Vaginitis: a common malady.
Approximately 90 per cent of all the vaginitides are caused by bacterial vaginosis, candidiasis, or trichomoniasis. Bacterial vaginosis is the most frequent, causing approximately 50 per cent of vaginal infections. As described by Amsel and colleagues, three of four findings indicate bacterial vaginosis: amine odor, pH greater than 4.5, clue cells, and a thin homogeneous discharge. Because G. vaginalis colonizes the vagina, treatment should not be instituted in an asymptomatic woman on the basis of a positive culture. For symptomatic patients, oral metronidazole 500 mg twice daily for 7 days is the treatment currently recommended. Vulvovaginal pruritus should be equated with candidiasis until proven otherwise. Mycelia or spores on 10 per cent KOH preparation are diagnostic of candidiasis in the presence of symptoms. Imidazole creams or suppositories are the treatment of choice. Trichomoniasis is characterized by malodor and mild pruritus. Demonstration of trichomonads on saline preparation or a positive culture provides the diagnosis. A single 2 gm dose of oral metronidazole is the initial treatment. Recurrences should provoke inquiry regarding predisposing factors and investigation of sexual partners. Vaginitis can recur, but if approached properly, these recurrences can be minimized, allowing the patient to proceed with daily life in comfort.


Biomass fuel as a risk factor for esophageal squamous cell carcinoma: a systematic review and meta-analysis.
The link between use of solid biomass fuel (wood, charcoal, coal, dung, and crop residues) for cooking and/or heating and esophageal squamous cell carcinoma (ESCC) is inconclusive. We systematically reviewed the literature and performed a meta-analysis to determine whether cooking fuel type influences esophageal squamous cell carcinoma. We searched MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating cooking fuel and ESCC from 2000 until March 2019. We performed random effects meta-analysis stratified by the continent, World Bank's country income classifications and fuel type and calculated pooled odds ratios and 95% CIs for the risk of esophageal squamous cell carcinoma in biomass fuel users compared with non-users. Our analysis included 16 studies (all case-control) with 16,189 participants (5233 cases and 10,956 controls) that compared risk of ESCC among those using nonsolid fuels and biomass fuels. We found use of biomass fuel was associated with Esophageal squamous cell carcinoma with a pooled odds ratio (OR) 3.02 (95% CI 2.22, 4.11, heterogeneity (I2) = 79%). In sub-group analyses by continent, Africa (OR 3.35, 95%CI 2.34, 4.80, I2 = 73.4%) and Asia (OR 3.08, 95%CI 1.27, 7.43, I2 = 81.7%) had the highest odds of ESCC. Use of wood as fuel had the highest odds of 3.90, 95% CI 2.25, 6.77, I2 = 63.5%). No significant publication bias was detected. Biomass fuel is associated with increased risk of Esophageal squamous cell carcinoma. Biomass fuel status should be considered in the risk assessment for Esophageal squamous cell carcinoma.


Colorimetric detection of thiol-containing amino acids using gold nanoparticles.
This paper reports findings of an investigation of the unusual colorimetric change of gold nanoparticles in the presence of thiol-containing amino acids such as homocysteine, cysteine and glutathione. The colorimetric change for homocysteine exhibits a rate that is about two orders of magnitude higher than that for cysteine, and at least five orders of magnitude higher than that for glutathione. The reactivity is effectively reduced or suppressed by the coexistence of either cysteine or glutathione. It is believed that the reactivity involves encapsulation of the particles by the thiol-containing amino acids which is followed by crosslinking at the encapsulating shells. In comparison with cysteine and glutathione, homocysteine has a slower encapsulating rate but a faster crosslinking rate. Implications of the findings of the interfacial encapsulation and crosslinking reactivities of gold nanoparticles to potential nanoparticle-enhanced analytical detection of thiol-containing amino acids are also briefly discussed.


Treatment of melanotic freckle with x-rays.
Sixteen patients were treated for melanotic freckle of Hutchinson (lentigo maligna) with the Miescher technique of x-ray therapy. Eleven patients had no local cutaneous recurrences of persistence following x-ray therapy. Five patients had local recurrence or persistence of their lesions. Three patients developed metastatic malignant melanoma. The first of these three patients had lentigo maligna melanoma, and the second patient had a melanotic freckle with atypical cells extending down the adnexae, including the sweat apparatus to the level of the coiled portion of one sweat gland. The third patient was considered to be in a precancerous phase at the time of irradiation. Nevertheless, metastases occurred. European colleagues indicate that they have not experienced such problems in using the Miescher technique. The procedure has been abandoned in our department, pending further clarification of the discrepancy between our results and those reported by our European colleagues.


Protein ubiquitination and formation of polyubiquitin chains without ATP, E1 and E2 enzymes.
Studying protein ubiquitination is difficult due to the complexity of the E1-E2-E3 ubiquitination cascade. Here we report the discovery that C-terminal ubiquitin thioesters can undergo direct transthiolation with the catalytic cysteine of the model HECT E3 ubiquitin ligase Rsp5 to form a catalytically active Rsp5∼ubiquitin thioester (Rsp5∼Ub). The resulting Rsp5∼Ub undergoes efficient autoubiquitination, ubiquitinates protein substrates, and synthesizes polyubiquitin chains with native Ub isopeptide linkage specificity. Since the developed chemical system bypasses the need for ATP, E1 and E2 enzymes while maintaining the native HECT E3 mechanism, we named it "Bypassing System" (ByS). Importantly, ByS provides direct evidence that E2 enzymes are dispensable for K63 specific isopeptide bond formation between ubiquitin molecules by Rsp5 in vitro. Additionally, six other E3 enzymes including Nedd4-1, Nedd4-2, Itch, and Wwp1 HECT ligases, along with Parkin and HHARI RBR ligases processed Ub thioesters under ByS reaction conditions. These findings provide general mechanistic insights on protein ubiquitination, and offer new strategies for assay development to discover pharmacological modulators of E3 enzymes.


The Present and Future of Genomics in Adult Reconstructive Orthopaedic Surgery.
As of 2015, members of the "baby boomer generation" comprise 75 million people in the growing United States population. Many of these individuals will be facing the need for total hip or knee replacement. Currently, the age of onset of osteoarthritis continues to decrease and the need for total joint replacements continues to increase. In current practice, nearly all patients undergoing joint replacement receive similar preoperative, intraoperative, and postoperative management strategies. However, wide variability in outcomes and satisfaction with total joint replacement still remain. The key to understanding the cause for such varied outcomes may lie in our understanding of the genetic basis of degenerative joint disease. The future of "orthogenomic" research should be centered on clinical application focusing on early preoperative identification of at-risk patients. The goal is to establish twenty-first-century patient-specific strategies for optimizing results and expectations after adult reconstructive surgery.


