Pathogenesis of systemic lupus erythematosus.
SLE is a syndrome characterized by diverse clinical signs and symptoms, including rash, serositis, nephritis, central nervous system disease, thrombocytopenia, and leukopenia. These and other manifestations are present in patients with immune abnormalities indicative of B cell hyperactivity: hypergammaglobulinemia, increased amounts of antibodies reactive with self-determinants (characteristically including nuclear antigens), and increased numbers of circulating antibody-producing cells. It is this immune hyperactivity, inclusive of anti-self responses, which groups the patients with diverse clinical manifestations into a single syndrome called lupus.


Modeling and analysis of soybean (Glycine max. L) Cu/Zn, Mn and Fe superoxide dismutases.
Superoxide dismutase (SOD, EC 188.8.131.52) is an important metal-containing antioxidant enzyme that provides the first line of defense against toxic superoxide radicals by catalyzing their dismutation to oxygen and hydrogen peroxide. SOD is classified into four metalloprotein isoforms, namely, Cu/Zn SOD, Mn SOD, Ni SOD and Fe SOD. The structural models of soybean SOD isoforms have not yet been solved. In this study, we describe structural models for soybean Cu/Zn SOD, Mn SOD and Fe SOD and provide insights into the molecular function of this metal-binding enzyme in improving tolerance to oxidative stress in plants.


Synergistic effect of reductase and keratinase for facile synthesis of protein-coated gold nanoparticles.
We have synthesized gold nanoparticles (GNPs) using chicken feathers (poultry waste) and Bacillus subtilis RSE163. Disulfide reductase and keratinase produced by Bacillus subtilis during the degradation of chicken feather has been used to reduce Au(3+) from HAuCl4 precursor to produce gold nanoparticles. The synthesized biogenic GNPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), and zeta potential measurements. Fourier transform infrared (FTIR) spectroscopy indicated the presence of protein capping on synthesized GNPs, imparting multifunctionality to the GNP surface. Furthermore, the nontoxic nature of biogenic GNPs was insured by interaction with Escherichia coli (ATCC11103), where TEM images and enhancement of growth rate of E. coli in log phase signified their nontoxic nature. The results indicate that the synthesis of biocompatible GNPs using poultry waste may find potential applications in drug delivery and sensing.


Cooperation and self-regulation in a model of agents playing different games.
A simple model for cooperation between "selfish" agents, which play an extended version of the prisoner's dilemma game, in which they use arbitrary payoffs, is presented and studied. A continuous variable, representing the probability of cooperation, p(k)(t) in [0,1], is assigned to each agent k at time t. At each time step t a pair of agents, chosen at random, interact by playing the game. The players update their p(k)(t) using a criterion based on the comparison of their utilities with the simplest estimate for expected income. The agents have no memory and do not use strategies based on direct reciprocity or "tags." Depending on the payoff matrix, the system self-organizes-after a transient-into stationary states characterized by their average probability of cooperation p(eq) and average equilibrium per-capita income p(eq),U(infinity). It turns out that the model exhibits some results that contradict the intuition. In particular, some games that a priori seem to favor defection most, may produce a relatively high degree of cooperation. Conversely, other games, which one would bet lead to maximum cooperation, indeed are not the optimal for producing cooperation.


[Development of acute epidural hematoma].
This study covers the evolution of 21 cases of pure acute epidural hematomas which have been classified as benign, semi-benign and malignant. For the authors immediate surgical treatment is only necessary for the cases of malignant evolution. For cases of semi-benign evolution surgical treatment can be delayed. No treatment is required for haematomas with a benign evolution.


[Thyroid Storm and Myxedema Coma].
Thyroid storm and myxedema coma are the most severe clinical forms of thyroid dysfunction. While both hyper- and hypothyroidsm are common diseases, thyroid storm and myxedema coma are rare. Due to their unspecific signs and symptoms they are often difficult to diagnose. Both disorders are medical emergencies, which still show a significant mortality. The following article summarizes diagnostic tools and treatment options for these disorders.


[Reliability study on establishing a rat tuberculosis wound model using Bacillus Calmette-Guérin].
Objective: To evaluate the reliability of a rat tuberculous wound model established by injecting Bacillus Calmette-Guérin (BCG). Methods: The experimental research was conducted. According to the random number table, fifteen 6-week-old male Sprague-Dawley rats were divided into normal control group and infection group, with 3 rats in normal control group and 12 rats in infection group. Rats in infection group were injected with Freund's complete adjuvant, 3 weeks later, they were injected subcutaneously with BCG bacterial solution to establish a model of tuberculous wounds in rats; rats in normal control group did not receive any treatment. On the 8th, 15th, 32nd, and 43rd day of infection, the skin condition at the injection sites of the rats in infection group was observed roughly. Skin tissue at the injection sites of 3 rats in infection group at each corresponding time point stated above and skin tissue at the corresponding sites of the rats in normal control group were stained with hematoxylin-eosin to observe the cell arrangement, necrosis and inflammation. On 43rd day of infection, acid-fast staining was performed on the skin tissue at the injection sites of the rats in infection group to observe the distribution of bacteria. Results: On the 8th, 15th, 32nd, and 43rd day of infection, tuberculous wound lesions were gradually developed at the skin tissues at the injection sites of the rats in infection group. The cells of the diseased tissue of the rats in infection group arranged disorderly or concentrically, and the number of granulomas and necrotic cells gradually increased, while the skin tissue cells in the corresponding parts of the rats in normal control group arranged regularly with no inflammatory cell infiltration. On the 43rd day of infection, a large number of rod-shaped bacteria were observed in the skin tissue at the injection sites of the rats in infection group. Conclusions: The rat tuberculous wound model established using BCG is stable and reliable, which can meet the experimental requirements.


A PAM of the α1A-Adrenergic receptor rescues biomarker, long-term potentiation, and cognitive deficits in Alzheimer's disease mouse models without effects on blood pressure.
α1-Adrenergic Receptors (ARs) regulate the sympathetic nervous system by the binding of norepinephrine (NE) and epinephrine (Epi) through different subtypes (α1A, α1B, α1D). α1A-AR activation is hypothesized to be memory forming and cognitive enhancing but drug development has been stagnant due to unwanted side effects on blood pressure. We recently reported the pharmacological characterization of the first positive allosteric modulator (PAM) for the α1A-AR with predictive pro-cognitive and memory properties. In this report, we now demonstrate the in vivo characteristics of Compound 3 (Cmpd-3) in two genetically-different Alzheimer's Disease (AD) mouse models. Drug metabolism and pharmacokinetic studies indicate sufficient brain penetrance and rapid uptake into the brain with low to moderate clearance, and a favorable inhibition profile against the major cytochrome p450 enzymes. Oral administration of Cmpd-3 (3-9 mg/kg QD) can fully rescue long-term potentiation defects and AD biomarker profile (amyloid β-40, 42) within 3 months of dosing to levels that were non-significant from WT controls and which outperformed donepezil (1 mg/kg QD). There were also significant effects on paired pulse facilitation and cognitive behavior. Long-term and high-dose in vivo studies with Cmpd-3 revealed no effects on blood pressure. Our results suggest that Cmpd-3 can maintain lasting therapeutic levels and efficacy with disease modifying effects with a once per day dosing regimen in AD mouse models with no observed side effects.


Growth hormone deficiency: an update.
Growth hormone (GH) deficiency (GHD) in humans manifests differently according to the individual developmental stage (early after birth, during childhood, at puberty or in adulthood), the cause or mechanism (genetic, acquired or idiopathic), deficiency intensity and whether it is the only pituitary-affected hormone or is combined with that of other pituitary hormones or forms part of a complex syndrome. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise mutation types and mechanisms for previously described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic, although less frequently when they are congenital and/or familial. The clinical and biochemical diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, probably because the diagnosis based on the so-called GH secretion stimulation tests will prove to be of limited usefulness for predicting therapy indications.


Effects of Carica papaya seed extracts on the physiology of the vas deferens of albino rats.
The physiology of vas deferens after administrating papaya seed extract (1 mg/0.2 ml/day/rat) for 7 and 15 days was studied with reference to organ weights, fertility rate, some biochemical parameters and contractile pattern of isolated right and left vas deferens. Studies on combined extract + ascorbic acid feeding and discontinuation of treatment for 1 and 2 1/2 months were also carried out. The results revealed that the treatment altered the biochemical parameters except cholesterol levels and the contractile pattern was reduced in comparison to control. However, significant recovery occurred by withdrawal of treatment in all parameters studied. AA feeding was efficaceous in restoring the androgenicity of vas deferens under treated conditions. On the whole, the distal vas deferens was affected more by the seed extract treatment than proximal vas and recovery was slower probably due to its higher threshold requirement for androgen. The results are discussed in the light of recent work.


