CA1 pyramidal cells have diverse biophysical properties, affected by development, experience, and aging.
Neuron types (e.g., pyramidal cells) within one area of the brain are often considered homogeneous, despite variability in their biophysical properties. Here we review literature demonstrating variability in the electrical activity of CA1 hippocampal pyramidal cells (PCs), including responses to somatic current injection, synaptic stimulation, and spontaneous network-related activity. In addition, we describe how responses of CA1 PCs vary with development, experience, and aging, and some of the underlying ionic currents responsible. Finally, we suggest directions that may be the most impactful in expanding this knowledge, including the use of text and data mining to systematically study cellular heterogeneity in more depth; dynamical systems theory to understand and potentially classify neuron firing patterns; and mathematical modeling to study the interaction between cellular properties and network output. Our goals are to provide a synthesis of the literature for experimentalists studying CA1 PCs, to give theorists an idea of the rich diversity of behaviors models may need to reproduce to accurately represent these cells, and to provide suggestions for future research.


Do plants contain g protein-coupled receptors?
Whether G protein-coupled receptors (GPCRs) exist in plants is a fundamental biological question. Interest in deorphanizing new GPCRs arises because of their importance in signaling. Within plants, this is controversial, as genome analysis has identified 56 putative GPCRs, including G protein-coupled receptor1 (GCR1), which is reportedly a remote homolog to class A, B, and E GPCRs. Of these, GCR2 is not a GPCR; more recently, it has been proposed that none are, not even GCR1. We have addressed this disparity between genome analysis and biological evidence through a structural bioinformatics study, involving fold recognition methods, from which only GCR1 emerges as a strong candidate. To further probe GCR1, we have developed a novel helix-alignment method, which has been benchmarked against the class A-class B-class F GPCR alignments. In addition, we have presented a mutually consistent set of alignments of GCR1 homologs to class A, class B, and class F GPCRs and shown that GCR1 is closer to class A and/or class B GPCRs than class A, class B, or class F GPCRs are to each other. To further probe GCR1, we have aligned transmembrane helix 3 of GCR1 to each of the six GPCR classes. Variability comparisons provide additional evidence that GCR1 homologs have the GPCR fold. From the alignments and a GCR1 comparative model, we have identified motifs that are common to GCR1, class A, B, and E GPCRs. We discuss the possibilities that emerge from this controversial evidence that GCR1 has a GPCR fold.


Nuclear DNA content in the genus Hepatica (Ranunculaceae).
Using flow cytometry, we measured the nuclear DNA contents of all known taxa in Hepatica. Nuclear DNA content of Hepatica falconeri (diploid, crenate leaf lobes) was significantly lower than that of diploid entire species. Among the tetraploid species, crenate species had lower DNA contents than the entire taxon H. nobilis var. pubescens. The DNA content of the tetraploid species was more than double that of the diploid species among the same leaf-type groups.


Salinity-controlled distribution of prokaryotic communities in the Arctic sea-ice melt ponds.
The thawing of snow and sea ice produces distinctive melt ponds on the surface of the Arctic sea ice, which covers a significant portion of the surface sea ice during summer. Melt-pond salinity impacts heat transfer to the ice below and the melting rate. It is widely known that melt ponds play a significant role in heat fluxes, ice-albedo feedback, and sea-ice energy balance. However, not much attention has been given to the fact that melt ponds also serve as a unique microbial ecosystem where microbial production begins as soon as they are formed. Here, we investigated the role of melt pond salinity in controlling the diversity and distribution of prokaryotic communities using culture-dependent and -independent approaches. The 16 S rRNA gene amplicon based next generation sequencing analysis retrieved a total of 14 bacterial phyla, consisting of 146 genera, in addition to two archaeal phyla. Further, the culture-dependent approaches of the study allowed for the isolation and identification of twenty-four bacterial genera in pure culture. Flavobacterium, Candidatus_Aquiluna, SAR11 clade, Polaribacter, Glaciecola, and Nonlabens were the dominant genera observed in the amplicon analysis. Whereas Actimicrobium, Rhodoglobus, Flavobacterium, and Pseudomonas were dominated in the culturable fraction. Our results also demonstrated that salinity, chlorophyll a, and dissolved organic carbon were the significant environmental variables controlling the prokaryotic community distribution in melt ponds. A significant community shift was observed in melt ponds when the salinity changed with the progression of melting and deepening of ponds. Different communities were found to be dominant in melt ponds with different salinity ranges. It was also observed that melt pond prokaryotic communities significantly differed from the surface ocean microbial community. Our observations suggest that complex prokaryotic communities develop in melt ponds immediately after its formation using dissolved organic carbon generated through primary production in the oligotrophic water.


Epigallocatechin-3-gallate induces telomere shortening and clastogenic damage in glioblastoma cells.
Epigallocatechingallate (EGCG) is the major polyphenol in green tea, to which many anticancer features, such as antioxidative, antigenotoxic, and antiangiogenetic properties, are attributed. Moreover, it is also well known as a telomerase inhibitor. In this work, we have chronically treated U251 glioblastoma cells with low, physiologically realistic concentrations, of EGCG, in order to investigate its effects both on telomeres and on genome integrity. Inhibition of telomerase activity caused telomere shortening, ultimately leading to senescence and telomere dysfunction at 98 days. Remarkably, we have observed DNA damage through an increase of phosphorylation of γ-H2AX histone and micronuclei also with doses and at timepoints when telomere shortening was not present. Therefore, we concluded that this DNA damage was not correlated with telomere shortening and that EGCG treatment induced not only an increase of telomere-shortening-induced senescence but also telomere-independent genotoxicity. This study questions the common knowledge about EGCG properties, but confirms the few works that indicated the clastogenic properties of this molecule, probably due to DNA reductive damage and topoisomerase II poisoning. Environ. Mol. Mutagen., 60:683-692, 2019. © 2019 Wiley Periodicals, Inc.


Endovenous laser treatment of the small saphenous vein with a 980-nm diode laser: early results.
Whereas numerous studies have been conducted regarding the outcome of the treatment of the great saphenous vein, few studies have been conducted on the small saphenous vein (SSV), especially concerning endovenous laser treatment. The objective was to evaluate the safety and efficacy of the 980-nm diode laser for the treatment of SSV reflux caused by saphenopopliteal junction (SPJ) incompetence. From October 2003 to April 2006, 390 SSVs in 344 subjects with varicose veins were treated with 980-nm diode laser energy delivered percutaneously into the SSV. Tumescent anesthesia (70-220 mL of 0.1% lidocaine) was delivered perivenously under ultrasound (US) guidance. The patients were evaluated clinically and with duplex US at 1 week, 1 month, 3 months, 6 months, 1 year, and thereafter to assess the efficacy of the treatment and the adverse reactions of the patients to it. Successful occlusion of the SSV, defined as the absence of flow on color Doppler imaging, was noted in 389 of the 390 SSVs (99.7%) after the initial treatment. The remaining 1 SSV was closed after the repeat treatment. Of 108 SSVs, 102 (94.4%) remained closed throughout the 12th-month follow-up. Bruising and tightness along the course of the treated vein was present in almost all the patients, but these disappeared in 1 to 2 weeks. Seven patients (2%) noted localized skin paresthesia, but there were no major complications like skin burns and deep vein thrombosis. Taking into account the high failure rates of incompetent SSV surgery and the anatomic complexity of SPJ, the endovenous 980-nm diode laser surgery is a safe and effective, cosmetically preferential procedure while a long-term follow-up is being awaited.


The immunological approach to pregnancy diagnosis: a review.
The developing embryo/fetus bears antigens which are foreign to the mother and it could be expected that immune rejection of the conceptus would occur. One of the reasons why the fetus is not rejected is because a depression of the maternal immune response takes place during pregnancy. Serum from pregnant animals of several species has been shown to contain a factor, early pregnancy factor (EPF), which is immunosuppressive. EPF has been detected as early as six hours after mating and its detection could aid diagnosis of early pregnancy in all species.


Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard.
Sunscreens containing metal oxide nanoparticles appear transparent on the skin and provide excellent protection against sunburn caused by UV radiation. While it is likely that nanoparticles remain on the surface of the skin of healthy adult humans, and thus are considered safe for use in sunscreens, there has been no comprehensive assessment of the impact on human health from exposure to the metal oxide nanoparticles destined for use in sunscreens, either in the workplace during the manufacturing process, in long-term use across a range of skin conditions, or upon release into the broader environment, either accidentally or consequent of normal sunscreen use. In this review, we focus on zinc oxide nanoparticles destined for use in modern sunscreens, and discuss the potential for human exposure and the health hazard at each stage of their manufacture and use. We highlight where there is a need for further research.


The role of the right hemisphere in processing negative sentences in context.
Given a pattern consisting of x1, x2,..., xn similar elements and y1, which is perceived as different from the former, it is more plausible to assert that y is not x rather than to assert that x is not y (Wason, J. verb. Learn verb. Behav. 4, 7-11, 1965). In order to appreciate such a difference, the entire set has to be considered. Right-hemisphere brain-damaged patients were submitted to a series of visually presented patterns, each pattern consisting of seven similar items and one dissimilar item. Their task was to complete a statement referring to a single element of each pattern. Statements were either simple affirmative or negative sentences. Errors and reaction times were recorded. Patients with a right-hemisphere injury were found to be insensitive to the plausible-implausible dimension in completing negative sentences. It is hypothesized that right-hemisphere brain-damaged patients are less adequate in this task because they are less capable in putting each element into the visual context.