The need for mandatory clinical recording standards.
Current health information initiatives and targets set by the UK government have brought about a flurry of activity in the National Health Service to try to reach those targets. One target is to implement an electronic patient record system as a replacement for the present paper-based system of record keeping. However, this will not be an easy task; simply introducing information technology into an already chaotic system will only compound existing problems. This article highlights the gaps that must be filled before an electronic record system can be effectively implemented. The two major elements that are missing are mandatory clinical recording standards and a profession that is responsible for monitoring and enforcing those standards. Some examples of relevant standards for clinical recording are provided and the role of a health information management profession is described.


Genetic systems of red cell blood groups in goats.
Evidence is presented for six genetic systems of goat red cell blood groups. The A system presently consists of one specificity, two alleles, two phenotypes (A1 and no-A1) and appears to be homologous to the A system of sheep. The B system, like its homologue in sheep, is very complex. Fourteen of 21 specificities detected in the present study, i.e. B2, B3, B4, B5, B7, B8, B9, B10, B11, B14, B15, B16, B17 and B20, belong to the B system which involves a large number of phenogroups (31 different B phenogroups identified in 26 sires). Because of their homology with sheep C and R systems, two other genetic systems of goat blood groups are named C and R respectively. Each of the two goat systems is presently a one blood group specificity, two phenotype (C12 and no-C12; R and no-R detectable on the red cells) two allele system. Two specificities, namely E6 and E18, belong to a genetic system called E in which four phenotypes are under the control of two alleles codominant and one recessive at a single locus. The F system involves but a single pair of alleles and two phenotypes (F19 and no-F19). Because of its low frequency in the goats tested, the X13 specificity remains unassigned.


Hemoglobin E disease and glycosylated hemoglobin.
Glycosylated hemoglobin (HbA1C) is a routinely measured parameter to monitor long-term glycemic control in people with diabetes mellitus. The presence of hemoglobin (Hb) variants can affect the accuracy of HbA1C methods. Hb E variant is the most common Hb variant in South-east Asia and North-east India. In the presence of Hb E, HbA1C may not be detectable by ion-exchange chromatography (high-pressure liquid chromatography), but may be estimated by immunoassay technique and boronate affinity chromatography. However, the result may be underestimated when correlated with plasma glucose and serum fructosamine levels. Clinicians should be aware of this limitation of HbA1C estimation in patients with Hb E and other Hb variants.


Wound healing for the dermatologic surgeon.
An understanding of the basic science of cutaneous wound repair is essential to the dermatologic surgeon for the management of the postoperative wound. This review discusses the stages of wound healing and then applies these principles to the preoperative, intraoperative, and postoperative management of the surgical patient.


[Not Available].
The ideas of such prominent geneticists as Vries, Cuenot, Guyenot, Johannsen, Tchetverykov, Philiptchenko are considered. The conjectures on the specific mechanisms of evolution above the species level may be found in many of them. The very terms of micro- and macroevolution have been proposed by Philiptchenko in 1927. But he denied any role of genetics in puzzling of the higher taxa origin, the letter being connected him with sexual sells plasma. The actual significance of Goldschmidt's conception about systemic mutations is mentioned.


[Questions and answers regarding the use of rivaroxaban in daily practice].
Several new oral anticoagulants are now on the Swiss market and the general practitioner faces new challenges regarding the management of these new drugs. This consensus document aims to answer to the most frequently asked questions regarding rivaroxaban and covers different topics such as indications, initiation of treatment, drug-drug interactions and perioperative management.


Pharmacogenetic approach to losartan in Marfan patients: a starting point to improve dosing regimen?
Losartan is under evaluation for managing Marfan patients with aortic root dilatation. Cytochrome P450 (CYP) enzymes convert losartan to E3174 active metabolite. The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. We genotyped 53 paediatric Marfan patients treated with losartan. The rate of aortic root dilatation was evaluated using the delta z-score variation. Differences in tolerated losartan daily doses with respect to CYP metabolic classes were assessed through the Kruskal-Wallis test. The losartan daily dose spans from 0.16 to 2.50 mg/kg (median 1.10 mg/kg). As we expect from the pharmacokinetics pathway, we observe highest tolerated dose in CYP2C9 poor metabolisers (median 1.50 mg/kg, interquartile range 1.08-1.67 mg/kg); however, this difference is not statistically significant. The optimal dose of angiotensin receptor blocker is not known, and no data are available about losartan pharmacogenetic profile in Marfan syndrome; we have proposed a strategy to tackle this issue based on evaluating the major genetic polymorphisms involved in the losartan conversion into active carboxylic acid metabolite. Further studies are needed to support the use of genetic polymorphisms as predictors of the right dose of losartan.


Production and characterization of xenogeneic antisera to tumor-associated antigen(s).
Tumor-associated antigen(s) from a specimen of human malignant melanoma and from spent culture medium of a melanoma cell line were extracted and purified. The incidence of antibody activity to these antigens, in sera from cancer patients with neoplasms of various histologic types, was higher (65--83%) than normal donors' (19--25%) by the complement fixation assay. These purified antigens were then used to raise antisera in rabbits and sheep. After absorption with various human normal tissues, these antisera reacted against melanoma, sarcoma, and carcinoma extracts, but not against human normal liver, skin, or muscle extracts. However, the antisera showed reactivity against a human fetal homogenate. Results indicate that the xenogeneic antisera contained antibodies to fetal antigens and to tumor-associated antigen(s). Xenogeneic antisera could be used to purify tumor-associated antigens and oncofetal antigen(s) from crude extracts by affinity chromatography.


Views of pediatric health care providers on the use of herbs and dietary supplements in children.
Herbs and dietary supplements (HDS) are widely used by adults for treating illnesses and/or preserving good health, and many parents use HDS for their children as well. Previous reports suggest parents will not divulge HDS use to health care providers for fear of their skepticism or disapproval. Yet the views of pediatric health care providers on HDS use in children are not well known. This study investigated the attitudes and practices of pediatric nurses and physicians regarding HDS use in children, in order to identify those characteristics associated with a high degree of confidence in initiating a dialogue on the topic of HDS with families in their practice. A written survey on attitudes and practices toward HDS was developed, piloted, revised, and then administered to a convenience sample of practitioners attending a regional postgraduate course in general pediatrics. Only 42% of 204 pediatric health care providers sampled felt confident in initiating discussions about the therapeutic use of herbs and dietary supplements with families in their practice. Confidence in discussing HDS with families correlated with both personal use of an HDS (OR 3.22; p=0.033) and length of time in practice less than 10 years (OR 8.26; p=0.007). Less than 18% felt that HDS were safe for children under 6 months of age; and only 35% felt they were safe for use in children < 24 months old. Only 7% felt that parents should be allowed to give their hospitalized child an herb or dietary supplement they had brought with them from home, although this increased to 35% if the herb or dietary supplement had been prescribed by a physician. Ninety-two percent of practitioners thought that HDS should be more closely regulated by the FDA. Only a minority of pediatric community practitioners felt confident in discussing HDS with families of children in their practice. Those who had been in practice for a shorter time and who had used HDS themselves were more likely to report confidence in initiating such discussions. The provision of more postgraduate educational opportunities to learn about herbs and dietary supplements may alleviate some practitioners' concerns about their own competency in discussing HDS with families in their practice.