Activation of inositol 1,4,5-trisphosphate receptor is essential for the opening of mouse TRP5 channels.
We studied the opening mechanism of Ca(2+)-permeable channels formed with mouse transient receptor potential type 5 (mTRP5) using Xenopus oocytes. After stimulation of coexpressed muscarinic M(1) receptors with acetylcholine (ACh) in a Ca(2+)-free solution, switching to 2 mM Ca(2+)-containing solution evoked a large Cl(-) current, which reflects the opening of endogenous Ca(2+)-dependent Cl(-) channels following Ca(2+) entry through the expressed channels. The ACh-evoked response was not affected by a depletion of Ca(2+) store with thapsigargin but was inhibited by preinjection of antisense oligodeoxynucleotides (ODNs) to G(q), G(11), or both. The mTRP5 channel response was also induced by a direct activation of G proteins with injection of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). The ACh- and GTP gamma S-evoked responses were inhibited by either pretreatment with a phospholipase C inhibitor, U73122, or an inositol-1,4,5-trisphosphate (IP(3)) receptor inhibitor, xestospongin C (XeC). An activation of IP(3) receptors with injection of adenophostin A (AdA) evoked the mTRP5 channel response in a dose-dependent manner. The AdA-evoked response was not suppressed by preinjection of antisense ODNs to G(q/11) or U73122 but was suppressed by either preinjection of XeC or a peptide mimicking the IP(3) binding domain of Xenopus IP(3) receptor. These findings suggest that the activation of IP(3) receptor is essential for the opening of mTRP5 channels, and that neither G proteins, phosphoinositide metabolism, nor depletion of the Ca(2+) store directly modifies the IP(3) receptor-linked opening of mTRP5 channels.


Comparison of international index of erectile function with nocturnal penile tumescence and rigidity testing in evaluation of erectile dysfunction.
We tried to compare the parameters of nocturnal penile tumescence and rigidity (NPTR) testing with erectile function (EF) domain score of International Index of Erectile Function (IIEF), which is used in diagnosis and determining the severity of erectile dysfunction (ED), and to assess the sufficiency of IIEF in the diagnosis of ED. A total of 90 men, mean age 46 years (24-75), presenting with ED to our clinic between January 2001 and March 2003 were included in the trial. All the men answered the standard IIEF (15 questions) forms and was divided into four groups as mild ED, moderate ED, severe ED and no ED according to the EF domain score that is obtained from 1st, 2nd, 3rd, 4th, 5th and 15th questions. Then NPTR testing with the RigiScan Plus monitoring device was performed for two consecutive nights on those men. The distribution of the six parameters of NPTR testing (number of erections, duration of erections, TAU base, RAU base, TAU tip, RAU tip) among the four groups and the correlation with IIEF-EF domain score were evaluated. Additionally, the distribution of the risk factors (diabetes mellitus, hypertension, atherosclerotic heart disease, dyslipidemia and smoking) was analyzed both among the four groups and in each group. According to IIEF-EF domain scores of 90 patients, 16 (18%) had severe ED, 21 (23%) moderate ED, 41 (46%) mild ED and 12 (13%) no ED. There was no statistically significant difference between the risk factors among the men in these groups (P > 0.05). When the IIEF-EF domain scores were compared with parameters of NPTR testing, no statistically significant difference was obtained among ED groups (mild, moderate, severe) (P > 0.05). However, we observed a statistically significant difference between three ED groups and no ED group (P < 0.05). If NPTR testing is considered as a gold standard test, sensitivity, specificity, positive predictive value and negative predictive value of IIEF-EF domain score in ED diagnosis are 100, 17.9, 29.4 and 100% respectively. In conclusion, we did not observe a clinical correlation between IIEF-EF domain scores and NPTR parameters in the whole population; however, we observed that if IIEF-EF domain scores were normal, NPTR parameters were also normal. In other words, we can say that if the initial IIEF-EF domain scores are normal, then we do not have to perform NPTR testing. This could be helpful to make a cost-effective diagnosis.


Controlled release reservoir mini tablets approach for controlling the drug release of Galantamine Hydrobromide.
The objective of this study is to explore and investigate the reservoir mini tablets approach to control the release of Galantamine Hydrobromide in comparison to desired release profile to the Innovator formulation Razadyne ER capsules as disclosed in US Patent 7,160,559 which is granted to Janseen Pharmaceutica NV. The core mini tablets were prepared using the direct compression and wet granulation methods. These core mini tablets were further coated with Galantamine Hydrobromide in two different portions; 70% as controlled release and 30% as immediate release and then filled in empty hard gelatin capsule shells. The dissolution profiles of each formulation were compared to those of Razadyne ER capsules and the mean dissolution time (MDT), dissolution efficiency (DE%) and dissolution similarity (f2 factor) were calculated. It was observed that core formulation plays an important role in controlling the drug release as well as maintaining pH independent drug release profile. The release mechanism of GAH from reservoir mini tablet formulation follows Higuchi and first order. These results imply that controlled release reservoir mini tablets which further filled into empty hard gelatin capsule shells can be a suitable method to formulate controlled release Galantamine hydrobromide.


Genetic screening: programs, principles, and research--thirty years later. Reviewing the recommendations of the Committee for the Study of Inborn Errors of Metabolism (SIEM).
Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information.


The Lombard effect and other noise-induced vocal modifications: insight from mammalian communication systems.
Humans and non-human mammals exhibit fundamentally similar vocal responses to increased noise, including increases in vocalization amplitude (the Lombard effect) and changes to spectral and temporal properties of vocalizations. Different research focuses have resulted in significant discrepancies in study methodologies and hypotheses among fields, leading to particular knowledge gaps and techniques specific to each field. This review compares and contrasts noise-induced vocal modifications observed from human and non-human mammals with reference to experimental design and the history of each field. Topics include the effects of communication motivation and subject-specific characteristics on the acoustic parameters of vocalizations, examination of evidence for a proposed biomechanical linkage between the Lombard effect and other spectral and temporal modifications, and effects of noise on self-communication signals (echolocation). Standardized terminology, cross-taxa tests of hypotheses, and open areas for future research in each field are recommended. Findings indicate that more research is needed to evaluate linkages among vocal modifications, context dependencies, and the finer details of the Lombard effect during natural communication. Studies of non-human mammals could benefit from applying the tightly controlled experimental designs developed in human research, while studies of human speech in noise should be expanded to include natural communicative contexts. The effects of experimental design and behavioural context on vocalizations should not be neglected as they may impact the magnitude and type of noise-induced vocal modifications.


Myeloid Slc2a1-Deficient Murine Model Revealed Macrophage Activation and Metabolic Phenotype Are Fueled by GLUT1.
Macrophages (MΦs) are heterogeneous and metabolically flexible, with metabolism strongly affecting immune activation. A classic response to proinflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, whereas alternative activation is primarily oxidative, which begs the question of whether targeting glucose metabolism is a viable approach to control MΦ activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow-derived MΦs (BMDM) from Slc2a1M-/- mice failed to uptake glucose and demonstrated reduced glycolysis and pentose phosphate pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MΦ lacking GLUT1, demonstrating an incomplete metabolic reprogramming. Slc2a1M-/- BMDMs displayed a mixed inflammatory phenotype with reductions of the classically activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1M-/- BMDMs had reduced proinflammatory metabolites, whereas metabolites indicative of alternative activation-such as ornithine and polyamines-were greatly elevated in the absence of GLUT1. Adipose tissue MΦs of lean Slc2a1M-/- mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/- mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1M-/- BMDMs may have contributed to unstable atheroma formation. Together, our findings suggest that although lack of GLUT1 blunted glycolysis and the pentose phosphate pathway, MΦ were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated, yet phagocytic defects hindered MΦ function in chronic diseases.


The macrokinetic behavior of an enzymatic system with an enzyme inactivated in the reaction.
This study deals with the behavior of a heterogeneous multisubstrate enzymatic system under enzyme inactivation in a reaction. Electronic computer modeling data have been obtained for its macrokinetics at different modes: (1) under mixed inflow of the substrates and (2) under their spatial separation. The enzymatic membrane exhibits low sensitivity to a change in the external conditions as the substrates are intermixed on the boundary. Quite the contrary, in the case of spatial separation of the substrates, the product flow from the membrane has displayed abrupt fluctuations at different boundary conditions. This work also looks into the arrangement of the reaction zones in the membrane and their transitions under different conditions.


The cellular and humoral immunity assay in patients with complicated urolithiasis.
Especially complicated, renal lithiasis contributes to the general inflammatory syndrome development that interferes with nonspecific, humoral and cellular immune system. The surgical treatment of nephrolithiasis is closely related to drug therapy of urinary infection, one of the reasons being the reduction of the immune status. The work is performed by evaluating the immunological status preoperatively in 58 patients with complicated lithiasis. The analysis of the status in these patients demonstrated that complicated urolithiasis results in significant changes in the immune system, these changes being expressed at the cellular and humoral level of immunity.


Evaluation of Gingival Health Status among 6- and 12-years-old Children in Dhamar City, Yemen: A Cross-sectional Study.
Epidemiological data on gingivitis in children are important for understanding the natural course of the disease, identifying its risk factors, and predicting its time trends. The objective of this study was to evaluate the prevalence and severity of gingivitis among 6- and 12-year-old school children in Dhamar city, Yemen. A total of 663 children (310 children of 6 years old and 353 children of 12 years old) were examined from 10 public primary schools. Gingival health status was assessed using the plaque index (PI), calculus index (CI), and gingival index (GI) on the six Ramfjord teeth. The latter index was used to categorize gingivitis severity at the subject level. Data were analyzed using independent f-test, chi-squared test, and Spearman's correlation. A p-value of < 0.05 was considered significant. Both age groups had high mean of PI and GI with nonsignificant difference. The 12-year-old children had calculus deposits much higher than the 6-year-old group with significant difference. There was a significant correlation between age and gender of the whole sample with CI [(odds ratio, OR = 1.65, p = 0.003) and (OR = 0.74, p = 0.05) respectively]. Most of the participants presented with gingival inflammation, which was less in 12-year-old females. Poor oral hygiene and mild gingivitis were highly prevalent among Yemeni school children. The early assessment and intervention of gingivitis and periodontitis will minimize the chance of tooth loss. It has been reported that marginal gingivitis begins early in childhood, increases in prevalence and severity at puberty, and then subsides slightly to the remainder of the second decade of life.


