Evaluation of Effectiveness of a Toothpaste Containing Tea Tree Oil and Ethanolic Extract of Propolis on the Improvement of Oral Health in Patients Using Removable Partial Dentures.
The aim of this study was to evaluate the effect of toothpaste containing natural tea tree essential oil (TTO) and ethanolic extract of propolis (EEP), on microflora and selected indicators of oral health in patients using removable acrylic partial dentures. Fifty patients with varying conditions of hygiene were divided into two groups. The study group received the toothpaste with TTO and EEP, while the control group received the same toothpaste but without TTO and EEP. At the first visit, oral hygiene and hygiene of the prostheses were carried out. Control visits took place 7 and 28 days later and compared to baseline. Indexes like API (Approximal Plaque Index), mSBI (modified Sulcus Bleeding Index), OHI-s (simplified Oral Hygiene Index), and DPI (Denture Plaque Index) were assessed in three subsequent stages, and swabs were collected from floor of the mouth area to assess the microbiota. After 7 and 28 days of using the toothpaste with TTO and EEP, a statistically significant decrease of the examined indicator values were observed in the study group as compared to the values upon the initial visit. The number of isolated strains of microorganisms in the study group was decreased or maintained at the same level, whereas in the control group an increase in the number of isolated strains was observed. The observed stabilization of oral microbiota in patients from the study group confirms the beneficial activity of toothpaste containing EEP and TTO compared to the control group.


Investigating the predictive validity of implicit and explicit measures of motivation on condom use, physical activity and healthy eating.
The literature on health-related behaviours and motivation is replete with research involving explicit processes and their relations with intentions and behaviour. Recently, interest has been focused on the impact of implicit processes and measures on health-related behaviours. Dual-systems models have been proposed to provide a framework for understanding the effects of explicit or deliberative and implicit or impulsive processes on health behaviours. Informed by a dual-systems approach and self-determination theory, the aim of this study was to test the effects of implicit and explicit motivation on three health-related behaviours in a sample of undergraduate students (N = 162). Implicit motives were hypothesised to predict behaviour independent of intentions while explicit motives would be mediated by intentions. Regression analyses indicated that implicit motivation predicted physical activity behaviour only. Across all behaviours, intention mediated the effects of explicit motivational variables from self-determination theory. This study provides limited support for dual-systems models and the role of implicit motivation in the prediction of health-related behaviour. Suggestions for future research into the role of implicit processes in motivation are outlined.


Acquired nonparalytic causes of superior oblique dysfunction.
To conduct a retrospective study to investigate the causes of acquired superior oblique dysfunction, excluding paralysis, in a consecutive series of adult patients and to compare presenting symptoms and clinical findings. A retrospective review of all adult patients with superior oblique dysfunction between the ages of 18 and 80 who met the study profile was conducted at Saint Louis University Medical Center between January 2000 and April 2012. The presenting symptoms, clinical findings, and treatment course for each patient was recorded. The study was approved by the Institutional Review Board of our institution. Acquired forms of nonparalytic superior oblique dysfunction were identified in forty-eight patients. These included superior oblique myokymia (twenty-three patients), superior oblique click syndrome or variable Brown syndrome (nine), canine tooth syndrome (five), spontaneous acquired Brown syndrome (four), iatrogenic or traumatic Brown syndrome (four), and ocular neuromyotonia affecting the superior oblique (three). Several nonparalytic entities were identified that caused superior oblique dysfunction. Clinical findings may be similar despite entirely different mechanisms. Subjective symptoms may be difficult for the patient to describe or for the examiner to elicit on the day of the examination. Specific techniques can be used in eliciting, differentiating, and documenting the conditions. These included trochlear palpation, modified head tilt technique, interpretation of torsion, and Hess charts.


Efficacy of Chewing Gum to Reduce Orthodontic Pain Compared to Placebo: A Blinded, Parallel-Group, Preliminary Clinical Trial.
To quantify the pain experienced by orthodontic patients during the first 10 days of appliance placement, to determine whether chewing gum reduces orthodontic pain compared to placebo, and to examine patients' overall perceptions of the impact of orthodontic pain. Patients bonded with fixed appliances were randomly assigned to one of two groups (gum group [GG] or placebo group [PG]) and then followed for 10 days. The main outcome was a visual analog scale (VAS) pain score, and the secondary outcomes included patients' subjective assessments of overall pain level, the impact of pain on hygiene habits and treatment decision, and the frequency of analgesics consumption. Eighty kits (40 for GG and 40 for PG) were pre-randomized and concealed before patient enrollment using a computer-generated random sequence. Operators and patients were blinded. Data were analyzed using generalized linear models and Mann-Whitney U, chi-square, and Fisher exact tests. A total of 75 patients were allocated to intervention groups; 37 participated and completed diaries (20 in GG and 17 in PG). No statistically significant differences were detected between the GG and PG groups in any tested variable. Pain negatively affected some patients' oral hygiene practices. A mismatch existed between patient expectations and actual pain experiences. Female patients used analgesics more frequently than male patients (P = .046). Chewing gum three times per day does not seem to significantly reduce orthodontic pain compared to placebo. Orthodontists should manage their patients' pain expectations.


DermaVir: a plasmid DNA-based nanomedicine therapeutic vaccine for the treatment of HIV/AIDS.
The HIV global pandemic continues to rage with over 33 million people living with the disease. Although multidrug therapy has improved the prognosis for those infected by the virus, it has not eradicated the infection. Immunological therapies, including therapeutic vaccines, are needed to supplement drug therapy in the search for a 'functional cure' for HIV. DermaVir (Genetic Immunity Kft, Budapest, Hungary and McLean, Virginia, USA), an experimental HIV/AIDS therapeutic vaccine, combines three key elements of rational therapeutic vaccine design: a single plasmid DNA (pDNA) immunogen expressing 15 HIV antigens, a synthetic pDNA nanomedicine formulation and a dendritic cell-targeting topical-vaccine administration. DermaVir's novel mechanism of action, natural transport by epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity, has been consistently demonstrated in mouse, rabbit, primate and human subjects. Safety, immunogenicity and preliminary efficacy of DermaVir have been clinically demonstrated in HIV-infected human subjects. The DermaVir technology platform for dendritic cell-based therapeutic vaccination might offer a new treatment paradigm for cancer and infectious diseases.


Preparation and UV Photoelectric Properties of Aligned ZnO-TiO2 and TiO2-ZnO Core-Shell Structured Heterojunction Nanotubes.
Large-area horizontal-aligned ZnO nanotubes (ZNTs), TiO2 nanotubes (TNTs), TiO2-ZnO core-shell nanotubes (TZNTs) and ZnO-TiO2 core-shell nanotubes (ZTNTs) were successfully synthesized by electrospinning combined with pulsed-laser deposition. The morphology, structure, and composition of the samples were characterized by scanning electron microscopy, high-resolution transmission electron microscopy, and Raman spectroscopy. The photoluminescence (PL) spectra of these samples indicate that the addition of a TiO2 layer greatly decreases the recombination of photogenerated carriers in the heterojunction nanotubes. The photodetectors (PDs) were fabricated by assembling horizontally ordered nanotubes on the gold interdigital electrode, and their ultraviolet (UV) detection performances were compared. The test results at room temperature show that the PD with aligned ZTNTs have the best UV response and a short response recovery time. In addition, the performance of ZTNT PDs and TZNT PDs are further improved under heating. The photo/dark current ratio, responsivity (Rλ), detectivity (D*), and external quantum efficiency (EQE) of ZTNTs increased to 388, 450 uA·W-1, 1.1 × 1010 cm·Hz1/2·W-1, and 0.15%, respectively, under the condition of 365 nm UV radiation with a power density of 4.9 mW·cm-2 and a 1 V bias at 90 °C. The UV response mechanism and structural superiority of the horizontally ordered coaxial heteronanotube were also discussed. In addition, this work provides an important method for the design of other ordered nanomaterials and structures, which have a wide range of applications in the fields of sensors, transistors, transparent flexible electrodes, and other multifunctional devices.


[Parotid metastasis of liposarcoma of the lower limbs].
Distant metastasis affecting the parotid gland are a rare entity, with origin in most cases from cutaneous tumors of the head and neck, mainly melanoma and epidermoid carcinoma. Other histological types of metastasis and tumors originated from distant organs or sites are very rare and may be a diagnostic and therapeutic challenge, for this reason, we consider it interesting for discussion. In this paper, we present the case of a patient with a metastatic tumor of the parotid gland secondary to a liposarcoma of the leg, extremely rare case, about which we have no found previous references in the literature.


"Acing" the Hidden Spade: Review of Diagnosis, Follow-up, Prognosis, and Various Associations of Apical Variant Hypertrophic Cardiomyopathy.
Apical variant hypertrophic cardiomyopathy (AHCM) is a known entity since its first introduction by Sakamoto and Yamaguchi. However, unlike classical hypertrophic cardiomyopathy (HCM), it is less explored in terms of its associated diagnosis and long-term outcomes. Through this case presentation, we aim to have an in-depth review to help physicians identify and better understand several aspects of AHCM. Given the increased availability and utilization of high precision cardiac imaging modalities, apical septal hypertrophic cardiomyopathy will increasingly be recognized as a distinct, clinically significant variant of classical HCM. Contrast echocardiogram is the most effective and diagnostic study when performed in the right setting with high suspicion on clinical examination findings and typical electrocardiogram (EKG) findings. Cardiac magnetic resonance imaging (MRI) has equal diagnostic yield as a contrast echocardiogram. It is associated with a wide spectrum of presentation ranging from asymptomatic course with incidental findings on imaging to rarely being associated with ventricular arrhythmia. The question of utility of implantable defibrillators in individuals, particularly without any underlying arrhythmias, remains unexplained and needs further evidence-based guidance.