Gardner-Diamond syndrome: Difficulties in the management of patients with unexplained medical symptoms.
The case of an adolescent girl who presented with unexplained bruising is reported. Subsequent investigations failed to elucidate an organic etiology. The diagnosis of Gardner-Diamond syndrome - a syndrome of predictable bruising preceded by pain and warmth at the bruise site, often associated with physical or psychosocial stress - was made. In the present report, the authors use their experience with this rare syndrome to highlight some important ethical and practical considerations with regard to investigation, treatment and communication in illnesses with unexplained medical symptoms.


[Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid].
Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.


Signal evaluations using singular value decomposition for Thomson scattering diagnostics.
This paper provides a novel method for evaluating signal intensities in incoherent Thomson scattering diagnostics. A double-pass Thomson scattering system, where a laser passes through the plasma twice, generates two scattering pulses from the plasma. Evaluations of the signal intensities in the spectrometer are sometimes difficult due to noise and stray light. We apply the singular value decomposition method to Thomson scattering data with strong noise components. Results show that the average accuracy of the measured electron temperature (Te) is superior to that of temperature obtained using a low-pass filter (<20 MHz) or without any filters.


[Evaluation of surgical treatment of mitral valve defect in patients with chronic renal failure].
Renal failure of patients qualified for open-heart surgical treatment seems to be very important problem since years. The operation with extracorporeal circulation is large burden for kidneys and there is huge risk of intensifying of existing failure. The aim of the study was the evaluation of renal parameters, complications occurrence and mortality of patients with chronic renal failure (ChRF) (grade II--mild ChRF) subjected to mitral valve replacement. To retro- and prospective analysis were subjected 34 patients with severe mitral valve defect, subjected to operation between 1998 and 2002 in Department of Cardiac Surgery in Lodz. All patients included to study had increased level of creatinine--1, 5-3, 0 mg/dl (at least in three measurements). All examined patients were subjected to artificial mitral valve replacement and 13 patients to simultaneous tricuspid valve plastic surgery. Postoperative evaluation of clinical condition and renal parameters was performed twice: early (till 30 day after operation) and long-term (after meanly 14 months). In seven patients, in early postoperative period, it was necessary to implement extracorporeal dialysis with artificial kidney dialysis machine. Among these patients we ascertained three deaths (intrahospital mortality was 8.8%). During long-term observation we noted two cases of infective endocarditis requiring reoperation and re-implantation of mitral valve. During this time of observation only one death was noted (post-hospital mortality was 3.2%). Dysfunction of kidneys, even in mild degree, causes significant increase of risk of early death (about 2.5 times). In most research population in long-term observation we ascertained the large improvement of kidney functions (significant decrease of creatinine level; p < 0.001). Concomitant tricuspid valve regurgitation, requiring plastic surgery is an additional factor incriminating long-term results of surgical treatment.


Conformation of peroxynitrite: determination by crystallographic analysis.
Peroxynitrite is an inorganic toxin of biological importance. It is formed in vivo from the diffusion-limited reaction of nitrogen monoxide with superoxide. Due to the partial double bond between the nitrogen and the first peroxide oxygen, peroxynitrite can occur in two conformations, cis and trans. The synthesis of tetramethylammonium peroxynitrite in ammonia [Bohle, D. S., et al. (1994) J. Am. Chem. Soc. 116, 7423-7424] yields small crystals if the ammonia is left to evaporate slowly. X-ray structure analysis shows that peroxynitrite crystallizes in the cis form, relative to the N-O bond. Crystal twinning or disorder prevents the determination of accurate bond lengths and bond angles. However, a nearly flat (torsion angle of 22 degrees ) molecule with O=N, N-O, and O-O bond lengths of 1.16, 1.35, and 1.41 A, respectively, would fit the observed electron density best. The space group of tetramethylammonium peroxynitrite is Pmmn (59), and it has the following unit cell dimensions: a = 7.1778(11) A, b = 8.6893(13) A, and c = 5.7266(9) A.


Using the theory of planned behaviour to predict nurse's intention to undertake dual practice in China: A multicentre survey.
To identify the intention of nurses to dual practice (DP) and inform policymaking in centralised government settings. DP is pervasive worldwide but was not permitted in China until 2009, with a primary goal of encouraging nurses from over-staffed health services to work additional shifts in understaffed settings. A descriptive cross-sectional survey. A DP questionnaire based on the theory of planned behaviour was developed and issued to nurses from three comprehensive public hospitals in 24 units selected by stratified random cluster sampling (n = 526). This study was reported based on STROBE checklist. The mean for intention was 3.47 with strongly disagree as one point, neutral as three point and strongly agree as five point in scaling. Nurses with any of these characteristics: female, aged between 40 and 49, married, working more than 15 years, and managers were significantly reluctant to undertake DP. The structural equation model showed that the level of positive attitude, subjective norm and perceived behavioural control could positively predict intention, and attitude had highest effect value. Perceived behavioural control and attitude acted as sequential mediators between subjective norm and intention. Nurses preferred large or private hospitals if conducting DP without restriction from the government. Nurses' intention to undertake DP was not strong, which was impacted by attitude, subjective norm, time and energy. Nurses preferred large or private hospitals; therefore, the goal of improving equity by DP in developing countries might be undermined. To encourage DP, attitude and subjective norm are important paths, the latter being the initial step. Reasonable incentives or restrictions, such as specifying regulations on practice place and time limitation, qualifications and legal liability and remuneration are recommended to ensure successful DP implementation from over-staffed health services to understaffed settings.


Specific beta-adrenergic receptor binding of carazolol measured with PET.
Carazolol is a promising high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using PET. Earlier investigations demonstrated specific receptor binding of carazolol in mice. These PET studies with S(-)-[2"-11C]carazolol in pigs were performed to explore the utility of the tracer for PET receptor studies. Tracer uptake in the heart and lung was measured by PET as a function of time. Receptors were blocked with propranolol and different doses of ICI 118,551 to estimate specific binding. Fluorine-18-1"-Fluorocarazolol and the less active R-enantiomer of [11C]-carazolol were also studied. Specific receptor binding was 75% of the total uptake in the heart, preventable and displaceable by propranolol. Dose-dependent competition showed that carazolol binds in vivo to beta 1 and to beta 2 subtypes. Uptake of the labeled R(+) enantiomer of carazolol was not receptor-specific. Carazolol labeled with 11C or 18F is a strong candidate for use in receptor estimation with PET. The in vivo observations were consistent with its known high affinity and slow receptor dissociation rate. Its high specific receptor uptake and low metabolism allow existing kinetic models to be applied for receptor measurements. The 11C label is convenient for repeated administrations, though 18F allowed the long observation periods necessary for measurement of the receptor dissociation rate. If needed, nonspecific uptake can be estimated without pharmacologic intervention by using the labeled R enantiomer.