Minimizing treatment planning errors in proton therapy using failure mode and effects analysis.
Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy.


Alginate/poly(amidoamine) injectable hybrid hydrogel for cell delivery.
A covalently cross-linked injectable hybrid hydrogel, namely, alginate/poly(amidoamine) (PAMAM), with the objective of cell delivery was innovatively designed and synthesized using tetra-amino-functional PAMAM dendrimer as the cross-linker. With the increase in percentage of PAMAM cross-linker, the pore size and swelling ratio of hydrogels were in the range of 57 ± 18 μm to 88 ± 25 μm and 110 ± 16 to 157 ± 20, respectively. The study of attachment and proliferation of MC3T3-E1 pre-osteoblasts using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay through indirect and direct contact methods indicated a continuous increase in metabolically active live cells with time, implying non-cytotoxicity of the synthesized hydrogel. The live-dead assay showed >95% of live cells for alginate/PAMAM hydrogels, suggesting viability of the encapsulated cells. When the percentage of PAMAM cross-linker in alginate/PAMAM hydrogel was increased from 5 to 25, the percentage degradation rate decreased from 1.1 to 0.29%/day. Given that the poly(ethylene glycol) is commonly used cross-linker for hydrogel syntheses, we compared the behavior with poly(ethylene glycol). The incorporation of poly(ethylene glycol) in alginate/PAMAM hydrogel reduced the activity of MC3T3-E1 cells and their viability compared to the alginate/PAMAM hydrogels. The protonation of amino groups in alginate/PAMAM injectables under physiological conditions led to the formation of cationic hydrogels. These cationic hydrogels showed enhanced cell encapsulation and attachment ability because of electrostatic interaction with negatively charged cell surface as determined by cell adhesion and extensions from scanning electron microscope and vinculin assay and ability of in situ calcium phosphate mineralization. These observations point toward the potential use as an injectable scaffold for cell delivery and tissue engineering applications.


Persistent ductus venosus without portal hypertension in a young alcoholic man.
The discovery of a large patent ductus venosus resulted from radiological investigations in a 34-year-old man, a chronic alcoholic of low mental status. Splenoportal and inferior caval venograms were performed because of recent exacerbation of the neurological symptoms and electroencephalographic criteria of portacaval encephalopathy. Portal pressure was 8 mm Hg. A liver scan, a laparoscopy, and a liver biopsy were performed. They showed that the gland was atrophic with a microscopic appearance of alcoholic fibrosis, but without any nodular regeneration. The relationship between the fistula, the mental state, and the atrophic liver is discussed. Such a malformation appears to be very uncommon.


Parenteral feeding in a patient with hypertriglyceridemia and increased liver enzyme levels.
To discuss nutritional support in a patient with hypertriglyceridemia and liver dysfunction. We describe the hospital course of a critically ill patient with hepatic dysfunction and hypertriglyceridemia who required nutritional support, and we provide an overview of lipid metabolism. A 27-year-old man with hepatic dysfunction and hypertriglyceridemia, who had undergone kidney transplantation 4 months previously, was admitted to the intensive-care unit with upper gastrointestinal bleeding. He was unable to tolerate enteral feeding, and central parenteral nutrition was initiated. Calories from dextrose and fat were limited because of the presence of increased liver enzyme levels and hypertriglyceridemia. A modified regimen of parenteral nutrition was developed for the patient. The short-term reduction of total calories to 75% of the predicted need is safe. Nutritional support in patients with liver dysfunction and hypertriglyceridemia is complicated and may require temporary underfeeding because of the need to limit fat and dextrose intake.


Clinical review: Controversies regarding transdermal androgen therapy in postmenopausal women.
Recently, the field of androgen therapy in postmenopausal women has received much attention and press. Although the ovary ceases to produce follicles and estrogen at menopause, it continues to produce androgens. Hence, many oophorectomized women complain of sexual dysfunction (despite adequate estrogenization). Previous studies of nontransdermal testosterone replacement have shown an improvement in libido and sexual frequency, although at the cost of supraphysiological testosterone levels. Transdermal testosterone patch (Intrinsa) was developed to deliver a physiological amount of testosterone. In 2004, the Food and Drug Administration voted not to approve Intrinsa until long-term safety data are available. Recent trials of Intrinsa in postmenopausal women were included. A MEDLINE search was conducted for articles published over the last 40 yr based on the key words androgen therapy/replacement and postmenopausal women. Relevant placebo-controlled trials of nontransdermal androgen therapy in postmenopausal women were also reviewed. Early results from industry-funded trials show that transdermal testosterone therapy results in only moderate (although statistically significant) improvement in libido in surgically menopausal women (on estrogen). However, the published data are of short duration (24 wk). Hence, long-term safety in these women remains unclear. We recommend a short-term trial (not to exceed 24 wk) of transdermal testosterone therapy (once approved) in surgically menopausal (estrogenized) women with distressful sexual dysfunction. Until the patch gets approval, a short trial of oral methyltestosterone in deserving estrogenized women may be justified.


hucMSC Conditioned Medium Ameliorate Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Oxidative Stress and Inflammation via Nrf2/NF-κB Signaling Pathway.
Acute lung injury (ALI) is a common clinical syndrome in the cardiac intensive care unit with a high mortality rate. Inflammation and oxidative stress have been reported to play a crucial role in the development of ALI. Previous studies have shown that human umbilical cord mesenchymal stem cells (hucMSCs) have anti-inflammatory and antioxidative effects in various diseases. However, the anti-inflammatory and antioxidative effects of the hucMSC conditioned medium (CM) on LPS-induced ALI remain unclear. Therefore, in this study, we assessed whether the hucMSC conditioned medium could attenuate LPS-induced ALI and the underlying mechanisms. Mice were randomly divided into four groups: the control group, PBS group, LPS+PBS group, and LPS+CM group. The lung histopathology and bronchoalveolar lavage fluid (BALF) were analyzed after intervention. The Nrf2/NF-κB signaling pathway and its downstream target genes were tested, and the cytokines and growth factors in CM were also measured. The results showed that CM significantly attenuated the histological alterations; decreased the wet/dry weight ratio; reduced the levels of MPO, MDA and ROS; increased SOD and GSH activity; and downregulated the level of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. Furthermore, CM promoted the expression of Nrf2 and its target genes NQ01, HO-1, and GCLC and inhibited the expression of NF-κB and its target genes IL-6, IL-1β, and TNF-α. These effects may be closely related to the large amounts of cytokines and growth factors in the CM. In conclusion, our results demonstrated that CM could attenuate LPS-induced ALI, probably due to inhibition of inflammation and oxidative stress via the Nrf2/NF-κB signaling pathway.


Evaluating non-technical skills and mission essential competencies of pilots in military aviation environments.
To develop and validate a classification of non-technical skills (NTS) in military aviation, a study was conducted, using data from real operations of F16 aircraft formations. Phase 1 developed a NTS classification based on the literature review (e.g. NOTECHS) and a workshop with pilots. The Non-TEChnical-MILitary-Skills (NOTEMILS) scheme was tested in Phase 2 in a series of Principal Component Analysis with data from After-Action-Review sessions (i.e. 900 records from a wide range of operations). The NTS were found to make a good prediction of Mission Essential Components (R2 > 0.80) above the effect of experience. Phase 3 undertook a reliability analysis where three raters assessed the NOTEMILS scheme with good results (i.e. all rwg > 0.80). To look into the consistency of classifications, another test indicated that, at least, two out of three raters were in agreement in over 70% of the assessed flight segments. Practitioner Summary: A classification scheme of Non-Technical Skills (NTS) was developed and tested for reliability in military aviation operations. The NTS scheme is a valuable tool for assessing individual and team skills of F-16 pilots in combat. It is noteworthy that the tool had a good capability of predicting Mission Essential Competencies.


Bacteremia as a cause of fever in ambulatory, HIV-infected Mozambican adults: results and policy implications from a prospective observational study.
Fever is typically treated empirically in rural Mozambique. We examined the distribution and antimicrobial susceptibility patterns of bacterial pathogens isolated from blood-culture specimens, and clinical characteristics of ambulatory HIV-infected febrile patients with and without bacteremia. This analysis was nested within a larger prospective observational study to evaluate the performance of new Mozambican guidelines for fever and anemia in HIV-infected adults (clinical trial registration NCT01681914, www.clinicaltrials.gov); the guidelines were designed to be used by non-physician clinicians who attended ambulatory HIV-infected patients in very resource-constrained peripheral health units. In 2012 (April-September), we recruited 258 HIV-infected adults with documented fever or history of recent fever in three sites within Zambézia Province, Mozambique. Although febrile patients were routinely tested for malaria, blood culture capacity was unavailable in Zambézia prior to study initiation. We confirmed bacteremia in 39 (15.1%) of 258 patients. The predominant organisms were non-typhoid Salmonella, nearly all resistant to multiple first-line antibiotics (ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole). Features most associated with bacteremia included higher temperature, lower CD4+ T-lymphocyte count, lower hemoglobin, and headache. Introduction of blood cultures allowed us to: 1) confirm bacteremia in a substantial proportion of patients; 2) tailor specific antimicrobial therapy for confirmed bacteremia based on known susceptibilities; 3) make informed choices of presumptive antibiotics for patients with suspected bacteremia; and 4) construct a preliminary clinical profile to help clinicians determine who would most likely benefit from presumptive bacteremia treatment. Our findings demonstrate that in resource-limited settings, there is urgent need to expand local microbiologic capacity to better identify and treat cases of bacteremia in HIV-infected and other patients, and to support surveillance. Data on the prevalence and susceptibility patterns of important pathogens can guide national formulary and prescribing practices.


