[The pain sensitivity of the skin in chronic psychoemotional stress in man].
The focused ultrasound has been used for the comparative study of skin sensitivity to pain in 51 healthy men and 64 patients with neurasthenia, natural model of the chronic psycho-emotional stress. The patients showed a distinct tendency to a decrease of the pain threshold, lowered adaptation to the repeated threshold stimulus, sensitization. With the presence of the above-mentioned factors the pain syndrome occurred relatively more often. Taking into account the fact that the focused ultrasound of rather high intensity affects, first of all, C-afferents which are not only cutaneous but visceral nociceptors as well, an assumption is made that changes in pain sensitivity in the neurasthenic patients are not limited by skin but develop also in the inner medium forming the pain syndrome.


Evaluation of prognostic factors in lung cancers with surgical complete response after induction treatment.
This study aims to evaluate long-term results of induction treatment and to investigate prognostic factors affecting survival in non-small cell lung cancer patients with a pathological complete response. Between January 2010 and December 2017, a total of 39 patients (38 males, 1 female; mean age: 56.2±8.3 years; range, 38 to 77 years) having locally advanced (IIIA-IIIB) non-small cell lung cancer who were given induction treatment and underwent surgery after induction treatment and had a pathological complete response were retrospectively analyzed. Survival rates of the patients and prognostic factors of survival were analyzed. Clinical staging before induction treatment revealed Stage IIB, IIIA, and IIIB disease in three (7.7%), 26 (66.7%), and 10 (25.6%) patients, respectively. The five-year overall survival rate was 61.2%, and the disease-free survival rate was 55.1%. In nine (23.1%) patients, local and distant recurrences were detected in the postoperative period. In patients with locally advanced non-small cell lung cancer undergoing surgery after induction treatment, the rates of pathological complete response are at considerable levels. In these patients, the five-year overall survival is quite satisfactory and the most important prognostic factor affecting overall survival is the presence of single-station N2.


Corneal clarity measurements in patients with keratoconus undergoing either penetrating or deep anterior lamellar keratoplasty.
To compare the corneal clarity measurement between penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) in patients with keratoconus, using densitometry software for the Oculus Pentacam. A retrospective comparative study was carried out at Manchester Royal Eye Hospital. Data were collected 12-18 months after corneal transplantation for keratoconus, including postoperative corneal densitometry, best corrected visual acuity (BCVA), central corneal thickness (CCT), and other relevant clinical details. Analysis of 37 keratoconus eyes from 36 patients found there was a significantly higher corneal densitometry measurement after DALK than PK. This was predominantly in the posterior layer of the concentric zone 0-2 mm of the cornea (P=0.0004). A significant correlation was found between postoperative BCVA and corneal densitometry in DALK groups at full thickness (P=0.03). This correlation was seen in the central 0-2 mm (P=0.03) and posterior 0-2 mm (P=0.04) zones. In addition, within the DALK group, a correlation was found between central corneal thickness and densitometry at full thickness 2-6 mm (P=0.007), central 0-2 (P=0.04), central 2-6 mm (P=0.01), and at posterior 2-6 mm (P=0.01) zones. This study showed that corneal densitometry measurement differs depending on the type of corneal transplantation used to treat keratoconus patients. Densitometry may have an important role to play in the final BCVA achieved by patients undergoing corneal transplantation for keratoconus. Analysis of Oculus Pentacam images provides an objective evaluation to monitor the cornea status after the surgery.


[Effect of calcium ions on adrenal glucocorticoid function].
In the experimental dogs and healthy humans it was shown that calcium ions promote activation of the adrenal glucocorticoids function, which duration is dependent on the day time. In patients the influence of calcium ions on the blood 11-hydroxycorticosteroid concentration is dependent on the initial steroid level and concentration of injected calcium chloride solution. The infusion of 1% calcium chloride solution exerted a stable effect. Possible mechanisms of the changes observed are discussed.


Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy.
The molecular basis of strain variation in scrapie diseases is unknown. The only identified component of the agent is the posttranslationally modified host prion protein (PrPSc). The biochemical and physical properties of PrP from two strains of transmissible mink encephalopathy (TME), called hyper (HY) and drowsy (DY), were compared to investigate if PrP heterogeneity could account for strain diversity. The degradation rate of PrPTME digested with proteinase K was found to be strain specific and correlated with inactivation of the TME titer. Edman protein sequencing revealed that the major N-terminal end of HY PrPTME commenced at least 10 amino acid residues prior to that of DY PrPTME after digestion with proteinase K. Analysis of the brain distribution of PrPTME exhibited a strain-specific pattern and localization of PrPTME to the perikarya of specific neuron populations. Our findings are consistent with HY and DY PrPTME having distinct protein conformations and/or strain-specific ligand interactions that influence PrPTME properties. We propose that PrPTME conformation could play a role in targeting TME strains to different neuron populations in which strain-specific formation occurs. These data are consistent with the idea that PrPTME protein structure determines the molecular basis of strain variation.


Hyperbaric oxygen therapy and chemokine administration - a combination with potential therapeutic value for treating diabetic wounds.
Non-healing wounds impart serious medical problems to people with diabetes. Amongst 15% of diabetic patients, the incidence of foot ulcer is the most prevailing, which confers a significant risk of limb amputation, mainly due to hypoxia and impairment in cell signaling. Alteration in the expression of chemokines and the related factors in diabetic conditions delays the recruitment of different cell types, including fibroblasts, keratinocytes, and immune cells such as macrophages to the site of injury, further impairing neovasculogenesis, re-epithelialization, and extracellular matrix formation. Thus, proper activation of effector cells through an accurate signal pathway is necessary for better therapeutic application. Hyperbaric oxygen therapy (HBOT) is the current treatment prescribed by medical practitioners, shown to have increased the wound healing rate by reducing the need for significant amputation among the diabetic population. However, the risk of morbidity associated with HBOT needs complete attention through rigorous research to avoid adverse outcomes. Altering the level of pro-angiogenic chemokines may regulate the inflammatory response, further promote vascularization, and enhance the complete healing of wounds in diabetic patients. Thus, a combination of better therapeutic approaches could pave the way for developing a successful treatment for diabetic foot and wound healing.


The prevention of prematurity.
The prevention of prematurity requires identification of the patients most likely to go into labour prematurely and early recognition of threatened premature labour. There are unfortunately few clinical signs to help identify these patients, but certain features in the history are helpful. As soon as premature labour is diagnosed, energetic and active treatment with corticosteroids to advance pulmonary maturity and uterine suppression should be instituted. It is important to bear in mind that these patients should be managed in units, where not only is such treatment feasible, but neonatal intensive care is available, if labour cannot be suppressed.


Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement.
The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that stent-induced remodeling is dominated by contact guidance.


Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications.
Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions. They have proven to potentially take up and process tumor-associated antigens (TAAs). In this regard, researchers have developed strategies such as genetically engineered or TAA-pulsed DC vaccines; these manipulated DCs have shown significant outcomes in clinical and preclinical models. Here, we review DC classification and address how DCs are skewed into an immunosuppressive phenotype in cancer patients. Additionally, we present the advancements in DCs as a platform for cancer immunotherapy, emphasizing the technologies used for in vivo targeting of endogenous DCs, ex vivo generated vaccines from peripheral blood monocytes, and induced pluripotent stem cell-derived DCs (iPSC-DCs) to boost antitumoral immunity.


The matrix metalloproteinase gene GmMMP2 is activated in response to pathogenic infections in soybean.
Matrix metalloproteinases (MMPs) play an important role in host defense responses against pathogens in mammals where their activities lead to the production of antimicrobial peptides. We have identified a novel soybean (Glycine max) metalloproteinase gene, GmMMP2, that is transcriptionally up-regulated in infected tissues. The deduced amino acid sequence indicates that this gene belongs to the MMP family. It is a preproprotein containing an N-terminal signal peptide, a cysteine switch, a zinc-binding catalytic motif, and a C-terminal transmembrane domain. The GmMMP2 expressed in and purified from Escherichia coli exhibited an in vitro enzymatic activity in digesting myelin basic protein. All plant metalloproteinases reported so far have no known functions. However, they have been suggested to be involved in extracellular cell matrix degradation during development or senescence. Our investigations demonstrate that the GmMMP2 transcript levels were rapidly increased in compatible and incompatible interactions of soybean tissues with the oomycete pathogen Phytophthora sojae or the bacterial pathogen Pseudomonas syringae pv. glycinea. In agreement with the GmMMP2 activation, a metalloproteinase activity was gradually increased in suspension-cultured cells following the bacterial infection. GmMMP2 was also activated in response to wounding and dehydration. However, GmMMP2 activation did not correlate with the oxidative burst leading to the hypersensitive response cell death or the tissue senescence progress that involves programmed cell death. Our investigations suggest that GmMMP2 may be involved in a novel defense response of soybean against pathogenic infections.


Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years.
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective observational multicenter study in the United States and United Kingdom that enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, valproate). In this article, we examine fetal AED exposure effects on motor, adaptive, and emotional/behavioral functioning in 229 children who completed at least one of these tests at 3 years of age. Adjusted mean scores for the four AED groups were in the low average to average range for motor functioning, parental ratings of adaptive functioning, and parental ratings of emotional/behavioral functioning. A significant dose-related performance decline in motor functioning was seen for both valproate and carbamazepine. A significant dose-related performance decline in parental ratings of adaptive functioning was also seen for valproate, with a marginal performance decline evident for carbamazepine. Further, parents endorsed a significant decline in social skills for valproate that was dose related. Finally, on the basis of parent ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy appear to be at a significantly greater risk for a future diagnosis of attention-deficit/hyperactivity disorder. Additional research is needed to confirm these findings, examine risks of other AEDs, define the risks in the neonate associated with AEDs for treatment of seizures, and determine the underlying mechanisms of adverse AED effects on the immature brain.


Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice.
Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that caveolin-1 functions as a suppressor of cell transformation. For example, the human CAV-1 gene maps to a suspected tumor suppressor locus (D7S522/7q31.1) that is frequently deleted in a number of carcinomas, including breast cancers. In addition, up to 16% of human breast cancers harbor a dominant-negative mutation, P132L, in the CAV-1 gene. Despite these genetic associations, the tumor suppressor role of caveolin-1 still remains controversial. To directly assess the in vivo transformation suppressor activity of the caveolin-1 gene, we interbred Cav-1 (-/-) null mice with tumor-prone transgenic mice (MMTV-PyMT) that normally develop multifocal dysplastic lesions throughout the entire mammary tree. Herein, we show that loss of caveolin-1 gene expression dramatically accelerates the development of these multifocal dysplastic mammary lesions. At 3 wk of age, loss of caveolin-1 resulted in an approximately twofold increase in the number of lesions (foci per gland; 3.3 +/- 1.0 vs. 7.0 +/- 1.2) and an approximately five- to sixfold increase in the total area occupied by these lesions. Similar results were obtained at 4 wk of age. However, complete loss of caveolin-1 was required to accelerate the appearance of these dysplastic mammary lesions, because Cav-1 (+/-) heterozygous mice did not show any increases in foci development. We also show that loss of caveolin-1 increases the extent and the histological grade of these mammary lesions and facilitates the development of papillary projections in the mammary ducts. Finally, we demonstrate that cyclin D1 expression levels are dramatically elevated in Cav-1 (-/-) null mammary lesions, consistent with the accelerated appearance and growth of these dysplastic foci. This is the first in vivo demonstration that caveolin-1 can function as a transformation suppressor gene.


[Images of Brazil: a Rockefeller Archive Center collection].
This article describes and comments on the collection of photographs of Brazil that belongs to the Rockefeller Foundation archives (Rockefeller Archive Center) in the United States. It also contains information about the origin of such documents and the way they were collected, as well as analyzes the context in which these visual documents were produced. They record the relationship between Rockefeller Foundation and Brazilian institutions engaged in the combat against yellow fever, malaria and ancyclostomaisis from 1920 to 1940.


Nitrosative Stress and Lipid Homeostasis as a Mechanism for Zileuton Hepatotoxicity and Resistance in Genetically Sensitive Mice.
Zileuton is an orally active inhibitor of leukotriene synthesis for maintenance treatment of asthma, for which clinical usage has been associated with idiosyncratic liver injury. Mechanistic understanding of zileuton toxicity is hampered by the rarity of the cases and lack of an animal model. A promising model for mechanistic study of rare liver injury is the Diversity Outbred (J:DO) mouse population, with genetic variation similar to that found in humans. In this study, female DO mice were administered zileuton or vehicle daily for 7 days (i.g.). Serum liver enzymes were elevated in the zileuton group, with marked interindividual variability in response. Zileuton exposure-induced findings in susceptible DO mice included microvesicular fatty change, hepatocellular mitosis, and hepatocellular necrosis. Inducible nitric oxide synthase and nitrotyrosine abundance were increased in livers of animals with necrosis and those with fatty change, implicating nitrosative stress as a possible injury mechanism. Conversely, DO mice lacking adverse liver pathology following zileuton exposure experienced decreased hepatic concentrations of resistin and increased concentrations of insulin and leptin, providing potential clues into mechanisms of toxicity resistance. Transcriptome pathway analysis highlighted mitochondrial dysfunction and altered fatty acid oxidation as key molecular perturbations associated with zileuton exposure, and suggested that interindividual differences in cytochrome P450 metabolism, glutathione-mediated detoxification, and farnesoid X receptor signaling may contribute to zileuton-induced liver injury (ZILI). Taken together, DO mice provided a platform for investigating mechanisms of toxicity and resistance in context of ZILI which may lead to targeted therapeutic interventions.


Dosimetry for Radiopharmaceutical Therapy: The European Perspective.
This review presents efforts in Europe over the last few years with respect to standardization of quantitative imaging and dosimetry and comprises the results of several European research projects on practices regarding radiopharmaceutical therapies (RPTs). Because the European Union has regulatory requirements concerning dosimetry in RPTs, the European Association of Nuclear Medicine released a position paper in 2021 on the use of dosimetry under these requirements. The importance of radiobiology for RPTs is elucidated in another position paper by the European Association of Nuclear Medicine. Furthermore, how dosimetry interacts with clinical requirements is described, with several clinical examples. In the future, more efforts need to be undertaken to increase teaching and standardization efforts and to incorporate radiobiology for further individualizing patient treatment, with the aim of improving the outcome and safety of RPTs.


Well-organized zeolite nanocrystal aggregates with interconnected hierarchically micro-meso-macropore systems showing enhanced catalytic performance.
Preparation and characterization of well-organized zeolitic nanocrystal aggregates with an interconnected hierarchically micro-meso-macro porous system are described. Amorphous nanoparticles in bimodal aluminosilicates were directly transformed into highly crystalline nanosized zeolites, as well as acting as scaffold template. All pores on three length scales incorporated in one solid body are interconnected with each other. These zeolitic nanocrystal aggregates with hierarchically micro-meso-macroporous structure were thoroughly characterized. TEM images and (29)Si NMR spectra showed that the amorphous phase of the initial material had been completely replaced by nanocrystals to give a micro-meso-macroporous crystalline zeolitic structure. Catalytic testing demonstrated their superiority due to the highly active sites and the presence of interconnected micro-meso-macroporosity in the cracking of bulky 1,3,5-triisopropylbenzene (TIPB) compared to traditional zeolite catalysts. This synthesis strategy was extended to prepare various zeolitic nanocrystal aggregates (ZSM-5, Beta, TS-1, etc.) with well-organized hierarchical micro-meso-macroporous structures.


In vivo, competitive blockade of N-methyl-D-aspartate receptors induces rapid changes in filamentous actin and drebrin A distributions within dendritic spines of adult rat cortex.
In vitro studies have demonstrated that prolonged N-methyl-D-aspartate receptor (NMDAR) blockade triggers a homeostatic up-regulation of NMDARs at synapses. Such upregulation can also be seen within 30 min in vivo in adult rats, implicating trafficking of reserve pools of NMDARs. Here, we evaluated the involvement of filamentous actin (F-actin), the major cytoskeletal component in spines, in this rapid in vivo homeostatic response, using biotinylated phalloidin as its probe. We also immuno-labeled spines for drebrin A, an F-actin-binding protein found at excitatory synapses and with a proposed role of modulating F-actin's cross-linking with one another and interactions with NMDARs. Quantitative 2-D analysis of ultrastructural images revealed that NMDAR blockade increased filamentous actin labeling per spine by 62.5% (P<0.005). The proportion of dendritic spines immuno-labeled for drebrin A also increased significantly, from 67.5% to 85% following NMDAR blockade (P<0.001), especially among larger spines. The frequency distributions of spine widths and postsynaptic density lengths were not affected by the D-(+)-2-amino-5-phosphonopentanoic acid (D-APV) treatment. However, the average postsynaptic density length was reduced by 25 nm among the fewer, drebrin A immuno-negative spines, indicating that drebrin A confers stability to synapse size. We propose that, in a homeostatic in vivo response, increases of drebrin A and F-actin within spines can enhance NMDAR trafficking by reducing cytoskeletal rigidity within the spine cytoplasm without changing the overt morphology of axo-spinous synapses. Alternatively or in addition, the cytoskeletal redistribution within spine cytoplasm may be triggered by the D-APV-induced, homeostatic up-regulation of NMDAR.


Reoperation Rates After Long Posterior Spinal Fusion: Use of Recombinant Bone Morphogenetic Protein in Idiopathic and Non-idiopathic Scoliosis.
Bone morphogenetic protein (BMP) can increase the likelihood of solid arthrodesis in spinal surgery. This would imply fewer reoperations for pseudarthrosis, but small cohort sizes are inadequate to monitor these events. We sought to examine adolescent idiopathic (AIS) and non-idiopathic scoliosis (NIS) for reoperation events with and without the use of BMP using a large statewide database. The 2008-2011 New York State Inpatient Database was queried using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Patients age 10 and older with a diagnosis of scoliosis and an index fusion of greater than 2 spinal motion segments were included. Patient identifiers and linkage variables were used to identify revisits. The relative risk of reoperation was calculated. The use of BMP at the initial inpatient stay was used to define the two cohorts for relative risk assessment. A total of 2,658 and 2,431 cases were identified of AIS and NIS, respectively. The use of BMP at the initial visit was performed at a rate of 4.5% for AIS and 21.0% for NIS fusion surgery. For posterior fusion cases longer than eight levels, the reoperation rate for pseudarthrosis was 1.0% in AIS and 18.4% in NIS (p < .001). For NIS fusions greater than eight levels, the rate of reoperation for pseudarthrosis after using BMP at the index surgery was 5% and 22% when BMP was not used, a relative risk of 4.0 (p < .001). For AIS, there was no substantial increase in risk when not using BMP for fusion greater than eight levels (p < .001). We found a significant decrease in the risk of reoperation for pseudarthrosis after long fusions when using BMP in the case of NIS. In contrast, use of BMP does not benefit the AIS population.


[Twelve year FEV1 changes and smoking habits among 556 workers in the Paris-area (author's transl)].
The aim of the study was to analyse the effects of smoking, in particular to show its causal role in the development of airflow obstruction, and to look at changes in smoking habits. The study was conducted among 556 men, aged 30 to 54 in 1960, surveyed twice, in 1960 and 1972. The hypothesis of tobacco as a causal factor of airflow obstruction is strengthened, following this study, by three results: 1) FEV1 slope was related to tobacco consumption, even after adjustement for FEV1 level (42 ml/yrs for non-smokers, 51 ml/yrs for heavy smokers); 2) FEV1 loss with age increased with the amount of tobacco consumption: one pack a day smoked for 25 years was equivalent to an aging of 5 years; 3) FEV1 loss decelerated if the subject gave up smoking, thus preventing any further risk. What appeared to be a spontaneous regulation in smoking habits was observed. The men who stopped smoking were those with low respiratory status. In this population, men who were ex-smokers in 1960 and maintained this status until 1972 had a FEV1 slope similar to that of the non-smokers.