[Depression--a serious, lifelong but treatable illness].
The prevalence of depressive disorders appears to be on the increase, and age at onset to be successively declining. In most cases, it is a question of a lifelong disorder with recurrent episodes, which it has been estimated will occupy 20 per cent of the patient's remaining lifespan. As a group, patients with depressive disorders are characterised by high mortality (even if suicide cases are excluded) on a par with the rates for cancer, diabetes and ischaemic heart disease: they often have somatic disorders, and are high consumers of pharmaceutical drugs of all categories. Modern classification systems with well defined criteria for the depressive disorders and new drugs have facilitated treatment. Studies have shown that increased knowledge among GPs of the diagnosis and treatment of depressive disorders can have a pronounced effect on the level of public health.


Emergency medicine education and health care disparities.
Education is the means by which learning occurs and, thereby, behavior is changed. One means of improving health care disparities is changing the behavior and understanding of key personnel in academic health centers. These individuals influence policy and procedure, design and evaluate health systems, and define curricular standards for graduate and undergraduate medical education. Emergency medicine provides many opportunities to educate at all levels, including faculty, residents, and students. In addition to our responsibilities in educating emergency medicine residents, the emergency department also provides an ideal learning environment for medical students and other health care providers. The broad issue of disparities in emergency health care may be approached from a variety of directions. The Consensus Group on Education chose to focus on cultural competency education at several levels as a means of tangibly changing its status for both the immediate and long terms.


Photoprotection: facts and controversies.
Excessive exposure of the skin to sunlight can lead to many negative effects, such as sunburn, photoaging and skin cancer development. Pollution and stratospheric ozone layer depletion are factors that increase exposure to ultraviolet radiation. This work is an accurate summary of the current state of knowledge on broad-spectrum photoprotection. Avoiding the sun, skin protection through the use of protective clothing and protective filters are currently the most effective methods of sunscreen provided that they are suitably used. In addition, discussed are controversial issues such as the toxicity of zinc used in sunscreen preparations and the potential for deficiency of vitamin D3 in relation with the application of strict photoprotection. The study has also addressed issues concerning the most recent lines of research in the exploration of modern methods of photoprotection both local and systemic, such as with the use of photolyase or examination of various enzymes repairing damage after sun exposure, as well as the promising future in photoprotection technology.


Clinical Efficacy of Tooth-Bone Graft: A Systematic Review and Risk of Bias Analysis of Randomized Control Trials and Observational Studies.
The objective of this systematic review was to assess the clinical efficacy of the tooth-bone graft as a bone substitute in the oral and maxillofacial region in humans as compared to ungrafted sites and other bone substitutes. Databases were electronically and manually searched up to January 2017 to identify animal and human studies and a risk of bias analysis and descriptive statistics was performed. Eighteen animal controlled trials (401 animals), 4 human randomized controlled trials, 1 cohort study, and 3 controlled trials (184 patients) were included. Graft processing was highly heterogeneous. 71.42% clinical and 55.56% animal studies reported no significant difference between tooth-bone graft and controls. Histologically, a dentin-bone complex was reported. A low risk of bias was noted in only 50% of the randomized controlled trials and 63.33% animal study entries. An independent analysis of 6 high-quality case reports (350 patients) revealed complications in 18.86% cases. Tooth-bone graft demonstrated no added benefits over conventional graft materials. Absence of standardized processing and heterogeneous study results limit its use in clinical practice. Until long-term studies determine its success, clinicians are recommended to use it with caution because of high variability in resorption time (2-24 weeks) and a risk of graft dehiscence (12.96%-34.38%).


Pathogenesis of venous thromboembolism: when the cup runneth over.
A comprehensive understanding of the pathogenesis of venous thrombosis is essential for identifying patients at increased risk and who may therefore benefit from more aggressive preventive and therapeutic measures. As for other pathologies, the pathogenesis of venous thromboembolism is multifactorial. All risk factors, either congenital or acquired, are relatively "innocent" when considered alone. However, when an individual is unlucky enough to inherit one or more abnormality, compounded in many cases by environmental hazards, that person may be propelled over a threshold that precipitates the development of thrombosis. An appropriate analogy is that where "the last drop makes the cup run over." A reinterpretation of the traditional Virchow's triad (abnormal vessel wall, abnormal blood flow, and abnormal blood constituents) was provided by Eberhard Mammen throughout his research, and this has contributed greatly to the understanding of the pathogenesis of this serious disorder. Mammen postulated immobility as the leading event, because it reduced blood flow as a result of decreased muscle contraction. The subsequent "stasis of flow" led to accumulation of blood within the intramuscular sinuses, especially of the calf, triggering hypercoagulability due to local accumulation of activated clotting factors and coagulation activation products and the simultaneous consumption of blood coagulation inhibitors. On Mammen's "hit list" nearly 20 years ago were included (among inherited abnormalities) decreased protein C, protein S, antithrombin III, plasminogen, and tissue plasminogen activator, and increased plasminogen activator inhibitor-1, whereas (among acquired predisposing conditions) surgery, trauma, previous thromboembolism, prolonged immobility and paralysis, malignancy, congestive heart failure, obesity, advanced age, pregnancy and puerperium, varicose veins, and oral contraceptives were also identified. Some two decades later, the situation has perhaps not changed so much, although studies continue to expand our knowledge of this topic, clarifying the relative contribution of each single risk factor in the pathogenesis of venous thrombosis.


In-depth investigation of the soybean seed-filling proteome and comparison with a parallel study of rapeseed.
To better understand the metabolic processes of seed filling in soybean (Glycine max), two complementary proteomic approaches, two-dimensional gel electrophoresis (2-DGE) and semicontinuous multidimensional protein identification technology (Sec-MudPIT) coupled with liquid chromatography-mass spectrometry, were employed to analyze whole seed proteins at five developmental stages. 2-DGE and Sec-MudPIT analyses collectively identified 478 nonredundant proteins with only 70 proteins common to both datasets. 2-DGE data revealed that 38% of identified proteins were represented by multiple 2-DGE species. Identified proteins belonged to 13 (2-DGE) and 15 (Sec-MudPIT) functional classes. Proteins involved in metabolism, protein destination and storage, and energy were highly represented, collectively accounting for 61.1% (2-DGE) and 42.2% (Sec-MudPIT) of total identified proteins. Membrane proteins, based upon transmembrane predictions, were 3-fold more prominent in Sec-MudPIT than 2-DGE. Data were integrated into an existing soybean proteome database (www.oilseedproteomics.missouri.edu). The integrated quantitative soybean database was compared to a parallel study of rapeseed (Brassica napus) to further understand the regulation of intermediary metabolism in protein-rich versus oil-rich seeds. Comparative analyses revealed (1) up to 3-fold higher expression of fatty acid biosynthetic proteins during seed filling in rapeseed compared to soybean; and (2) approximately a 48% higher number of protein species and a net 80% higher protein abundance for carbon assimilatory and glycolytic pathways leading to fatty acid synthesis in rapeseed versus soybean. Increased expression of glycolytic and fatty acid biosynthetic proteins in rapeseed compared to soybean suggests that a possible mechanistic basis for higher oil in rapeseed involves the concerted commitment of hexoses to glycolysis and eventual de novo fatty acid synthesis pathways.


Effects of carbendazim on rat thyroid, parathyroid, pituitary and adrenal glands and their hormones.
The purpose of this study is to determine the effects of low and high dose of carbendazim on the level of certain hormones and endocrine glands (thyroid, parathyroid, adrenal and pituitary glands) of male rats. Carbendazim is a systemic fungicide with activity against a number of plant pathogens. In this study, daily doses of 0, 150, 300 and 600 mg/kg per day carbendazim were applied to male rats by gavage for 15 weeks. At the end of the experiment, T3, T4, TSH, ACTH and GH levels in rat serum were analysed. Thyroid, parathyroid, adrenal and pituitary glands of rats were taken. A significant increase was observed in serum T3 levels of the rats, which were exposed to 300 mg/kg per day carbendazim doses, compared to the serum T3 levels of the control group. There were no differences between the control and carbendazim-treated group of rats regarding serum TSH, T4, ACTH and growth hormone levels. This showed us that carbendazim caused histopathological damages in thyroid, parathyroid and adrenal glands of rats. No changes were observed in pituitary glands of treated rats. These results suggest that a high quantity of subchronic carbendazim exposure affects thyroid, parathyroid and adrenal glands.


Polarization and motility of one-dimensional multi-cellular trains.
Collective cell migration, whereby cells adhere to form multi-cellular clusters that move as a single entity, play an important role in numerous biological processes, such as during development and cancer progression. Recent experimental work focused on migration of one-dimensional cellular clusters, confined to move along adhesive lanes, as a simple geometry in which to systematically study this complex system. One-dimensional migration also arises in the body when cells migrate along blood vessels, axonal projections, and narrow cavities between tissues. We explore here the modes of one-dimensional migration of cellular clusters ("trains") by implementing cell-cell interactions in a model of cell migration that contains a mechanism for spontaneous cell polarization. We go beyond simple phenomenological models of the cells as self-propelled particles by having the internal polarization of each cell depend on its interactions with the neighboring cells that directly affect the actin polymerization activity at the cell's leading edges. Both contact inhibition of locomotion and cryptic lamellipodia interactions between neighboring cells are introduced. We find that this model predicts multiple motility modes of the cell trains, which can have several different speeds for the same polarization pattern. Compared to experimental data, we find that Madin-Darby canine kidney cells are poised along the transition region where contact inhibition of locomotion and cryptic lamellipodia roughly balance each other, where collective migration speed is most sensitive to the values of the cell-cell interaction strength.


Disease-free survival at 2 or 3 years correlates with 5-year overall survival of patients undergoing radical cystectomy for muscle invasive bladder cancer.
The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival. We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic. Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival. Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.


Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells.
(Pro)renin receptor ((P)RR) regulates the renin-angiotensin system and functions as an essential accessory subunit of vacuolar H+ -ATPase. There is accumulating evidence that shows close relationship between (P)RR and autophagy. Soluble (P)RR consisting of the extracellular domain of (P)RR is generated from (P)RR by proteolytic enzymes. The aim of the present study was to clarify the influence of autophagy inhibition on soluble (P)RR expression in cancer cells. Autophagy was inhibited by treatment of bafilomycin A1 or chloroquine in MCF-7 and A549 cells for 72 hr. Western blot analysis showed that protein levels of soluble (P)RR were markedly elevated by autophagy inhibition, whereas no noticeable increases were observed in full-length (P)RR. Secretion of soluble (P)RR into the medium was increased dose-dependently by bafilomycin A1 or chloroquine. Autophagy inhibition was confirmed by enhanced accumulation of autophagy-related proteins, LC3, p62 and LAMP1 in intracellular vesicles. Increased amount of soluble (P)RR by autophagy inhibition was decreased by site-1 protease inhibitor, whereas no noticeable increase in site-1 protease immunoreactivity was observed in cells with autophagy inhibition by immunocytochemistry. These findings suggest that soluble (P)RR protein accumulates by autophagy inhibition, possibly because of the reduced degradation of soluble (P)RR in the intracellular vesicles during autophagy inhibition.


Development and testing of an improved parenteral formulation of phenytoin using 2-hydroxypropyl-beta-cyclodextrin.
The objective of this study was to increase the solubility of phenytoin by complexing it with varying concentrations of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and create an entirely aqueous formulation with a pH significantly closer to physiologic pH (7.4). The phenytoin-HPBCD complexation was characterized using phase-solubility analysis at HPBCD concentrations ranging from 10 to 50% w/v over the pH range of 7.4-11.0. The two most promising formulations, i.e., a formulation consisting of 40% HPBCD at pH 10.4, and a second formulation consisting of 20% HPBCD at pH 11.0, were selected for further study. Both formulations were entirely aqueous and had a significantly decreased pH compared to the original commercial formulation (Parke-Davis, pH 12.0). These formulations also exhibited a significantly decreased tendency to precipitate in vitro. The tissue irritation potential of the 20% w/v HPBCD formulation at pH 11.0 was found to be reduced considerably compared to the commercial injection in a BALB/c mouse model.


Regulators of an ancient polyphenism evolved through episodic protein divergence and parallel gene radiations.
Polyphenism is a form of developmental plasticity that transduces environmental cues into discontinuous, often disparate phenotypes. In some cases, polyphenism has been attributed to facilitating morphological diversification and even the evolution of novel traits. However, this process is predicated on the origins and evolutionary maintenance of genetic mechanisms that specify alternate developmental networks. When and how regulatory loci arise and change, specifically before and throughout the history of a polyphenism, is little understood. Here, we establish a phylogenetic and comparative molecular context for two dynamically evolving genes, eud-1 and seud-1, which regulate polyphenism in the nematode Pristionchus pacificus. This species is dimorphic in its adult feeding-structures, allowing individuals to become microbivores or facultative predators depending on the environment. Although polyphenism regulation is increasingly well understood in P. pacificus, the polyphenism is far older than this species and has diversified morphologically to enable an array of ecological functions across polyphenic lineages. To bring this taxonomic diversity into a comparative context, we reconstructed the histories of eud-1 and seud-1 relative to the origin and diversification of polyphenism, finding that homologues of both genes have undergone lineage-specific radiations across polyphenic taxa. Further, we detected signatures of episodic diversifying selection on eud-1, particularly in early diplogastrid lineages. Lastly, transgenic rescue experiments suggest that the gene's product has functionally diverged from its orthologue's in a non-polyphenic outgroup. In summary, we provide a comparative framework for the molecular components of a plasticity switch, enabling studies of how polyphenism, its regulation, and ultimately its targets evolve.


Ventilation and perfusion magnetic resonance imaging of the lung.
A close interaction between the respiratory pump, pulmonary parenchyma and blood circulation is essential for a normal lung function. Many pulmonary diseases present, especially in their initial phase, a variable regional impairment of ventilation and perfusion. In the last decades various techniques have been established to measure the lung function. Besides the global pulmonary function tests (PFTs) imaging techniques gained increasing importance to detect local variations in lung function, especially for ventilation and perfusion assessment. Imaging modalities allow for a deeper regional insight into pathophysiological processes and enable improved planning of invasive procedures. In contrast to computed tomography (CT) and the nuclear medicine techniques, magnetic resonance imaging (MRI), as a radiation free imaging modality gained increasing importance since the early 1990 for the assessment of pulmonary function. The major inherent problems of lung tissue, namely the low proton density and the pulmonary and cardiac motion, were overcome in the last years by a constant progress in MR technology. Some MR techniques are still under development, a process which is driven by scientific questions regarding the physiology and pathophysiology of pulmonary diseases, as well as by the need for fast and robust clinically applicable imaging techniques as safe therapy monitoring tools. MRI can be considered a promising ionizing-free alternative to techniques like CT or nuclear medicine techniques for the evaluation of lung function. The goal of this article is to provide an overview on selected MRI techniques for the assessment of pulmonary ventilation and perfusion.


Tramadol SR in arthrosic and neuropathic pain.
Chronic pain requires adequate treatment to control the severity of pain, allowing it to be well tolerated for the long term. Slow release formulations represent a useful method for the treatment of lasting pain because they allow for more simple pain management. The aim of this study was to verify the efficacy and tolerability of tramadol SR for the treatment of two of the most common kinds of chronic pain: arthrosic and neuropathic pain. A total of 100 patients (32 M/68 F), with a mean age of 61 years (+/-12) with non-oncologic pain (71 with arthrosic pain and 29 with neuropathic pain) were enrolled in an open prospective study. In most cases, the SR formulation of tramadol was prescribed at a dose of 100-200 mg/day; the initial follow-up appointments were two to four weeks later, and then at monthly intervals. During the study, a good analgesic response was recorded in all patients, irrespective of the type of pain they suffered. In fact, the intensity of the pain decreased rapidly and clearly, from severe (mean+SD 7.66+1.6 on an 11 point numerical scale) to mild residual pain (70.5% less than the baseline; P<0.05 between the times, NS between the groups), with pain relief and sleep quality displaying parallel improvement. Thus, all parameters of efficacy improved in both groups of patients, with no clinically important differences between the responses of the subjects with arthrosis and those of the subjects with neuropathic pain (P<0.05 between the times, NS between groups). Patient compliance was high. The tolerability was excellent in 75% of the patients. In the remaining 25%, the side effects that appeared were modest, as demonstrated by the fact that the drug was suspended in just 10 cases. These results confirm that the efficacy of tramadol in the treatment of neuropathic pain is also present in the SR formulation. The safety profile is reassuring, and, fundamentally, tramadol treatment only requires identification of the optimal dose without particular warnings or precautions.


Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas.
In this study, we showed that renal tumors contain substantial subsets of CD8(+) p58(+) T cells. From 1 of these tumors, T cells were amplified in mixed lymphocytes-tumor cell cultures and p58(+) T cells were selected immunologically. After expansion, phenotypic and functional features of p58(+) and p58(-) T cells were examined. The p58(+) T cells expressed p58.2 receptor and corresponded to CD3(+), CD8(+), T-cell receptor (TCR) alpha/beta(+) T cells that were CD56(+) and CD28(-). Functionally, p58(+) T cells showed a low level of lytic activity against autologous tumor cells that was dramatically and specifically increased by anti-p58.2 monoclonal antibody. On the other hand, p58(-) CD8(+) T cells did not lyse autologous tumor cells and had non-major histocompatibility complex-restricted cytotoxicity against K562 and Daudi cells. A p58(+) cytotoxic T lymphocyte (CTL) clone (4C7) with the same characteristics as the p58(+) T-cell line was derived. This CTL clone did not lyse autologous normal B cells but lysed several HLA-A1(+) renal tumor cell lines. Analysis of TCR repertoire diversity showed that the p58(+) T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58(-) T cells was polyclonal. Interestingly, TCR transcripts of p58(+) T cells and of CTL clone 4C7 were detected as prominent ex vivo in tumor cells but not in peripheral blood mononuclear cells, suggesting that these cells are antigen specific and amplified at the tumor site. (Blood. 2000;95:2883-2889)


Total laparoscopic hysterectomy - clinical comparison of the method using two types of uterine manipulators.
Comparison of two types of uterine manipulators used in total laparoscopic hysterectomy (TLH) and clinical evaluation of the method in patients in a two-year group supplemented by subjective evaluation. Prospective observational study. Department of Gynecology and Obstetrics, Masaryk University, Faculty of Medicine and University Hospital Brno. A group of patients operated in the years 2018-2019 by the TLH method using one of two types of uterine manipulators - Karl Storz HOHL (group No. 1) vs. plastic ring of Koh's manipulator (group No. 2). We compared surgical time (min), blood loss (ml), perioperative complications, length of hospital stay (days), early and late complications. We were interested in the possible influence of BMI, uterine on these parameters. Subjective evaluation of the method by patients took place before the procedure and 12 weeks after the operation with a standardized questionnaire. A total of 134 patients were enrolled in the study (75 in group 1 vs. 59 in group 2). The monitored parameters: age, BMI, operative time, blood loss and length of hospitalization did not differ statistically significantly. When comparing the individual groups with different manipulators, the total number of complications (mild difficulties, serious complications) was without statistical significance (p = 0.58), but the spectrum of symptoms was different in both groups. More than a third of the patients in the group were obese. There were more serious complications than non-obese ones, the performance was longer, however, for a small number it was statistically insignificant (p = 0.11). In patients with uterine surgery, we recorded more adhesiolysis. We did not show that previous surgery on the uterus was associated with a higher incidence of complications (p = 0.6). We did not notice any statistically significant difference in the subjective evaluation (p = 0.3). TLH is the dominant method of uterine removal in our workplace. In a group of 134 women, we did not show a statistically significant difference in the monitored parameters. The HOHL manipulator has proved to be more user-friendly due to its technical parameters and better clarity of the operating field. Subjective evaluation of the method was positive in patients.