Vortex-induced vibrations of a flexible cylinder at large inclination angle.
The free vibrations of a flexible circular cylinder inclined at 80° within a uniform current are investigated by means of direct numerical simulation, at Reynolds number 500 based on the body diameter and inflow velocity. In spite of the large inclination angle, the cylinder exhibits regular in-line and cross-flow vibrations excited by the flow through the lock-in mechanism, i.e. synchronization of body motion and vortex formation. A profound reconfiguration of the wake is observed compared with the stationary body case. The vortex-induced vibrations are found to occur under parallel, but also oblique vortex shedding where the spanwise wavenumbers of the wake and structural response coincide. The shedding angle and frequency increase with the spanwise wavenumber. The cylinder vibrations and fluid forces present a persistent spanwise asymmetry which relates to the asymmetry of the local current relative to the body axis, owing to its in-line bending. In particular, the asymmetrical trend of flow-body energy transfer results in a monotonic orientation of the structural waves. Clockwise and counter-clockwise figure eight orbits of the body alternate along the span, but the latter are found to be more favourable to structure excitation. Additional simulations at normal incidence highlight a dramatic deviation from the independence principle, which states that the system behaviour is essentially driven by the normal component of the inflow velocity.


Blood supply and vasculature of mycetoma.
The blood supply to the mycetoma lesion and its vasculature were studied in patients with various types of mycetoma using histological, ultrastructural, angiographic and sonographic techniques. The mycetoma lesion proved to be well vascularized. However, certain vascular abnormalities were demonstrated. In histological sections, the small arteries and arterioles showed medial muscular hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis obliterans with narrowed lumen in 7% of the patients. No vascular occlusion, ischaemic changes or arteriovenous shunts were observed. These changes were confirmed ultrastructurally. Angiography of the lesion showed a brisk pathological circulation which was more evident in eumycetoma. The vascular Doppler study showed normal blood flow pattern in the affected limb. Regional intra-arterial chemotherapy for mycetoma is suggested as a possible treatment modality.


Effects of endurance training only versus same-session combined endurance and strength training on physical performance and serum hormone concentrations in recreational endurance runners.
This study investigated the effects of endurance training only (E, n = 14) and same-session combined training, when strength training is repeatedly preceded by endurance loading (endurance and strength training (E+S), n = 13) on endurance (1000-m running time during incremental field test) and strength performance (1-repetition maximum (1RM) in dynamic leg press), basal serum hormone concentrations, and endurance loading-induced force and hormone responses in recreationally endurance-trained men. E was identical in the 2 groups and consisted of steady-state and interval running, 4-6 times per week for 24 weeks. E+S performed additional mixed-maximal and explosive-strength training (2 times per week) immediately following an incremental running session (35-45 min, 65%-85% maximal heart rate). E and E+S decreased running time at week 12 (-8% ± 5%, p = 0.001 and -7% ± 3%, p < 0.001) and 24 (-13% ± 5%, p < 0.001 and -9% ± 5%, p = 0.001). Strength performance decreased in E at week 24 (-5% ± 5%, p = 0.014) but was maintained in E+S (between-groups at week 12 and 24, p = 0.014 and 0.011, respectively). Basal serum testosterone and cortisol concentrations remained unaltered in E and E+S but testosterone/sex hormone binding globulin ratio decreased in E+S at week 12 (-19% ± 26%, p = 0.006). At week 0 and 24, endurance loading-induced acute force (-5% to -9%, p = 0.032 to 0.001) and testosterone and cortisol responses (18%-47%, p = 0.013 to p < 0.001) were similar between E and E+S. This study showed no endurance performance benefits when strength training was performed repeatedly after endurance training compared with endurance training only. This was supported by similar acute responses in force and hormonal measures immediately post-endurance loading after the training with sustained 1RM strength in E+S.


A putative amino acid transporter is specifically expressed in haustoria of the rust fungus Uromyces fabae.
A cDNA library constructed from haustoria of the rust fungus Uromyces fabae was screened for clones that are differentially expressed in haustoria. One family of cDNAs (in planta-induced gene 2 [PIG2] was isolated and found to encode a protein with high homologies to fungal amino acid transporters. A cDNA clone containing the complete coding region of PIG2 and the corresponding genomic clone were isolated and sequenced, revealing the presence of 17 introns in the PIG2 gene. Expression of PIG2 mRNA appeared to be restricted to haustoria. With antibodies raised against synthetic peptides, the PIG2-encoded protein was found in membranes fractions of isolated haustoria but not of germinated rust spores. With immunofluorescence microscopy, the putative amino acid transporter was localized to plasma membranes of the haustorial bodies, but not detected in the haustorial neck, haustorial mother cells, or intercellular fungal hyphae growing within infected leaf tissue. These data present for the first time molecular evidence that the rust haustorium plays a special role in the uptake of nutrients from an infected host cell.


Aerobic training increases the expression of adiponectin receptor genes in the peripheral blood mononuclear cells of young men.
Little is known about the effect of exercise training on the expression of adiponectin receptor genes in peripheral blood mononuclear cells (PBMCs). In this study, we investigated the effects of aerobic training on the expression of AdipoR1 and AidpoR2 mRNAs in PBMCs, whole body insulin sensitivity, and circulating adiponectins in men. Thirty young men were randomly assigned to either a control (n=15) or an exercise (n=15) group. Subjects assigned to the exercise group underwent a 12-week jogging and/or running programme on a motor-driven treadmill at an intensity of 60%-75% of the age-based maximum heart rate with duration of 40 minutes per session and a frequency of 5 days per week. Two-way mixed ANOVA with repeated measures was used to test any significant time-by-group interaction effects for the measured variables at p=0.05. We found significant time-by-group interaction effects for waist circumference (p=0.001), VO2max (p<0.001), fasting insulin (p=0.016), homeostasis model assessment for insulin resistance (HOMA-IR) (p=0.010), area under the curve (AUC) for insulin response during the 75-g oral glucose tolerance test (p=0.002), high-molecular weight (HMW) adiponectin (p=0.016), and the PBMC mRNA levels of AdipoR1 (p<0.001) and AdipoR2 (p=0.001). The exercise group had significantly increased mRNA levels of AdipoR1 and AdipoR2 in PBMCs, along with increased whole body insulin sensitivity and HMW adiponectin, decreased waist circumference, and increased VO2max compared with the control group. In summary, the current findings suggest that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in PBMCs, implying that manipulation of the expression of these genes could be a potential surrogate for lifestyle intervention-mediated improvements of whole body insulin sensitivity and glucose homeostasis.