Dopamine-Supported Metallization of Polyolefins─A Contribution to Transfer to an Eco-friendly and Efficient Technological Process.
Metallization is a common method to produce functional or decorative coatings on plastic surfaces. State-of-the-art technologies require energy-intensive process steps and the use of organic solvents or hazardous substances to achieve sufficient adhesion between the polymer and the metal layer. The present study introduces a facile bio-inspired "green" approach to improve this technology: the use of dopamine, a small-molecule mimic of the main structural component of adhesive mussel proteins, as an adhesion promoter. To understand dopamine adhesion and identify conditions for successful metallization, polyethylene surfaces were dip-coated with dopamine and metallized with nickel by electroless metallization; essential parameters such as temperature, pH value, concentration of dopamine and buffer, and the deposition time were systematically varied. Effects of adding oxidants to the dopamine bath, cross-linking, thermal and UV post-treatment of the polydopamine film, and plasma pretreatment of the substrate were investigated. The properties of the polydopamine layer and the quality of the metal film were studied by physico-chemical, optical, and mechanical techniques. It was shown that simple dip-coating of the substrate with dopamine under optimal conditions is sufficient to support metal layers with a good optical quality. Technologically relevant metal layer quality and adhesion were obtained with annealed and UV-treated polydopamine films and enhanced by plasma pretreatment of the substrate. The study shows that dopamine provides a new interfacial design for plastic metallization that can reduce energy consumption, use of hazardous substances, and reject rate during manufacturing. The results are essential findings for further technological developments of a universal platform to promote adhesion between plastics and metal or potentially also other material classes, enabling economic material development and more eco-friendly applications.


Relevance of the Internal Jugular Vein for Surgery in the Upper Parapharyngeal Space.
Objective: Tumors arising from the upper parapharyngeal space (UPPS) may have intimate relationships with the internal carotid artery (ICA) and the internal jugular vein (IJV). The significance of the ICA in UPPS has been sufficiently articulated, whereas the relevance of the IJV has not been addressed. This study aimed to assess the anatomical variations of the IJV within the UPPS, and to explore its implications for surgical procedures. Methods: An endoscopic dissection of the IJV was performed on 10 cadaveric specimens. In addition, 30 patients who underwent transoral or transcervical resection of UPPS tumors were retrospectively reviewed to characterize the IJV and its relation to the tumor. Results: On the cadaveric specimens, the IJV was located at the posteromedial and posterolateral aspects of the styloid process in 13 (65%) and 7 (35%) sides, respectively. In our clinical series, the IJV was not encountered in 18 patients with pre-styloid tumors. In 12 patients harboring retro-styloid tumors, the IJV was partially (n = 5) or completely (n = 7) compressed and was displaced into the posterolateral aspect of the tumor. The IJV was injured intraoperatively in 1 patient, requiring an immediate conversion to an open transcervical corridor that allowed its exposure and ligation without difficulty. Conclusion: This study characterizes the IJV and its relationship with adjacent neurovascular structures in the UPPS, which may provide further safeguards during transoral and transcervical procedures in the UPPS.


Intensive care units, communication between nurses and physicians, and patients' outcomes.
Various factors in hospitals can adversely affect patients' outcomes, including faulty communication between nurses and physicians. Whether specific communication elements (timeliness, accuracy, openness, understanding) can influence adverse outcomes is unknown. To determine the relationships between patients' outcomes and (1) nurses' perceptions of elements of communication between nurses and physicians and (2) characteristics of the practice environment. A cross-sectional survey design was used. Information on ventilator-associated pneumonia, bloodstream infection associated with a central catheter, and pressure ulcers was collected from 25 intensive care units in southeastern Michigan. Simultaneously, 462 nurses in those units (response rate, 53.3%) were anonymously surveyed. The Conditions for Work Effectiveness Questionnaire-II and the Practice Environment Scale of the Nursing Work Index were used to measure characteristics of the practice environment. The Intensive Care Unit Nurse-Physician Questionnaire was used to measure communication between nurses and physicians. Statistical tests included correlation and multiple regression. Analyses were conducted at the unit level. Unit response rates varied from 6% to 100%. Together, variability in understanding communication and capacity utilization were predictive of 27% of the variance in ventilator-associated pneumonia. Timeliness of communication was inversely related to pressure ulcers (r= -0.38; P=.06), and workplace empowerment and scores on the Acute Physiology and Chronic Health Evaluation III were positive predictors of ventilator-associated pneumonia (R(2)=0.36; P=.005). Not all elements of communication were related to the selected adverse outcomes. The connection between characteristics of the practice environment at the unit level and adverse outcomes remains elusive.


The thalamic ataxia syndrome.
We identified 10 patients with contralateral ataxia and hemisensory loss following unilateral thalamic lesions. Seven patients had ischemic infarcts, and three had hemorrhages. Hemiparesis, when present, was only a transient finding, whereas ataxia, dysmetria, dysdiadochokinesia, rebound, and hemisensory loss persisted. Two patients had cerebellar outflow tremor. Another developed a severe Déjerine-Roussy pain syndrome. Four patients had lesions of the dominant hemisphere, and two had visual field deficits. None had mutism, aphasia, or astasia. On radiographic evaluation, all patients had lesions in the mid to posterior thalamus, a localization consistent with a lesion of the dentatorubrothalamic and ascending sensory pathways into the thalamus. The thalamic ataxia syndrome has a distinct localizing value that is distinguishable from the ataxic hemiparesis syndrome. Strokes occurring in the ventral lateral and posterior nuclei of the thalamus produce the clinical picture of contralateral "cerebellar" dysfunction and sensory loss with only transient weakness.


Red cell enzymopathies of the glycolytic pathway.
The delineation of specific erythrocyte glycolytic enzyme defects during the past three decades has clarified hitherto unexplained hereditary hemolytic syndromes. The glycolytic enzymopathies have proven to be important, not as a public health problem, but because the investigation of these experimental models of nature has provided information to increase our understanding of control of glycolysis and interrelationships of the Rapoport-Luebering shunt, mechanism of hemolysis, erythrocyte ageing, role of isozymes in various organs, and genetic control of enzyme structure/function. The application of ever improving techniques of recombinant DNA should yield a bonanza of new information to improve our comprehension of the pathogenesis and heterogeneity of these disorders as well as provide increased knowledge of regulation of these enzymes. It should be an exciting era.


Coronavirus Disease 2019 (COVID-19) Vaccination and Assisted Reproduction Outcomes: A Systematic Review and Meta-analysis.
To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis. We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate. Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included. Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88-1.01, P=.10), number of oocytes retrieved (mean difference -0.26, 95% CI -0.68 to 0.15, P=.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI -0.14 to 0.75, P=.18), fertilization rate (OR 0.99, 95% CI 0.87-1.11, P=.83), implantation rate (OR 0.92, 95% CI 0.84-1.00, P=.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86-1.06, P=.40), or live-birth rate (OR 0.95, 95% CI 0.78-1.17, P=.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results. Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies. PROSPERO, CRD42023400023.


Anti-Planktonic and Anti-Biofilm Properties of Pentacyclic Triterpenes-Asiatic Acid and Ursolic Acid as Promising Antibacterial Future Pharmaceuticals.
Due to the ever-increasing number of multidrug-resistant bacteria, research concerning plant-derived compounds with antimicrobial mechanisms of action has been conducted. Pentacyclic triterpenes, which have a broad spectrum of medicinal properties, are one of such groups. Asiatic acid (AA) and ursolic acid (UA), which belong to this group, exhibit diverse biological activities that include antioxidant, anti-inflammatory, diuretic, and immunostimulatory. Some of these articles usually contain only a short section describing the antibacterial effects of AA or UA. Therefore, our review article aims to provide the reader with a broader understanding of the activity of these acids against pathogenic bacteria. The bacteria in the human body can live in the planktonic form and create a biofilm structure. Therefore, we found it valuable to present the action of AA and UA on both planktonic and biofilm cultures. The article also presents mechanisms of the biological activity of these substances against microorganisms.


Cadmium affects the expression of metallothionein (MT) and glutathione peroxidase (GPX) mRNA in goldfish, Carassius auratus.
Cadmium (Cd) is a widespread non-essential heavy metal that enters the aquatic environment as a result of natural and human-caused activities, including industrial effluent, mining, and agricultural runoff. In the present study, we investigated time and dose-related effect of CdCl(2) on metallothionein (MT) and glutathione peroxidase (GPX) mRNA levels in a number of goldfish tissues, in vivo. Basal MT and GPX mRNA levels remained unchanged in the tissues tested throughout the experiment. Injection with CdCl(2) significantly increased MT mRNA levels in the brain, liver, kidney and intestine in a dose-dependant manner at all time tested (6, 12, 24 and 36 h). We isolated the full length GPX cDNA from goldfish kidneys, and found it to contain 785 nucleotides, including an open reading frame, predicted to encode a protein of 142 amino acids. In contrast, injection with CdCl(2) significantly decreased GPX mRNA levels in the liver and kidney in a time-, and dose-, dependant, and became undetectable after 12, 24 and 36 h. The findings provide molecular characterization of MT and GPX in goldfish and suggest that exposure to Cd results in significant physiological changes in goldfish.


Estrogen receptor in the rabbit corpus luteum.
The rabbit corpus luteum contains a cytoplasmic estrogen receptor substance in concentrations comparable to those found in the uterus. Receptor in corpora lutea of nonpregnant rabbits was highest at midluteal phase and decreased before physical regression of corpora was evident. These results support the view that the corpus luteum in this species is an estrogen-responsive tissue.