Accurate Preoperative Evaluation of the Location of Esophagogastric Junction Adenocarcinoma Using Positron Emission Tomography-Computed Tomography.
The surgical procedure for esophagogastric junction (EGJ) adenocarcinoma usually depends on the location of its epicenter or proximal margin, but accurate evaluation of these positions is often difficult. The usefulness of positron emission tomography-computed tomography (PET-CT) for this purpose is unknown. Between June 2005 and February 2015, we enrolled 30 patients with cT2-4 EGJ adenocarcinoma (Siewert type I/II) who underwent surgical resection. We ascertained the sensitivity and specificity of preoperative PET-CT for identifying the primary tumor and regional lymph node metastasis, and compared PET-CT and pathological findings in terms of the distance from the EGJ to the tumor epicenter or proximal tumor margin. PET-CT detected the primary tumor with a sensitivity of 97% (29/30), and detected lymph node metastasis with a sensitivity and specificity of 22% (4/18) and 100% (8/8), respectively. No significant association was observed between the maximal standardized uptake value and histological type, tumor size, or pT status. Regarding the accuracy of evaluating tumor location, the median differences between PET-CT and pathological measurements were .6 cm for the tumor epicenter and .5 cm for the proximal margin from the EGJ. PET-CT and pathological findings showed agreement regarding Siewert classification type (I or II) and lengths of esophageal involvement exceeding 4 cm or 2 cm in 77% (10/13), 85% (11/13), and 85% (11/13) of cases, respectively. PET-CT had high sensitivity for primary EGJ adenocarcinoma. It may effectively locate the tumor epicenter and proximal margin and thus help clinicians determine the optimal surgical procedure.


Scheduling of taxanes: a review.
The taxanes are widely used in the cytotoxic treatment of many solid tumours. Their optimal scheduling, however, remains unconfirmed. Here we review the development of both paclitaxel and docetaxel to identify evidence influencing the choice of schedule. Early work with paclitaxel identified that it exhibits non-linear pharmacokinetics which has important clinical implications. Paclitaxel has been administered with a wide range of infusion times, especially 3-weekly and recently weekly schedules. Clinical activity of a weekly schedule appears at least non-inferior, and, in certain circumstances superior, to the 3-weekly schedule, with improved tolerability. Similarly, docetaxel has been investigated for 3-weekly versus weekly schedule, reporting equivalent efficacy and improved side effect profile for weekly dosing with regards myelosuppression. Both paclitaxel and docetaxel are often used with the monoclonal antibodies trastuzumab and bevacizumab. It would appear that in this setting, activity may be again improved by administering the taxane weekly, especially in combination with trastuzumab. A further recent development is the use of nab-paclitaxel, nanoparticle albumin-bound paclitaxel; this Cremaphor EC-free preparation allows shorter infusion times without premedication. Benefits of a weekly schedule with this newer drug are also emerging from the limited randomised data. Whether the possibly greater efficacy of weekly paclitaxel in particular reflects a biological effect of more frequent exposure of cancer cells to the cytotoxic is less clear as this schedule also allows a higher dose intensity to be delivered. Nevertheless, that after more than 20 years, weekly administration has emerged as the optimal schedule, especially for paclitaxel. In practice, the choice of schedule is a balance between the better tolerability (and possibly efficacy) of weekly treatment balanced against the inconvenience for both the patient and clinic of more frequent visits for chemotherapy.


A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.
Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.


Glucocorticoid suppression of oestrus, follicles, LH and ovulation in the mare.
Dexamethasone, a synthetic glucocorticoid, was administered (30 mg/day) from Day 10 after ovulation to assess the involvement of the adrenal glands in the ovulatory cycle. Only 1 of 8 mares treated in this way exhibited behavioural oestrus, compared to 7 of 8 control mares. Mean maximum LH concentration and follicle size were significantly reduced. Ovulation occurred in 1 and possibly in 2 other treated mares, compared to all 8 control mares. The results demonstrated that dexamethasone can interfere with ovulation and associated events in the mare, but the mechanism of action is uncertain.


Energy expenditure in patients with inflammatory bowel disease.
The basal energy expenditure (BEE) calculated from the Harris-Benedict equation was compared with the resting energy expenditure (REE) measured by indirect calorimetry in 12 consecutive hospitalized patients with inflammatory bowel disease. The BEE proved to be equivalent to the REE in the prediction of daily caloric requirements. Patients weighing less than 90% of their ideal body weight had significantly increased energy requirements on a per-kilogram-weight basis as compared with those weighing more than 90% of their ideal body weight. Daily caloric requirements based on 1.75 X BEE would provide 45 kcal/kg/24 hr, which is consistent with reported values necessary for anabolism.


Effect of anesthesia on intraocular pressure measurement in children.
Measurement of the intraocular pressure (IOP) is central to the diagnosis and management of pediatric glaucoma. An examination under anesthesia is often necessary in pediatric patients. Different agents used for sedation or general anesthesia have varied effects on IOP. Hemodynamic factors, methods of airway management, tonometry technique, and body positioning can all affect IOP measurements. The most accurate technique is one that reflects the awake IOP. We review factors affecting IOP measurements in the pediatric population and provide recommendations on the most accurate means to measure IOP under anesthesia based on the present literature.


Tetracycline-resistant Ureaplasma urealyticum: a cause of persistent nongonococcal urethritis.
We treated 289 men with nongonococcal urethritis in a randomized, double-blind study with minocycline, 100 mg once or twice daily for 7 or 21 days. Ureaplasma urealyticum was isolated before treatment from 167 (58%). The pretherapy isolates from 82 men re-examined 6 to 8 days after initiation of treatment were viable. In six (7%) isolates were resistant to 256 microgram/mL or more of tetracycline. Tetracycline resistance was significantly correlated with persistence of U. urealyticum and persistence of nongonococcal urethritis during treatment. Recurrence of nongonococcal urethritis after initial resolution and recurrence of U. urealyticum after interim negative cultures were not correlated with tetracycline resistance of U. urealyticum. Thus tetracycline-resistant strains of U. urealyticum are a cause of persistent but not of recurrent nongonococcal urethritis.


Stereodefined acyclic trisubstituted metal enolates towards the asymmetric formation of quaternary carbon stereocentres.
Reactions that involve metal enolate species are amongst the most versatile carbon-carbon bond forming processes available to synthetic chemists. Enolate species are involved in a multitude of powerful applications in asymmetric organic synthesis, but the generation of fully substituted enolates in a geometrically defined form is not easily achieved especially in acyclic systems. In this Feature Article we focus on the most prominent examples reported in the literature describing the formation of highly diastereo- and enantiomerically enriched quaternary stereocentres in acyclic molecules derived from stereodefined non-cyclic trisubstituted metal enolates.


Heteroleptic platinum(II) isocyanide complexes: convenient synthetic access, polymorphs, and vapoluminescence.
A convenient synthetic scheme was developed to access a series of square-planar Pt(II) complexes of the form (TBA)[Pt(CN)3(CNR)] (TBA = tetra-n-butyl ammonium cation, R = CH3, c-C6H11, p-(C2H5)-C6H4). These heteroleptic complexes were characterized by combustion analyses, single-crystal X-ray structure determinations, HRFAB-MS, (1)H NMR, ATR-IR, solution UV-Vis, and solid-state emission spectroscopies. Surprisingly, each of these complexes exhibit low energy room temperature solid-state luminescence in the absence of intermolecular Pt-Pt interactions. Additionally, the polymorphic behavior of (TBA)[Pt(CN)3(CN-c-C6H11)] was elucidated through a combination of single-crystal X-ray structure determinations, X-ray powder diffraction, and mass uptake experiments. Vapoluminescence and polymorphic transformations of (TBA)[Pt(CN)3(CN-c-C6H11)] were concomitant with water vapor absorption. A new double-salt complex [Pt(terpy)Cl] [Pt(CN)3(CNCH3)] (terpy = 2,2',6',2''-terpyridine) was also synthesized and characterized by combustion analysis, ATR-IR, HRFAB-MS, and solid-state UV-Vis and emission spectroscopies. The vapoluminescent properties of this salt in response to water were examined by mass uptake experiments, ATR-IR, and solid-state emission spectroscopy. A principal component analysis (PCA) of the solid-state emission changes induced by water vapor confirmed the presence of an intermediate emissive species.


Peripartum Care of the Jehovah's Witness Patient.
Postpartum hemorrhage is a leading cause of maternal mortality. Jehovah's Witnesses (JWs) refuse allogeneic blood transfusion, and thus treatment of hemorrhagic complications in this patient population is complex. Recognition and respect for religious beliefs are essential when caring for the JW parturient and several ethical and legal considerations must be taken into account. Interdisciplinary teamwork and communication as well as active patient participation are critical in the decision-making process for JW patients. Various techniques and technologies are available to optimize red blood cell mass, minimize bleeding, increase tolerance to anemia and support multiorgan derangements derived from antepartum and postpartum hemorrhage.