Building an insurance against modern pandemics.
The response to the first influenza pandemic of the 21st century benefited from the extensive preparation for an avian influenza pandemic and the mild nature of the 2009 A/H1N1 swine influenza virus. However, the pandemic demonstrated the limited ability to predict influenza pandemics, to anticipate levels of cross-protection, and to deliver vaccines in a timely manner, particularly to low income countries. The lessons learned from the 2009 H1N1 pandemic are of paramount importance to develop more effective preparations against future pandemics.


Why is less cationic lipid required to prepare lipoplexes from plasmid DNA than linear DNA in gene therapy?
The most important objective of the present study was to explain why cationic lipid (CL)-mediated delivery of plasmid DNA (pDNA) is better than that of linear DNA in gene therapy, a question that, until now, has remained unanswered. Herein for the first time we experimentally show that for different types of CLs, pDNA, in contrast to linear DNA, is compacted with a large amount of its counterions, yielding a lower effective negative charge. This feature has been confirmed through a number of physicochemical and biochemical investigations. This is significant for both in vitro and in vivo transfection studies. For an effective DNA transfection, the lower the amount of the CL, the lower is the cytotoxicity. The study also points out that it is absolutely necessary to consider both effective charge ratios between CL and pDNA and effective pDNA charges, which can be determined from physicochemical experiments.


Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues.
To investigate the effect of acute in vivo administration of ethanol on acetylation or methylation of histone H3 at lysine9 in different tissues in rat. Ethanol was injected into the stomach of Sprague-Dawley rats (8-weeks-old) using blunt tipped needle. The rats were divided into three groups based on ethanol exposure times (1, 3, and 12 h). Each group was compared with water-injected control group. The tissues from 14 different organs were removed. We essentially used similar type of protocol, tissue homogenization method, and sucrose density gradient centrifugation for isolation of nuclei with only minor modifications for some organs. Histone was isolated from the nuclei using acid extraction method. Acetylation of histone H3 at lysine9 (Ac-H3-lys9) and methylation of histone H3 at lysine9 (Me-H3-lys9) were analysed by western blotting. Effect of ethanol on Ac-H3-lys9 was investigated in 11 out of 14 rat tissues. In liver, we observed an increase in Ac-H3-lys9 with maximal increase of approximately 6-fold after 12 h exposure. Lung also showed approximately 3-fold increase. In spleen, ethanol-induced Ac-H3-lys9 in all three ethanol-treated groups with similar increase (1.5- to 1.6-fold). Testes showed significant increase (3-fold increase) of Ac-H3-lys9 only at 1 h ethanol exposure. Ethanol had no affect on Ac-H3-lys9 in other tissues: kidney, brain, heart, stomach, colorectum, pancreas, and vessels. Ethanol had little effect on Me-H3-lys9 in all rat tissues examined. After in vivo administration of ethanol, analogous to binge drinking condition, the acetylations of H3-lys9 in rat tissues are not universal but tissue-specific events with different patterns of responses. Ac-H3-Lys9 in liver, lung, and spleen were significantly affected and it was demonstrated that ethanol causes this epigenetic alteration in rat tissues selectively.


Efficacy and maintenance of an education program for a consumer cooperative.
We examined the effects of contingency management on participation in and maintenance of an education program by new members of a student housing cooperative. With credit and fine contingencies in place, the percentage of participants completing study guides was five times higher than without the contingencies. Members continued to implement the program for 9 years without researcher involvement.


Treatment of low back pain: First extended follow up of an original trial (NCT00600197) comparing a multidisciplinary group-based rehabilitation program with oral drug treatment alone up to 24 months.
This study aimed to examine the effects of the extended follow-up of an original trial (NCT00600197) which has been published in The Clinical Journal of Pain. Eighty-three percent (165 of 197) of the original study, including 82 patients in intervention and 83 patients in the control group, provided extended 24-month follow-up data. The intervention was a group-based multidisciplinary rehabilitation program which was continued by monthly motivational consultation. Data on measures of Short Form 36 (SF-36), Quebec Disability Scale (QDS) and Ronald Morris Disability (RDQ) were collected at 12-, 18- and 24-month follow-ups and analyzed through repeated measures analysis of variance. The patients who responded (n = 165) and who did not respond (n = 32) to the questionnaires were the same in terms of all baseline data except for physical function which was better for respondents (P < 0.05). Among the respondents, both intervention and control groups were the same at baseline except for education level and mental health which was better in the intervention group (P < 0.05). As a result, the intervention group had consistently better outcomes regarding all variables except for social function at all follow-up times. Furthermore, in the intervention group only for mental health the interaction between time and group was significant (P = 0.01). The designed multidisciplinary program could improve health-related quality of life and disability up to 24 months in chronic low back pain patients.


The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts.
As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with long-duration spaceflight and demonstrate the need for closer study of fluid shifts.


Legal rights, constitutional controversies, and access to health care: lessons from Canada.
This paper provides a critical analysis of the use of legal claims to assert rights to access health care. Using Canada's system of public health insurance as an example, the paper discusses two significant Supreme Court of Canada cases in which claimants use legal mechanisms to influence health care reform. While one case seeks to expand the range of services covered by public health insurance, the other challenges the government "monopoly" over health care and advocates an expanded role for private health care. These legal claims play out in an adversarial setting where the focus is on the rights claims advanced by individual litigants. Yet, the outcomes of these cases involve broad implications regarding allocation of scarce health care resources and the very structure of the health care system. This paper discusses the benefits and limits of using legal claims in this context and also considers the role of courts in making decisions that may have the effect of constraining policy options available to government decision-makers.


Concise review: Clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein).
The importance of P-glycoprotein (P-gp) in drug-drug interactions is increasingly being identified. P-gp has been reported to affect the pharmacokinetics of numerous structurally and pharmacologically diverse substrate drugs. Furthermore, genetic variability in the multidrug resistance 1 gene influences absorption and tissue distribution of drugs transported. Inhibition or induction of P-gp by coadministered drugs or food as well as herbal constituents may result in pharmacokinetic interactions leading to unexpected toxicities or undertreatment. On the other hand, modulation of P-gp expression and/or activity may be a useful strategy to improve the pharmacological profile of anticancer P-gp substrate drugs. In recent years, the use of complementary and alternative medicine (CAM), like herbs, food, and vitamins, by cancer patients has increased significantly. CAM use substantially increases the risk for interactions with anticancer drugs, especially because of the narrow therapeutic window of these compounds. However, for most CAMs, it is unknown whether they affect metabolizing enzymes and/or drug transporter activity. Clinically relevant interactions are reported between St John's wort or grapefruit juice and anticancer as well as nonanticancer drugs. CAM-drug interactions could explain, at least in part, the large interindividual variation in efficacy and toxicity associated with drug therapy in both cancer and noncancer patients. The study of drug-drug, food-drug, and herb-drug interactions and of genetic factors affecting pharmacokinetics and pharmacodynamics is expected to improve drug safety and will enable individualized drug therapy. Disclosure of potential conflicts of interest is found at the end of this article.


Analysis of Infusion Patterns of Propofol and Remifentanil During Rigid Bronchoscopy Under Total Intravenous Anesthesia.
We analyzed the dosage pattern of anesthetic drugs administered to maintain anesthesia during rigid bronchoscopy. We enrolled a total of 81 patients who underwent rigid bronchoscopy under total intravenous anesthesia between April 2015 and March 2019. Anesthesia was maintained using propofol (target brain concentration 2.0 - 6.0 µg/mL) and remifentanil (target brain concentration 2.0 - 6.0 ng/mL). We analyzed the dosage patterns of the anesthetic agents during the procedure, as well as the changes in the dose of the anesthetic agents and the number of procedures repeated in the same patient. The dose of propofol administered per minute to maintain anesthesia was inversely correlated with the total operation time (r2 = 0.355, β = -0.067, P < 0.000) but was not significantly correlated with the number of times the procedure was repeated. The dose of remifentanil did not significantly differ during repeated procedures in the same patient. The dose of propofol infusion tended to decrease over time during the rigid bronchoscopy procedure. This pattern was specific to propofol but not to remifentanil using TIVA. Understanding the pharmacokinetic properties of anesthetic drugs will help in their appropriate administration.


Laparoscopic Cystogastrostomy in Children with Pancreatic Pseudocysts: A Preliminary Experience of Eight Cases.
Pancreatic pseudocysts (PPCs) and walled-off necrosis (WON) in children following acute pancreatitis are uncommon. The various modalities of therapy possible are conservative treatment, external drainage, endoscopic stenting, and internal surgical drainage procedures. There are no existing guidelines for the management of PPC in children. We evaluate the outcomes of laparoscopic cystogastrostomy (LCG) performed at our center. Eight children (median age: 10 years) underwent LCG for large PPC (median size: 12.5 cm). There were seven patients with PPC and one with WON. Seven underwent LCG by a transgastric approach and one underwent LCG by a retrogastric approach. Seven out of the eight patients had complete resolution of symptoms and the PPC. The median follow-up period was 32 months (interquartile range: 9.5-55.5 months). There were no conversions. There was one patient with a WON who developed a recurrence. LCG is a safe and effective treatment option for large PPC/WON in children. A posterior retrogastric approach, when indicated, is a safe approach with a comparable outcome.