The role of mitochondria in sepsis-induced cardiomyopathy.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial dysfunction, often termed sepsis-induced cardiomyopathy, is a frequent complication and is associated with worse outcomes. Numerous mechanisms contribute to sepsis-induced cardiomyopathy and a growing body of evidence suggests that bioenergetic and metabolic derangements play a central role in its development; however, there are significant discrepancies in the literature, perhaps reflecting variability in the experimental models employed or in the host response to sepsis. The condition is characterised by lack of significant cell death, normal tissue oxygen levels and, in survivors, reversibility of organ dysfunction. The functional changes observed in cardiac tissue may represent an adaptive response to prolonged stress that limits cell death, improving the potential for recovery. In this review, we describe our current understanding of the pathophysiology underlying myocardial dysfunction in sepsis, with a focus on disrupted mitochondrial processes.


From β-hCG values to counseling in tubal pregnancy: what do women want?
Tubal pregnancy represents an entity that every gynecologist will encounter during professional life. Because of the high prevalence among the pregnant population, standardized protocols are needed in order to choose the optimal strategy for each case. Accurate ultrasound pictures are supporting a more precise diagnosis of ectopic tubal pregnancy, the evolution of which should be closely monitored in follow-up with serial β-hCG values. Laparoscopy, intramuscular methotrexate, and active expectant management are all involved, however, tailoring the best treatment to the patient's needs is the challenge to focus on. This manuscript describes how in routinary practice an evidence-based diagnostic process should be the key factor to go for the best possible management. When possible, a longsighted less invasive approach should be preferred, aiming to preserve the patient's fertility for years to come. An optimal choice of the management should involve the patient or the couple in the decision-making process to reach the ultimate goal of compliance.


Physicians and DRGs. Hospital management alternatives.
Rising health care costs in general and hospital costs in particular have placed significant financial strain on federal programs such as Medicare. It was with this in mind that the Reagan administration in 1983 initiated Medicare's new prospective payment system based on diagnostic-related groups (DRGs) to reduce the growth rate of Medicare expenditures. The introduction of DRGs has generated significant controversy in the health care community. The DRG system may necessitate consideration of four new management alternatives by hospital administrators: increased monitoring and regulation of physicians, profit-loss sharing arrangements between physicians and hospital management, development of collective protocols among physicians, and bedside budget balancing. This study examines the opinions of a random sample of 838 physicians from the West North-Central region regarding these management alternatives. The findings suggest that physicians have strong negative opinions about these management alternatives and believe that they will have a negative impact on the health care system. The development of collective protocols emerges as the most likely acceptable alternative among physicians, but even collective protocols as an alternative promise limited success.


Temperament, Bullying, and Dating Aggression: Longitudinal Associations for Adolescents in a Romantic Relationship.
Adolescent bullying perpetration has previously been associated with dating benefits and costs in the short- and long-term, yet it is unclear how early temperament traits facilitate these associations. Therefore, the developmental pathways from temperament in early adolescence to bullying perpetration in middle adolescence and to dating outcomes in late adolescence were examined. Participants included 463 individuals who completed self-report measures on temperament traits at age 12, bullying perpetration at age 14, dating outcomes at age 19, and were in a romantic relationship at age 19. Findings from a path analysis revealed that an early adolescent temperament trait reflecting difficulty with self-regulation (i.e., lower inhibitory control) was associated with middle adolescent bullying perpetration and bullying perpetration was associated with late adolescent dating benefits (i.e., more dating partners) and costs (i.e., higher dating aggression perpetration). Lower inhibitory control also had significant indirect associations to the late adolescent dating outcomes through middle adolescent bullying perpetration. Findings suggest that although a temperament trait can facilitate adaptive dating outcomes through bullying, it can also come at a cost for romantic relationships. Results highlight the importance of early tailoring of bullying interventions to the self-regulatory difficulties of youth to prevent adverse long-term outcomes and to also recognize the challenges of developing interventions for behavior that can result in benefits.


Effect of expansive optic flow and lateral motion parallax on depth estimation with normal and artificially reduced acuity.
When an observer moves in space, the retinal projection of a stationary object either expands if the motion is toward the object or shifts horizontally if the motion contains a lateral component. This study examined the impact of expansive optic flow and lateral motion parallax on the accuracy of depth perception for observers with normal or artificially reduced acuity and asked whether any benefit is due to the continuous motion or to the discrete object image displacement. Stationary participants viewed a virtual room on a computer screen. They used an on-screen slider to estimate the depth of a target object relative to a reference object after seeing 2-second videos simulating five conditions: static viewing, expansive optic flow, and lateral motion parallax in either continuous motion or image displacement. Ten participants viewed the stimuli with normal acuity in Experiment 1 and 11 with three levels of artificially reduced acuity in Experiment 2. Linear regression models represented the relationship between the depth estimates of participants and the ground truth. Lateral motion parallax produced more accurate depth estimates than expansive optic flow and static viewing. Depth perception with continuous motion was more accurate than that with displacement under mild and moderate, but not severe, acuity reduction. For observers with both normal and artificially reduced acuity, lateral motion parallax was more helpful for object depth estimation than expansive optic flow, and continuous motion parallax was more helpful than object image displacement.


Effects of proteolytic digestion by chymotrypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase from bovine heart mitochondria.
1. Incubation of NADH-ubiquinone oxidoreductase (Complex I) with chymotrypsin caused loss of rotenone-sensitive ubiquinone-1 reduction and an increase in rotenone-insensitive ubiquinone reduction. 2. Within the same time-course, NADH-K(3)Fe(CN)(6) oxidoreductase activity was unaffected. 3. Mixing of chymotrypsin-treated Complex I with Complex III did not give rise to NADH-cytochrome c oxidoreductase activity. 4. Gel electrophoresis in the presence of sodium dodecyl sulphate revealed selective degradation of several constituent polypeptides by chymotrypsin. 5. With higher chymotrypsin concentrations and longer incubation times, a decrease in NADH-K(3)Fe(CN)(6) oxidoreductase was observed. The kinetics of this decrease correlated with solubilization of the low-molecular-weight type-II NADH dehydrogenase (subunit mol.wts. 53000 and 27000) and with degradation of a polypeptide of mol.wt. 30000. 6. Phospholipid-depleted Complex I was more rapidly degraded by chymotrypsin. Specifically, a subunit of mol.wt. 75000, resistant to chymotrypsin in untreated Complex I, was degraded in phospholipid-depleted Complex I. In addition, the 30000-mol.wt. polypeptide was also more rapidly digested, correlating with an increased rate of transformation to type II NADH dehydrogenase.


Secular Trends on Birth Parameters, Growth, and Pubertal Timing in Girls with Turner Syndrome.
Whether children with chromosomal disorders of growth and puberty are affected by secular trends (STs) as observed in the general population remains unanswered, but this question has relevance for expectations of spontaneous development and treatment responses. The aim of the study was to evaluate STs in birth parameters, growth, and pubertal development in girls with Turner syndrome (TS). Retrospective analysis of KIGS data (Pfizer International Growth Database). We included all TS patients who entered KIGS between 1987 and 2012 and were born from 1975 to 2004, who were prepubertal and growth treatment naïve at first entry (total number: 7,219). Pretreatment height and ages at the start of treatment were compared across 5-year birth year groups, with subgroup analyses stratified by induced or spontaneous puberty start. We observed significant STs across the birth year groups for birth weight [+0.18 SD score (SDS), p < 0.001], pretreatment height at mean age 8 years (+0.73 SDS, p < 0.001), height at the start of growth hormone (GH) therapy (+0.38 SDS, p < 0.001) and start of puberty (+0.42 SDS, p < 0.001). Spontaneous puberty onset increased from 15 to 30% (p < 0.001). Mean age at the start of GH treatment decreased from 10.8 to 7.4 years (-3.4 years; p < 0.001), and substantial declines were seen in ages at onset of spontaneous and induced puberty (-2.0 years; p < 0.001) and menarche (-2.1 years; p < 0.001). Environmental changes leading to increased height and earlier and also more common, spontaneous puberty are applicable in TS as in normal girls. In addition, greater awareness for TS may underlie trends to earlier start of GH therapy and induction of puberty at a more physiological age.


Consumption of meat, animal products, protein, and fat and risk of breast cancer: a prospective cohort study in New York.
Epidemiologic studies have focused on the association between diet and breast cancer with conflicting results. Whereas a majority of case-control studies indicate a role for the intake of total fat and saturated fat, most prospective cohort studies either are negative or indicate very modest associations. Only a few authors have examined the role of meat intake in relation to breast cancer risk. The aim of this study was to examine the relation between risk of breast cancer and dietary intake of meat, animal products, fat, and protein. Between 1985 and 1991, we recruited 14,291 New York City women in a prospective cohort study of endogenous hormones, diet, and cancer in which they reported on their recent diet using a food frequency questionnaire self-administered at enrollment. From the cohort, 180 invasive breast cancer cases diagnosed before December 1990 and five times as many controls, individually matched by age, calendar time at enrollment, menopausal status, and, if premenopausal, phase of menstrual cycle, were included in a nested case-control study. There was an evident increase in the relative risk (RR) of breast cancer for increasing consumption of meat. Women in the upper quintile of meat consumption, as compared with the lowest quintile, had an energy-adjusted RR of 1.87 (95% confidence interval = 1.09-3.21). There was a modest RR increase in the upper quintile of total and saturated fat and no apparent association for other types of fat, protein, dairy products, poultry, or fish.(ABSTRACT TRUNCATED AT 250 WORDS)


Pituitary function after transsphenoidal surgery including measurement of basal morning cortisol as predictor of adrenal insufficiency.
Patients with pituitary adenomas undergoing transsphenoidal surgery require pre- and post-surgery examination of pituitary hormones. There is currently no consensus on how to evaluate the adrenal axis post-surgery. The aims of this study were to investigate factors that may predict postoperative adrenal insufficiency (AI) and to investigate the overall effect of transsphenoidal surgery on pituitary function. One hundred and forty-three consecutive patients who had undergone transsphenoidal surgery for pituitary adenomas were included. Data on tumour size, pituitary function pre-surgery, plasma basal cortisol measured within 48 h post-surgery and pituitary function 6 months post-surgery were collected. Patients with AI prior to surgery, perioperative glucocorticoid treatment, Cushing's disease and no re-evaluation after 1 month were excluded (n = 93) in the basal cortisol analysis. Low plasma basal cortisol post-surgery, tumour size and previous pituitary surgery were predictors of AI (all P < 0.05). A basal cortisol cut-off concentration of 300 nmol/L predicted AI 6 months post-surgery with sensitivity and negative predictive value of 100%, specificity of 81% and positive predictive value of 25%. New gonadal, thyroid and adrenal axis insufficiencies accounted for 2, 10 and 10%, respectively. The corresponding recovery rates were 17, 7 and 24%, respectively. Transsphenoidal surgery had an overall beneficial effect on pituitary endocrine function. Low basal plasma cortisol measured within 48 h after surgery, tumour size and previous surgery were identified as risk factors for AI. Measurement of basal cortisol post-surgery may help to identify patients at risk of developing AI.