Osteoporosis guidelines.
The Position Statement from the International Menopause Society (IMS) in 2004 recommends the use of hormone therapy for the 'avoidance of bone-wasting and fractures'. It also states that 'prevention, not treatment, is the most feasible goal'. In updating the Statement, this paper considers the relevance of Osteoporosis Guidelines. Relevant documents will be of two broad types. These may be consensus statements/position statements that summarize the 'state of the art' for practitioners, based on the work of expert groups, or they may be formal Guidelines generated through formal 'evidence-based' methodology. The former approach is generally used by Societies and can be generated through relatively efficient consensus processes. The latter approach will normally involve extensive work and cost, necessarily becomes very detailed, involving systematic review and technology appraisal and can lead to highly specific recommendations on intervention thresholds. For the revision of the general IMS Position Statement, the specific IMS Paper on Postmenopausal Osteoporosis (2005) must be a key reference document. This provides a description of the international consensus on the management of osteoporosis up to late 2004 and which remains relevant today. Additionally, other consensus statements and systematic guidelines need to be considered. Across these documents providing guidance, the substantial influence of the International Osteoporosis Foundation/National Osteoporosis Foundation Position Paper, defining a 'New approach to the development of assessment guidelines for osteoporosis', can be seen. This flagged the importance of a shift from guidance, tying the diagnostic threshold to the intervention threshold, and instead advised linking the intervention threshold to estimated fracture risk probability. This moves the intervention decision away from a simple bone density threshold to a more complex, but more realistic, threshold estimate, taking into account a range of important clinical risk factors and bone mineral density. This thinking is reflected in the IMS Paper on Postmenopausal Osteoporosis (2005).


Pullout forces of sutures in muscle lacerations.
The purpose of this study was to determine if complex suture techniques had higher pullout forces from muscle tissue than conventional stitching. Using transected cadaver muscle bellies, we performed repairs with various suture techniques and measured pullout forces. Epimyseal repair with conventional stitches (Kessler, figure eight, horizontal mattress) was inferior to complex stitches (modified Mason-Allen, perimeter). The combined complex stitches (perimeter and Mason-Allen) were strongest. Conventional stitches failed longitudinally through the muscle, whereas complex stitches failed transversely across the muscle. The complex combination of perimeter and Mason-Allen stitches had superior pullout resistance compared to conventional stitches.


Behavioral Research in Cancer Prevention and Control: Emerging Challenges and Opportunities.
It is estimated that behaviors such as poor diet, alcohol consumption, tobacco use, sedentary behavior, and excessive ultraviolet exposure account for nearly one-half of all cancer morbidity and mortality. Accordingly, the behavioral, social, and communication sciences have been important contributors to cancer prevention and control research, with methodological advances and implementation science helping to produce optimally effective interventions. To sustain these contributions, it is vital to adapt to the contemporary context. Efforts must consider ancillary effects of the 2019 coronavirus disease pandemic, profound changes in the information environment and public understanding of and trust in science, renewed attention to structural racism and social determinants of health, and the rapidly increasing population of cancer survivors. Within this context, it is essential to accelerate reductions in tobacco use across all population subgroups; consider new models of energy balance (diet, physical activity, sedentary behavior); increase awareness of alcohol as a risk factor for cancer; and identify better communication practices in the context of cancer-related decisions such as screening and genetic testing. Successful integration of behavioral research and cancer prevention depends on working globally and seamlessly across disciplines, taking a multilevel approach where possible. Methodological and analytic approaches should be emphasized in research training programs and should use new and underused data sources and technologies. As the leadership core of the National Cancer Institute's Behavioral Research Program, we reflect on these challenges and opportunities and consider implications for the next phase of behavioral research in cancer prevention and control.


Investigation of a common physiological mechanism underlying progesterone-induced and maternal nesting in mice, Mus musculus.
These experiments addressed the possibility that genetic differences in plasma progesterone levels underlie genetic differences observed in maternal nesting (nest building by pregnant mice). Because this hypothesis requires that different circulating levels of progesterone result in a corresponding elevation of nesting, groups of outbred females were treated with varying doses of progesterone, and their nesting was measured. The relation between progesterone dose and nesting was not linear; rather, there appeared to be a threshold dose above which all groups responded similarly. Next, the progesterone levels of four inbred strains and lines selectively bred for differences in nonpregnant (thermoregulatory) nesting were measured directly by radioimmunoassay. The rank order of the inbred strains' and selected lines' progesterone levels did not correspond to the rank order of their nesting. Thus, genetically based differences in maternal nesting are not due to differences in circulating progesterone levels. Other results are presented which suggest a thermo-regulatory mechanism underlying progesterone-mediated maternal nesting which may involve genetic differences in thermal set point.


Exploring early career researchers' perspectives of training and funding opportunities: Motivations and setbacks when applying for the UK's National Institute for Health and Care Research's fellowships and research funding.
Despite the availability of training and funding opportunities with the UK's National Institute for Health and Care Research (NIHR), early career researchers (ECRs) invariably experience concern in sustaining an academic career in health research given the uncertainties of success following rejection from peer-reviewed funding bodies. The objective of this study was to consider what motivates ECRs when applying for funding to NIHR programmes and how they overcome funding setbacks. Eleven ECRs took part in a one-to-one virtual in-depth interview; the sample included more women (n = 8) than men (n = 3) and participants included pre-doctoral researchers (n = 5), and both doctoral (n = 2) and post-doctoral (n = 4) ECRs. The interviews were analysed using the logic of a systems theory framework identifying factors impacting on ECRs occurring within an individual, within their social system and within their broader environment. The central themes that emerged from the data focussed on: (1) facilitators for ECRs to apply for NIHR funding; (2) exploring ECRs' setbacks and disappointments; (3) improving chances of funding; and (4) deciding to apply with a view to re-applying in future. The participants' responses provided an honest and frank reflection of the uncertainties and challenges as ECRs in the current climate. Further strategies to support ECRs could be facilitated through local NIHR infrastructure, mentorship, better access to local support networks and hard-wiring research into an organisation's strategic priorities.


A review of the automated detection and classification of acute leukaemia: Coherent taxonomy, datasets, validation and performance measurements, motivation, open challenges and recommendations.
Acute leukaemia diagnosis is a field requiring automated solutions, tools and methods and the ability to facilitate early detection and even prediction. Many studies have focused on the automatic detection and classification of acute leukaemia and their subtypes to promote enable highly accurate diagnosis. This study aimed to review and analyse literature related to the detection and classification of acute leukaemia. The factors that were considered to improve understanding on the field's various contextual aspects in published studies and characteristics were motivation, open challenges that confronted researchers and recommendations presented to researchers to enhance this vital research area. We systematically searched all articles about the classification and detection of acute leukaemia, as well as their evaluation and benchmarking, in three main databases: ScienceDirect, Web of Science and IEEE Xplore from 2007 to 2017. These indices were considered to be sufficiently extensive to encompass our field of literature. Based on our inclusion and exclusion criteria, 89 articles were selected. Most studies (58/89) focused on the methods or algorithms of acute leukaemia classification, a number of papers (22/89) covered the developed systems for the detection or diagnosis of acute leukaemia and few papers (5/89) presented evaluation and comparative studies. The smallest portion (4/89) of articles comprised reviews and surveys. Acute leukaemia diagnosis, which is a field requiring automated solutions, tools and methods, entails the ability to facilitate early detection or even prediction. Many studies have been performed on the automatic detection and classification of acute leukaemia and their subtypes to promote accurate diagnosis. Research areas on medical-image classification vary, but they are all equally vital. We expect this systematic review to help emphasise current research opportunities and thus extend and create additional research fields.