Trace elements present in airborne particulate matter--stressors of plant metabolism.
Changes of amino acid concentrations (glutamic acid, glutamine, asparagine, aspartate, proline, tryptophan, alanine, glycine, valine and serine), gas-exchange parameters (net photosynthetic rate, transpiration rate, stomatal conductance and intercellular CO(2) concentration) and nitrate levels in Lactuca serriola L. under airborne particulate matter (PM) contamination reported here reveal their role in plant chronic stress adaptation. Results of the pot experiment confirmed the toxic effect of trace elements present in PM for lettuce. PM applied to soil or on the lettuce leaves were associated with the strong inhibition of above-ground biomass and with the enhancement of plant trace element contents. The significant changes of amino acid levels and leaf gas-exchange parameters of the plants showed strong linear dependences on PM contamination (R(2)=0.60-0.99). PM application on leaves intensified toxic effect of trace elements (As, Pb, Cr and Cd) originating from PM by shading of the leaf surface. The plant accumulation of nitrate nitrogen after PM contamination confirmed to block nitrate assimilation.


iTRAQ-based protein profiling provides insights into the central metabolism changes driving grape berry development and ripening.
Grapevine (Vitis vinifera L.) is an economically important fruit crop. Quality-determining grape components such as sugars, acids, flavors, anthocyanins, tannins, etc., accumulate in the different grape berry development stages. Thus, correlating the proteomic profiles with the biochemical and physiological changes occurring in grape is of paramount importance to advance in our understanding of berry development and ripening processes. We report the developmental analysis of Vitis vinifera cv. Muscat Hamburg berries at the protein level from fruit set to full ripening. An iTRAQ-based bottom-up proteomic approach followed by tandem mass spectrometry led to the identification and quantitation of 411 and 630 proteins in the green and ripening phases, respectively. Two key points in development relating to changes in protein level were detected: end of the first growth period (7 mm-to-15 mm) and onset of ripening (15 mm-to-V100, V100-to-110). A functional analysis was performed using the Blast2GO software based on the enrichment of GO terms during berry growth. The study of the proteome contributes to decipher the biological processes and metabolic pathways involved in the development and quality traits of fruit and its derived products. These findings lie mainly in metabolism and storage of sugars and malate, energy-related pathways such as respiration, photosynthesis and fermentation, and the synthesis of polyphenolics as major secondary metabolites in grape berry. In addition, some key steps in carbohydrate and malate metabolism have been identified in this study, i.e., PFP-PFK or SuSy-INV switches among others, which may influence the final sugar and acid balance in ripe fruit. In conclusion, some proteins not reported to date have been detected to be deregulated in specific tissues and developmental stages, leading to formulate new hypotheses on the metabolic processes underlying grape berry development. These results open up new lines to decipher the processes controlling grape berry development and ripening.


[Tay-Sachs disease].
GM2-gangliosidosis is a group of neurological disorders resulting from genetically defective catabolism, and consequent abnormal accumulation, of GM2-ganglioside. Three major types are distinguished: the B variant (Tay-Sachs disease), the O variant (Sandhoff disease), and the AB variant, caused by genetic abnormalities in the genes coding for the beta-hexosaminidase alpha- or beta-subunit, or the GM2-activator protein, respectively. A number of gene abnormalities responsible for Tay-Sachs disease have already been identified and the correlation between the beta-hexosaminidase alpha gene abnormality and the clinical phenotype has been explained in many cases. In the severest phenotype of Tay-Sachs disease (infantile form), mRNA of beta-hexosaminidase alpha subunit is not produced or is unstable such as in French Canadian patients or in Jewish patients with infantile Tay-Sachs disease, or the polypeptide does not have any catalytic activities because of the alteration of glycosylation such as the mutation of Glu482-to-Lys found in a Italian patient or the altered structure of polypeptide. The mutation identified in a large majority of the Japanese infantile Tay-Sachs disease patients, which is a G-to-T substitution at 3'-end of intron 5, generates a short mRNA with complete skipping of exon 6 and a polypeptide lacking 34 amino acids is generated but catalytically inactive. On the other hand, some active alpha beta dimers must be generated in patients with milder phenotypes of Tay-Sachs disease such as Gly269-to-Ser mutation in an adult form. Some of the mutations appear in high frequency among certain ethnic groups such as Ashkenazi Jewish patients and French Canadians.(ABSTRACT TRUNCATED AT 250 WORDS)


Mesophyll cell protoplasts of potato: isolation, proliferation, and plant regeneration.
Mesophyll cell protoplasts were isolated from potato (Solanum tuberosum L. cv. Russet Burbank) leaves and induced to proliferate in culture. Protoplast division was observed only among preparations isolated from plants previously conditioned under short periods of low intensity illumination. Sustained growth and development of protoplast-derived calli (p-calli) occurred when they were maintained on defined media at 24 C under 500 lux lighting. Shoot bud development within p-calli was controlled by a number of factors including light, temperature, basic medium composition, nature and source of phytohormones, the continued presence of an osmoticum, low concentrations of a utilizable carbohydrate, and the developmental stage of the p-callus.


NHS Direct: issues for education, management and research.
The NHS Plan (Department of Health (DoH), 2000) specifically highlights the role of NHS Direct in its vision of a health service designed around the patient. Despite this, the new nurse-led service has come under critical attack. NHS Direct is in the process of developing an evidence base to underpin its practice. It is recognized that telephone management skills are important clinical skills and while decision support computer software can help elicit an appropriate client history, the interpersonal skills necessary to establish a professional telephone relationship are commensurate with the suitability of the appropriate education programme. This article will explore the ramifications of NHS Direct for curriculum development and evaluation. Factors such as skill mix, career pathways, recruitment and research and development will also be discussed. In a previous article the implications of NHS Direct for practice were examined (Glasper et al, 2000).


Damnacanthal: a promising compound as a medicinal anthraquinone.
The Noni fruit, or scientifically known as Morinda citrifolia can be found in various parts of the world, especially in the pacific region. It is a small evergreen bushy-like tree originated from the Rubiaceae family. The plant has been used by polynesians as a medicinal herb for more than 2000 years. A substantial amount of phytochemicals can be found in the roots of this plant. Among all, damnacanthal has been found to be the most interesting, versatile and potent compound. Damnacanthal or chemically known as,3- hydroxy-1-methoxyanthraquinone-2-caboxaldehyde (C16H10O5), appears as pale yellow crystals with a melting point of 210-211 °C. This compound is of particular interest due to its striking pharmacological properties. Damnacanthal was shown to inhibit the oncogene Ras, p56lck tyrosine kinase, NF-KB pathway and induce apoptosis in vitro. This review aims to discuss the biological properties of damnacanthal, specifically on its anti-cancer activity that has been reported.


Renal Interstitial Fibrosis Is Reduced in High-Fat Diet-Induced Obese Pigs following Renal Denervation from the Intima and Adventitia of the Renal Artery.
This study aims to compare whether 2 different routes of renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n = 6) or a hypertension model group (high-fat diet, n = 18). The model group was randomly divided into the intima-RDN group (n = 6), the adventitia-RDN group (n = 6), or the renal arteriography-only group (sham group, n = 6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin staining and Masson staining; superoxide dismutase activity and the malondialdehyde content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-β 1 (TGF-β1), α-smooth muscle actin (α-SMA), and Smad3 was assessed by Western blot, and electron microscopy was used to examine changes in the kidney microstructure. After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed p < 0.05); the blood lipid levels of the control group did not change significantly from baseline (p > 0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (p < 0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high-fat-induced renal fibrosis. The antifibrotic effect of RDN may be related to inhibition of the TGF-β1/Smad3 pathway.


Did Napoleon suffer from chronic rhonchopathy?
If Napoleon had been treated, Europa would then have doubtless been different, and perhaps would not have known the last two World wars. This study plans to demonstrate that Napoleon very probably suffered from Chronic Rhonchopathy. Between 1983-1993, the author led their ENT department of CHU Saint-Antoine to contribute in the knowledge of chronic snoring and Obstructive Sleep Apneas Syndrome (OSAS), and to define the treatment of their consequences. As a result of these efforts, in Paris in 1987 the First International Congress on Chronic Rhonchopathy was organized. Obstructive Sleep Apnoea Syndrome (OSAS) is caused by anatomical and intermittent obstruction of the upper airway, which impedes passage of air to the lungs during sleep. Recent literature demonstrates that chronic snoring frequently precedes this obstruction by several years, and always accompanies this syndrome. All life long, there is a severity increasing continuum between more light snoring and more severe OSAS, i.e. Pickwick Syndrome. This continuum is described as a new disease called Chronic Rhonchopathy. This term was never discussed; since 2006, it has been implicitly recognized. Napoleon would sleep very little. He used to wake up in the night and then grasp the chance to work. Brief sleeping time in day repaired his fatigue. He also had a short and thick neck. In the last quarter of his life he had progressively suffered from obesity, daily involuntary sleepiness, and his intellectual capabilities had been undoubtedly decreasing. In the vast literature concerning Napoleon's behavior, the author brought together the clinical elements which could be due to this disease. This study looked for the morphological peculiarities of this OSAS in sculpture and painting, that had the Emperor as the model. Napoleon presented surely diurnal somnolence, asthenia, obesity, neck shortness, retrognatia, and nasal pathology. He did not suffer from these troubles while he was young. On the contrary, he took advantage of his multiple awakenings, doubtlessly due to apnea occurring during his paradoxical sleep, to deal with some of his main masterpieces, e.g. the French Code Civil. With age, the Emperor's chronic rhonchopathy became more severe. If he had benefitted of modern treatments, maybe Moskowa would not have been a French defeat and Waterloo would have been a victory for France.