Responses of Korean physical therapy students after practice with a virtual anatomical system in Japan.
[Purpose] To investigate responses of Korean physical therapy students, receiving medical terminology education in physical therapy both in Korean and English, after practice with a virtual anatomical system. [Subjects and Methods] The participants were 25 physical therapy students from Konyang University in South Korea visiting the International University of Health and Welfare for training purposes. The virtual anatomy practice was conducted in English using 3 dimensional virtual anatomy software constructed using real cadaver photographs. A questionnaire about this practice and anatomy was completed after the practice. [Results] The results of the questionnaire showed a trend toward high scores for virtual anatomy practice. [Conclusion] The present virtual anatomy system was created using multi-directional photographs from a real cadaver; therefore, it can be used as an auxiliary means of education using cadavers.


Towards novel anti-tumor strategies for hepatic cancer: ɛ-viniferin in combination with vincristine displays pharmacodynamic synergy at lower doses in HepG2 cells.
Hepatocellular carcinoma is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The efficacy of novel combination treatments are increasingly evaluated with use of integrative biology research and development (R&D) strategies and methodological triangulation. We investigated the anti-tumor effect of ɛ-viniferin alone, and the putative synergy of ɛ-viniferin with vincristine on the growth of HepG2 cells in vitro. Growth inhibition and apoptosis induction were determined by MTT assay and annexin V/propidium iodide (PI), respectively. Morphological changes and DNA fragmentation were investigated under electron microscopy and by agarose gel electrophoresis, respectively. The results collectively showed that treating cells with ɛ-viniferin and vincristine significantly inhibited cell viability at lower doses as compared to each agent applied alone. IC(50) values for ɛ-viniferin and vincristine were determined as 98.3 and 52.5 μM at 24 h, respectively. IC(50) value of ɛ-viniferin in combination with vincristine was 15.8+11.25 μM (mean/SD) at 24 h. The viability of cells treated with 17.9 μM vincristine alone for 24 h was 79.62%; it reduced to 26.53% when 25 μM ɛ-viniferin was added in combination with vincristine (p<0.05). We found that combination of drugs promoted the sensitivity of cells against to vincristine treatment. The effect of combined use was in support of a synergistic pharmacodynamic effect. Moreover, low doses of the combination regimen induced phosphatidyl re-localization, morphological changes, and DNA fragmentation, and therefore caused apoptotic death. This study thus suggests that low concentrations of ɛ-viniferin and vincristine can enhance the anti-tumor effects efficiently by inducing HepG2 cell apoptosis. Further studies in other model systems are warranted with a view to potential future applications in the clinic of such combination regimens and their putative mechanism of action in the observed synergy reported here.


Hox proteins have different affinities for a consensus DNA site that correlate with the positions of their genes on the hox cluster.
The hox genes, members of a family of essential developmental regulators, have the intriguing property that their expression in the developing murine embryo is colinear with their chromosomal organization. Members of the hox gene family share a conserved DNA binding domain, termed the homeodomain, which mediates interactions of Hox proteins with DNA regulatory elements in the transcriptional control regions of target genes. In this study, we characterized the DNA binding properties of five representative members of the Hox family: HoxA5, HoxB4, HoxA7, HoxC8, and HoxB1. To facilitate a comparative analysis of their DNA binding properties, we produced the homeodomain regions of these Hox proteins in Escherichia coli and obtained highly purified polypeptides. We showed that these Hox proteins interact in vitro with a common consensus DNA site that contains the motif (C/G)TAATTG. We further showed that the Hox proteins recognize the consensus DNA site in vivo, as determined by their ability to activate transcription through this site in transient transfection assays. Although they interact optimally with the consensus DNA site, the Hox proteins exhibit subtle, but distinct, preferences for DNA sites that contain variations of the nucleotides within the consensus motif. In addition to their modest differences in DNA binding specificities, the Hox proteins also vary in their relative affinities for DNA. Intriguingly, their relative affinities correlate with the positions of their respective genes on the hox cluster. These findings suggest that subtle differences in DNA binding specificity combined with differences in DNA binding affinity constitute features of the "Hox code" that contribute to the selective functions of Hox proteins during murine embryogenesis.


Expression profile‑driven discovery of AURKA as a treatment target for liposarcoma.
Liposarcoma (LPS) is one of the most frequently reported type of soft‑tissue sarcoma (STS). Well‑differentiated (WD) LPS and dedifferentiated (DD) LPS are the two most common subtypes. Chemotherapy has been considered to be ineffective in LPS, and novel treatment agents are thus necessary. In this study, we reanalyzed two published microarray data sets of LPS. By comparing the top 50 upregulated genes in DD LPS in both sets of data, we identified 12 overlapping genes. Of note, the top five gene sets enriched in DD LPS in both sets of data were involved in cell cycle regulation. Among the 12 overlapping genes, aurora kinase A (AURKA) is a well‑known gene involved in cell cycle regulation; we thus further investigated this gene. AURKA was significantly upregulated in DD LPS, compared with WD LPS. Among 40 cases of DD LPS in GSE30929, patients with high AURKA expression in tumors had significantly worse distant recurrence‑free survival than those with low expression. In an in vitro model, MLN8237, an AURKA inhibitor, could inhibit AURKA in LPS cell lines with a resultant G2/M arrest. MLN8237 was also reported to exert a cytotoxic effect by inducing apoptosis in LPS cell lines. Furthermore, except for cisplatin, MLN8237 had a significantly synergistic effect with chemotherapy agents against LPS. MLN8237 induced cellular senescence in LPS cell lines with increased expression of DcR2, a senescence biomarker, and upregulated expression of cytokines associated with the senescence‑associated secretory phenotype, including interleukin (IL)‑1α, IL‑6 and IL‑8. Our study identified AURKA as a potential biomarker for predicting poor prognosis in LPS. The findings of the present study suggested the potential of AURKA as a therapeutic target in LPS cell line models, while the novel combination of AURKA inhibitors and chemotherapy requires further investigation.


[The development of very low birth weight preterm infants].
During the last decade we have witnessed a sharp rise in the number of premature labors followed by an increase in the survival rate of premature babies. Therefore, there is an increase in the general morbidity in the premature infant population, especially in the long term morbidity. Very low birth weight infants suffer from severe disabilities, but we found that even if they are healthy as a group, they suffer from a larger proportion of developmental difficulties in comparison to the general population. Their academic, social and behavioral achievements are lower as a group than full term AGA infants. The source of the developmental risk factors is both biological and environmental in origin. It is hypothesized that the source of these risk factors is at least partially due to differences in the development of specific brain areas such as the hippocampus. Since premature infants and especially very low birth weight infants suffer from developmental risks, and since early intervention can alter their development, it is imperative that these infants should be evaluated, followed-up and treated as soon as possible, starting from the hospital discharge through their childhood.


Stimulation of prostacyclin synthesis in vascular cells by mononuclear cell products.
Supernatants were obtained from human peripheral blood mononuclear cells stimulated with phytohemagglutinin or in a mixed lymphocyte reaction. The effect of mononuclear cell products on vascular prostacyclin (PGI2) production was measured using cultured rat aortic smooth muscle cells (SMC) or aortic rings. PGI2 was measured by radioimmunoassay of its metabolite, 6-keto-PGF1 alpha. Supernatants containing mononuclear cell products induced PGI2 production in vascular tissue. Supernatant-induced PGI2 production of SMC was relatively slow, requiring more than six hours of incubation with supernatants, and was completely prevented by aspirin, a cyclooxygenase inhibitor. The regulation of arachidonic acid metabolism by products of stimulated mononuclear cells, which is critical to the physiology and pathology of blood vessels, may be an important aspect of the interaction between immunocompetent cells and vascular tissue.


Psychological Symptoms in Late Adolescence and Long-Term Risk of Suicide and Suicide Attempt.
Mental disorders in the general population are associated with increased risk of suicidality, but less is known about the independent predictive ability of self-reported psychological symptoms. We followed 49,321 screened and interviewed Swedish conscripts through 36-year follow-up to test whether psychological symptoms predicted suicide and hospitalization for suicide attempts. There were 619 suicides and 1,230 suicide attempts during the follow-up period. After excluding subjects with any psychiatric diagnoses (n = 5,691, 12%) and controlling for other psychological symptoms, severe symptoms of anger, trouble falling asleep, and feeling down predicted suicide. Similarly anger, headaches, feeling down, and nervousness predicted suicide attempt. Self-reported psychological symptoms may have a predictive value beyond psychiatric diagnosis.