An Electrical Storm Is Coming!: Ventricular Storm Case Study.
A 65-year-old man presented to the emergency department (ED) for evaluation of epigastric and chest pain. On presentation, a 12-lead electrocardiogram revealed a patient in rapid atrial fibrillation (AFib) with anteroseptal myocardial infarction. Treatment of ST-elevation myocardial infarction (STEMI) and rapid AFib were initiated, and the patient was flown to a regional percutaneous coronary intervention center. Two weeks later, the patient presented to the same ED with a LifeVest external defibrillator (Zoll Medical, Chelmsford, MA). The patient received electrical shock in excess of 10 times from the LifeVest prior to ED arrival where he promptly developed ventricular tachycardia (VT). After cardioversion, the VT storm persisted and required multiple cardioversions, resuscitation, intubation, and transfer back to a tertiary cardiac center for electrophysiology studies and internal cardiac defibrillator placement. This case explores the course of a patient's anteroseptal infarction, utilization and description of the LifeVest external defibrillator, and the subsequent visit to the ED in VT storm. It provides insight into the team approach, decision-making process, and managing a complex medical illness. Furthermore, it helps identify methods for emergency providers to improve their approach in both complex and rare cases.


Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data.
DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events. The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis. The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed. This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.


Biomarkers of response to preoperative chemoradiation in esophageal cancers.
To identify a panel of biomarkers that predicts response of esophageal cancers to preoperative chemoradiation, our group profiled the gene expression of pretreatment cancer biopsies from patients with esophageal cancer. Six (32%) of these patients had pathologic complete response. All cancers except one that achieved pathologic complete response (83%) clustered in one molecular type (type I), while cancers that achieved less than pathologic complete response with one exception clustered in another molecular type (type II). Activated NF-kappaB was significantly associated with aggressive pathology. These data indicate that expression analysis of a limited set of biomarkers selected from the list of genes that were differentially regulated between the two subtypes can increase predictive power, and suggest that esophageal cancer with activated NF-kappaB may result in poor treatment outcome.


[Effect of anesthesia on blood coagulation factor XIII].
57 patients who had undergone surgical operations because of varicosis were examined for the influence of the mode of anaesthesia on the plasma levels of factor XIII. Within a randomized study the patients were given by alternate order halothane (NA) (n = 19), neurolept-analgesia (NLA) (n = 19) or peridural anesthesia (PA) (n = 19). Pre- and postoperatively as well as at the 1st, 3rd, 5th, and 7th p.o. day the plasma levels of factor XIII, fibrinogen (factor I) and fibrinogen-degradation-products (FDP) were measured. FDP were not found. The levels of factor XIII remained within the normal range. Fibrinogen showed an identical course: the postoperative findings were lower than the initial ones. 24 h later the levels were higher. At the 7th p.o. day the most important readings were found. In comparing the three methods of anaesthesia the most obvious differences in the data on factor XIII were in the peridural anesthesia-group, especially on the 3rd p.o. day with significant lower results than in the other groups. The modes of anaesthesia used had no visible influence on the range of factor XIII.


The development of antimicrobial γ-AApeptides.
Host-defense peptides (HDPs) are promising next generation of antibiotic agents, as they have the potential to circumvent emerging drug resistance, due to their mechanism of bacterial killing through disruption of their membranes. Nonetheless, HDPs have intrinsic drawbacks such as low-to-moderate activity, susceptibility to enzymatic degradation. In the past few years, we developed a new class of peptidomimetics named 'γ-AApeptides', which have superior resistance to proteolysis and a variety of diversification via straightforward synthesis. Our recent studies suggested that γ-AApeptides can mimic the bactericidal mechanism of HDPs and show potent and broad-spectrum activity against both Gram-positive and Gram-negative multidrug-resistant bacteria. In this review, we summarize our current studies of antimicrobial γ-AApeptides and discuss their potential future development as antimicrobial peptidomimetics.


Diagnosis of central nervous system lupus.
Central nervous system (CNS) involvement in systemic lupus erythematosus is a major source of patient morbidity and mortality. The recognition of nervous system lupus is hampered by the diagnostic insensitivity and non-specificity of the various testing modalities that are currently available. A review of the effectiveness of diagnostic tests for CNS lupus is presented. Areas of current research in this area are examined. Because of the diversity of neurologic manifestations in this disorder and their complex pathogenesis, no single test is sufficient to establish the diagnosis rapidly and accurately in all cases, now or for the foreseeable future.


Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. A 2017 update.
Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine disease in developed countries. It mainly occurs as sporadic cases (about 90-95% of cases), while only the remaining 5-10% is represented by familial inherited parathyroid disorders due to causative mutations in specific target genes. Clinical variability among the different familial parathyroid syndromes is generally linked to the specific mutated gene and it can predispose subjects to different manifestations of parathyroid pathology, various degrees of PHPT severity, persistence and/or after-surgery recurrences. Genetic tests is helpful in differential diagnosis favouring the recognition of the specific familial PHPT syndrome and, subsequently, in planning the most suitable surgical procedures and/or pharmacological interventions. Moreover, genetic test is important to recognise mutation carriers, within PHPT familial forms, even before the appearance of biochemical and/or clinical symptoms. This review resumes general concepts about genetic diagnosis of PHPT in familial hereditary syndromes, specifically describing why, when, and which genetic screenings should be performed in every specific PHPT-associated parathyroid disease.


Risk factors for increased postoperative drainage of calcaneal fractures after open reduction and internal fixation: An observational study.
Sufficient drainage is very important for preventing wound complications after open reduction and internal fixation (ORIF) of calcaneal fractures. However, the drainage amount varies among patients. The objective of this study was to identify factors associated with increased postoperative drainage after ORIF of calcaneal fractures.A retrospective study including 87 patients with 92 calcaneal fractures in our hospital was performed. Patients were divided into 2 groups based on whether they had increased drainage, which was defined as a total drainage of ≥340 mL (50th percentile). We gathered the following data on each patient: age; sex; smoking history; body mass index (BMI); American Society of Anesthesiologists (ASA) classification; fracture type; the time from injury to surgery; operative time; bone grafting; preoperative labs including prothrombin time (PT), activated partial thromboplastin time (APTT), hematocrit, and D-dimer level; and histories for hypertension, diabetes, and heart disease. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors associated with increased drainage.Total drainage ranged from 105 to 1185 mL, and the average drainage for this cohort was 393.6 ± 232.4 mL (mean ± standard deviation). 57.6% (n = 53) of patients had increased drainage. Smoking history, Sanders type, operative time, and bone grafting were significantly associated with increased drainage on univariate analysis. Multivariate logistic regression analysis then demonstrated that active smoking and higher Sanders type were independent risk factors for increased drainage.Patients with calcaneal fractures who smoked or had a higher level of Sanders type had a higher risk of increased postoperative drainage. Therefore, we suggest that active precautions be taken for these patients to reduce the rate of postoperative wound complications.


Monoclonal and polyclonal antibodies reactive with the 1-32 amino terminal sequence of the alpha subunit of human 32K inhibin.
A monoclonal antibody was made after immunization of mice with the 1-32 amino terminal peptide of the alpha subunit of 32K human ovarian inhibin. The IgG2a mouse antibody reacted 6 times better with bovine 1-32 peptide than it did with 32K bovine inhibin. By contrast sheep polyclonal antibodies made by a similar method had a 29 fold bias in reactivity towards the immunizing peptide. Relative to homologous 1-32 peptide standards, the monoclonal antibody measured apparently higher amounts of immunoreactive material(s) in human (13.5 fold) and bovine (27 fold) follicular fluids than did the polyclonal anti 1-32 peptide antibodies. Immunochemical studies revealed that the epitope recognized by the monoclonal antibody was different from the major epitope recognized by the polyclonal antibodies. The monoclonal antibody reacted much better with human inhibin 1-32 sequences than with bovine (73 fold) or porcine (23 fold). Although the 32K form of human inhibin has not yet been purified, it can be inferred that the monoclonal antibody would be able to detect as little as 2 ng/ml of 32K human inhibin in competitive radioimmunoassays. The antibody must also react with some of the multiple molecular forms of inhibin found in human follicular fluids, and it was shown to function well in the quantitative immunoaffinity extraction of inhibin-like immunoreactivity from follicular fluid. It seems likely that this monoclonal antibody will prove a useful tool for research on human inhibin.