Regenerable Polyelectrolyte Membrane for Ultimate Fouling Control in Forward Osmosis.
This study demonstrated the feasibility of using regenerable polyelectrolyte membranes to ultimately control the irreversible membrane fouling in a forward osmosis (FO) process. The regenerable membrane was fabricated by assembling multiple polyethylenimine (PEI) and poly(acrylic acid) (PAA) bilayers on a polydopamine-functionalized polysulfone support. The resulting membrane exhibited higher water flux and lower solute flux in FO mode (with the active layer facing feed solution) than in PRO mode (with the active layer facing draw solution) using trisodium citrate as draw solute, most likely due to the unique swelling behavior of the polyelectrolyte membrane. Membrane regeneration was conducted by first dissembling the existing PEI-PAA bilayers using strong acid and then reassembling fresh PEI-PAA bilayers on the membrane support. It was found that, after the acid treatment, the first covalently bonded PEI layer and some realigned PAA remained on the membrane support, acting as a beneficial barrier that prevented the acid-foulant mixture from penetrating into the porous support during acid treatment. The water and solute flux of the regenerated membrane was very similar to that of the original membrane regardless of alginate fouling, suggesting an ultimate solution to eliminating the irreversible membrane fouling in an FO process. With a procedure similar to the typical membrane cleaning protocol, in situ membrane regeneration is not expected to noticeably increase the membrane operational burden but can satisfactorily avoid the expensive replacement of the entire membrane module after irreversible fouling, thereby hopefully reducing the overall cost of the membrane-based water-treatment system.


Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV.
The histone deacetylase inhibitor (HDACi) suberoylanilide hydroxyamic acid (SAHA), also known as vorinostat, has recently been reported to activate latent HIV-1 in patients undergoing antiretroviral therapy. It is possible that SAHA reactivation of latent viruses may involve effects on cellular transcription factors such as positive transcription elongation factor b (P-TEFb), a protein kinase whose core is composed of CDK9 and Cyclin T1. P-TEFb is recruited by the HIV-1 Tat protein to activate productive RNA polymerase II elongation of the integrated provirus. We found that SAHA treatment of isolated resting CD4(+) T cells induced CDK9 Thr-186 (T-loop) phosphorylation in six of eight healthy donors and increased Cyclin T1 expression in one donor; Thr-186 phosphorylation is required for P-TEFb function. Disulfiram, another small molecule currently under evaluation in clinical trials for reactivation of latent HIV-1, was also found capable of inducing CDK9 Thr-186 phosphorylation and Cyclin T1 levels in resting CD4(+) T cells from healthy donors. In a Jurkat CD4(+) T cells HIV-1 latency system, disulfiram reactivated the latent provirus and induced CDK9 Thr-186 phosphorylation. Our findings suggest that small molecules capable of reactivating latent HIV-1 in resting CD4(+) T cells may function in part by increasing CDK9 Thr-186 phosphorylation and perhaps Cyclin T1 expression, thereby up-regulating P-TEFb function.


Estrogen inhibits the growth of estrogen receptor-negative, but not estrogen receptor-positive, human mammary epithelial cells expressing a recombinant estrogen receptor.
Estrogen is essential for the growth of the normal mammary gland and most estrogen receptor (ER)-positive mammary carcinomas. To better understand the differences between the estrogen response pathways in normal and tumor cells, we have stably transfected ER-negative immortal, nontumorigenic human mammary epithelial cells and ER-negative breast cancer cells with an ER-encoding expression vector. Unexpectedly, estrogen treatment (1.0 nM) inhibited the proliferation of ER-transfected nontumorigenic and tumor-derived cells. The control transfectants and parental cells exhibited no response to estrogen concentrations as high as 1.0 microM. This inhibitory effect was attributed to a decreased growth rate and a perturbation of the cell cycle distribution by estrogen treatment of the ER transfectants. The inhibitory response was blocked by cotreatment with the antiestrogen ICI 164,384 as predicted for a pure antagonist of estrogen action. However, treatment with the antiestrogen hydroxytamoxifen caused growth inhibition, implying that hydroxytamoxifen acts as an agonist of estrogen action in ER-transfected cells. Since estrogen is a mitogenic and not a growth-inhibitory stimulus for ER-positive breast cancers and cell lines, we tested the effect of constitutive, high level expression of the ER in ER-positive tumor cells. Stable transfection of ER-positive MCF-7 and T47D cells with the ER expression vector yielded cells with varying amounts of ER. At ER levels comparable to those found in the ER-negative transfected cells, the MCF-7 and T47D ER transfectants were not inhibited by estrogen. These data suggest that ER-positive breast cancer cells can tolerate higher constitutive levels of ER expression than ER-negative cells. The mechanism by which this is accomplished may be an essential step in the process which yields ER-positive tumors.


Microcalcification detectability for four mammographic detectors: flat-panel, CCD, CR, and screen/film).
Amorphous silicon/cesium iodide (a-Si:H/CsI:Tl) flat-panel (FP)-based full-field digital mammography systems have recently become commercially available for clinical use. Some investigations on physical properties and imaging characteristics of these types of detectors have been conducted and reported. In this perception study, a phantom containing simulated microcalcifications (microCs) of various sizes was imaged with four detector systems: a FP system, a small field-of-view charge coupled device (CCD) system, a high resolution computed radiography (CR) system, and a conventional mammography screen/film (SF) system. The images were reviewed by mammographers as well as nonradiologist participants. Scores reflecting confidence ratings were given and recorded for each detection task. The results were used to determine the average confidence-rating scores for the four imaging systems. Receiver operating characteristics (ROC) analysis was also performed to evaluate and compare the overall detection accuracy for the four detector systems. For calcifications of 125-140 microm in size, the FP system was found to have the best performance with the highest confidence-rating scores and the greatest detection accuracy (Az = 0.9) in the ROC analysis. The SF system was ranked second while the CCD system outperformed the CR system. The p values obtained by applying a Student t-test to the results of the ROC analysis indicate that the differences between any two systems are statistically significant (p<0.005). Differences in microC detectability for the large (150-160 microm) and small (112-125 microm) size microC groups showed a wider range of p values (not all p values are smaller than 0.005, ranging from 0.6 to <0.001) compared to the p values obtained for the medium (125-140 microm) size microC group. Using the p values to assess the statistical significance, the use of the average confidence-rating scores was not as significant as the use of the ROC analysis p value for p value.


Influence of Protein Synthesis on NO(3) Reduction, NH(4) Accumulation, and Amide Synthesis in Suspension Cultures of Paul's Scarlet Rose.
Changes in the concentrations of NH(4) (+) and amides during the growth of suspension cultures of rose (Rosa cv. Paul's Scarlet) cells were examined. When cells were grown in medium possessing only NO(3) (-) as a nitrogen source, the concentrations of NH(4) (+) and amides increased to 4.0 x 10(-1) and 5.9 micromoles per gram fresh weight, respectively. The amounts of both constituents declined during the later stages of growth. When a trace amount of NH(4) (+) was added to the NO(3) (-) base starting medium, the concentration of NH(4) (+) in the cells was increased to 7.0 x 10(-1) micromoles per gram fresh weight.A comparison between the concentration of NH(4) (+) in the cells (4.3 x 10(-4) molar) with the K(m) values for glutamate dehydrogenase (5 x 10(-3) molar) and glutamine synthetase (1.7 x 10(-5) molar) showed that the endogenous NH(4) (+) would have to be concentrated 10-fold in compartments possessing glutamate dehydrogenase in order for the substrate to reach one-half the saturation level for that enzyme.The influence of protein synthesis on the level of NH(4) (+) and amides was examined by blocking protein synthesis with cycloheximide or puromycin and measuring changes in NH(4) (+) and amide concentration over the subsequent 4 hours. The level of both NH(4) (+) and amides showed substantial increases when protein synthesis was blocked. Ammonium accumulated to concentrations surpassing those reported by other authors to be toxic to plants. The reduction of NO(3) (-) did not appear to be influenced by the blockage of protein synthesis.


In vitro and in vivo evaluations of sodium lauryl sulfate and dextran sulfate as microbicides against herpes simplex and human immunodeficiency viruses.
The efficacy of sodium lauryl sulfate (SLS), a sulfated anionic chaotropic surfactant, and dextran sulfate (DS), a polysulfated carbohydrate, against herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections was evaluated in cultured cells and in different murine models of HSV infection. Results showed that both SLS and DS were potent inhibitors of the infectivities of various HSV-1 and HSV-2 strains. Pretreatment of HIV-1 (strain NL4-3) with SLS also reduced its infectivity to 1G5 cells. DS prevented the binding of HSV to cell surface receptors and therefore its entry into cells. Pretreatment of HSV-1 (strain F) with 50 microM SLS resulted in a complete loss of virus infectivity to Vero cells. However, viruses were able to enter into cells and to produce in the nuclei capsid shells devoid of a DNA core. The amount of the glycoprotein D gene produced in these cells remained unchanged compared to controls, suggesting that SLS could interfere with the maturation of the virus. At a higher SLS concentration (100 microM), HSV was highly damaged by SLS pretreatment and only a few viral particles could enter into cells to produce abnormal capsids. Although DS was a more potent inhibitor of HSV infectivity in vitro, it was unable to provide any protection in murine models of HSV infection. However, SLS conferred a complete protection of animals infected cutaneously with pretreated viruses. In addition, skin pretreatment of mice with a polymer formulation containing SLS completely prevented the development of cutaneous lesions. More interestingly, intravaginal pretreatment of mice with SLS in a buffered solution also completely protected against lethal HSV-2 infection. Taken together, our results suggest that SLS could thus represent a candidate of choice as a microbicide to prevent the sexual transmission of HIV, HSV, and possibly other pathogens that cause sexually transmitted diseases.