Myricetin protects against H2 O2 -induced oxidative damage and apoptosis in bovine mammary epithelial cells.
High-producing dairy cows are prone to oxidative stress due to their high secretion and strong metabolism, and excessive oxidative stress may cause the apoptosis of bovine mammary epithelial cells (bMECs). Myricetin (Myr) has been shown to have a wide range of pharmaceutical activities. The aim of this study was to evaluate the effect of Myr on hydrogen peroxide (H2 O2 )-induced oxidative stress and apoptosis in bMECs and to clarify the underlying mechanism. bMECs were pretreated with or without Myr and then stimulated with H2 O2 . The results showed that Myr significantly increased the total antioxidant capacity and superoxide dismutase levels and decreased the malondialdehyde (MDA) and reactive oxygen species (ROS) levels in a model of oxidative stress induced by H2 O2 in bMECs. Mechanistic studies found that Myr inhibited H2 O2 -induced oxidative stress in bMECs through the adenosine monophosphate-activated protein kinase/nuclear factor erythroid-2 related factor 2 (AMPK/NRF2) signaling pathway. Additional research found that Myr could also inhibit H2 O2 -induced apoptosis in bMECs through NRF2. These data suggest that Myr effectively alleviated oxidative stress and apoptosis in H2 O2 -induced bMECs through the activation of the AMPK/NRF2 signaling pathway.


Early senescence and cell death in Arabidopsis saul1 mutants involves the PAD4-dependent salicylic acid pathway.
Age-dependent leaf senescence and cell death in Arabidopsis (Arabidopsis thaliana) requires activation of the transcription factor ORESARA1 (ORE1) and is not initiated prior to a leaf age of 28 d. Here, we investigate the conditional execution of events that regulate early senescence and cell death in senescence-associated ubiquitin ligase1 (saul1) mutants, deficient in the PLANT U-BOX-ARMADILLO E3 ubiquitin ligase SAUL1. In saul1 mutants challenged with low light, the switch of age-dependent cell death was turned on prematurely, as indicated by the accumulation of ORE1 transcripts, induction of the senescence marker gene SENESCENCE-ASSOCIATED GENE12, and cell death. However, ORE1 accumulation by itself was not sufficient to cause saul1 phenotypes, as demonstrated by double mutant analysis. Exposure of saul1 mutants to low light for only 24 h did not result in visible symptoms of senescence; however, the senescence-promoting transcription factor genes WRKY53, WRKY6, and NAC-LIKE ACTIVATED BY AP3/PI were up-regulated, indicating that senescence in saul1 seedlings was already initiated. To resolve the time course of gene expression, microarray experiments were performed at narrow intervals. Differential expression of the genes involved in salicylic acid and defense mechanisms were the earliest events detected, suggesting a central role for salicylic acid in saul1 senescence and cell death. The salicylic acid content increased in low-light-treated saul1 mutants, and application of exogenous salicylic acid was indeed sufficient to trigger saul1 senescence in permissive light conditions. Double mutant analyses showed that PHYTOALEXIN DEFICIENT4 (PAD4) but not NONEXPRESSER OF PR GENES1 (NPR1) is essential for saul1 phenotypes. Our results indicate that saul1 senescence depends on the PAD4-dependent salicylic acid pathway but does not require NPR1 signaling.


Expression of chorionic gonadotrophin in human pituitary adenomas.
In addition to the classical anterior pituitary hormones, many human pituitary adenomas express hormone genes ectopically. Expression of glycoprotein hormone alpha-subunit and, less commonly, free luteinizing hormone beta (LH-beta) or follicle-stimulating hormone beta is characteristic of endocrinologically inactive adenomas, a subgroup thought to be derived predominantly from the gonadotroph line. Thyrotrophin beta expression in these tumours is unusual, and specific chorionic gonadotrophin beta (CG-beta) expression, identified using oligonucleotide probes that reliably distinguish LH-beta and CG-beta in situ, is not well described. Using in situ hybridization histochemistry with a CG-beta transcript-specific oligonucleotide probe and a non-specific LH/CG-beta oligonucleotide and riboprobe, we have demonstrated specific CG-beta expression in two of 35 random pituitary adenomas; LH-beta expression occurred in a further eight adenomas. Unlike prolactin, growth hormone and proopiomelanocortin, which are transcribed in the vast majority of cells in their respective hormone-positive tumour subtypes, the pattern of LH/CG-beta was typically a scattering of single or small clusters of hormone-positive cells in a predominantly LH/CG-beta-negative tumour. Finally, although bona fide CG-beta expression in human pituitary adenomas does occur, it is only at an incidence similar to that described for carcinomas of other tissues.


[Determination of 23 phthalate esters in scallion and other vegetables by solid-phase extraction coupled with gas chromatography-tandem mass spectrometry].
A method for the simultaneous determination of 23 phthalate esters in vegetables by solid-phase extraction coupled with gas chromatography-triple quadrupole mass spectrometry (SPE-GC-MS/MS) was developed and evaluated. The samples were extracted with acetonitrile, and cleaned-up with glass Florisil SPE columns, and diluted with n-hexane. The separation was performed on a DB-5MS UI capillary column (30 m x 0.25 mm x 0.25 µm) with temperature programming. The identification and quantification were performed by GC-MS/MS in selected reaction monitoring (SRM) mode. The external standard method was used. The processes of extraction and clean-up of scallion and other vegetables were investigated, and the chromatographic and MS parameters were optimized. The matrix effect was compensated by matrix spiked calibration. The extraction processes were investigated. The calibration curves of the phthalate esters showed good linearities in the ranges of 0.02-1 mg/L (0.1-5 mg/L for diisononyl phthalate (DINP) and diisodecyl-o-phthalate (DIDP)) with the correlation coefficients (r) over 0.99 except for bis(2-methoxyethyl) phthalate (DMEP). The limits of detection of phthalate esters in samples ranged from 0.01 to 0.05 mg/kg (S/N = 3) and the limits of quantification ranged from 0.02 to 0.1 mg/kg (S/N = 10). The average recoveries of the 23 analytes spiked in scallions ranged from 81.3% to 104.2% with the relative standard deviations (RSDs, n = 6) of 3.2%-11.2%. The method is suitable for the determination of the 23 phthalate esters simultaneously in vegetables with easy operation, high accuracy and precision.


Single Molecule Surface Enhanced Raman Scattering in a Single Gold Nanoparticle-Driven Thermoplasmonic Tweezer.
Surface enhanced Raman scattering (SERS) is optically sensitive and chemically specific to detect single-molecule spectroscopic signatures. Facilitating this capability in optically trapped nanoparticles at low laser power remains a significant challenge. In this letter, we show single molecule SERS signatures in reversible assemblies of trapped plasmonic nanoparticles using a single laser excitation (633 nm). Importantly, this trap is facilitated by the thermoplasmonic field of a single gold nanoparticle dropcasted on a glass surface. We employ the bianalyte SERS technique to ascertain the single molecule statistical signatures and identify the critical parameters of the thermoplasmonic tweezer that provide this sensitivity. Furthermore, we show the utility of this low power (≈ 0.1 mW/μm2) tweezer platform to trap a single gold nanoparticle and transport assembly of nanoparticles. Given that our configuration is based on a dropcasted gold nanoparticle, we envisage its utility to create reconfigurable plasmonic metafluids in physiological and catalytic environments and to be potentially adapted as an in vivo plasmonic tweezer.


Preliminary evidence supports circulating microRNAs as prognostic biomarkers for type 2 diabetes.
Circulating microRNAs are emerging as potential prognostic biomarkers for the development of type 2 diabetes. However, microRNAs are also associated with complications from impaired glucose metabolism (e.g. endothelial cell function). Prior studies have not evaluated for associations between trajectories of circulating microRNAs with trajectories of fasting blood glucose over time and the responses to behavioral interventions to reduce risk. This study performed longitudinal assessment of microRNAs and fasting blood glucose and identified relationships between microRNAs and behavioral risk reduction interventions. MicroRNAs (n = 353) were measured in subsets (n = 10, n = 8) of participants from previously completed clinical trials that studied behavioral risk reduction interventions. Fasting blood glucose trajectories were associated with changes in 45 microRNAs over 12 months. Following a 3-month physical activity and dietary intervention compared with baseline, 13 microRNAs were differentially expressed. Seven microRNAs (i.e. miR-106b, miR-20b, miR-363, miR-486, miR-532, miR-92a and miR-93) were commonly identified between the two analyses. Further studies are needed to determine which microRNAs are prognostic biomarkers of risk for type 2 diabetes versus consequences of impaired glucose metabolism. Additional future directions of this research are to differentiate whether microRNAs are prognostic and/or diagnostic biomarkers for risk for type 2 diabetes and predictive biomarkers of responses to risk reduction interventions.


An Investigation of RSN Frequency Spectra Using Ultra-Fast Generalized Inverse Imaging.
With the advancements in MRI hardware, pulse sequences and reconstruction techniques, many low TR sequences are becoming more and more popular within the functional MRI (fMRI) community. In this study, we have investigated the spectral characteristics of resting state networks (RSNs) with a newly introduced ultra fast fMRI technique, called generalized inverse imaging (GIN). The high temporal resolution of GIN (TR = 50 ms) enables to sample cardiac signals without aliasing into a separate frequency band from the BOLD fluctuations. Respiration related signal changes are, on the other hand, removed from the data without the need for external physiological recordings. We have observed that the variance over the subjects is higher than the variance over RSNs.


The effect of freezing and storage in liquid nitrogen on the viability and growth of Mycobacterium leprae.
The effects of rapid and slow rates of freezing in liquid nitrogen, storage in liquid nitrogen for 12 months, and the rate of subsequent thawing on the viability and growth of M. leprae in the mouse footpad were studied. Some loss of viability of M. leprae was detected, and this was found to be associated with the freezing process, rather than with storage or thawing. Slow freezing was less deleterious than quick freezing, with a loss of viability of 90% compared with 98%. The growth pattern of M. leprae was unaffected except for a delay in the appearance of growth caused by the loss of viability, though there was some evidence of an increased lag phase of one strain, possibly due to the repair of sub-lethally damaged organisms.