[Myocardial and Arterial Stiffness Important Determinant of NT-ProBNP at Development of Heart Failure in Survivors of Myocardial Infarction].
To study diagnostic value of myocardial-arterial stiffness (MAS) as a determinant of N-terminal pro-brain natriuretic peptide (NT-proBNP) expression in patients with chronic heart failure (CHF) with ischemic or postinfarction left ventricular (LV) dysfunction. We analyzed 6 months prognosis of 54 patients (mean age 61.7+/-8.6 years) with II-III NYHA class CHF divided into 2 groups: (I, n=18) with class II CHF and preserved LV ejection fraction (EF) (55+/-10.4%), (II, n=36) with class III CHF and low LF EF (30.4+/-6.8%). MAS was measured by echocardiography as ratio of arterial elasticity (Ea) and end-systolic elasticity of LV myocardium (Es). Serum NT-proBNP was measured by immunoenzyme assay. During 6 months follow-up one group II patient with initial NT-proBNP level 2020 rg/ml died. NT-proBNP level in group I was significantly lower than in group II (313 and 647 rg/ml, respectively). Ea/Es ratio was significantly higher (p=0.001) in group II. Multifactorial analysis demonstrated moderate correlation of NT-proBNP with Ea/Es ratio (r=0.50, p=0.0001) and negative correlation with LVEF (r=-0.45, =0.003) among patients with II-III class CHF. As correlation between symptoms and severity of clinical manifestations of ischemic or postinfarction cardiac dysfunction at development of CHF was not high it appears rational to consider MAS estimated by Ea/Es ratio as independent predictor of cardiovascular complications. Sufficiently close correlation between NT-proBNP and Ea/Es ratio allows to improve stratification of risk and to assess objectively prognosis of the disease using easier obtainable parameter Ea/Es in cases when possibility to measure NT-proBNP is not available.


Integration and expression of provirus in human cells transformed by avian sarcoma virus.
Previously, human diploid fibroblasts from some donors infected in vitro by avian sarcoma virus (ASV) were transformed and found, by electron microscopy, to produce small numbers of virus particles that were infectious by bioassay; also, a line of human osteosarcoma cells infected with ASV developed additional characteristics of transformation and released a small number of infectious virus particles. In this study the complete proviral sequence was shown to be integrated in the genome of these cells. The env-related proteins gp85 and gp37 and the gag-related proteins pr76, pr60, and p19 can be detected in cytoplasmic extracts of ASV-infected human cells. Comparable amounts of pp60v-src were found in human and avian cells infected with ASV. The associated kinase activity in infected human cells was dramatically increased as compared to that of uninfected controls; the enzyme had the same cation and substrate requirements as those from ASV-transformed avian cells. Replicating particles from infected human cells were purified and were significantly modified compared to those from avian hosts as shown by a) higher specific gravity, b) the presence of RSV gag-related but not env-related antigens, and c) the fact that the virus-associated reverse transcriptase preferred the divalent cations Mn2+ and Fe2+ over Mg2+.


Radiographic Assessment of Dental Maturation in Children With Dental Agenesis.
Dental agenesis is the most common developmental anomaly in humans, frequently associated with disorders in dental development and maturation. The purpose of this study is to determine radiographic variations in dental maturation in a group of Venezuelan children with dental agenesis. 1,188 panoramic radiographs, from healthy patients ages 5 to 12 years old were studied for agenesis of permanent teeth. Dental maturation was assessed by relative eruption and dental age according to Nolla, comparing children affected with dental agenesis to a stratified control group selected from the same population, excluding children with premature loss of primary teeth in the left quadrants and unclear radiographs. Descriptive analysis, and differences between means and medians (Student t test, Kruskall-Wallis p=0.05) were performed. Medians for Nolla stages were similar between groups, with delay in tooth formation in the agenesis group for second molars (p<0.05) and maxillary lateral incisors and second premolars. Dental age was significantly underestimated for both groups, -0.89 (±0.78) for the control group and -1.20 (±0.95) for the study group. Tooth eruption was similar between groups. Dental age was significantly delayed in Venezuelan children with dental agenesis, with variable significance for tooth formation of studied teeth.


Chronic low-dose L-NAME treatment increases nitric oxide production and vasorelaxation in normotensive rats.
N(G)-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112+/-3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickness/diameter ratio of the aorta and the femoral artery of L-NAME-treated rats. NO synthase activity (determined by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline) was not altered in the hypothalamus of L-NAME-treated rats. Interestingly, chronic low-dose L-NAME treatment significantly elevated NO synthase activity in the left ventricle and aorta, increased endothelium-dependent acetylcholine-induced vasorelaxation and reduced serotonin-induced vasoconstriction of the femoral artery. The data suggest that chronic low-dose L-NAME treatment can increase NO production and vasorelaxation in normotensive rats without negative structural changes in the cardiovascular system.


Study of conjunctival flora in patients after peripheral blood stem cell transplantation and its correlation with tear secretion.
Dry eye is a major ocular complication of peripheral blood stem cell transplantation (PBSCT) and may predispose bacterial colonization to the conjunctiva. To investigate the conjunctival bacterial flora in patients receiving PBSCT, we encompassed patients who received PBSCT at least 1 year from 2002 to 2008 in this cross-sectional study. Patients were divided into three groups in accordance to the result of the Schirmer Ia test. In the control group, we enrolled dry-eye patients with underlying disease other than hematopoietic stem cell transplantation of which the age range was similar to the study group. Thirty-six patients with 72 eyes were included in our study. The culture rates were 22% (8 in 36) in the first group (Schirmer Ia= 0-5 mm), 20% (4 in 20) in the second group (Schirmer Ia= 6-9 mm), and 0% (n=16) in the third group (Schirmer Ia ≥ 10 mm). The flora in patients receiving PBSCT were coagulase-negative Staphylococci, Staphylococcus aureus and Corynebacterium sp. The bacterial colonization rate in the post-PBSCT group was not higher than the control group (22.2% vs. 30.8% ), and coagulase-negative Staphylococci was the most common flora in the control group. In conclusion, despite not having statistical significance, there seems to be a positive correlation between the colonization rate and the severity of dry eye. However, bacterial profile isolated in post-PBSCT patients is not significantly different from other dry eye patients.


Surface detail reproduction and dimensional accuracy of molds: influence of disinfectant solutions and elastomeric impression materials.
This study compared the surface detail reproduction and dimensional accuracy of molds after disinfection using 2% sodium hypochlorite, 2% chlorhexidine digluconate or 0.2% peracetic acid to those of molds that were not disinfected, for four elastomeric impression materials: polysulfide (Light Bodied Permlastic), polyether (Impregum Soft), polydimethylsiloxane (Oranwash L) andpolyvinylsiloxane (Aquasil Ultra LV). The molds were prepared on a matrix by applying pressure, using a perforated metal tray. The molds were removed following polymerization and either disinfected (by soaking in one of the solutions for 15 minutes) or not disinfected. The samples were thus divided into 16 groups (n=5). Surface detail reproduction and dimensional accuracy were evaluated using optical microscopy to assess the 20-μm line over its entire 25 mm length. The dimensional accuracy results (%) were subjected to analysis of variance (ANOVA) and the means were compared by Tukey's test (a=5%). The 20-μm line was completely reproduced by all elastomeric impression materials, regardless of disinfection procedure. There was no significant difference between the control group and molds disinfected with peracetic acid for the elastomeric materials Impregum Soft (polyether) and Aquasil Ultra LV (polyvinylsiloxane). The high-level disinfectant peracetic acid would be the choice material for disinfection.


Theories behind the effect of starch‑ and sucrose‑reduced diets on gastrointestinal symptoms in irritable bowel syndrome (Review).
Increased amounts of starch and sugar have been added to the diet in the Western world during the last decades. Undigested carbohydrates lead to bacterial fermentation and gas production with diffusion of water, causing abdominal bloating, pain and diarrhea. Therefore, dietary advice is the first line of treatment of irritable bowel syndrome (IBS), a disease characterized by abdominal pain and altered bowel habits without any organic findings. Recently, a diet with a reduction of starch and sucrose led to a marked effect on gastrointestinal (GI) symptoms. The mechanism is unknown, but three possible mechanisms are presented in the present review. First, functional variants of the enzyme sucrase‑isomaltase (SI) have been described in IBS. A subgroup of patients with IBS may thus suffer from partial SI deficiency with reduced digestion of starch and sucrose. Second, fructose absorption is less efficient than glucose absorption, which may lead to a physiological fructose malabsorption when ingesting high amounts of sucrose. A third mechanism is that high‑sugar diets causing hyperglycemia, hyperinsulinemia and weight gain have led to painful neuropathy in animal models; whereas, improved metabolic control in humans has led to improvement of neuropathy. Starch‑ and sucrose‑reduced diets lead to decreased levels of C‑peptide, insulin, gastric inhibitory peptide, leptin and weight reduction. These metabolic changes may reduce the excitability of the hypersensitive nervous system often found in IBS and, thereby, lead to the reduced symptoms found after the diet. In conclusion, further studies are needed to investigate the pathophysiology behind development of symptoms after starch and sucrose intake, and the mechanisms behind symptom relief after reduced intake.


[Prepared evening primrose oil microspheres by spray drying].
To explore the best technique parameters on preparing evening primrose oil microspheres by spray drying technique. GC and internal standard method were used to determine the content of gamma-linolenic acid methyl esters, the technological parameters were investigated by orthogonal experimental design with the yield and entrapment rate as indexes. The charging rate as 3 mL x min(-1), atomizing pressure as 100 kPa and the temperature of inlet as 105 degrees C were the best technique parameters. Evening primrose oil microspheres accorded with the expecting demand. The main influencing factor is the charging rate. Spray drying is reasonable and practical for preparing evening primrose oil microspheres.