ALK-negative anaplastic large cell lymphoma with loss of CD30 expression during treatment with brentuximab vedotin.
A 59-year-old woman with anaplastic large cell lymphoma (ALCL), ALK-negative, was treated with brentuximab vedotin (BV) against relapse after 6 regimens of systemic chemotherapy and radiation. Despite achieving an initial response, skin lesions worsened after 11 courses. A skin biopsy after the development of resistance to BV confirmed loss of CD30 expression by the tumor cells, suggesting a possible cause of resistance. This case shows that down-regulation of CD30 does occur during BV treatment, resulting in resistance to this drug. Because of this possibility, in the future, expression of CD30 should be carefully monitored with extended use of BV against ALCL.


A comparative study of the inhibitory effects by caffeic acid, catechins and their related compounds on the generation of radicals in the reaction mixture of linoleic acid with iron ions.
Caffeic acid and (+)-catechin, which are abundantly contained in coffee and tea, are typical polyphenols. In order to know the relative magnitudes of antioxidant activity, effects by caffeic acid, (+)-catechin and their derivatives on the formation of 4-POBN/carbon-centered linoleic acid-derived radical adducts were examined in the control reaction mixture of linoleic acid with FeCl3 at 30°C for 168 h. In the presence of 1.0 mM of the polyphenols, peak to peak heights of the third ESR signal resulted in 7.7 ± 2.4% (n = 3) (caffeic acid), 145 ± 13% (n = 3) (quinic acid), 4.4 ± 0.0% (n = 3) (chlorogenic acid), 104 ± 4.4% (n = 3) (ferulic acid), 4.3 ± 0.0% (n = 3) (noradrenaline), 12.5 ± 10.9% (n = 3) (gallic acid), 38.1 ± 7.1% (n = 3) [(+)-catechin], 47.9 ± 11.7% (n = 3) [(-)-epicatechin], 56.5 ± 1.6% (n = 3) (epigallocatechin), 13.5 ± 1.7% (n = 3) (catechol) and 83.7 ± 7.8% (n = 3) (resorcinol) of the control reaction mixture. All the compounds with catechol moiety exerted potent inhibitory effects on the radical formation except for (+)-catechin, (-)-epicatechin and epigallocatechin. (+)-Catechin, (-)-epicatechin and epigallocatechin may not exert the inhibitory effect as much possibly because they are less stable compared with caffeic acid. The resorcinol moiety in these molecules may also weaken their antioxidant activity.


Longitudinal study on the effect of autogenous vaccine application on the sequence type and virulence profiles of Escherichia coli in broiler breeder flocks.
Colibacillosis is one of the most common problems in the poultry industry. Escherichia coli strains on farms are often genetically diverse and therefore commercial vaccines provide little protection to the flocks. Here, we investigated the effect of the autogenous E. coli vaccines on the prevalence of 84 virulence-associated genes in E. coli isolated from four and five consecutive flocks on two broiler breeder farms, respectively. 115 E. coli isolates were sequenced using Illumina technologies, and compared based on both their set of housekeeping genes and their virulence profiles, defined through the composition of virulence genes. Predominantly, phylogenetic analysis showed obvious distinction between the isolates originating from different farms suggesting spatial-dependent transmission of pathogenic strains. We detected 23 sequence types, while 52.58 % of the isolates belonged to two clonal complexes. Analysis of the virulence genes showed highest prevalence (>85 %) of feoB, uspA, uspB, uspG, uspE, fimH, ompA, astA, focA, hlyE, uspC, crl, csgA, ompT and iss, of which 50 % are toxin associated genes, demonstrating the importance of competition in the pathogenesis process. Interestingly, usp genes, which are primarily associated with uropathogenic E. coli strains, were detected in all investigated isolates. The heatmap analysis demonstrated that strains belonging to same phylogenetic groups often share similar virulence profiles, confirming the usefulness of quick tests for phylogenetic typing. However, our results suggest the need to update the list of the minimal predictors used for the identification of avian pathogenic strains. Overall results indicate that continuous application of autogenous vaccines led to lower genetic diversity of E. coli housekeeping genes, but not virulence genes.


Ofloxacin otic drops vs neomycin-polymyxin B otic drops as prophylaxis against early postoperative tympanostomy tube otorrhea.
To evaluate the incidence of tympanostomy tube (TT) sequelae, tube otorrhea, and tube obstruction immediately postoperatively in patients receiving TT for otitis media and to compare patients receiving postoperative otic drops with controls. Blinded randomized control trial. A tertiary pediatric otolaryngology practice. The study population comprised 306 patients undergoing TT placement. The 306 patients were enrolled into the following 3 groups: (1) those receiving no postoperative otic drop prophylaxis (control group), (2) those receiving ofloxacin otic drops (FLOX group), and (3) those receiving neomycin sulfate-polymyxin B sulfate-hydrocortisone otic drops (COS group). Overall otorrhea rates postoperatively were 14.9% for the control group, 8.1% for the FLOX group, and 5.5% for the COS group. When controlling for disease severity, the rate of otorrhea was significantly higher for the control group than for both the FLOX (P = .04) and COS (P = .01) groups. Nonpatent, plugged, tube rates were added to otorrhea rates for a TT failure analysis postoperatively. The control group demonstrated a significantly greater failure rate (29.9%) than both the FLOX (12.1%) and COS (7.7%) groups. The only differences between the patients in the 2 groups receiving drops were that ofloxacin was more well liked by patients (P = .04) and caused less pain (P = .004). Nonpatency and otorrhea are the most frequent sequelae immediately following TT placement. Few studies have compared different treatment regimens in a randomized controlled trial. These results demonstrate that otic drops clearly provide benefit postoperatively in preventing TT plugging and otorrhea but primarily in patients who have middle ear fluid at the time of TT placement. In addition, consideration of drop choice should be based on patient tolerance and medication safety profiles.


[Diagnostic and therapeutic problems of congenital pseudarthrosis of the lower leg in children].
So-called pseudarthrosis of the lower leg is a rare condition whose treatment entails major therapeutic problems. The first symptoms of this disease are structural changes thinning, and sclerosis of the tibia and fibula, as well as varus and antecurvation malposition? of the axis. In all of the authors' patients the pseudarthrosis occurred as a secondary phenomenon, three times in attempts to correct the lower leg axis surgically; in two children spontaneous fractures occurred due to fatigue and in two others after stumbling. In all seven of the surgically treated children and in three of the six in the outpatient group café-au-lait spots were seen. The neurofibromatosis was also confirmed by histological examinations in all of the surgically treated children. Not only the views concerning etiology, but also therapy have changed. Our present treatment method is undoubtedly a success as compared to that used on our first patients. On the basis of our surgical experience so far we can recommend the following method: resection of the pseudarthrosis with removal of all pathologically changed tissue (also by fraising), insertion of Küntscher nails from the heel to the tibia, adequate covering of the pseudarthrosis location with spongiosa grafts from the pelvic ridge. If necessary, the intervention should be repeated.