Cyclic adenosine 3':5-monophosphate receptor proteins in hormone-dependent and -independent rat mammary tumors.
The molecular species of cyclic adenosine 3':5'-monophosphate (cAMP) receptor proteins (high-affinity-binding proteins) present in hormone-dependent and -independent rat mammary carcinomas were identified and characterized. Three major types of cAMP receptor proteins, with molecular weights of 39,000, 48,000, and 56,000, specifically incorporated the photoaffinity label, 8-azido-cyclic adenosine 3':5'-[32P]monophosphate and were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the tumor cytosols. The M.W. 48,000 and 56,000 receptor proteins appeared to be the regulatory subunits of cAMP-dependent protein kinase types I and II, respectively, and the M.W. 39,000 receptor protein was the proteolytic fragment of the M.W. 56,000 receptor protein. The relative amounts of these cAMP receptor proteins varied from one tumor type to another and showed no correlation with respect to the hormone dependency of tumors. Under two-dimensional gel electrophoresis, however, the M.W. 56,000 receptor protein from hormone-dependent tumors migrated as a doublet and shifted to either a more acidic or more basic charge than that of the receptor protein of hormone-dependent tumors. The alteration of the charge of the receptor did not affect the affinity for cAMP binding, because both hormone-dependent and hormone-independent tumor cytosols exhibited the dissociation constant for cAMP of approximately 10(-8) M. The M.W. 56,000 cAMP receptor protein from hormone-dependent tumors exhibited self-phosphorylation, but that from hormone-independent tumors did not. The diethylaminoethyl cellulose elution profiles of cAMP receptor proteins also differed between hormone-dependent and -independent tumors; cAMP binding activity from hormone-dependent tumors coeluted with cAMP-dependent protein kinase activity, whereas most of the cAMP binding activity from hormone-independent tumors eluted at a higher ionic strength than did cAMP-dependent protein kinase activity. These results suggest that the charge alteration of cAMP receptor proteins, which appears to occur at a site remote from that of cAMP binding, may be associated with the hormone independency of mammary tumors.


RNA polymerase I-driven minigenome system for Ebola viruses.
In general, Ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. However, despite substantial sequence homology to other members of the family Filoviridae, Reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. In order to develop a tool to explore potential roles for transcription and replication in the reduced pathogenicity of Reston ebolavirus, we developed an RNA polymerase I (Pol I)-driven minigenome system. Here we demonstrate successful Reston ebolavirus minigenome rescue, including encapsidation, transcription, and replication, as well as the packaging of minigenome transcripts into progeny particles. The Pol I-driven Reston ebolavirus minigenome system provides a higher signal intensity with less background (higher signal-to-noise ratio) than a comparable T7-driven Reston ebolavirus minigenome system which was developed simultaneously. Successful Reston ebolavirus minigenome rescue was also achieved by the use of helper plasmids derived from the closely related Zaire ebolavirus or the more distantly related Lake Victoria marburgvirus. The use of heterologous helper plasmids in the Reston ebolavirus minigenome system yielded levels of reporter expression which far exceeded the level produced by the homologous helper plasmids. This comparison between minigenomes and helper plasmids from different filovirus species and genera indicates that inherent differences in the transcription and/or replication capacities of the ribonucleoprotein complexes of pathogenic and apathogenic filoviruses may exist, as these observations were confirmed in a Lake Victoria marburgvirus minigenome system.


Unraveling the immune and metabolic changes associated with metritis in dairy cows.
The objective was to unravel the peripartum immune and metabolic changes associated with metritis in Holstein cows. Holstein cows (n = 128) had blood collected at -14, 0, 3, and 7 d relative to parturition (DRP). Flow cytometry was used to evaluate blood leukocyte counts, proportions, and activation. Total cells, live cells (LiveDead-), single cells, monocytes (CD172α+/CD14+), polymorphonuclears (PMN; CD172α+/CD14-/SSChigh), B-cells (CD21+/MHCII+), CD4+ T-cells (CD4+), CD8+ T-cells (CD8+), and γδ T-cells (γδTCR+) were evaluated. CD62L and CD11b were used as markers of cell activation. Major histocompatibility complex class II was used as a marker of antigen presentation in monocytes. A MILLIPLEX Bovine Cytokine/Chemokine 08-plex kit was used to evaluate plasma concentrations of interferon-γ, Interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The body weight (BW) change prepartum was calculated as the difference between calving BW and prepartum BW divided by the number of days between measurements. Plasma fatty acids (FA) were measured at -14 and 0 DRP using untargeted gas chromatography with time-of-flight mass spectrometry. Data were analyzed by ANOVA for repeated measures. Cows that developed metritis (n = 57) had greater prepartum BW, prepartum BW loss, and greater FA concentrations at calving. Plasma FA at calving was positively correlated with IL-1β. Cows that developed metritis had persistent systemic inflammation, which was demonstrated by greater B-cell activation, greater pro-inflammatory cytokine concentrations, and greater cell damage pre- and postpartum. Postpartum, we observed greater polymorphonuclear cell activation and extravasation but lesser monocytes and CD4+ T-cells activation and extravasation, which suggests postpartum immune tolerance. Greater prepartum adiposity in cows that developed metritis may lead to systemic inflammation pre- and postpartum and immune tolerance postpartum, which may lead to failure to prevent bacterial infection, and development of puerperal metritis.


Male-female interactions drive the (un)repeatability of copula duration in an insect.
Across the animal kingdom the duration of copulation varies enormously from a few seconds to several days. Functional explanations for this variation are largely embedded within sperm competition theory in which males modulate the duration of copula in order to optimize their fitness. However, copulation is the union of two protagonists which are likely to have separate and often conflicting reproductive interests, yet few experimental designs specifically assess the effect of male-female interactions on the duration of copulation. This can result in inexact assertions over which sex controls copulatory behaviour. Here we analyse the repeatability of copulatory behaviour in the seed beetle Callosobruchus maculatus to determine which sex exerts primary influence over copulation duration. In C. maculatus, copulation follows two distinct phases: an initial quiescent phase followed by a period of vigorous female kicking behaviour that culminates in the termination of copulation. When males or females copulated with several novel mates, copulatory behaviour was not significantly repeatable. By contrast, when males or females mated repeatedly with the same mate, copula duration was repeatable. These data suggest copulatory behaviour in C. maculatus to be largely the product of male-female interactions rather than the consistent, sex-specific modulation of copula duration of one protagonist in response to the phenotypic variation presented by the other protagonist.


Effects of changing Ca2+-to-H+ ratio on Ca2+ uptake by cardiac sarcoplasmic reticulum.
Ca uptake by fragments of cardiac sarcoplasmic reticulum (SR) in the absence of oxalate depends on the ratios between concentrations of free Ca2+ and H+ and on the level of Ca loading. Using a rapid quenching technique, we showed that at [Ca2+]f less than 1 microM or in short time intervals after ATP addition (less than or equal to 1 s), pH decrease led to a significant inhibition of Ca accumulation. If Ca transport was quenched in 1 s, [Ca2+]f for half-maximal stimulation of the process would be 0.3, 1.0, and 4.0 microM at pH 7.2, 6.8, and 6.2, respectively. At higher [Ca2+]f and at longer intervals, low pH increases the amount of Ca taken up by SR. These phenomena could not be explained by an interaction of ethyleneglycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) with the Ca2+-pump system since they were also demonstrated without application of Ca-EGTA buffers. Scatchard plot analysis of ATP-independent Ca binding to SR shows that apparent Kd for Ca increases from 0.3 microM at pH 7.2 to 7.4 microM at pH 6.2. pH shifts do not change the number of high-affinity Ca-binding sites. The results suggest a competition between Ca2+ and H+ for high-affinity binding sites on Ca2+-ATPase molecules. This may cause a delay of myocardial relaxation during ischemia when a decrease in intracellular pH takes place.


Remedial Treatment of Corroded Iron Objects by Environmental Aeromonas Isolates.
Using bacteria to transform reactive corrosion products into stable compounds represents an alternative to traditional methods employed in iron conservation. Two environmental Aeromonas strains (CA23 and CU5) were used to transform ferric iron corrosion products (goethite and lepidocrocite) into stable ferrous iron-bearing minerals (vivianite and siderite). A genomic and transcriptomic approach was used to analyze the metabolic traits of these strains and to evaluate their pathogenic potential. Although genes involved in solid-phase iron reduction were identified, key genes present in other environmental iron-reducing species are missing from the genome of CU5. Several pathogenicity factors were identified in the genomes of both strains, but none of these was expressed under iron reduction conditions. Additional in vivo tests showed hemolytic and cytotoxic activities for strain CA23 but not for strain CU5. Both strains were easily inactivated using ethanol and heat. Nonetheless, given a lesser potential for a pathogenic lifestyle, CU5 is the most promising candidate for the development of a bio-based iron conservation method stabilizing iron corrosion. Based on all the results, a prototype treatment was established using archaeological items. On those, the conversion of reactive corrosion products and the formation of a homogenous layer of biogenic iron minerals were achieved. This study shows how naturally occurring microorganisms and their metabolic capabilities can be used to develop bio-inspired solutions to the problem of metal corrosion.IMPORTANCE Microbiology can greatly help in the quest for a sustainable solution to the problem of iron corrosion, which causes important economic losses in a wide range of fields, including the protection of cultural heritage and building materials. Using bacteria to transform reactive and unstable corrosion products into more-stable compounds represents a promising approach. The overall aim of this study was to develop a method for the conservation and restoration of corroded iron items, starting from the isolation of iron-reducing bacteria from natural environments. This resulted in the identification of a suitable candidate (Aeromonas sp. strain CU5) that mediates the formation of desirable minerals at the surfaces of the objects. This led to the proof of concept of an application method on real objects.