Biosynthesis of stress ethylene induced by water deficit.
Wheat leaves normally produced very little ethylene, but following a water deficit stress which caused a loss of 9% initial fresh weight, ethylene production increased more than 30-fold within 4 hours and declined rapidly thereafter. The changes in ethylene production were paralleled by an increase and subsequent decrease in 1-aminocyclopropanecarboxylic acid (ACC) content. The level of S-adenosylmethionine was unaffected, suggesting that the conversion of S-adenosylmethionine to ACC is a key reaction in the production of water stress-induced ethylene. This view was further supported by the observation that application of ACC to nonstressed leaf tissue caused a 70-fold increase in ethylene production, while aminoethoxyvinylglycine, a known inhibitor of the conversion of S-adenosylmethionine to ACC, inhibited ACC accumulation as well as the surge in ethylene production if the inhibitor was applied prior to the stress treatment. Cycloheximide, an inhibitor of protein synthesis, effectively blocked both ethylene production and ACC formation, suggesting that water stress induces de novo synthesis of ACC synthase, which is the rate-controlling enzyme in the pathway of ethylene biosynthesis.


[Factors in the development of arterial hypoxemia in middle-aged and elderly people].
Partial pressure of oxygen and carbon dioxide in alveolar air and arterial blood, lung diffusion capacity and its components, ventilation parameters, ventilation-perfusion ratio were determined in healthy people aged 60-89 (45 subjects) and aged 20-31 (19 subjects, controls). In elderly and old people PO2 in arterial blood was found to decrease with increasing alveolar-arterial PO2 gradient. In other words, arterial hypoxemia was determined by the disturbance in gas exchange between alveolar air and blood of lung capillaries. The diffusion capacity of lung decreased at the expense of membrane factor. Its age-related dynamics was mainly due to a decrease in the pulmonary diffusion surface occurring because of improper coordination of ventilation and perfusion in the lungs. The discrepancy of pulmonary ventilation and perfusion proved to be the leading factor of arterial hypoxemia in late ontogenesis.


Proteolytic Cleavage of the Linker Region of the Human P-glycoprotein Modulates Its ATPase Function.
P-glycoprotein (Pgp), an anticancer drug-translocating ATPase, is responsible for multidrug resistance in cancer. We have previously shown (Nuti, S. L., Mehdi, A., and Rao, U. S. (2000) Biochemistry 39, 3424-3432) that tryptic cleavage of Pgp results in the activation of basal and drug-stimulated ATPase functions of Pgp. To understand this phenomenon, we determined the sites cleaved by trypsin and further examined whether the modulation of Pgp function is trypsin-specific or the result of proteolysis in general. The effects of chymotrypsin and proteinase K on Pgp ATPase function were studied. The results show that proteolysis of Pgp irrespective of the protease employed resulted in the activation of basal ATPase activity. However, drug-stimulated ATPase activities were differentially modulated. Immunoblot analysis of proteolytic digests indicated that, irrespective of the protease employed, Pgp was predominantly cleaved in the middle of the molecule. N-terminal amino acid sequencing of Pgp tryptic and chymotryptic peptides indicated Arg(680) and Leu(682) as the sites of cleavage, respectively. These two cleavage sites are part of the predicted linker region that joins the two halves of Pgp. Together, these results suggest that the linker region in Pgp is primarily accessible to protease action and that cleavage of this region modulates Pgp ATPase function.


Transsynovial distribution of ibuprofen in arthritic patients.
Free and total ibuprofen levels in serum and synovial fluid (SF) were determined in one male and 14 female arthritic patients (mean age 56 yr, range 19 to 77) after 400 mg three times daily for 2 days. Free drug was separated by ultrafiltration and assayed by a new highly sensitive and precise gas chromatographic-mass spectrometric technique. Total protein and albumin were assayed by automatic analyzer, and the routine serum biochemical profile obtained. Serum and SF nonesterified fatty acids (NEFAs) were methylated and assayed by gas chromatography. While both total protein and albumin levels were lower (P less than 0.01) in SF, NEFA levels did not differ (p greater than 0.05). Ibuprofen readily partitions into and binds strongly to joint fluid, the total level being about half that in serum. The ratio of total ibuprofen in SF to that in serum (x = 0.41 +/- 0.17) correlated with the albumin concentration ratio (r = 0.886) indicating that albumin binding is an important determinant of ibuprofen transsynovial distribution. A low total ibuprofen SF/serum ratio, apparent for three patients on concomitant aspirin therapy, is consistent with reports of an ibuprofen-salicylate interaction. Free ibuprofen in SF (0.192 +/- 0.086 microgram ml-1) did not differ (p greater than 0.05) from serum free levels (x = 0.251 +/- 0.139 microgram ml-1), supporting the concept of the synovial cavity as a compartment readily accessible to unbound drug species. Multiple regression analyses revealed relative independence of free concentration on total levels, and the small positive and negative influences of NEFAs and albumin concentrations. Bilirubin, uric acid, cholesterol, triglycerides, and chloride ion did not correlate with serum free concentration.


[Prevalence of Spirometra mansoni infections in hosts in Jiangsu Province].
To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.


Regulation of phospholipase C-gamma2 and phosphoinositide 3-kinase pathways by adaptor proteins in B lymphocytes.
The importance of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC)-gamma2 in B cell function and development has been highlighted by gene targeting experiments in mice. In fact, these knockout mice exhibit a profound inhibition of proliferative responses upon B cell receptor (BCR) engagement. The molecular connections between these effectors and upstream tyrosine kinases such as Syk have been studied intensively in the past few years. This mechanism involves the action of cytoplasmic adaptor molecules, which participate in forming multicomponent signaling complexes, thereby directing the appropriate subcellular localization of effector enzymes. In addition to these cytoplasmic adaptor proteins, cell surface coreceptors can be viewed as transmembrane adaptor proteins, because coreceptors can also change the localization of effector enzymes, which in turn modulates the BCR-initiated signals.


Nutrient Influences on Leaf Photosynthesis: EFFECTS OF NITROGEN, PHOSPHORUS, AND POTASSIUM FOR GOSSYPIUM HIRSUTUM L.
The net rate of CO(2) uptake for leaves of Gossypium hirsutum L. was reduced when the plants were grown at low concentrations of NO(3) (-), PO(4) (2-), or K(+). The water vapor conductance was relatively constant for all nutrient levels, indicating little effect on stomatal response. Although leaves under nutrient stress tended to be lower in chlorophyll and thinner, the ratio of mesophyll surface area to leaf area did not change appreciably. Thus, the reduction in CO(2) uptake rate at low nutrient levels was due to a decrease in the CO(2) conductance expressed per unit mesophyll cell wall area (g(cell) (CO(2) )). The use of g(cell) (CO(2) ) and nutrient levels expressed per unit of mesophyll cell wall provides a new means of assessing nutrient effects on CO(2) uptake of leaves.


Combined analysis of allograft inflammatory factor-1, interleukin-18, and Toll-like receptor expression and association with allograft rejection and coronary vasculopathy.
In cardiac transplantation settings, the initial myocardial ischemia and reperfusion may cause myocyte tissue injury and the release of allograft inflammatory factor-1 (AIF-1). This in part may trigger the innate immune response through the modulation of Toll-like receptor-2 (TLR-2) and AIF-1 expression and function, causing the release of proinflammatory cytokines. The goal was to demonstrate these markers in the peripheral blood and biopsy specimen from recipients with cardiac allograft rejection and coronary vasculopathy (CV). Peripheral blood and endomyocardial specimens were tested by reverse transcriptase-polymerase chain reaction and immunohistochemistry stains for identification of TLR-2, -4, interleukin-18, and AIF-1 markers and analyzed against clinical rejection grades for rejection. The differences for mRNA transcript levels were determined by one-way analysis of variance. The mRNA expression levels were significantly varied for TLR-2 in monocytes with different rejection grades (P < 0.0001). The mean +/- SEM level of mRNA expression for 3A grade rejection was 64.21 +/- 3.8; grade 1A, 38.4 +/- 3.5; and for Grade 0 was 38.46 +/- 2.8. The TLR-4 mRNA expression was increased but the specificity was not statistically significant. The TLR-2 immunoreactivity was strongly detected in infiltrating mononuclear cells and cardiac myocytes in Grade 3A rejection. AIF-1 expression was increased significantly in the group with 3A rejection and Grade III CV as compared with Grade 0 or 1A. Interleukin-18 receptors were strongly detected in Grade 3A rejection and CV. The expression profiles of AIF-1, TLR-2, and interleukin-18 were correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting a potential for diagnostic biomarkers for early detection of allograft rejection.


Antihyperlipidemic activity of chickpea sprouts supplementation in ovariectomy-induced dyslipidemia in rats.
Phytoestrogens are increasingly becoming popular as alternatives for hormone replacement therapy in postmenopausal condition. In this study, the antihyperlipidemic effect of chickpea (Cicer arientum) sprouts was evaluated in ovariectomy-induced dyslipidemia in rat model in comparison with standard antihyperlipidemic agent atorvastatin. A total of 24 female adult Wistar rats were divided into four groups that is, Group I - Control; Group II - Ovariectomized (OVX) rats; Group III - OVX + germinated chickpea sprouts (20% in diet) and Group IV OVX + atorvastatin (1.2 mg/kg b.wt, p.o.). Body and organ weights, serum, and liver lipid profile were assessed at the end of 8 weeks. The results indicated that ovariectomy significantly (P < 0.05) increased total cholesterol, nonhigh-density lipoprotein cholesterol and triglycerides (TGs) in serum and liver. The total lipid and phospholipid content in liver were also significantly (P < 0.05) increased. The weights of uterus and heart were significantly (P < 0.05) decreased. Dietary supplementation with germinated chickpea normalized the lipid profile in serum and liver. Further, high-density lipoprotein (HDL) cholesterol, body weight, uterine, heart, and spleen weights were significantly (P < 0.05) increased. Atorvastatin administration showed similarly normalized lipid profile, but showed no improvement on decreased uterus and heart weights. Histopathological examination revealed fatty changes in liver, uterine atrophy, and subintimal fat accumulation in aorta in OVX group. The changes were mild in chickpea group with no improvement in statin group. Germinated seeds of chickpea showed significant antihyperlipidemic activity, which was comparable to atorvastatin. Further, germinated chickpea improved organ weights and helped in the reversal of histopathological changes suggesting its usefulness in postmenopausal condition.