Uterine and systemic inflammation influences ovarian follicular function in postpartum dairy cows.
The objective of this study was to determine the effects of uterine and systemic inflammatory responses to uterine bacterial contamination at calving in dairy cows on the growth and ovulatory outcomes of the first dominant follicle postpartum. Ovulatory capability of the first dominant follicle postpartum was predicted in 53 multiparous cows by using a combination of follicle growth characteristics and circulating estradiol concentrations. Endotoxin levels were assayed in follicular fluid samples that were aspirated the day after ovulatory outcome prediction. Plasma levels of haptoglobin, a proinflammatory acute phase protein, and paraoxonase, a negative acute phase protein were determined. Uterine bacteria and inflammation were evaluated in three uterine fluid samples from each cow collected on the day of calving, the day after follicle aspiration, and at 35 days postpartum. Cows that had a strong initial uterine inflammatory response (robust recruitment of polymorphonuclear leukocytes of ≥ 35% and cows with uterine pH < 8.5 on the day of calving) were more likely to have an ovulatory first dominant follicle. Follicular fluid endotoxin levels were higher in non-ovulatory cows compared with ovulatory cows. Endotoxin levels in circulation were not different between ovulatory groups but were higher prepartum than on day 7 and 14 postpartum. Systemic inflammation characterized by elevated haptoglobin concentrations was higher in non-ovulatory cows despite similar bacterial contamination and circulating endotoxin levels. Paraoxonase activity in follicular fluid was significantly associated with the paraoxonase activity in plasma, however, plasma paraoxonase concentrations were not different between non-ovulatory and ovulatory cows. Cows with a higher uterine bacterial load on the day of calving had slower ovarian follicle growth. In summary, a robust uterine inflammatory response on the day of calving was positively associated with ovarian function while elevated systemic inflammation during the early postpartum period was negatively associated with the ovulatory status of the first dominant follicle postpartum.


Conformation and dynamics of single polymer chain studied by optical microscopy techniques beyond the diffraction limit.
The origin of the unique properties of a polymer material is the large entropic term of a single molecule, which has a chain-like structure with a large molecular weight. From the viewpoint of understanding the fundamental polymer physics, conformation of the single polymer chain is one of the most important matters; however, it has been difficult to examine the behavior of a single chain because of the limitation of conventional experimental methods. Recent developments in optical microscopy allow the fluorescence imaging beyond the diffraction limit of light, and the author's group showed that the conformation and the dynamics of a single polymer chain can be examined by the high-resolution fluorescence imaging. This review presents the application of optical microscopy with nanometric spatial resolution to study the polymer materials at the single-chain level.


[New Insights into Maternal Cardiopulmonary Resuscitation--Significance of Simulation Research and Training].
Pregnancy-related mortality, estimated to occur in approximately 1: 50,000 deliveries, is rare in developed countries. The 2010 American Heart Association (AHA) Guidelines for Resuscitation emphasize the importance of high-quality chest compression as a key determinant of successful cardiopulmonary resuscitation. During pregnancy, the uterus can compress the inferior vena cava, impeding venous return and thereby reducing stroke volume and cardiac output. To maximize the effectiveness of chest compressions in pregnancy, the AHA guidelines recommend the 27-30 degrees left-lateral tilt (LLT) position. When CPR is performed on parturients in the LLT position, chest compressions will probably be more effective if performed with the operator standing on the left side of the patient. The videolaryngoscope Pentax-AWS Airwayscope (AWS) was found to be an effective tool for airway management during chest compressions in 27 LLT simulations, suggesting that the AWS may be a useful device for airway management during maternal resuscitation.


Is coarse-to-fine strategy sensitive to normal aging?
Theories on visual perception agree that visual recognition begins with global analysis and ends with detailed analysis. Different results from neurophysiological, computational, and behavioral studies all indicate that the totality of visual information is not immediately conveyed, but that information analysis follows a predominantly coarse-to-fine processing sequence (low spatial frequencies are extracted first, followed by high spatial frequencies). We tested whether such processing continues to occur in normally aging subjects. Young and aged participants performed a categorization task (indoor vs. outdoor scenes), using dynamic natural scene stimuli, in which they resorted to either a coarse-to-fine (CtF) sequence or a reverse fine-to-coarse sequence (FtC). The results show that young participants categorized CtF sequences more quickly than FtC sequences. However, sequence processing interacts with semantic category only for aged participants. The present data support the notion that CtF categorization is effective even in aged participants, but is constrained by the spatial features of the scenes, thus highlighting new perspectives in visual models.


Resistance of multidrug-resistant lines to natural killer-like cell-mediated cytotoxicity.
Multidrug resistance (MDR) refers to a complex phenotype that describes a number of features characterized primarily by resistance to a wide range of structurally unrelated drugs. In this paper we investigated the relationship between drug resistance and resistance to NK-mediated cytotoxicity. Studies with two independently selected multidrug-resistant cell lines indicated that increased drug resistance was associated with both an increased resistance to NK-mediated cytotoxicity and increased levels of membrane P-glycoprotein expression. This resistance to cytotoxicity appears to result partly from an alteration in the membrane structure of the target cells inasmuch as there was a reduction in effector:target cell recognition. Resistance to NK-mediated cytotoxicity should be included with the numerous pleiotropic changes associated with the multidrug resistance phenotype.


Does Vitamin K2 Influence the Interplay between Diabetes Mellitus and Intervertebral Disc Degeneration in a Rat Model?
Intervertebral disc (IVD) degeneration is a common cause of low back pain in diabetes mellitus type 2 (T2DM) patients. Its pathogenesis and the vitamin (vit.) K2 influence on this disease remain unclear. Lumbar motion segments of male Zucker Diabetes Fatty (ZDF) rats (non-diabetic [control] and diabetic; fed without or with vit. K2) were used. Femur lengths and vertebral epiphyseal cross-section areas were measured. IVDs were histopathologically examined. Protein synthesis and gene expression of isolated IVD fibrochondrocytes were analyzed. T2DM rats showed histopathological IVD degeneration. Femur lengths and epiphyseal areas were smaller in T2DM rats regardless of vit. K2 feeding. Fibrochondrocytes synthesized interleukin (IL)-24 and IL-10 with no major differences between groups. Alpha smooth muscle actin (αSMA) was strongly expressed, especially in cells of vit. K2-treated animals. Gene expression of aggrecan was low, and that of collagen type 2 was high in IVD cells of diabetic animals, whether treated with vit. K2 or not. Suppressor of cytokine signaling (Socs)3 and heme oxygenase (Hmox)1 gene expression was highest in the cells of diabetic animals treated with vit. K2. Vit. K2 influenced the expression of some stress-associated markers in IVD cells of diabetic rats, but not that of IL-10 and IL-24.