Outcome and toxicity of ifosfamide, carboplatin, and etoposide versus gemcitabine and vinorelbine regimen for pediatric patients with relapsed or refractory Hodgkin's lymphoma.
Pediatric classical Hodgkin lymphoma (CHL) is a curable disease; however, the optimal salvage regimen is unclear for relapsed/refractory (R/R) disease. This study aimed to compare response rates, toxicity, event-free survival (EFS), and overall survival (OS) of ifosfamide, carboplatin, and etoposide (ICE) with gemcitabine and vinorelbine (GV) regimen after first-line doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in pediatric patients with R/R CHL. This is a retrospective cohort study of 132 pediatric patients with R/R CHL treated from July 2012 to December 2020 with ICE (n = 82) or GV (n = 50). The median age at relapse was 13.9 years, and 68.2% were men. Rates of complete response, partial response, and progressive disease before consolidation were 50.6%, 3.7%, and 45.7% for ICE and 28.5%, 0%, and 71.5% for GV (P = 0.011). By multivariate analysis, regimen (P = 0.002), time to relapse (P = 0.0001), and B-symptoms (P = 0.002) were independent factors to lower response rates. Hematological toxicity, electrolyte disturbance, hemorrhagic cystitis, infectious complications, and hospital admission for fever neutropenia were statistically significant higher for the ICE regimen. Treatment-related mortalities were 2.4% for ICE and 2% for GV (P = 0.86). The 3-year EFS was 39.3% ± 11.4% for ICE and 24.9% ± 12.5% for GV (P = 0.0001), while 3-year OS was 69.3% ± 10.6% and 74% ± 12.9% (P = 0.3), respectively. By multivariate analysis, regimen (P = 0.0001), time to relapse (P = 0.011), B-symptoms (P = 0.001), and leukocytosis (P = 0.007) were significant for EFS, while anemia (P = 0.008), and progressive disease on early response evaluation (P = 0.022) were significant for OS. The ICE regimen had a better overall response rate and EFS, but higher toxicity, than GV; however, OS and mortality were similar.


Disposition kinetics of ethambutol in nephrectomized dogs.
The effect of nephrectomy on the disposition of ethambutol was investigated in seven adult mongrel dogs: five were nephrectomized and two served as the control. Each dog was intravenously administered 500 mg ethambutol, followed by blood sample collection for 12 h. Total urine was collected over 24 h from the normal control dogs. Ethambutol contents in plasma and urine were assayed by a GC method. The nephrectomized group and the control group exhibited differences in the following pharmacokinetic parameters: half-life, 5.0 versus 4.1 h (significant at p less than 0.1); total body clearance, 8.4 versus 13.2 mL/min/kg (significant at p less than 0.1); and volume of distribution, 2.7 versus 3.8 L/kg (significant at p less than 0.1). Comparison of pharmacokinetic parameters among rabbits, dogs, and humans revealed distinct interspecies differences with regard to total body clearance, renal clearance, volume of distribution, and fractional renal excretion. One comparable parameter shared by all species is the beta-phase half-life.


Purification and characterization of a prothrombin activator from the venom of the Australian brown snake, Pseudonaja textilis textilis.
A simple procedure, involving chromatography on concanavalin A-Sepharose and gel filtration, has been developed for the purification of a prothrombin activator from the venom of the Australian brown snake Pseudonaja textilis textilis. The prothrombin activator, which is a major venom component, is a high molecular weight protein (Mr greater than or equal to 200,000) which yields a number of subunits when examined by SDS-PAGE. It is related antigenically to the venom prothrombin activator of the taipan Oxyuranus scutellatus. P. textilis prothrombin activator is able to coagulate citrated plasma, warfarin plasma, and Factor V- and Factor X-deficient plasmas; to convert purified human prothrombin to thrombin; and to hydrolyse the peptide p-nitroanilide substrate S-2222. Calcium ions and phospholipids had little if any effect on the rates of coagulation of citrated plasma or S-2222 hydrolysis catalysed by this enzyme.


The prevalence and prognostic effect of hyponatremia in children with COVID-19 pneumonia: a retrospective study.
The aim of the study was to examine the effect of hyponatremia at admission as a negative prognostic factor in children hospitalized with COVID-19 pneumonia. The data of patients aged 1 month-18 years, who were followed with the diagnosis of pneumonia at Çanakkale Onsekiz Mart University Hospital, Department of Pediatrics, between January 2018 and May 2021 were examined, retrospectively. Patients (n=661) were divided into two main groups; COVID-19 pneumonia (n=158) and the other pneumonias [other viral pneumonia (n=161) and pneumonia of unknown etiology (n=342)]. Six hundred and twenty-three patients with a median (Q1-Q3) age of 4 (1.5-8) years, 59.4% of whom were male were included in the study. The overall prevalence of hyponatremia at admission was 11.2% and was lower in those with COVID-19 pneumonia than in those with other viral pneumonia (6.4% vs. 15.2%, p=0.013). When evaluated irrespective of their COVID-19 status, hyponatremic patients had a higher supplemental oxygen requirement (OR 2.5 [1.4-4.3], p < 0.001), higher need for intensive care unit (ICU) admission (OR 3.7 [1.3-10.2], p=0.009) and longer duration of hospitalization (p=0.016) than the normonatremic patients. In patients with COVID-19 pneumonia, being hyponatremic had no effect on supplemental oxygen requirements or the duration of hospitalization. When hyponatremic patients were evaluated, the supplemental oxygen requirements and duration of hospitalization of those with COVID-19 pneumonia were similar to the other pneumonias (p > 0.05 for all comparisons). However, normonatremic COVID-19 pneumonias had higher supplemental oxygen requirements than other viral pneumonias and pneumonia of unknown etiology (OR 4.7 [2.2-10.3], p < 0.001; OR 1.6 [1 -2.7], p=0.043, respectively). This study found that hyponatremia at admission is rarer in children with COVID-19 pneumonia than other viral pneumonias and has no effect on supplemental oxygen requirements or the duration of hospitalization.


Endogenous testosterone and endothelial function in postmenopausal women.
It is well known that coronary heart disease incidence increases in women after menopause. This phenomenon was related to reduced levels of female sex hormones. Estrogen decline, however, is not the only hormonal change during the postmenopausal period and estrogen administration did not protect women from cardiovascular disease. Therefore, it is justified to explore other hormonal changes. The role of androgens is still controversial. The aim of the present study was to investigate the relationship between endogenous sex hormones and endothelial function, measuring the brachial artery flow-mediated dilation. Sixty postmenopausal women were consecutively enrolled and underwent a clinical and biochemical examination. Brachial artery flow-mediated dilation was also evaluated by ultrasound. After correction for confounding variables, testosterone was positively correlated to flow-mediated dilation (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow-mediated dilation smaller than that in the highest tertile (P=0.02). This result could suggest that the development of cardiovascular disease after menopause is due not only to estrogen decline but also to androgen decline. More studies are needed to evaluate the role of androgen replacement therapy on postmenopausal women with low level of this hormone.


Applying Social Cognitive Theory in Predicting Physical Activity Among Chinese Adolescents: A Cross-Sectional Study With Multigroup Structural Equation Model.
This cross-sectional study aimed to assess the applicability of social cognitive determinants among the Chinese adolescents and examine whether the predictability of the social cognitive theory (SCT) model on physical activity (PA) differs across gender (boys and girls) and urbanization (urban and suburban). A total of 3,000 Chinese adolescents ranging between the ages of 12-15 years were randomly selected to complete a set of questionnaires. Structural equation modeling (SEM) was applied to investigate the relationships between social cognitive variables and PA in the urbanization and gender subgroups. The overall model explained 38.9% of the variance in PA. Fit indices indicated that the structural model of SCT was good: root mean square error of approximation (RMSEA) = 0.047, (root mean square residual) RMR = 0.028, goodness of fit index (GFI) = 0.974, adjusted goodness of fit index (AGFI) = 0.960, Tucker-Lewis coefficient (TLI) = 0.971, and comparative fit index (CFI) = 0.978. Regarding the subgroup analysis, social support (critical ratios [CRs] = 2.118; p < 0.001) had a more substantial impact on the PA of adolescents in suburban areas than that in urban areas, whereas self-regulation (CRs = -2.896, p < 0.001) had a more substantial impact on the PA of adolescents in urban areas than in suburban areas. The results indicate that the SCT model predicts the PA of Chinese adolescents substantially. An SCT model could apply over a range of subgroups to predict the PA behavior and should be considered comprehensively when designing interventions. These findings would benefit PA among the Chinese adolescents, especially across genders and urbanization.