The impacts of climate change on water resources and agriculture in China.
China is the world's most populous country and a major emitter of greenhouse gases. Consequently, much research has focused on China's influence on climate change but somewhat less has been written about the impact of climate change on China. China experienced explosive economic growth in recent decades, but with only 7% of the world's arable land available to feed 22% of the world's population, China's economy may be vulnerable to climate change itself. We find, however, that notwithstanding the clear warming that has occurred in China in recent decades, current understanding does not allow a clear assessment of the impact of anthropogenic climate change on China's water resources and agriculture and therefore China's ability to feed its people. To reach a more definitive conclusion, future work must improve regional climate simulations-especially of precipitation-and develop a better understanding of the managed and unmanaged responses of crops to changes in climate, diseases, pests and atmospheric constituents.


Nonstochastic effects of different energy beta emitters on the mouse skin.
The effect of irradiating varying areas of mouse skin from 860 down to 0.8 mm2 with different energy beta emitters was studied to clarify protection problems of localized doses to the skin. Both 90Sr and 170Tm sources show area effects for dose-response curves. The 90Sr doses that produced moist desquamation in 50% of irradiated fields (MD-50 doses) were 22, 42, 70, and 1000 Gy for 400-, 95-, 20-, and 0.8-mm2 sources. The MD-50 doses for 170Tm were 50, 54, 90, and 170 Gy for 860-, 64-, 20-, and 3.1-mm2 sources. Thus for the larger 170Tm sources there is much less area effect. There was no significant difference in effect between the different energy 90Sr and 170Tm sources for moist desquamation. A simple hypothesis based upon the repopulation of epithelial cells from the edges of the irradiated field and/or from surviving follicle basal cells can explain these area and energy effects in the mouse and in parallel pig skin experiments. The doses needed for 50% of the mice to show ulceration after 64-, 20-, and 3.1-mm2 170Tm sources were 260, 550, and 8300 Gy, respectively, while those for 90-, 20-, and 0.8-mm2 90Sr sources were 150, 210, and 3100 Gy. Thus there is a definite area and energy effect for these sources for this deep dermal damage. The steep rise in dose needed to produce given skin reactions for the smallest area (0.8 mm2) should reassure those faced with assessing the hazard of sub-millimeter-sized particles in/on human skin.


Regulation of the Na(+)-K(+)-2Cl(-) cotransporter by cGMP/cGMP-dependent protein kinase I after furosemide administration.
Sodium chloride reabsorption in the thick ascending limb of the loop of Henle is mediated by the Na(+)-K(+)-2Cl(-) cotransporter (NKCC2). The loop diuretic furosemide is a potent inhibitor of NKCC2. However, less is known about the mechanism regulating the electrolyte transporter. Considering the well-established effects of nitric oxide on NKCC2 activity, cGMP is likely involved in this regulation. cGMP-dependent protein kinase I (cGKI; PKGI) is a cGMP target protein that phosphorylates different substrates after activation through cGMP. We investigated the potential correlation between the cGMP/cGKI pathway and NKCC2 regulation. We treated wild-type (wt) and cGKIα-rescue mice with furosemide. cGKIα-rescue mice expressed cGKIα only under the control of the smooth muscle-specific transgelin (SM22) promoter in a cGKI deficient background. Furosemide treatment increased the urine excretion of sodium and chloride in cGKIα-rescue mice compared to that in wt mice. We analyzed the phosphorylation of NKCC2 by western blotting and immunostaining using the phosphospecific antibody R5. The administration of furosemide significantly increased the phosphorylated NKCC2 signal in wt but not in cGKIα-rescue mice. NKCC2 activation led to its phosphorylation and membrane translocation. To examine whether cGKI was involved in this process, we analyzed vasodilator-stimulated phosphoprotein, which is phosphorylated by cGKI. Furosemide injection resulted in increased vasodilator-stimulated phosphoprotein phosphorylation in wt mice. We hypothesize that furosemide administration activated cGKI, leading to NKCC2 phosphorylation and membrane translocation. This cGKI-mediated pathway could be a mechanism to compensate for the inhibitory effect of furosemide on NKCC2.


Initial identification and characterization of sigma receptors on human peripheral blood leukocytes.
Phencyclidine (PCP) has been reported to suppress a variety of immune functions in vitro. Because PCP binds with high affinity to both PCP and sigma receptors, the identity of the receptor(s) mediating the immunological effects of PCP is unknown. The aim of the present study was to identify and characterize the sites of PCP action (sigma and/or PCP receptors) in human peripheral blood leukocytes (PBL) using [3H]haloperidol or 1,3 di(2-([5-3H]tolyl)guanidine ([3H]DTG) to specifically label sigma receptors and 3,4-[3H]-(N)-[1-(2-thienyl)-cyclohexyl]-piperidine ([3H]TCP) to specifically label PCP receptors. [3H]Haloperidol binding was saturable and of high affinity with comparable KD values in human PBL (0.44 +/- 0.10 nM) and rat cerebellum (0.51 +/- 0.09 nM). Similarly, [3H]DTG binding was saturable with comparable KD values of 29.5 +/- 3.5 and 26.4 +/- 3.6 nM in rat cerebellum and human PBL, respectively. In contrast, there was a notable absence of [3H]TCP-labeled PCP receptors in human PBL and rat cerebellum. In competition studies, the pharmacologic profile of [3H]haloperidol-labeled sigma receptors in human PBL was virtually identical with that in rat cerebellum (slope, 0.87; correlation coefficient, 0.96); the rank order of potency of competing drugs was haloperidol greater than l-butaclamol = pentazocine greater than d-3-(hydroxyphenyl)-N-(1-propyl)-piperidine greater than DTG = d-butaclamol = d-SKF 10,047 greater than levallorphan greater than or equal to PCP greater than or equal to l-SKF 10,047 greater than TCP greater than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)


Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in leukopenic patients with advanced HIV disease.
In order to assess the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of HIV-associated leukopenia, 35 subjects suffering from severe leukopenia/neutropenia (24 with a previous diagnosis of AIDS, 11 with AIDS-related complex), received rHuGM-CSF at 0.5-3 micrograms/Kg/day subcutaneously for a mean period of 9.7 +/- 12.5 weeks (range 2-43 weeks). Five patients have been treated continuously for more than 6 months. rHuGM-CSF administration led to a significant (at least two-fold; P < .001) increase in total leukocyte, neutrophil and monocyte count by the second week of treatment, subsequently maintained through the entire course of therapy. No considerable effects on other hematological, immunological and virological parameters have been detected. Patients treated with rHuGM-CSF did not suffer from novel opportunistic diseases, while bacterial infections occurred in only 3 cases (pneumonia in 2, otitis/mastoiditis in 1). Long-term treatment with rHuGM-CSF allowed continuation or resumption of potentially myelotoxic drugs in 22 patients out of 35. A self-limited flu-like syndrome represented the most common adverse event (observed in 15 patients), while no other significant clinical or laboratory abnormalities were found. In conclusion, long-term rHuGM-CSF therapy showed a good efficacy and safety profile in the treatment of HIV-related leukopenia, also increasing tolerability to potentially myelosuppressive drugs, and leading to a significant reduction in morbidity due to secondary infections.


Experimental heterotopic heart transplantation: an easier technique.
The use of heterotopic heart transplantation (HHT) in experimental surgery is an extended method to evaluate cardiac graft viability. To study endothelial injury after ischemia-reperfusion, the technique described by Matsui et al. in 1988 for HHT was chosen. A modification, which consists of replacing the atrium-to-atrium anastomosis for the tip of a 30-Fr venous cannula, was developed with the purpose of using this technique in small pigs. Both techniques were compared. Twenty-seven consecutive HHTs in 17- to 20-kg pigs using Matsui's original technique and the modified technique were performed. Ischemia time, bleeding volume, mean gradient and anastomosis complications were measured to compare both techniques. Statistically significant decreases in ischemia time, bleeding volume and mean gradient with the modified technique were found. Furthermore, there were two cases of suture dehiscence with the original technique. The replacement of the atrium-to-atrium anastomosis for the venous cannula is a modification that statistically decreases the ischemia time, blood loss and avoids suture complications. This modification makes Matsui's technique easier, faster and safer in small pigs and it may be used in bigger animals and in any kind of non-permanent anastomosis.


Beta-cell function and visceral fat in lactating women with a history of gestational diabetes.
Lactation has been recommended as beneficial for the maternal metabolic abnormalities associated with glucose intolerance and diabetes risk, although associations between breastfeeding (BF), glucose tolerance, and adipose tissue distribution are unknown. Therefore, a population of women with recent gestational diabetes (GDM) was evaluated with comparison of results for lactating versus nonlactating women. A total of 26 women participated (14 BF and 12 nonbreastfeeding [nonBF]) with a singleton vaginal delivery after 36 weeks gestation. At 3 months postpartum, each woman completed a 75-g oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), and computed tomography (CT) scanning for adipose distribution and mass. Insulin sensitivity was not significantly different between BF and nonBF groups (4.97 +/- 0.78 v 3.44 +/- 1.0 x 10(-4) min(-1)/(microU/mL) nor was glucose effectiveness (1.92 +/- 0.22 v 1.56 +/- 0.19 x 10(-2) min(-1)). However, the disposition index (DI) (insulin sensitivity [S(I)] x acute insulin response to glucose [AIRg]) was higher in the BF group (129.9 +/- 26.0 v 53.4 +/- 18.0 x 10(-4) min(-1); P =.03). Visceral fat (103 +/- 14 v 97 +/- 15 cm(2)) and subcutaneous fat (362 +/- 36 v 460 +/- 68 cm(2)) were similar between the groups. We conclude that 3 months of BF in a population with previous GDM was associated with improved pancreatic beta-cell function, but not with any difference in measures of adiposity.


