beta-lactamase of type TEM.


Recent advances in enhancement of oil content in oilseed crops.
Plant oils are very valuable agricultural commodity. The manipulation of seed oil composition to deliver enhanced fatty acid compositions, which are appropriate for feed or fuel, has always been a main objective of metabolic engineers. The last two decennary have been noticeable by numerous significant events in genetic engineering for identification of different gene targets to improve oil yield in oilseed crops. Particularly, genetic engineering approaches have presented major breakthrough in elevating oil content in oilseed crops such as Brassica napus and soybean. Additionally, current research efforts to explore the possibilities to modify the genetic expression of key regulators of oil accumulation along with biochemical studies to elucidate lipid biosynthesis will establish protocols to develop transgenic oilseed crops along much improved oil content. In this review, we describe current distinct genetic engineering approaches investigated by researchers for ameliorating oil content and its nutritional quality. Moreover, we will also discuss some auspicious and innovative approaches and challenges for engineering oil content to yield oil at much higher rate in oilseed crops.


Felbamate metabolism in the rat, rabbit, and dog.
Two major and one minor metabolite of felbamate (FBM) as well as unchanged drug were isolated and identified by electron impact and chemical ionization mass spectrometry from rat and dog urine after dosing with [14C]FBM. The metabolites were 2-(4-hydroxyphenyl)-1,3-propanediol dicarbamate (p-OHF), 2-hydroxy-2-phenyl-1,3-propanediol dicarbamate, and 2-phenyl-1,3-propanediol monocarbamate. The metabolites and FBM were excreted mainly in urine, where their sum accounted to 81-94% of the radioactivity in hydrolyzed rat urine samples, 71-82% in rabbit urine samples, and 69-83% in dog urine samples. The amount of metabolites in the conjugated form was estimated to be 20-35% in rat, 20-30% in rabbit, and 10-20% in dog urine. The major biliary metabolite in all three species was p-OHF, whereas the amount of FBM was small. Metabolites found in dog feces were the same as those in the urine.


Organellar proteomics reveals Golgi arginine dimethylation.
The Golgi complex functions to posttranslationally modify newly synthesized proteins and lipids and to sort them to their sites of function. In this study, a stacked Golgi fraction was isolated by classical cell fractionation, and the protein complement (the Golgi proteome) was characterized using multidimensional protein identification technology. Many of the proteins identified are known residents of the Golgi, and 64% of these are predicted transmembrane proteins. Proteins localized to other organelles also were identified, strengthening reports of functional interfacing between the Golgi and the endoplasmic reticulum and cytoskeleton. Importantly, 41 proteins of unknown function were identified. Two were selected for further analysis, and Golgi localization was confirmed. One of these, a putative methyltransferase, was shown to be arginine dimethylated, and upon further proteomic analysis, arginine dimethylation was identified on 18 total proteins in the Golgi proteome. This survey illustrates the utility of proteomics in the discovery of novel organellar functions and resulted in 1) a protein profile of an enriched Golgi fraction; 2) identification of 41 previously uncharacterized proteins, two with confirmed Golgi localization; 3) the identification of arginine dimethylated residues in Golgi proteins; and 4) a confirmation of methyltransferase activity within the Golgi fraction.


A new approach to construct pathway connected networks and its application in dose responsive gene expression profiles of rat liver regulated by 2,4DNT.
Military and industrial activities have lead to reported release of 2,4-dinitrotoluene (2,4DNT) into soil, groundwater or surface water. It has been reported that 2,4DNT can induce toxic effects on humans and other organisms. However the mechanism of 2,4DNT induced toxicity is still unclear. Although a series of methods for gene network construction have been developed, few instances of applying such technology to generate pathway connected networks have been reported. Microarray analyses were conducted using liver tissue of rats collected 24h after exposure to a single oral gavage with one of five concentrations of 2,4DNT. We observed a strong dose response of differentially expressed genes after 2,4DNT treatment. The most affected pathways included: long term depression, breast cancer regulation by stathmin1, WNT Signaling; and PI3K signaling pathways. In addition, we propose a new approach to construct pathway connected networks regulated by 2,4DNT. We also observed clear dose response pathway networks regulated by 2,4DNT. We developed a new method for constructing pathway connected networks. This new method was successfully applied to microarray data from liver tissue of 2,4DNT exposed animals and resulted in the identification of unique dose responsive biomarkers in regards to affected pathways.