Reduced toxin binding associated with resistance to Vip3Aa in the corn earworm (Helicoverpa zea).
Helicoverpa zea is a major crop pest in the United States that is managed with transgenic corn and cotton that produce insecticidal proteins from the bacterium, Bacillus thuringiensis (Bt). However, H. zea has evolved widespread resistance to the Cry proteins produced in Bt corn and cotton, leaving Vip3Aa as the only plant-incorporated protectant in Bt crops that consistently provides excellent control of H. zea. The benefits provided by Bt crops will be substantially reduced if widespread Vip3Aa resistance develops in H. zea field populations. Therefore, it is important to identify resistance alleles and mechanisms that contribute to Vip3Aa resistance to ensure that informed resistance management strategies are implemented. This study is the first report of reduced binding of Vip3Aa to midgut receptors associated with resistance.


[Neglected ipsilateral simultaneous ruptures of patellar and quadriceps tendon].
Neglected patellar and quadriceps tendon rupture is a rare injury, but ipsilateral simultaneous patellar and quadriceps tendon rupture was not described in the literature to our knowledge. In this article, we report a 40-year-old healthy male patient with neglected ipsilateral patellar and quadriceps tendon ruptures treated by peroneus longus tendon autograft. Patient had received some conservative and surgical treatments for patellar fracture before applying to our clinic. After our treatment using peroneus longus autograft and interference nails, patient was immobilized for six weeks in cylindrical cast. Flexion exercises and full weight bearing were started after cast removal. Patient had no complaint at postoperative second year. Patient was a neglected case. Surgical repair and early rehabilitation enabled us to achieve a satisfactory outcome.


[Immunochemical and physico-chemical characteristics of lactoferrin in human body fluids].
It is proved that lactoferrins of different human body fluids (sperm, saliva, milk, tears, urine, bile, sweat, liquor, lymph, blood serum) are immunochemically identical. The lactoferrin is purified from milk, saliva and sperm and the identity of physical and chemical properties of lactoferrins of various origins is proved. The quantitative estimation of the contents of this protein in normal body fluids is given. It is detected the dependence of this protein' electrophoretic mobility and isoelectric point of degree of iron saturation. It is found that lactoferrin is capable to form complexes with esterase.


Thermoascus aurantiacus is a promising source of enzymes for biomass deconstruction under thermophilic conditions.
Thermophilic fungi have attracted increased interest for their ability to secrete enzymes that deconstruct biomass at high temperatures. However, development of thermophilic fungi as enzyme producers for biomass deconstruction has not been thoroughly investigated. Comparing the enzymatic activities of thermophilic fungal strains that grow on targeted biomass feedstocks has the potential to identify promising candidates for strain development. Thielavia terrestris and Thermoascus aurantiacus were chosen for characterization based on literature precedents. Thermoascus aurantiacus and Thielavia terrestris were cultivated on various biomass substrates and culture supernatants assayed for glycoside hydrolase activities. Supernatants from both cultures possessed comparable glycoside hydrolase activities when incubated with artificial biomass substrates. In contrast, saccharifications of ionic liquid pretreated switchgrass (Panicum virgatum) revealed that T. aurantiacus enzymes released more glucose than T. terrestris enzymes over a range of protein mass loadings and temperatures. Temperature-dependent saccharifications demonstrated that the T. aurantiacus proteins retained higher levels of activity compared to a commercial enzyme mixture sold by Novozymes, Cellic CTec2, at elevated temperatures. Enzymes secreted by T. aurantiacus released glucose at similar protein loadings to CTec2 on dilute acid, ammonia fiber expansion, or ionic liquid pretreated switchgrass. Proteomic analysis of the T. aurantiacus culture supernatant revealed dominant glycoside hydrolases from families 5, 7, 10, and 61, proteins that are key enzymes in commercial cocktails. T. aurantiacus produces a complement of secreted proteins capable of higher levels of saccharification of pretreated switchgrass than T. terrestris enzymes. The T. aurantiacus enzymatic cocktail performs at the same level as commercially available enzymatic cocktail for biomass deconstruction, without strain development or genetic modifications. Therefore, T. aurantiacus provides an excellent platform to develop a thermophilic fungal system for enzyme production for the conversion of biomass to biofuels.


Referral criteria from community clinics to pediatric emergency departments.
Referral of patients to a pediatric emergency department (PED) should be medically justified and the need for referral well communicated. The objectives of this paper were (1) to create a list of criteria for referral from the community to the PED, (2) to describe how community physicians categorize their need for referral, and (3) to determine agreement between the physician's referral letter and the selected criteria. We present a descriptive study of referrals to the PED of Soroka University Medical Center, Beer-Sheva, Israel, during February to April 2003. A list of 22 criteria for referral was created, using the Delphi method for reaching consensus. One or more criteria could be selected from this list for each referral, by the referring community physicians and, independently, based on the physicians' referral letters, by two consultants, and compared. There were 140 referrals included in the study. A total of 262 criteria for referral were selected by the referring community physicians. The criteria most frequently selected were: "Need for same-day consultation/laboratory/imaging result not available in the community" (32.1%), "Suspected life- or organ-threatening infection" (16.4%), and "Need for hospitalization" (15.7%). Rates of agreement regarding criteria for referral between the referring physicians and the two consultants, and a senior community pediatrician and a senior PED pediatrician, were 57.9 and 48.6%, respectively. We conclude that the standard referral letter does not convey in full the level of need for referral to the PED. A list of criteria for referral could augment efficient utilization of emergency department services and improve communication between community physicians and the PED.


Conduction velocity along muscle fibers in situ in healthy infants.
The muscle fibers of the biceps brachii were stimulated distally with low voltages by means of two monopolar needles in twenty-two infants aged 2 to 14 years. The electrical activity was recorded proximally by means of a SFEMG electrode. Conduction velocity of the muscle fibers (MFCV) in situ calculated with this method had a bimodal distribution in the youngest individuals of less than 4 years, and a Gaussian distribution in children aged 5 to 14 years. Propagation velocity along muscle fibers increases with children's age and is significantly slower than in adults, in good correlation with the shorter limb perimeter and with the significantly smaller fiber diameter found in muscle biopsies in infancy. The latency of the evoked potentials was linearly related with the distance between stimulating and recording points, and muscle activity and propagation velocities were the same before and after curarization, that is consistent with the reliability of the method in infancy.


Elastic stable intramedullary nailing for midclavicular fractures in athletes: indications, technical pitfalls and early results.
This prospective consecutive case series was done to evaluate indications, technical pitfalls and functional outcome of elastic stable intramedullary nailing of displaced midclavicular fractures in 14 athletes. Constant score and radiographs were evaluated after 1 and 6 weeks, 3 months and 6 months in 13 patients. Mean age was 28 years. The average follow-up was 17 months. Mean operation time was 62 minutes. Open reduction through an additional small incision was necessary for 7 fractures. Mean hospital stay was 1.2 days. Secondary fracture displacement was observed in 1 patient. The Constant score averaged 81 after 1 week, 96 after 6 weeks and 98 after 6 months. Compared to the contralateral side, average shortening of the clavicle was 1.7 mm. Overall, elastic stable intramedullary nailing provided good restoration of the length of the clavicle and allowed immediate active mobilisation with early return to normal activity. Functional results were excellent.


Decrease of fertility in a broiler breeder flock due to testicular atrophy.
Two weeks after spiking, a decrease in fertility from 96% to 82% was observed in a 48-week-old broiler breeder flock. Hatchability in the flock was about 86%. Necropsy of 25 males revealed severe testicular atrophy in 60% of the birds. Histopathology of the testes demonstrated no spermatogenesis in most of these birds. No evidence of infectious disease was discovered, and no infectious agents were isolated. Further investigation on the farm revealed standing water in the house, due to heavy rains, and wet and caked litter; this resulted in decreased feed consumption, for at least 5 days prior to submission to the diagnostic laboratory, and a corresponding decrease in body weight of the birds. In conclusion, a combination of a recent introduction of replacement (spiking) males, poor environmental conditions, and decreased feed consumption led to the loss of weight, testicular atrophy, and decreased or no spermatogenesis in individual birds, collectively resulting in decreased flock fertility.


[Methodical approach to the construction of the index of doctors' confidence in their activities].
The COVID-19 pandemic has demonstrated the importance of developing a state policy to increase the attractiveness of a doctor's work and counteract professional burnout. The trust of doctors in their work determines the state of human resources in the field of healthcare. The development of an approach to the organization of monitoring the trust of doctors will allow identifying organizations at an early stage in which there is a decrease in the confidence of doctors in their activities. The purpose of the study is to develop and test a methodological approach to calculating the index of trust of doctors. To construct the index, a list of statements was developed that are applicable for a comprehensive assessment of the doctor's activities. The approbation of the developed approach was carried out as part of a pilot sociological study in which 346 doctors from different regions of Russia took part. The significance of the statements used in the assessment was confirmed by binary probit regression. The analysis made it possible to calculate the index of doctors' trust for the obtained sample, equal to 62,5%. The results of the study can be used to assess the attitude of doctors to their activities both at the regional level and at the level of individual organizations. The Ministry of Health of the Russian Federation can use the results obtained to develop approaches to increasing the attractiveness of the medical profession to increase the public health of Russia.