The 2D Hotelling filter - a quantitative noise-reducing principal-component filter for dynamic PET data, with applications in patient dose reduction.
In this paper we apply the principal-component analysis filter (Hotelling filter) to reduce noise from dynamic positron-emission tomography (PET) patient data, for a number of different radio-tracer molecules. We furthermore show how preprocessing images with this filter improves parametric images created from such dynamic sequence.We use zero-mean unit variance normalization, prior to performing a Hotelling filter on the slices of a dynamic time-series. The Scree-plot technique was used to determine which principal components to be rejected in the filter process. This filter was applied to [11C]-acetate on heart and head-neck tumors, [18F]-FDG on liver tumors and brain, and [11C]-Raclopride on brain. Simulations of blood and tissue regions with noise properties matched to real PET data, was used to analyze how quantitation and resolution is affected by the Hotelling filter. Summing varying parts of a 90-frame [18F]-FDG brain scan, we created 9-frame dynamic scans with image statistics comparable to 20 MBq, 60 MBq and 200 MBq injected activity. Hotelling filter performed on slices (2D) and on volumes (3D) were compared. The 2D Hotelling filter reduces noise in the tissue uptake drastically, so that it becomes simple to manually pick out regions-of-interest from noisy data. 2D Hotelling filter introduces less bias than 3D Hotelling filter in focal Raclopride uptake. Simulations show that the Hotelling filter is sensitive to typical blood peak in PET prior to tissue uptake have commenced, introducing a negative bias in early tissue uptake. Quantitation on real dynamic data is reliable. Two examples clearly show that pre-filtering the dynamic sequence with the Hotelling filter prior to Patlak-slope calculations gives clearly improved parametric image quality. We also show that a dramatic dose reduction can be achieved for Patlak slope images without changing image quality or quantitation. The 2D Hotelling-filtering of dynamic PET data is a computer-efficient method that gives visually improved differentiation of different tissues, which we have observed improve manual or automated region-of-interest delineation of dynamic data. Parametric Patlak images on Hotelling-filtered data display improved clarity, compared to non-filtered Patlak slope images without measurable loss of quantitation, and allow a dramatic decrease in patient injected dose.


LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway.
The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be upregulated and be involved in oncogenic growth and drug resistance in nasopharyngeal carcinoma (NPC). However, the exact roles of NEAT1 and its underlying mechanisms in the drug resistance of NPC remain largely unclear. In this study, the expressions of NEAT1, let-72-5p and Rsf-1 mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of NEAT1 and let-72-5p on cell proliferation and cisplatin resistance of NPC cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-20-deoxyuridine (EdU) assay. Western blot analysis was performed to detect the protein levels of Rsf-1, Ras, p-Raf1, Raf1, p-MEK1, MEK1, p-ERK1/2 and ERK1/2. Xenograft tumor assay was done to elucidate the role of NEAT1 involved in NPC tumor growth in vivo. We found that NEAT1 was upregulated and let-7a-5p was downregulated in NPC tissues, as well as NPC cell lines. Inhibition of NEAT1 markedly repressed the cisplatin resistance of NPC cells. NEAT1 was demonstrated to interact with let-7a-5p. Besides, a negative correlation between NEAT1 and let-7a-5p expression was observed in NPC tissues. Rsf-1 was confirmed as a target of let-7a-5p. NEAT1 remarkably reversed the inhibitory effect of let-7q-5p on the cisplatin resistance of NPC cells in vitro. Additionally, NEAT1 knockdown inhibited the Ras-MAPK pathway in NPC cells. NEAT1 knockdown suppressed tumor growth in the presence of cisplatin in vivo. Overall, these findings suggest that NEAT1/let-7a-5p axis regulates the cisplatin resistance in NPC by targeting Rsf-1 and modulating the Ras-MAPK signaling pathway.


Connective tissue metabolism including cytokines in scleroderma.
The currently published literature on systemic sclerosis underscores the importance of vascular-leukocyte adhesion and perturbations of cytokines and growth factors that reflect T-cell activation and abnormal stimulation of fibroblast growth and matrix synthesis. Articles dealing with these topics are reviewed.


CTCF binding is not the epigenetic mark that establishes post-fertilization methylation imprinting in the transgenic H19 ICR.
Imprinted expression of the mouse Igf2/H19 locus is controlled by parent-of-origin-specific methylation of the imprinting control region (ICR). We previously demonstrated that when placed in a heterologous genomic context, the H19 ICR fragment contains an intrinsic activity that allows it to acquire differential methylation in somatic cells but not in germ cells. In the present study, we investigated the requirements for the CTCF-binding sites of the ICR in the acquisition of post-fertilization methylation. To this end, two mutant ICR fragments were introduced into the human beta-globin locus in a yeast artificial chromosome transgenic mouse (TgM) model: 4xMut had mutations in all four ICR CTCF-binding sites that prevented CTCF binding but retained the methylation target CpG motifs, and -9CG harbored mutations in the CpG motifs within the CTCF-binding sites but each site retained constitutive CTCF-binding activity. In TgM germ cells and pre-implantation blastocysts, the absence of CTCF-binding sites (4xMut) did not lead to hypermethylation of the transgenic H19 ICR. However, after implantation, the mutations of CTCF sites (4xMut and -9CG) affected the maintenance of methylation. These results demonstrated that although the CTCF-binding sites are indispensable for maintenance of the unmethylated state of the maternal ICR in post-implantation embryos, they are not required to establish paternal-allele-specific methylation of the transgenic H19 ICR in pre-implantation embryos.


CpG traffic lights are markers of regulatory regions in human genome.
DNA methylation is involved in the regulation of gene expression. Although bisulfite-sequencing based methods profile DNA methylation at a single CpG resolution, methylation levels are usually averaged over genomic regions in the downstream bioinformatic analysis. We demonstrate that on the genome level a single CpG methylation can serve as a more accurate predictor of gene expression than an average promoter / gene body methylation. We define CpG traffic lights (CpG TL) as CpG dinucleotides with a significant correlation between methylation and expression of a gene nearby. CpG TL are enriched in all regulatory regions. Among all promoters, CpG TL are especially enriched in poised ones, suggesting involvement of DNA methylation in their regulation. Yet, binding of only a handful of transcription factors, such as NRF1, ETS, STAT and IRF-family members, could be regulated by direct methylation of transcription factor binding sites (TFBS) or its close proximity. For the majority of TF, an alternative scenario is more likely: methylation and inactivation of the whole regulatory element indirectly represses functional TF binding with a CpG TL being a reliable marker of such inactivation. CpG TL provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to gene expression. CpG TL methylation can be used as reliable markers of enhancer activity and gene expression in applications, e.g. in clinic where measuring DNA methylation is easier compared to directly measuring gene expression due to more stable nature of DNA.


Multidisciplinary approach to congenital Toxoplasma infection: an Italian nationwide survey.
Italy provides a free voluntary serological screening for toxoplasmosis in pregnancy supported by public health system, as there is an estimated congenital toxoplasmosis rate of 1-2/10,000. The aim of this study was to make an inventory of diagnostic and therapeutic protocols in use in Italy in the absence of a national guideline. A semistructured questionnaire was distributed to AMCLI (Italian Association of Clinical Microbiologists) members who were asked to involve other specialists to fill in the form. Data from 26 centers show: a) a general use of the IgG avidity test to solve diagnosis in IgG/IgM positive, pregnant women; b) a widespread attitude to spyramicin antenatal treatment in suspected, unconfirmed maternal infection; c) avoidance of invasive antenatal diagnosis only in suspected early or late (>24 weeks), even confirmed, maternal infection d) fetal diagnosis performed by PCR assays on amniotic fluid; e) variability of both indications and dosage of pyrimethamine-sulfadiazine (P-S) as fetal treatment; f) use of comparative mother and newborn IgG/IgM Immuneblot in most centers; g) no diagnostic tests performed on placenta and cord blood; h) spyramicin is no longer used in congenital infections; i) no P-S-based treatment for children at high risk of congenital infection (late maternal infection) in the absence of diagnosis. As there is the opportunity to test pregnant women for Toxoplasma gondii infection in Italy free of charge, standardized diagnostic and therapeutic national guidelines would focus on a more uniform approach.


Health related quality of life in irritable bowel syndrome patients, Kashan, Iran: A case control study.
Irritable bowel syndrome has significant impacts on the quality of life (QOL) but IBS subtypes may be different in QOL. This study aimed to assess QOL in IBS subtypes and also two prevalent questionnaires applied to evaluate the QOL in IBS. In this case-control study conducted in Kashan in 2010-2013. One hundred and eighty- eight patients with IBS with 215 of non-IBS patients were included in the baseline. Subjects divided into three subtypes based on symptoms of diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) and IBS with mixed bowel habits (IBS-M) and in each subtype were 42, 62 and 84 patients, respectively. All IBS subjects completed questionnaires containing the disease-specific QOL for IBS (IBSQOL), World Health Organization QOL Assessment-BREF (WHOQOL-BREF) and IBS severity scores (IBSSS). The non-IBS subjects completed the WHOQOL-BREF only. Mean scores of IBSQOL in person with subtypes of IBS-D, IBS-C and IBS-M were 74.34 ± 19.01, 76.77 ± 22.91 and 73.15 ± 26.51, respectively which was not significantly different (P value = 0.507). As well as mean scores of WHOQOL-BREF in person with subtypes of IBS-D, IBS-C and IBS-M were 81.01 ± 16.23, 88.32 ± 15.66, and 82.65 ± 16.67, respectively, which were not significantly different (P value = 0.412) but mean scores of WHOQOL-BREF in non-IBS subjects was 89.53 ± 11.71 which was significantly different from IBS subjects (P value = 0.022). Strong positive relationship between two instruments was shown (r = 0.826 when P < 0.05). The WHOQOL-BREF instrument showed poorer QOL in IBS patients. The QOL was not different significantly among IBS-M, IBS-C, and IBS-D subtypes. We found that WHOQOL-BREF instrument strongly correlate with QOLIBS instrument.