Monitoring of Pb exposure in waterfowl ten years after a mine spill through the use of noninvasive sampling.
Lead exposure in waterfowl was studied using noninvasive fecal sampling in the Guadalquivir Marshes in Spain, an area affected by the 1998 Aznalcóllar mine disaster. Feces of greylag geese (Anser anser, n = 191) and purple gallinule (Porphyrio porphyrio, n = 91) were collected from three different impacted sites (Entremuros, Caracoles and Cerro de los Ánsares) during the winters of 2004 to 2008. Lead and aluminium (an indicator of sediment ingestion) and Pb isotope signatures (to discriminate between sources of Pb exposure) were analyzed in freeze-dried, acid digested samples. The concentrations of fecal porphyrins and biliverdin were determined as noninvasive biomarkers to study Pb exposure effects. Results showed a decrease in Pb exposure over time in wintering greylag geese. In contrast, for purple gallinule resident in the Entremuros a clear trend was not evident. For both species, sediment ingestion appeared to be the main source of exposure to Pb. In the Entremuros, some samples from purple gallinule were detected with higher Pb levels than expected for simple soil ingestion, and these had Pb isotopic profiles compatible with mining sludge or Pb shot. Whilst fecal Pb isotopic profiles were effective in differentiating between samples from sites with different levels and sources of pollution, the combined use of element ratios (such as Pb/Al) and other non-traditional stable isotope signatures may also prove worthwhile. Overall, the fecal Pb levels detected were below those described in feces for waterfowl from other uncontaminated areas(<10 µg/g d.w.). Despite this, for both species fecal Pb levels were positively correlated with porphyrin excretion, and for purple gallinule, with the coproporphyrin III/I ratio, suggesting some subtle effects on heme synthesis in birds. Ten years after the mine spill, Pb contamination in birds by this pollution source was still detectable and subtlethal effects may persist.


The Leishmania major LACK antigen with an immunodominant epitope at amino acids 156 to 173 is not required for early Th2 development in BALB/c mice.
The Leishmania major LACK antigen contains an immunodominant epitope at amino acids 156 to 173 (LACK(156-173)) that is believed to nucleate the pathological Th2 immune response in susceptible BALB/c mice. To test this hypothesis, we generated L. major parasites that express a mutated LACK that fails to activate Vbeta4/Valpha8 T-cell receptor transgenic T cells specific for this epitope. Although mutant parasites attenuated the expansion of endogenous LACK-specific, interleukin-4 (IL-4)-expressing, CD4 T cells compared to wild-type parasites in vivo, the overall frequency of IL-4 and gamma interferon-secreting lymphocytes was similar to that elicited by wild-type L. major. Mutant parasites demonstrated diminished amastigote viability and delayed lesion development in mice, although parasites could be recovered over 200 days after infection. Complementation with a wild-type lack fusion construct partially rescued these defects, indicating a role for endogenous LACK in parasitism. Mice inoculated with mutant parasites were not protected against subsequent infection with wild-type L. major.


Structure of the SPXX motif.
To understand the structure of the DNA-binding SPXX motif, an analysis of Ser1-Pro2-X3-X4 and Thr1-Pro2-X3-X4 structures observed in proteins is presented. About half (43-46%) of the (S or T) PXX sequences fold into a beta-turn of type (I) or one of a few closely related turn structures. The turn structure has either or both of two compatible hydrogen bonds, one between CO of (Ser or Thr) and NH of X4 (a standard beta-turn type), and the other between OH of (Ser or Thr) and NH of X3 (which we name the sigma type). Within the beta-turn of the TPXX sequence, another type of hydrogen bond (which we name the tau type) occurs between OH of Thr and NH of X4 with the frequency of 72%. These observations support a previous proposal that the (S or T) PXX sequences of DNA-binding proteins fold into a compact beta-turn stabilized by a side-chain-main-chain interaction, which may be suitable to fit into the groove of DNA.


A systematic review of training programmes for recruiters to randomised controlled trials.
Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.


Electron correlation driven non-adiabatic relaxation in molecules excited by an ultrashort extreme ultraviolet pulse.
The many-body quantum nature of molecules determines their static and dynamic properties, but remains the main obstacle in their accurate description. Ultrashort extreme ultraviolet pulses offer a means to reveal molecular dynamics at ultrashort timescales. Here, we report the use of time-resolved electron-momentum imaging combined with extreme ultraviolet attosecond pulses to study highly excited organic molecules. We measure relaxation timescales that increase with the state energy. High-level quantum calculations show these dynamics are intrinsic to the time-dependent many-body molecular wavefunction, in which multi-electronic and non-Born-Oppenheimer effects are fully entangled. Hints of coherent vibronic dynamics, which persist despite the molecular complexity and high-energy excitation, are also observed. These results offer opportunities to understand the molecular dynamics of highly excited species involved in radiation damage and astrochemistry, and the role of quantum mechanical effects in these contexts.


Trends in utilization of agro-industrial byproducts for production of bacteriocins and their biopreservative applications.
Bacteriocins are proteinaceous, ribosomally synthesized bio-molecules having major roles in food preservation due to their antimicrobial action against food spoilage microorganisms. These have gained importance in the last decades because of increasing interest in natural products and their applications in the field of biopreservation, pharmaceutical, aquaculture, livestock, etc. Their production is quite expensive which includes the cost of synthetic media and downstream processing of which 30% of the total production cost relies on synthetic media and nutritional supplements used for growth of microorganisms. The low cost agro-industrial by-products, rich in nutritional supplements, can act as a good substitute for high valued synthetic media. This review provides comprehensive information on the use of cost effective, renewable agro-industrial by-products as substrates for the production of bacteriocins and their application in food as biopreservatives.


[Photoreduction of Se (VI) by marine algae-transitional metals-light system].
Seven marine phytoplankton, including five green algae (Tetraselmis levis, Chlorella autotrophica, Dunaliella salina, Nannochloropsis sp. and Tetraselmis subcordiformis), one diatom (Phaeodactylum tricornutum), one red alga (Porphyridium purpureum), and three usual transitional metals (Fe(III), Cu(II), Mn(II)) were used to make up marine phytoplankton-light or transitional metals-light or marine phytoplankton-transitional metals-light system. In such system, Se(VI) could be transformed into Se(IV) by photoreduction. The species transformation of selenium could be photo-induced by redox reaction of transitional metals. The photochemical activity of marine phytoplankton was confirmed for the first time, because marine phytoplankton could adsorb and concentrated of selenium, transitional metals and organic substances (including the exudation of algae, as reducing agent) which redox potentials were changed. The ratios of Se(VI) to Se(IV) were dominated by the species, the concentration of marine phytoplankton and transitional metals, and it could be enhanced through increasing the concentration of marine algae or the combined effect from marine algae and transitional metals. After photoreduction by ternary system, the ratio of Se(VI) to Se(IV) ranges from 1.17 to 2.85, which is close to the actual value in euphotic layer of seawater. The photochemical process that is induced by marine algae and transitional metals dominative the leading effects on the distribution of oxidation states of selenium.


Structural Information for Conjugated Polymers from Optical Modeling.
We use a Frenkel-Holstein model of uncoupled chains in the adiabatic limit to simulate the optical spectra of the conjugated polymer ladder-type poly( p-phenylene) derivative (MeLPPP), which is a planar conjugated polymer with especially low interchain interactions. The theoretical calculations correctly reproduce the vibronic spectra and yield reasonable torsion angles between adjacent phenyl rings. The success of this approach indicates that, in contrast to interchain coupling, the strong electronic coupling along a polymer chain is more appropriately described in the adiabatic limit.


De novo sequencing and analysis of the transcriptome of Panax ginseng in the leaf-expansion period.
Panax ginseng, a traditional Chinese medicine, is used worldwide for its variety of health benefits and its treatment efficacy. However, it is difficult to cultivate due to its vulnerability to environmental stresses. The present study provided the first report, to the best of our knowledge, of transcriptome analysis of ginseng at the leaf‑expansion stage. Using the Illumina sequencing platform, >40,000,000 high‑quality paired‑end reads were obtained and assembled into 100,533 unique sequences. When the sequences were searched against the publicly available National Center for Biotechnology Information protein database using The Basic Local Alignment Search Tool, 61,599 sequences exhibited similarity to known proteins. Functional annotation and classification, including use of the Gene Ontology, Clusters of Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes databases, revealed that the activated genes in ginseng were predominantly ribonuclease‑like storage genes, environmental stress genes, pathogenesis-related genes and other antioxidant genes. A number of candidate genes in environmental stress‑associated pathways were also identified. These novel data provide useful information on the growth and development stages of ginseng, and serve as an important public information platform for further understanding of the molecular mechanisms and functional genomics of ginseng.


Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study.
Dietary fish oil, rich in omega-3 polyunsaturated fatty acids, decreases TNF-alpha, IL-1beta and IL-2 levels, which may benefit renal transplant recipients. To explore this possibility, we studied the effect of fish oil on the incidence of acute rejection, in situ expression of interleukins (TNF-alpha, IL-1beta and IL-2) and renal function after renal transplantation. In a double-blind clinical trial, 86 subjects with no immunological risk randomly received either 6 g/day of fish oil (fish oil group; n=46) or soy oil (control group; n=40) during the first 3 months after transplantation. The mRNA expression of interleukins (TNF-alpha, IL-1beta and IL-2) was determined by RT-PCR using fine-needle aspiration during follow-up (at baseline and the 1st, 2nd and 3rd month after renal transplantation), as well as during acute rejection episodes and after anti-rejection therapy. The glomerular filtration rate was determined at baseline, and at 1 and 3 months post-graft by [(51)Cr]EDTA clearances. The incidence of acute rejection during the first post-transplant year was similar in both groups (44 vs. 47%), as was 1-year graft survival (86 vs. 89%). There were no differences between groups in overall renal expression of interleukins in patients who did not suffer rejections during the study. At rejection episodes, the fish oil group showed a trend toward a lower renal expression of TNF-alpha (3.7+/-6.8 vs. 15+/-18.6 TNF-alpha/actin, ratio of arbitrary optical units; P=0.05). In addition, a trend toward a lower IL-1beta expression after therapy was observed in the fish oil group (49.3+/-54 vs. 84.4+/-59 IL-1beta/actin, ratio of arbitrary optical units; P=0.05). However, the severity of acute rejections (Banff criteria) as well as renal function after anti-rejection treatment were similar in both groups. Finally, a greater reduction in triglyceride levels was observed in the fish oil group compared with the control group (-6.6+/-52.7 vs. 12.7+/-40.2%; P<0.05). Treatment with fish oil during the first 3 months post-transplantation does not influence acute rejection rate and has no beneficial effect on renal function or graft survival.