Ca10Na10[Te9O42](H2O): a hydrothermally synthesized quaternary tellurium(vi) oxide containing edge-sharing octahedral trimers.
A new tellurium(vi) oxycompound, Ca10Na10[Te9O42](H2O), was synthesized by a high-temperature, high-pressure hydrothermal reaction at 550 °C, its structure determined by single-crystal X-ray diffraction, and further characterized by energy dispersive, infrared, and X-ray photoelectron spectroscopy. The compound crystallizes in the centrosymmetric trigonal space group R3[combining macron]c (no. 167) with a = 9.743(2), c = 66.337(13) Å, and Z = 6. The structure consists of discrete linear edge-sharing octahedral trimers with the composition Te3O1410-, which is a new type of finite Te-O oligomer with Te6+ only. The large complex anions form a hexagonal close-packed lattice with the octahedral and tetrahedral interstices being filled with Ca2+ and Na+ cations and water molecules. The octahedral trimers in every other h.c.p. layer rotate around the 31 screw axis for 120°; therefore the unit cell has a very long c axis. This work is one of the few examples of the synthesis of metal tellurates by supercritical hydrothermal techniques.


Preparing the healthcare workforce in South Africa for short-course rifampicin-resistant TB treatment: inter-professional training and task-sharing considerations.
Treatment for rifampicin-resistant Mycobacterium tuberculosis (RR-TB) is complex, however, shorter treatment, with newer antimicrobials are improving treatment outcomes. The South African National Department of Health (NDoH) recently accelerated the rollout of 9-month, all-oral, RR-TB short-course regimens. We sought to evaluate an inter-professional training program using pre-test and post-test performance of Professional Nurses (PNs), Advanced Practice Professional Nurses (APPNs) and Medical Officers (MOs) to inform: (a) training needs across cadres; (b) knowledge performance, by cadres; and (c) training differences in knowledge by nurse type. A 4-day didactic and case-based clinical decision support course for RR-TB regimens in South Africa (SA) was developed, reviewed and nationally accredited. Between February 2017 and July 2018, 12 training events were held. Clinicians who may initiate RR-TB treatment, specifically MOs and PN/APPNs with matched pre-post tests and demographic surveys were analyzed. Descriptive statistics are provided. Pre-post test evaluations included 25 evidence-based clinically related questions about RR-TB diagnosis, treatment, and care. Participants (N = 842) participated in testing, and matched evaluations were received for 800 (95.0%) training participants. Demographic data were available for 793 (99.13%) participants, of whom 762 (96.1%) were MOs, or nurses, either PN or APPNs. Average correct response pre-test and post-test scores were 61.7% (range 7-24 correct responses) and 85.9% (range 12-25), respectively. Overall, 95.8% (730/762) of participants demonstrated improved knowledge. PNs improved on average 25% (6.22 points), whereas MOs improved 10% (2.89 points) with better mean test scores on both pre- and post-test (p < 0.000). APPNs performed the same as the MOs on post-test scores (p = NS). The inter-professional training program in short-course RR-TB treatment improved knowledge for participants. MOs had significantly greater pre-test scores. Of the nurses, APPNs outperformed other PNs, and performed equally to MOs on post-test scores, suggesting this advanced cadre of nurses might be the most appropriate to initiate and monitor treatment in close collaboration with MOs. All cadres of nurse reported the need for additional clinical training and mentoring prior to managing such patients.


Characterization of glucosinolate uptake by leaf protoplasts of Brassica napus.
The uptake of radiolabeled p-hydroxybenzylglucosinolate (p-OHBG) by protoplasts isolated from leaves of Brassica napus was detected using silicone oil filtration technique. The uptake was pH-dependent with higher uptake rates at acidic pH. Imposition of a pH gradient (internal alkaline) across the plasma membrane resulted in a rapid uptake of p-OHBG, which was inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone, indicating that the uptake is dependent on a proton motive force. Dissipation of the internal positive membrane potential generated a small influx as compared with that seen for pH gradient (DeltapH). Kinetic studies demonstrated the presence of two uptake systems, a saturable and a linear component. The saturable kinetics indicated carrier-mediated translocation with a K(m) of 1.0 mm and a V(max) of 28.7 nmol/microl/h. The linear component had very low substrate affinity. The carrier-mediated transport had a temperature coefficient (Q(10)) of 1.8 +/- 0.2 in the temperature range from 4-30 degrees C. The uptake was against a concentration gradient and was sensitive to protonophores, uncouplers, H(+)-ATPase inhibitors, and the sulfhydryl group modifier p-chloromercuriphenylsulfonic acid. The carrier-mediated uptake system had high specificity for glucosinolates because glucosinolate degradation products, amino acids, sugars, or glutathione conjugates did not compete for p-OHBG uptake. Glucosinolates with different side chains were equally good competitors of p-OHBG uptake, which indicates that the uptake system has low specificity for the glucosinolate side chains. Our data provide the first evidence of an active transport of glucosinolates by a proton-coupled symporter in the plasma membrane of rape leaves.


Surgical management of multiple rib fractures/flail chest.
Rib fractures in the setting of trauma carries a high morbidity and mortality. Forty-three percent of patients presenting with trauma will have rib fractures. Fifty-five percent of patients, greater than 60 years of age, who die following chest trauma, have isolated rib fractures. Mortality associated with rib fractures starts to increase from the age of 45. Rib fixation is being utilised more for the management of rib fractures. Following the review of literature, we propose a pathway for the management of both simple rib fractures and flail segments. Furthermore, we review the various methods of rib fixation, discussing the advantages and disadvantages of each.


Microstructure dependent filament forming kinetics in HfO2 programmable metallization cells.
Variability remains the principal concern for commercialization of HfO2 based resistance switching devices. Here, we investigate the role of thermal processing conditions on internal structure of atomic layer deposited HfO2 thin films, and the impact of that structure on filament forming kinetics of p+ Si/HfO2/Cu and TiN/HfO2/Cu devices. Regardless of bias polarity or electrode metal, filament formation times are at least one order of magnitude shorter in polycrystalline than in amorphous films, which we attribute to the presence of fast ion migration along grain boundaries. Within polycrystalline films, filament formation times are correlated with degree of crystalline orientation. Inter-device variability in forming time is roughly equivalent across HfO2 film processing conditions. The kinetics of filament forming are shown to be highly dependent on HfO2 microstructure, with possible implications for the inter-device variability of subsequent switching cycles.


Palliative percutaneous balloon valvuloplasty in a cyanotic child with tetralogy of Fallot.
We have presented the case of an 8-month-old child who had tetralogy of Fallot with severe pulmonary stenosis and minimal infundibular stenosis. Because of the relatively small annulus (10 mm) and young age of the infant, total correction was deferred, and a percutaneous palliative pulmonary balloon valvuloplasty was done. At the end of the procedure, he had neither cyanosis nor signs of congestive heart failure, and after four months of follow-up, he had only mild cyanosis with activities.


Chronic aortic dissection (DeBakey type II) with infective thrombus in the false channel.
A 68-year-old man with a DeBakey type II chronic aortic dissection developed bacteremia secondary to a urinary tract infection with the Serratia species. This resulted in an infected thrombus in the false channel and a subsequent rupture of the ascending aorta. An emergency resection of the ascending aorta and a Dacron graft interposition were performed. The patient suffered from severe neurological insufficiency and died of pneumonia 6 months postoperatively. The optimal operation time and surgical options of an infected aortic dissection should be determined.


Saxitoxin and tetrodotoxin: comparison of nerve blocking mechanism.
Saxitoxin at concentrations of 3 x 10(-8) to 3 x 10(-7) mole per liter blocks the conduction of lobster giant axon with no change in resting potential. Recovery of washed axons is faster in those that had been treated with saxitoxin than it is in those that were treated with tetrodotoxin. Peak transient increase in nerve membrane conductance is selectively blocked by saxitoxin with no change in late steady-state increase in conductance. The major mechanism of saxitoxin blockage is the same that of tetrodotoxin blockage.


[Lipid peroxidation and the antioxidant system in the therapeutic effect of hypobaric hypoxia in patients with neurologic manifestations of lumbar osteochondrosis].
The hypobaric therapeutic effect dependence on the initial state of lipid peroxidation (LPO) and on its short-term activation after 3-4 sessions has been shown. The peroxidation action of hypobaric therapy (HBT) was consistent with a substantial increase of the correlation coefficient and regression between diene conjugates (DC) and tocopherol as well as a decrease of ascorbic acid and glutathione peroxidase activity. LPO activation did not take place in patients without changes in the clinical symptoms. Clinical improvement was shown by 94% of patients with the initial content of DC less than 2 o. u/ml. At higher DC values the therapeutic effect was lacking in 50% of cases and in 14% of cases where HBT was employed in combination with unithiol++. The normal level of LPO did not require the use of antioxidants in HBT. Recommendations have been made for differentiated use of HBT and of HBT plus antioxidants. The role of the prooxidant action of HBT in the formation of adaptation mechanisms is discussed.