High-resolution X-ray emission spectroscopy of molybdenum compounds.
High-resolution molybdenum K-edge X-ray emission spectroscopy (XES) was used to characterize the K beta(4) and K beta' ' valence-to-core transition bands in the oxo-Mo compounds K(2)MoO(4), MoO(S(2)CNEt(2))(2), and MoO(2)(S(2)CNEt(2))(2). The K beta(4) and K beta' ' emission bands are attributed to transitions to the Mo 1s core hole from molecular orbitals possessing primarily molybdenum 4d and oxygen 2s character, respectively. This communication describes the first assignment of the K beta' ' interatomic band in the emission spectra of molybdenum complexes. Additionally, the K beta(4) and K beta' 'transitions are shown to be sensitive to the chemical and electronic environment of the metal, suggesting that high-resolution XES might be an effective method for elucidating the nature of the molybdenum centers in biological systems.


Stereoselective S-oxygenation of 2-aryl-1,3-dithiolanes by the flavin-containing and cytochrome P-450 monooxygenases.
The reaction of NalO4, highly purified flavin-containing monooxygenase (EC 22.214.171.124), and microsomes from hog liver with 2-aryl-1,3-dithiolanes and 2-aryl-1,3-dithiolane S-oxides was investigated. The initial rates determined for the microsome- and purified flavin-containing monooxygenase-catalyzed rate of S-oxidation of para-substituted 2-aryl-1,3-dithiolanes were similar, demonstrating that S-oxidation of these substrates occurred with similar velocities at saturating concentrations of substrate and, at least for the first S-oxidation, the reaction was insensitive to the nature of the para-substituent. The diastereoselectivity of S-oxygenation of 2-aryl-1,3-dithiolanes was determined and, in general, a marked preference for addition of oxygen to the sulfide sulfur atom was observed to occur trans to the aryl groups. In all cases examined, enantioselective enzymatic S-oxidation was observed. For S-oxide formation in microsomes, the data provided evidence for a minor role of cytochrome P-450 in S-oxide formation, but the flavin-containing monooxygenase was mainly responsible for production of S-oxide. In contrast to previous reports, the enantioselectivity of S-oxidation catalyzed by highly purified cytochrome P-450IIB-1 and cytochrome P-450IIB-10 was not always opposite to that catalyzed by hog liver flavin-containing monooxygenase activity. 2-Aryl-1,3-dithiolane S-oxides were also oxidized a second time by NalO4, microsomes, or highly purified flavin-containing monooxygenase from hog liver but not cytochrome P-450IIB-1 or P-450IIB-10. The rate of the second oxidation was 10-15-fold slower than the corresponding first S-oxidation and S,S'-dioxide formation was markedly dependent on the electronic nature of the para-substituent (Hammett correlation rho value of -1.3 and -1.1 for microsomes and highly purified flavin-containing monooxygenase from hog liver, respectively). The large dependence of the rate of S,S'-dioxide formation on the nature of the para-substituent demonstrates that velocity values at saturating concentrations of S-oxide were not the same for all 2-aryl-1,3-dithiolane S-oxides and suggests that the chemical nature of the 2-aryl-1,3-dithiolane S-oxide contributes to the rate-determining step of this enzymatic reaction.


Giant mucinous cystadenoma: case report with review of literature.
Cystic tumors of the pancreas are rare and can be confused with hydatid cyst especially in endemic areas like ours. We present a 30-year-old woman with a huge mucinous cystadenoma of the pancreas initially diagnosed and prepared on table as hydatid cyst. After incising the cyst the diagnosis of cystic tumor was considered and underwent total excision with spleen and healthy pancreatic margin. Histologically and biochemistry of fluid confirmed potentially benign mucinous cystic tumor of pancreas tumor excision after histological diagnosis. Sensitivity of radiological imaging values in differentiating between cystic pancreatic tumors and other limited. Cyst wall histology is diagnostic and biopsy of cyst wall should be done in cases with inconclusive preoperative diagnosis or questionable operative findings.


EXCITATION OF NERVE FIBERS IN THE SQUID (LOLIGO PEALII).
1. Strength-duration data for the giant fiber of the great stellar nerve of the squid (Loligo pealii) can be approximately described by several mathematical formulations. 2. Excitation time constants for isolated giant fibers are essentially the same as constants of the giant fibers in the intact nerve. 3. The strength-duration curves of the fibers in the intact nerve lie higher on the voltage axis than those of the isolated fibers. It is concluded that the principal effect of other fibers upon the excitation of one fiber in a nerve trunk is that of shunting the stimulating current. 4. Deterioration of the nerve shifts the curve upward and to the left, resulting in shorter time constants. 5. Decreasing interelectrode distance also shifts the curve upward and to the left. 6. Excitation time constants of the giant fibers are larger with plate electrodes than with wire or pore electrodes. 7. The strength-duration curves of the smaller fin nerve fibers lie consistently to the right of, and the time constants are longer than those of the giant fibers.


Cloning and characterization of the KlDIM1 gene from Kluyveromyces lactis encoding the m2(6)A dimethylase of the 18S rRNA.
The KlDIM1 gene encoding the m2(6)A rRNA dimethylase was cloned from a Kluyveromyces lactis genomic library using a PCR amplicon from the Saccharomyces cerevisiae ScDIM1 gene as probe. The KlDIM1 gene encodes a 320-amino acid protein which shows 81% identity to ScDim1p from S. cerevisiae and 25% identity to ksgAp from Escherichia coli. Complementation of the kasugamycin-resistant ksgA-mutant of E. coli lacking dimethylase activity demonstrates that KlDim1p is the functional homologue of the bacterial enzyme. Multiple alignment of dimethylases from prokaryotes and yeasts shows that the two yeast enzymes display distinctive structural motives including a putative nuclear localization signal.


[Effects of fats of diverse nature on the acid-base equilibrium in animals of various ages].
The effects of fats of different origin (butter, sunflower oil, butter margarine) on the acid-base equilibrium (ABE) were studied in young and old animals (white male rats). The shifts developing within the ABE system were determined by the nature of the fat and the animals' age. Intake of butter and margarine entailed the development of acidosis which was more demonstrable in old animals whereas vegetable oil did not produce any appreciable effect. A close relationship was discovered between acidosis in the ABE system and lipidemia as well as the fatty acid composition of the fats under study.


Protein chemotaxonomy of the solanaceae. VI. Amino acid sequence of ferredoxin from Nicotian tabacum.
The complete amino acid sequence of [2Fe-2S] ferredoxin from Nicotiana tabacum has been determined by automated Edman degradation of the entire Cm-protein and of the peptides obtained by trypsin and Asp-N endoproteinase digestions. This ferredoxin exhibited 9, 10, 8, and 10 differences respectively in its amino acid sequence, when compared with the ferredoxins of Datura stramonium, D. metel, D. arborea, and Physalis alkekengi var.francheti but 17-28 differences for other angiosperms, and 34-37 differences for fern and horsetails. These results are in agreement with the taxonomic position for these plants.


Irritable bowel syndrome and chronic gastritis, hemorrhoid, urolithiasis.
Approximately 10-20% of the general population has irritable bowel syndrome (IBS), and IBS patients usually suffer from chronic gastritis (CG), hemorrhoids (H), and urolithiasis (U). We randomly chose consecutive patients with upper abdominal discomfort. All possible causes of IBS including celiac sprue, giardiasis, lactose intolerance, and cholelithiasis were investigated. U was diagnosed either by medical history or as a result of laboratory findings. IBS patients (51) and patients without IBS (70) were studied. CG was diagnosed in 78.4% (40) of IBS cases, whereas this ratio was 50.0% (35) in cases without IBS (p<0.001). Similarly, H was detected in 33.3% (17) of IBS cases, but it was only detected in 15.7% (11) of cases without IBS (p<0.05). Additionally, U was detected in 17.6% (9) of IBS cases and in 5.7% (4) of cases without IBS (p<0.05). Relationships between IBS and CG, H, and U are significant. IBS is a cascade of many physiologic events that is initiated by infection, inflammation, and psychological disturbances like many stresses, and this eventually terminates with gut dysfunction. Gastric acid is probably not involved in the etiology of IBS, but psychological factors also seem to be important in CG. The significant association between CG and IBS also support this hypothesis. Therefore, we believe CG is one of terminating points of the physiologic cascade of events in IBS. Bearing these associations in mind will be helpful during prevention, treatment, and follow up of these disorders, especially in internal medicine, urology, and general surgery polyclinics and primary health centers.


A suppression subtractive hybridization approach reveals niche-specific genes that may be involved in predator avoidance in marine Synechococcus isolates.
Picocyanobacteria of the genus Synechococcus are important contributors to marine primary production and are ubiquitous in the world's oceans. This genus is genetically diverse, and at least 10 discrete lineages or clades have been identified phylogenetically. However, little if anything is known about the genetic attributes which characterize particular lineages or are unique to specific strains. Here, we used a suppression subtractive hybridization (SSH) approach to identify strain- and clade-specific genes in two well-characterized laboratory strains, Synechococcus sp. strain WH8103 (clade III) and Synechococcus sp. strain WH7803 (clade V). Among the genes that were identified as potentially unique to each strain were genes encoding proteins that may be involved in specific predator avoidance, including a glycosyltransferase in strain WH8103 and a permease component of an ABC-type polysaccharide/polyol phosphate export system in WH7803. During this work the genome of one of these strains, WH7803, became available. This allowed assessment of the number of false-positive sequences (i.e., sequences present in the tester genome) present among the SSH-enriched sequences. We found that approximately 9% of the WH8103 sequences were potential false-positive sequences, which demonstrated that caution should be used when this technology is used to assess genomic differences in genetically similar bacterial strains.


The Movement of Substances Through a Two-phased Solution System.
The tendencies for movement of either solvent or solute in solution through a two-phased system are expressed in terms of specific (volumed) free energies. These are based on the concept of escaping tendency or free energy of a constituent component of a solution. This scheme is particularly useful to the biologist for evaluating the movement of water and solutes into cells or organs.