The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers.
Liver cells from p21(Cip1-/-) mice subjected to partial hepatectomy (PH) progress into DNA synthesis faster than those from wild-type mice. These cells also show a premature induction of cyclin E/cyclin-dependent kinase (CDK) 2 activity. We studied the mechanisms whereby cells lacking p21(Cip1) showed a premature induction of this activity. Whereas the levels of CDK2, cyclin E, and p27(Kip1) were similar in both wild-type and p21(Cip1-/-) mice, those of the activator CDC25A were much higher in p21(Cip1-/-) quiescent and regenerating livers than in wild-type animals. Moreover, p21(Cip1-/-) cells also showed a premature translocation of CDC25A from cytoplasm into the nucleus. The ectopic expression of p21(Cip1) into mice embryo fibroblasts from p21(Cip1-/-) mice decreased the levels of CDC25A and delayed its nuclear translocation. The levels of CDC25A messenger RNA in p21(Cip1-/-) cells were higher than in wild-type cells, suggesting that this increase might be responsible, at least in part, for the high levels of CDC25A protein in these cells. Thus, the results reported here indicate that p21(Cip1) regulates the levels and the intracellular localization of CDC25A. We also found a good correlation between CDC25A nuclear translocation and cyclin E/CDK2 activation. In conclusion, premature translocation of CDC25A to the nucleus might be involved in the advanced induction of cyclin E/CDK2 activity and DNA replication in cells from animals lacking p21(Cip1).


Orbital follicular hyperplasia in common variable immune deficiency syndrome.
Common variable immune deficiency (CVID) is characterized by reduced serum immune globulins and impaired or absent antibody responses. Patients become more susceptible to infections and to lymphoproliferation and granulomatous inflammation. Ophthalmic manifestations of CVID are rare. The authors describe a case of orbital follicular hyperplasia in a 15-year-old girl with CVID syndrome causing proptosis and exposure keratopathy.


Imaging Bronchopulmonary Dysplasia-A Multimodality Update.
Bronchopulmonary dysplasia is the most common form of infantile chronic lung disease and results in significant health-care expenditure. The roles of chest radiography and computed tomography (CT) are well documented but numerous recent advances in imaging technology have paved the way for newer imaging techniques including structural pulmonary assessment via lung magnetic resonance imaging (MRI), functional assessment via ventilation, and perfusion MRI and quantitative imaging techniques using both CT and MRI. New applications for ultrasound have also been suggested. With the increasing array of complex technologies available, it is becoming increasingly important to have a deeper knowledge of the technological advances of the past 5-10 years and particularly the limitations of some newer techniques currently undergoing intense research. This review article aims to cover the most salient advances relevant to BPD imaging, particularly advances within CT technology, postprocessing and quantitative CT; structural MRI assessment, ventilation and perfusion imaging using gas contrast agents and Fourier decomposition techniques and lung ultrasound.


Progress Towards a Therapeutic HIV DNA Vaccine.
Antiretroviral therapy (ART) reduces HIV replication to undetectable levels and prevents AIDS but cannot cure the infection and discontinuing ART results in viral rebound. Therefore, a primary goal of HIV therapeutic vaccine research is to induce potent HIV-specific immunity that could control viremia without ART, a so-called "functional cure" that eliminates the need for lifelong ART. DNA vaccines have several features that make them an attractive modality for an HIV therapeutic vaccine: they are easy to manufacture, induce T-cell and antibody responses without anti-vector immunity, and do not involve ex vivo manipulations of patient cells. This review covers the progress in developing therapeutic HIV DNA vaccines, emphasizing delivery innovations to enhance vaccine immunogenicity. A central theme is a transition from needle injection delivery to the muscle toward using more sophisticated devices to target the skin and/or increasing transfection efficiency. There are multiple barriers to an effective therapeutic HIV DNA vaccine. While variables such as delivery, adjuvants, and immunogen design have been extensively explored, combining DNA vaccines with complementary approaches is underdeveloped. Complementary approaches include co-administration with latency reversal agents, immune checkpoint blockade, and targeting conserved fitness-constrained portions of the virus.


Patient profile card used in clinical pharmacy services.
The patient profile card used in the provision of clinical pharmacy services at the University of Iowa Hospitals and Clinics is discussed. The desirable aspects of the profile card are its (1) completeness, (2) flexibility, (3) portability and (4) documentation of service. Its current applications and possible additional applications in patient monitoring are described.


Effects of dietary calcium intake on body weight and prevalence of osteoporosis in early postmenopausal women.
High calcium intakes seem to be ineffective at reducing bone loss in early postmenopausal women. However, the inverse relation between calcium intake and body weight can attenuate the negative effect of a low dietary calcium intake. The objective was to assess the role of dietary calcium and body mass index (BMI) on osteoporosis, defined according to World Health Organization criteria as a lumbar bone density >2.5 SD below the T score. This was a cross-sectional, retrospective, observational study conducted in 1771 healthy, early postmenopausal women, who were not taking calcium supplements at the first densitometric evaluation. Weekly frequency of dairy food consumption was used to estimate the relative intake of dietary calcium. Total dairy intake was classified into 4 categories by quartile cutoffs. Multiple logistic regression analyses were used to study this sample. BMI and prevalence of overweight showed significant inverse trends with increasing dairy intake. Calcium intake was not associated with osteoporosis when overweight was not considered. However, when overweight was considered in the analysis, women with the lowest calcium intake were more likely to have osteoporosis (odds ratio: 1.46; 95% CI: 1.12, 1.89; P = 0.008) than were women with the highest calcium intake. In early postmenopausal women, a low dietary calcium intake may increase the risk of osteoporosis, but its negative effect can be offset by the greater BMI found in women with a low calcium intake.


Protection of chicks against Salmonella infantis infection induced by strict anaerobically cultured intestinal microflora.
In two experiments newly hatched broilers were orally inoculated either with intestinal microfloras cultured under different conditions or with a suspension of intestinal homogenate and challenged with high doses (3 X 10(5) c.f.u. per chick) of Salmonella infantis organisms. Inocula were prepared from intestinal material of mature SPF WL hens under aerobic or strictly anaerobic conditions (less than 5 ppm oxygen), and protected against atmospheric oxygen during storage. A very significant reduction of the number of Salmonella infantis bacteria in caecal content was achieved one and two weeks after challenge in those groups of chicks which were inoculated with anaerobically cultured flora or with intestinal homogenate. In order to induce protection, obligate anaerobes had to be accompanied by facultative anaerobes. Amprolium or Monensin dit not interfere with protection. Protection induced by intestinal microflora depends on anaerobiosis during preparation, culturing, storage, and application of the protective bacteria. Starvation on the first day of life appeared to have a negative effect on protection.


A genome scan for selection signatures comparing farmed Atlantic salmon with two wild populations: Testing colocalization among outlier markers, candidate genes, and quantitative trait loci for production traits.
Comparative genome scans can be used to identify chromosome regions, but not traits, that are putatively under selection. Identification of targeted traits may be more likely in recently domesticated populations under strong artificial selection for increased production. We used a North American Atlantic salmon 6K SNP dataset to locate genome regions of an aquaculture strain (Saint John River) that were highly diverged from that of its putative wild founder population (Tobique River). First, admixed individuals with partial European ancestry were detected using STRUCTURE and removed from the dataset. Outlier loci were then identified as those showing extreme differentiation between the aquaculture population and the founder population. All Arlequin methods identified an overlapping subset of 17 outlier loci, three of which were also identified by BayeScan. Many outlier loci were near candidate genes and some were near published quantitative trait loci (QTLs) for growth, appetite, maturity, or disease resistance. Parallel comparisons using a wild, nonfounder population (Stewiacke River) yielded only one overlapping outlier locus as well as a known maturity QTL. We conclude that genome scans comparing a recently domesticated strain with its wild founder population can facilitate identification of candidate genes for traits known to have been under strong artificial selection.


School-based health clinics: three years of experience.
In the last three years, comprehensive school-based clinics have proliferated throughout the United States: There are currently 138 clinics in 30 states and the District of Columbia, and at least 65 more are in the planning stage. Clinic programs differ widely in their organizational structure, operating costs, range of services and funding sources. Although some clinics are funded by private foundations, increasingly, programs are being initiated by local public health departments supported by state funds. Only 10-25 percent of all clinic visits are for family planning services. While all of the clinics provide counseling on family planning, most of the state-funded clinics either prohibit the use of funds for contraceptive supplies and abortion referral or allow grantees to decide what to do about the issue of pregnancy prevention. To date, no study has found that rates of sexual activity increase among students who participate in clinic programs. There is some evidence indicating that participation in school-based clinics may have a positive impact on contraceptive practice.