The Immunomodulatory Properties of the Human Amnion-Derived Mesenchymal Stromal/Stem Cells Are Induced by INF-γ Produced by Activated Lymphomonocytes and Are Mediated by Cell-To-Cell Contact and Soluble Factors.
Human mesenchymal stromal/stem cells (MSCs), being immunoprivileged and having immunomodulatory ability, represent a promising tool to be applied in the field of regenerative medicine. Based on numerous in vitro evidences, the immunological effects of MSCs on immune cells could depend on different mechanisms as cell-to-cell contact and paracrine signals. Furthermore, recent studies have shown that the immunomodulatory activity of MSCs is initiated by activated immune cells; thus, their interaction represents a potential homeostatic mechanism by which MSCs regulate the immune response. MSCs also release exosomes able to give different effects, in a paracrine manner, by influencing inflammatory processes. In this study, we aimed to establish the potential role of human amnion-derived MSCs (hAMSCs), in immunomodulation. We found that the immunosuppressive properties of hAMSCs are not constitutive, but require "supportive signals" capable of promoting these properties. Indeed, we observed that hAMSCs alone are not able to produce an adequate amount of soluble immunomodulatory factors. Here, we studied, in depth, the strong immunomodulatory licensing signal deriving from the direct interaction between hAMSCs and stimulated peripheral blood mononuclear cells. We found that the immunomodulatory effect of hAMSCs also depends on cell-to-cell contact through the contribution of the PDL-1/PD-1 axis. We then investigated the IFN-γ priming of hAMSCs (γ-hAMSCs), which induce the increase of PDL-1 expression, high production of IDO, and upregulation of different immunomodulatory exosome-derived miRNAs. Our miRNA-target network analysis revealed that nine of the deregulated miRNAs are involved in the regulation of key proteins that control both T cell activation/anergy and monocyte differentiation pathways. Finally, we observed that γ-hAMSCs induce in monocytes both M2-like phenotype and the increase of IL-10 production. The extensive implications of MSCs in modulating different aspects of the immune system make these cells attractive candidates to be employed in therapeutic application in immune-based diseases. For these reasons, we aimed, with this study, to shed light on the potential of hAMSCs, and how they could become a useful tool for treating different inflammatory diseases, including end-stage pathologies or adverse effects in transplanted patients.


Influence of computed tomography on pretherapeutic tumor staging in head and neck cancer patients.
Refinements in radiographic techniques have resulted in increased use of radiographic studies in the evaluation of patients with head and neck cancer over the past 20 years. To assess the impact of such studies, we compared tumor clinical stages based solely on physical-examination findings with those obtained with the addition of CT findings. This study was accomplished through case review of 81 head and neck cancer patients who underwent CT after preliminary TNM-stage assignment as determined on the basis of physical examination alone. In this cohort, 44 patients (54%) had a change in assigned clinical stage. We reviewed individual anatomic sites to determine where CT was found to be most useful in modifying tumor stage. Changes in tumor and nodal stage were found across all major sites of the head and neck. Tumors of the hypopharynx were the most likely to change stage (90%) on the basis of CT findings, whereas tumors of the glottic larynx were least likely to undergo a change in stage (16%). The therapeutic implications of these findings are discussed in the context of the published literature.


Diastolic ventricular interaction in normal and dilated heart during head-up tilting.
The normal human heart behaves as a single functional unit during preload reduction; adaptations of the left ventricle to head-up tilting is mediated through ventricular interdependence and biventricular-lung interaction. We hypothesized that reduction of venous return in dilated cardiomyopathy is likely to have a great effect on ventricular chamber geometry and filling. The aim of this study was to evaluate the effects of gradual head-up tilting in normal subjects and in patients with dilated cardiomyopathy, addressing special attention to right (RV) and left ventricular (LV) dimensions, geometry, and filling, and to biventricular-lung interaction. Twenty normal subjects and 23 patients with moderate heart failure due to dilated cardiomyopathy were studied with two-dimensional and Doppler echocardiography in supine position and after 20 degrees, 40 degrees, and 60 degrees tilting. Right ventricular and LV dimensions, LV geometry, and tricuspid, mitral, and pulmonary venous flow patterns were recorded at each step of the study. Geometric changes of the LV were evaluated by measurements of volumes and diameters in the apical four-chamber view (which identifies the interventricular septum and lateral wall) and apical two-chamber view (which identifies the inferior and anterior wall of the LV). In the two groups, tilting was associated with reduction of RV area and LV diameter and volumes; percent variations in LV diameter and volumes recorded in four-chamber view were lower at each step of tilting than with those derived from the two-chamber view in controls and in patients. In normal subjects, mitral and tricuspid peak early flow velocities were decreased at any tilting level; peak late velocities were unchanged; peak velocity of systolic forward flow of the pulmonary vein was reduced, diastolic forward flow was unchanged, and the difference in duration between reverse pulmonary flow and forward mitral A wave was reduced. Doppler findings were qualitatively similar in patients, but tilting induced a more marked redistribution of LV filling to late diastole because of a significant increase in atrial contribution. Preload reduction by tilting induces profound effects on left and right dimensions, geometry, and filling in normal and dilated heart; reduction or RV dimensions are associated with changes in LV ventricular geometry (minimal reduction in septal-lateral diameter, marked reduction in anterior-posterior diameter), redistribution of right and left diastolic filling to late diastole, and redistribution of pulmonary venous flow to early diastole. These mechanisms are probably due to a favorable interaction between heart and lungs, which increases compliance within the pericardial space and facilitates redistribution of flow from the lungs. Even a minimal amount of preload reduction causes more marked effects in LV filling patterns in dilated cardiomyopathy than in normal hearts, confirming that ventricular interaction and pericardial constraint are increased when heart volume enlarges.


Audiologic manifestations of patients with post-treatment Lyme disease syndrome.
The purpose of this study was to characterize auditory function in patients diagnosed with post-treatment Lyme disease syndrome (PTLDS). Eighteen patients with PTLDS were evaluated and compared to a normal population. Evaluations consisted of pure tone and speech thresholds, word recognition (WRS), acoustic immittance battery, auditory brain stem response (ABR), and loudness discomfort level (LDL). Both seropositive and seronegative patients were evaluated. Audiologists were blinded to patient status. Forty four percent of the patients had one or more abnormal pure tone thresholds compared to gender- and age-adjusted norms. Thirty-one percent showed abnormally reduced LDLs, and 17% had abnormal acoustic reflexes at one or more frequencies. This paper catalogs previously unstudied long-term auditory system sequelae resulting from PTLDS. Our most significant finding was the dramatically reduced loudness tolerance in the presence of either normal or minimally impaired hearing. The clinician is encouraged to consider PTLDS when confronted with these or similar findings in patients having history of Borrelia burgdorferi infection and continued complaints.


Role of heat shock protein DnaK in osmotic adaptation of Escherichia coli.
Escherichia coli can adapt and recover growth at high osmolarity. Adaptation requires the deplasmolysis of cells previously plasmolyzed by the fast efflux of water promoted by osmotic upshift. Deplasmolysis is essentially ensured by a net osmo-dependent influx of K+. The cellular content of the heat shock protein DnaK is increased in response to osmotic upshift and does not decrease as long as osmolarity is high. The dnaK756(Ts) mutant, which fails to deplasmolyze and recover growth, does not take up K+ at high osmolarity; DnaK protein is required directly or indirectly for the maintenance of K+ transport at high osmolarity. The temperature-sensitive mutations dnaJ259 and grpE280 do not affect the osmoadaptation of E. coli at 30 degrees C.


[Our initial experience with stent implantation for aortic coarctation in adults].
We evaluated the procedural success and short-mid term results of stent implantation for aortic coarctation in adults. The study included 15 consecutive patients (9 women, 6 men; mean age 27±7 years; range 17 to 45 years) treated with stent implantation for aortic coarctation. Fourteen patients had native, one patient had recurrent coarctation. Nine patients received bare metal and six patients received covered Cheatham-Platinum stents. Covered stents were used in patients with accompanying patent ductus arteriosus (n=2), severe coarctation (n=3), and recurrent coarctation (n=1). Procedural success was defined as the reduction in the pressure gradient across the coarctation site to less than 20 mmHg. The mean follow-up period was 10.4±4.6 months (range 3 to 18 months). Stent implantation was successful in all the patients. Compared to the preprocedure figures, systolic gradient across the aortic coarctation decreased from 37.2±11.3 mmHg to 3.5±2.9 mmHg, the diameter of the coarcted aortic segment increased from 5.4±1.5 mm to 17.2±1.4 mm, and systolic blood pressure declined from 154±9.7 mmHg to 130±7.3 mmHg following stenting (for all, p<0.001). There were no procedure-related major complications. Stent implantation for aortic coarctation in adults is a safe and effective alternative to surgical correction.


Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN).
This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients.


A plan to overcome resistance to managed care.
A managed-care plan is attempting to reverse New Yorkers' negativity toward managed care. The focus is on giving consumers adequate information and access to allow them to make prudent health care choices.


Pancreatic neuroendocrine tumor in a child with a tuberous sclerosis complex 2 (TSC2) mutation.
Pancreatic neuroendocrine tumors (PanNETs) are rare in children with tuberous sclerosis complex (TSC). The objective of this report is to describe a case of PanNET in a boy with TSC. We describe the patient's clinical presentation, biochemical workup, and laboratory tests. A 10-year-old boy with a TSC2 mutation presented with a nonsecretory PanNET discovered during routine annual abdominal ultrasound. Surgical distal pancreatectomy with spleen preservation was undertaken. The excised tumor appeared nodular, whitish, and encapsulated. The tumor was composed of pancreatic endocrine monomorphic cells, and the solid appearance of the tumor was interrupted by areas of cystic degeneration. Mitoses were rare; the proliferation index was estimated around 4%. Local lymph nodes showed hyperplasia but were free of metastatic disease. Immunohistochemical examinations were positive for the neuroendocrine markers chromogranin, neurospecific enolase, synaptophysin, CAM52, and vimentin and were negative for CD10 and alpha-1 antitrypsin. The immunohistochemistry also showed a lack of hyperactivation of mammalian target of rapamycin (mTOR) mTOR pathway. All data supported the diagnosis of a grade II well-differentiated neuroendocrine neoplasm, according to the World Health Organization (WHO). Thirteen non-secretory PanNET cases associated with TSC have been reported, including our patient (9 men and 4 women; 7 with TSC2 mutation). These tumors are usually asymptomatic and can be associated with metastasis; therefore, early diagnosis is crucial for prompt treatment. It is still unclear whether PanNETs should be considered a feature of TSC; however due to this association, we suggest that pancreas investigation should be included in routine examinations in men with TSC2 mutation.