Characterization of taurine as anti-obesity agent in C. elegans.
Taurine plays an important role in reducing physiological stress. Recent studies indicated that taurine may serve as an anti-obesity agent at the cellular level. This study characterizes taurine's potential anti-obesity function in C. elegans, which have become a popular in vivo model for understanding the regulatory basis of lipid biosynthesis and deposition. Two strains of C. elegans were raised on a normal or high-fat diet: N2 (normal) and RB1600, a mutant in tub-1 that serves as a tubby homologue and functions parallel to the 3-ketoacyl-CoA thiolase gene (kat-1) in regulating lipid accumulation. Taurine's effect on lipid deposition was characterized according to assays of Sudan black B staining, triglyceride content measurement, food consumption, and mobility comparison. When N2 was treated with taurine after the culture in the high-fat media, the worms showed lower lipid accumulation in the assays of the Sudan black B staining and the triglyceride quantification. The anti-obesity effect was less evident in the experiment for RB1600. When the amount of taurine was increased for the high-fat-diet-treated N2 strain, fat deposition decreased and mobility increased in a dose-dependent manner. In the food consumption assays, taurine did not cause a significant change in food intake. Taken together, these results strongly imply that taurine plays an important role in reducing fat deposition by modulating cellular pathways for lipid accumulation and stimulating mobility, but not the pathways for lipid biosynthesis and food intake.


How Much Hypertension is Attributed to Overweight, Obesity, and Hyperglycemia Using Adjusted Population Attributable Risk in Adults?
High blood pressure (HBP) is a proven risk factor for cardiovascular diseases. So, determining the extent of the contribution of the factors associated with HBP seems to be necessary. Accordingly, this study aimed to investigate how much the prevalence of HBP attributed to obesity and high blood glucose (HBG). Data were collected from 7612 participants extracted from a screening program in 2018, in Iran, which was conducted on the subjects with the age of 30 years old and older to investigate the prevalence of HBP and their associated risk factors. To collect data, we used a standard checklist in terms of the WHO STEPS manual, and a stratified multistage sampling method was also applied. The adjusted population attributable risk of overweight, obesity, and HBG for HBP was calculated by the logistic regression model using the aflogit module. Among the studied people, 7.4% of male and 10.8% of female subjects were hypertensive. The adjusted analysis showed that, in men, 27% and 41% and, among women, 19% and 37% of HBP prevalence rates were attributable to obesity (BMI ≥ 30) and fast blood sugar (FBS) (≥126), respectively. In people with both obesity and HBG, 59% of the prevalence rate of HBP in men and 46% of the prevalence in women were due to the abovementioned risk factors altogether. The results show that, if obesity and HBG were eliminated, the prevalence of HBP could be theoretically decreased from 7.4% to 5.4% and 4.3% in male subjects and from 10.8% to 8.7% and 6.8% in female subjects, respectively. Our findings indicate that how much the prevalence of HBP attributes to obesity and HBG in middle-age and older population. It seems that the prevention programs should be administered in the general population, and excess body weight prevention programs should also be implemented in childhood.


The Mediating Role of Social Support in the Relationship Between Parenting Styles and Adolescent Drug Abuse Identification.
Adolescent drug abuse is a social issue of global concern, causing a serious burden of diseases for individuals, families and society. To design effective prevention and intervention strategies for adolescent drug abusers, the predictive factors associated with drug abuse must be quantified and assessed. This study explores the similarities and differences between the parenting styles of adolescent drug abusers and non-drug abusers and applies a structural equation model to analyze the mechanisms involved between parenting styles, social support and adolescent drug abuse identification. Data were derived from adolescent drug abusers (n = 363) and non-drug abusers (n = 229) between the ages of 18 and 35 in China, and the data were collected and analyzed by SPSS 26 and AMOS 24. The results show that parenting styles significantly predict adolescent drug abuse identification, and different parenting styles have different influencing mechanisms, which further indicates that poor parenting styles are a risk factor for adolescent drug abuse. Additionally, social support plays a mediating role between parenting styles and drug abuse identification (χ2/df = 4.52, CFI = 0.939, TLI = 0.914, RMSEA = 0.077, IFI = 0.939, PCFI = 0.671). The specific pathways involved are as follows: Paternal parenting style → Social support → Drug abuse identification and Maternal parenting style → Social support → Drug abuse identification. However, beyond this, the mediation model of social support shows good adaptability and stability between adolescent drug abusers and non-drug abusers. Since parenting styles and social support are important predictors of adolescent drug abuse, the importance of integrating family-social support antidrug programs into adolescent prevention and intervention strategies should be considered.


Identification of putative homology between horse microsatellite flanking sequences and cross-species ESTs, mRNAs and genomic sequences.
In this study the flanking sequences of 1534 horse microsatellites were used in a BLAST search to identify putative human-horse homologies. BLAST searches revealed 129 flanking sequences with significant blastn matches [alignment scores (S) > or = 60 and sum probability values (E) < or = 3.0E-6], also, 25 of these produced significant blastx matches. To provide a reference point in the human genome the flanking sequences with matches were subjected to a BLAT search of the University of California Santa Cruz (UCSC) human genome assembly (July 2003 freeze). Eighty-three of the flanking sequences showed high similarity to sequence of known or putative human genes and the remaining 46 demonstrated high similarity to human intragenic regions. Interestingly, 87 of the microsatellites showed conservation of the tandem repeat in addition to flanking regions. Overall, 41 of the microsatellites had been mapped in the horse and of these 37 localized to the expected syntenic location. The other four did not and represent new putative regions of human-horse synteny. The results of this study contribute 79 new putative human-horse homologies, increasing the density of markers on the human-horse comparative map.


Politics, public policy, and the development of community mental retardation services in the United States.
Data emanating from the community services component of the Third National Study of Public Spending for Mental Retardation and Developmental Disabilities was analyzed. An empirical model of community services spending in the states was tested in a hierarchical regression analysis using cumulative community services fiscal effort in the states across 1977-1988 as the dependent variable. Strength of consumer advocacy organizations in the states coupled with states' historical orientations toward the adoption of policies promoting racial equality were highly significant predictors of state-by-state variance in community spending patterns. The implications of this and other findings emerging from the national study were discussed.


Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.
To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.


Calcium supplementation increases blood creatinine concentration in a randomized controlled trial.
Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied. We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675) aged 45-75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations. After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2-6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment. Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation. ClinicalTrials.gov NCT00153816.


[Uniformity and diversity of the human image in scientifically oriented human medicine].
Nowadays, hardly anyone would oppose the demand for more rationally based medicine--the catchword here being "evidence-based medicine" (EBM). Anyone trying to comply with this demand will be faced with the question of what is meant by "evidence". It would be false to think that rationality is guaranteed by applying the Galilean method of exact induction. Exact induction aims at objective propositions free of subjectivity. Such propositions are regarded as generally valid, or "true". They lead us toward the transcendent platonic "idea", which is by definition beyond our reach. Exact induction enables us to derive representations of a transcendent idea by means of experimental research. These representations may or may not be useful in actuality, for example in medical therapeutic strategies. Strictly speaking, reproducibility, which is generally taken as proof of a given hypothesis, is not equivalent to identity. Identity implies, among other things, simultaneity.


Chlamydia trachomatis infection in male partners of infertile couples: incidence and sperm function.
Chlamydia trachomatis infection is one of the most common sexually transmitted diseases. Its effect on male fertility, however, is still controversial. In this study, 284 male partners of infertile couples consulting the Center of Studies in Reproductive Biology (CEBRE) were analyzed. The incidence of C. trachomatis infection among male partners of infertile couples was 38.6%. There were no significant differences between infected and noninfected infertile men in any of the sperm parameters assessed (sperm concentration, motility and morphology). The results of the three bioassays developed to evaluate sperm physiology, namely spermatozoa-zona pellucida binding, acrosome reaction stimulated with human follicular fluid and zona-free hamster oocyte penetration, showed no differences between infected and noninfected men. Electron microscopy studies suggest that spermatozoa are active agents in the dissemination of the chlamydial infection; they could be acting as 'vehicles' for the pathogens. These, and other results, suggest that the possible effect of C. trachomatis on male fertility is not due to alterations in sperm 'quality' or function, but rather to the transmission of the disease to female partners, causing inflammatory processes and promoting the generation of antisperm antibodies.


[Experimental study on antagonism of ginkgolides against effect of platelet-activating factor on lung strip of guinea pigs].
To investigate the action of ginkgolides antagonizing the contraction of guinea pigs' lung strip induced by the mixture of platelet-activating factor (PAF) and platelets and its effect of preventing the PAF caused damage of beta-adrenergic receptors. The contraction of guinea pigs' isolated lung strip was measured. The mixture of PAF and platelet could produce a serious contraction of lung strip, the IC50 reached 4.69 x 10(-7) mol/L, while the contraction induced by PAF alone was relatively mild, its IC50 only 6.66 x 10(-4) mol/L, the difference between them was significant (P < 0.05). When the platelets were preincubated with ginkgolides for 10 minutes in Tris-Tyrode's buffered saline, the effects of PAF and platelets mixture were significantly inhibited (P < 0.05). Exposure of guinea pigs' lung strip to PAF in vitro resulted in a loss of beta-adrenergic receptors and weakened its respones to isoproterenol, a receptor activating factor, the EC50 would be increased from 1.38 x 10(-6) mol/L to 6.25 x 10(-6) mol/L, P < 0.05. This effect of PAF could also be inhibited by ginkgolides (P < 0.05). Ginkgolides is a promising PAF antagonist, and might be used in treating bronchial asthma.