Insulin-like growth factor binding protein-3 secretion from cultured rat sertoli cells: dual regulation by follicle stimulating hormone and insulin-like growth factor-I.
The insulin-like growth factors (IGFs) are found in extracellular fluids bound to carrier proteins which influence the biological activity of the IGFs. Three structurally different binding proteins (BPs) have been isolated and cloned; each has distinct tissue specific expression and unique properties. We report here that testicular cells synthesize a specific subset of these binding proteins. Ligand blot analysis and RNA blot hybridization indicates that cultured peritubular cells synthesize primarily IGFBP-2. In contrast, as determined by ligand blot, RNA blot hybridization and N-linked deglycosylated studies, IGFBP-3 is predominantly synthesized by the Sertoli cell. In a dose dependent fashion, FSH markedly reduces the levels of IGFBP-3 in Sertoli cell conditioned medium. Similarly, isoproterenol, (Bu)2cAMP and cholera toxin also markedly reduce the abundance of IGFBP-3 in conditioned media. In contrast, IGF-I increases the concentrations of IGFBP-3 with the concentration required for half-maximal stimulation, approximately 20 ng/ml. Consistent with a peritubular cell origin, IGFBP-2 may be the predominant species found in interstitial fluid. In summary, our data reveal that the IGFBPs are expressed in a cell type specific manner in the testis. The opposing effects of FSH and IGF-I on Sertoli cell IGFBP-3 expression suggests a mechanism by which the IGF-I biological activity on Sertoli cell might be influenced.


Hypertension due to renal artery stenosis in transplanted kidneys.
Hypertension appeared to be related to stenosis of the hypogastricrenal artery system in 5 patients among 153 recipients of renal allografts. Renin assay and arteriography were crucial in the comprehensive evaluation of patients whose hypertension was not clearly related to rejection or excessive sodium intake. Hypereninemia was persistent in 4 of the 5 patients. Stenoses of the transplant renal arteries in three patients were caused by extensive intimal plaque formation. In one patient, periarterial fibrosis caused reduction of flow; 180 degrees torsion of the anastomosis resulted in stenosis in the fifth patient. Surgical correction is difficult and may be facilitated by a transabdominal approach. Vein bypass is probably preferable to patch angioplasty for intimal lesions. Following operation, hypertension was ameliorated and function improved in all patients. Rejection, which has been suggested as one of the causes of intimal plaque formation, ultimately led to the loss of the transplant in one patient. Function is normal in two patients; two patients have evidence of chronic rejection. No effort should be spared to evaluate this special group of patients whose transplant function can predictably be prolonged by decisive surgical management.


Privileged structures: applications in drug discovery.
Over the past 15 years the privileged structure concept has emerged as a fruitful approach to the discovery of novel biologically active molecules. Privileged structures are molecular scaffolds with versatile binding properties, such that a single scaffold is able to provide potent and selective ligands for a range of different biological targets through modification of functional groups. In addition, privileged structures typically exhibit good drug-like properties, which in turn leads to more drug-like compound libraries and leads. The net result is the production of high quality leads that provide a solid foundation for further development. The identification of privileged structures will be discussed, emphasizing the importance of understanding the structure-target relationships that confer "privileged" status. This understanding allows privileged structure based libraries to be targeted at distinct target families (e.g. GPCRs, LGIC, enzymes/kinases). Privileged structures have been successfully exploited across and within different target families and promises to be an effective approach to the discovery and optimization of novel bioactive molecules. The application of the privileged structure approach, both in traditional medicinal chemistry and in the design of focused libraries, will be discussed with the aid of illustrative examples.