Impaired insulin-stimulated nonoxidative glucose metabolism in glucose-tolerant women with previous gestational diabetes.
Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes. Twelve women with previous gestational diabetes and 11 controls were examined by oral and intravenous glucose tolerance tests and a hyperinsulinemic euglycemic clamp including indirect calorimetry. All women were lean and had normal oral glucose tolerance test results. Activities of glycogen synthase, phosphofructokinase, and hexokinase were measured in vastus lateralis muscle biopsy specimens obtained in the basal state and after insulin stimulation. Women with previous gestational diabetes had a decreased glucose disposal rate (p<0.01) because of a reduced insulin-stimulated nonoxidative glucose metabolism (6.63 +/- 0.47 vs 9.04 +/- 0.57 mg/kg fat-free mass per minute, p<0.01). The muscle activities of glycogen synthase, phosphofructokinase, and hexokinase were similar in the two groups. The first-phase insulin response to the intravenous glucose tolerance test was, in absolute terms, comparable in the two groups. However, when the decreased insulin sensitivity was taken into account, women with previous gestational diabetes had a relative insulin secretion deficiency. Women with previous gestational diabetes have a decreased insulin sensitivity and a relative impairment of insulin secretion.


The expression of long non-coding RNA HOTAIR in advanced hepatocellular carcinoma and its prognostic correlation with sunitinib therapy.
The study was designed to assess the expression of long non-coding RNA HOTAIR (lncRNA HOTAIR) in tissues and peripheral blood of patients with advanced hepatocellular carcinoma (HCC). In addition, we also investigated the prognostic correlation between the expression level of lncRNA HOTAIR in tumour tissues and peripheral blood of patients with advanced HCC and sunitinib monotherapy. A total of 60 patients with advanced HCC who received sunitinib monotherapy and another 60 healthy individuals who were examined at the physical examination centre during the same period were included in the study. Real-time quantitative PCR (RT-QPCR) was used to determine the relative expression of lncRNA HOTAIR in tumour tissue, adjacent tissue, and peripheral blood of HCC patients as well as peripheral blood of healthy controls. Moreover, the clinicopathological information, overall survival (OS), and progression-free survival (PFS) were collected, followed by correlation analysis with lncRNA HOTAIR expression. The expression of lncRNA HOTAIR was significantly higher in tumour tissues compared to that in adjacent tissues (t = 9.03, p < 0.001). The expression of lncRNA HOTAIR in peripheral blood of HCC patients was higher than that in healthy controls (t = 8.04, p < 0.001). There was a correlation between the expression of lncRNA HOTAIR in tumour tissue and peripheral blood in HCC patients (r = 0.638, p < 0.001). Patients with low lncRNA HOTAIR expression in tumour tissues harboured significantly longer OS (13.4 vs. 9.5, p < 0.001) and PFS (8.4 vs. 6.2, p < 0.001) compared to those with high expression. Consistently, patients with low lncRNA HOTAIR expression in peripheral blood had significantly prolonged OS (12.8 vs. 9.1, p < 0.001) and PFS (8.9 vs. 6.4, p < 0.001) compared to those with high expression. Patients with low expression both in tumour tissue and peripheral blood had prolonged OS (14.3 vs. 8.8, p < 0.001) and PFS (10.6 vs. 6.0, p < 0.001) compared to the rest of the patients. Cox regression analysis indicated that the expression level of lncRNA HOTAIR in tumour tissue and peripheral blood was an independent predictive factor of OS and PFS in patients with advanced HCC treated by sunitinib. The expression of lncRNA HOTAIR was up-regulated in tumour tissue and peripheral blood in patients with advanced HCC. In addition, the expression level of lncRNA HOTAIR was one of the indicators predicting the effectiveness of sunitinib therapy.


An imaging algorithm for the differential diagnosis of adrenal adenomas and metastases.
The purpose of this study was to develop an algorithm using CT and chemical-shift MR imaging for the characterization of adrenal masses in patients with a primary cancer and no other evidence of metastatic disease. Thirty-three patients with 37 adrenal masses (19 metastases, 18 adenomas), all of whom had a known primary cancer, were studied with noncontrast CT and chemical-shift MR imaging (1.5 T). Lesion size and density in Hounsfield units (H) were determined by CT. Adrenal signal intensity normalized to that of spleen was used to calculate adrenal-spleen ratio (ASR), defined as the percentage of signal remaining in the opposed-phase image relative to the in-phase image. Lesions less than or equal to 0 H were classified as benign, lesions greater than 20 H were regarded as malignant, and lesions between 0 and 20 H were regarded as indeterminate. Diagnoses were confirmed by biopsy (for 19 lesions) or by follow-up imaging (for 18 lesions). An imaging algorithm was derived by determining the relative value of CT and MR imaging for diagnosing the lesions. The reimbursement rates for CT-guided biopsy and MR imaging of the abdomen were obtained from Medicare. All 13 lesions of 0 or less H were correctly classified as benign by CT. ASR was less than 70 in 10 of these 13. In another 13 lesions, H was greater than 20; all were malignant and all had an ASR greater than 80. Of 11 CT-indeterminate lesions, four of five adenomas had an ASR less than 70, and four of six metastases had an ASR greater than 80. Two malignant lesions had ASRs between 70 and 80 and were diagnosed by biopsy findings. One CT-indeterminate adenoma had an ASR of 84 and was diagnosed by biopsy findings. The reimbursement rate by Medicare is similar for CT-guided biopsy with pathologic interpretation and for MR imaging of the abdomen. An algorithm was developed for diagnosis of adrenal lesions that uses the density reading on noncontrast CT as the first step, with chemical-shift MR imaging for CT-indeterminate lesions. In this algorithm, lesions of 0 H or less may be regarded as benign and further work-up is not required. Lesions with a density greater than 20 H are likely malignant and should be biopsied when the result will influence management. For CT-indeterminate lesions, we recommend chemical-shift MR imaging. An ASR threshold of 70 indicates a benign lesion, and no further workup is required in these patients. Lesions with an ASR greater than 70 should have a biopsy performed, depending on the clinical situation. The above algorithm is cost-effective and reduces the number of biopsies required without reducing the sensitivity of detecting malignant lesions.


Cognitive impairment related to arterial stiffness in cardiovascular disease patients with severe periodontitis.
Severe periodontal disease (SPD) associated with systemic peripheral inflammation, cognitive impairment (CI) and arterial stiffness (AS) has been recognized. The aim of this study was to investigate whether CI and arterial stiffness (AS) occur in cardiovascular disease (CVD) patients with SPD. A crosssectional case-control study included hospitalized patients with CVD. Demographic characteristics, CVD and atherogenic risk factors were recorded. SPD was diagnosed by clinical and radiographic dental examinations. Dental clinical attachment level (CAL) and CAL % were recorded. A Mini-Mental State Examination test (MMSE) assessed cognition, a MMSE score of < 27 was set as the cut-off point of CI; a score ≥ 27 was considered as no CI. Patients were categorized into: MMSE<27 (cases) and MMSE≥27 (controls). AS was evaluated by pulse wave velocity (PWV). Serum VCAM-1 levels were determined in a random sample. Results: This study comprised 91 patients (cases, n=26; 29.6%; controls, n=65, 71.4%); aged 73±8 vs. 73±7 years, respectively (p=0.73), of whom 53.8% and 36.9% respectively, were women; SPD was found to be a risk factor for CI; the presence of SPD increased the risk for MMSE <27 by an average 5.39 times (model 1). PWV was associated with MMSE < 27 in the three models. The risk of having MMSE < 27 increased an average of 2.404-fold for each 1-unit increase in PWV. SPD and AS had significant and independent associations on the risk for development CI. MMSE negatively correlated with CAL% (r=0.69) and PWV (r=0.70). PWV positively correlated with CAL% (r=0.67). Serum VCAM-1 levels were higher in SPD with lower MMSE scores. In conclusion, SPD increases the risk of development of cognitive decline in CVD patients. PWV was directly associated with the risk of cognitive decline. These findings denote a significant opportunity to improve periodontal health in order to avert CI in CVD patients.


CircFOXP1: A novel serum diagnostic biomarker for non-small cell lung cancer.
Emerging evidence suggests that circular RNAs (circRNAs) were aberrantly expressed in the patients of non-small cell lung cancer (NSCLC). This study aims to evaluate the diagnostic value of potential serum biomarker in circRNAs. Serum circRNAs were extracted and purified by RNA isolated kit and identified by quantitative real time-polymerase chain reaction (qRT-PCR) assay. We then performed a receiver operating characteristic (ROC) curve to estimate the diagnostic efficacy. The relationship between circRNA and clinic characteristics of patients was analyzed by SPSS 25.0. Univariate and multivariate analyses were also used to evaluate its diagnostic capability. The mechanism of circFOXP1 was further excavated by bioinformatics analysis. By performing qRT-PCR assay, we identified that circFOXP1 (hsa_circ_0008234) and conventional tumor markers (carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA21-1)) were all significantly overexpressed in the serum of patients with NSCLC when compared with healthy controls (P < 0.05). While the ROC curves analysis demonstrated that area under the curve of circFOXP1 was obviously superior to CEA and CYFRA21-1, which exerted more diagnostic advantage. Univariate and multivariate analyses revealed that serum circFOXP1 was an independent diagnostic molecule, and was significantly correlated with T stage and lymphatic metastasis in NSCLC (P < 0.05). Mechanistically, circFOXP1 might target hsa-miR-370-3p and hsa-miR-18a-5p, and be involved in vascular endothelial growth factor signaling pathways to regulate proliferative and metastasis processes. Our results highlight the preferable diagnostic potential of serum circFOXP1 in NSCLC.