HSV-induced blastogenesis in splenic mononuclear cells from inbred mice.
The severity of HSV stromal keratitis varies among inbred mouse strains, with A/J and BALB/c greater than C57BL/6. Since cell-mediated immunity (CMI) is thought to play a role in the pathogenesis of HSV stromal keratitis, we measured the proliferative response of primed splenic mononuclear cells (SMC) from these strains to HSV antigen in vitro. Primed SMC from all three strains showed increased thymidine uptake after incubation with UV-inactivated HSV-1 antigen (UV-HSV) in vitro when compared with control antigen. Uptake by SMC from BALB/c and A/J mice was greater than that by SMC from C57BL/6 mice. The difference between BALB/c and A/J was not significant. Uptake by non-primed SMC cultured with UV-HSV was not significantly greater than uptake induced by control antigen. Thus, among the strains studied, A/J and BALB/c mice, which are relatively susceptible to stromal keratitis, have the greatest proliferative response to UV-HSV antigen. C57BL/6 mice, which are relatively resistant to stromal keratitis, have the least response. These findings suggest that genetically determined differences in CMI may influence the course of HSV keratitis and are consistent with the hypothesis that the host immune response plays a role in the pathogenesis of HSV stromal keratitis.


Effects of force levels on error compensation in periodic bimanual isometric force control.
The authors examined whether force level interacts with the presence or absence of vision in bimanual force control. Participants produced periodic isometric forces such that the sum of the 2 finger forces was the target force under 4 force levels cycling between lower levels (5-40%) of maximum voluntary contraction with an interval of 1000 ms. Without vision, the correlation between the 2 finger forces was strongly positive over all force levels. However, with vision the correlation changed from negative to positive with force level. The result with vision indicated that the strategy of the bimanual force control changed from force error compensation to force coupling and the available redundancy thus decreased with an increase in force.


Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats.
Rat migration inhibitory factor-related protein 8 (MRP8) and MRP14 were identified during screening of a subtracted cDNA library generated to identify differences in gene expression between LEW/N and F344/N rats. The predicted amino acid sequence of rat MRP8 and MRP14 is 60-80% identical with that from human and mouse. Expression of these genes correlated with chronic inflammation in LEW/N rats, but were absent in F344/N rats which do not develop arthritis in response to streptococcal cell wall peptidoglycan-polysaccharide complexes (SCW). These differences suggest a role for MRP8 and MRP14 in susceptibility to SCW-induced chronic disease.


Heterotopic Ossification Bone Formation in the Frontal Bones of an African Grey Parrot (Psittacus erithacus).
A 5-year-old, male African grey parrot (Psittacus erithacus) was presented with multiple, slow-growing, firm, bilateral masses around the dorsal orbital rims. Computer tomographic imaging revealed mild, incomplete bridging bone formation on the rostrodorsal aspects of the head. A moderate amount of smooth bone formation was identified at the rostrodorsal aspect to the left orbit, with minimal associated soft tissue swelling. Surgical biopsies were collected from the masses and histopathological analysis of the most rostral right mass showed well-differentiated bone, surrounded by dense fibrous connective tissue. Scattered, well-differentiated osteocytes were present within the bone. No evidence of neoplastic changes or infectious agents were identified. The histopathological changes were consistent with metaplastic bone formation. History obtained from the owner revealed recent head trauma, which likely induced the cranial heterotopic ossification in the African grey parrot.


Telomere length among the elderly and oldest-old.
Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.


[The significance of gene expression and post-translational modifications of collagen for the origin of fibrosis].
An account is given in this paper of processes relating to molecular and cellular biology in collagen synthesis, with reference being made to autoradiographic evidence to secretion of 3H-proline containing precursors of collagen fibre from fibroblasts of granulation tissue into extracellular space. Findings made in this context in the wake of in situ hybridisation have shown collagenisation to be regulated primarily by gene expression rather than by post-translational modifications. Reference is made to new possible approaches to the control of fibrosis and sclerosis, resulting from knowledge of molecular biological foundations and principles underlying collagen synthesis.


Recurrence of Guinea Worm Disease in Chad after a 10-Year Absence: Risk Factors for Human Cases Identified in 2010-2011.
A decade after reporting its last case of Guinea worm disease (GWD), a waterborne parasitic disease targeted for eradication, Chad reported 20 confirmed human cases from 17 villages-10 cases in 2010 and 10 cases in 2011. In 2012, the first GWD dog infections were diagnosed. We conducted a case-control study during April-May 2012 to identify human transmission risk factors and epidemiologic links. We recruited 19 cases and 45 controls matched by age, sex, time, and location of exposure based on the case patients' periods of infection 10-14 months earlier. Data were analyzed with simple conditional logistic regression models using Firth penalized likelihood methods. Unusually, GWD did not appear to be associated with household primary water sources. Instead, secondary water sources, used outside the village or other nonprimary sources used at home, were risk factors (matched odds ratio = 38.1, 95% confidence interval = 1.6-728.2). This study highlights the changing epidemiology of GWD in Chad-household primary water sources were not identified as risk factors and few epidemiologic links were identified between the handfuls of sporadic cases per year, a trend that continues. Since this investigation, annual dog infections have increased, far surpassing human cases. An aquatic paratenic host is a postulated mode of transmission for both dogs and humans, although fish could not be assessed in this case-control study due to their near-universal consumption. GWD's evolving nature in Chad underscores the continued need for interventions to prevent both waterborne and potential foodborne transmission until the true mechanism is established.


Caeruloplasmin: a multi-functional metalloprotein of vertebrate plasma.
Ceruloplasmin is a blue copper protein found in the alpha 2-globulin fraction of vertebrate plasma. It is a single-chain glycoprotein of molecular weight 132 000. It contains six copper atoms per molecule, comprising three or possibly four different types of copper. Its many functions may be related to the heterogeneous nature of these six copper atoms and to the various catalytic activities which they provide. Caeruloplasmin resembles albumin and transferrin in that all three serum proteins are regarded primarily as transport proteins. However, each has numerous other action as important as this transport function. Caeruloplasmin directly mobilizes iron into the serum and provides the major molecular link between copper and iron metabolism; it is the most prominent serum antioxidant, preventing deleterious oxidation of polyenoic acids and other substrates; it scavenges superoxide radicals; it serves as an acute-phase reactant (an endogenous modulator) of the inflammatory response; finally, caeruloplasmin may regulate the serum concentration of the biogenic amines, adrenaline (epinephrine) and serotonin (5-HT).


Immunosuppression based on everolimus in liver transplant recipients with severe early post-transplantation neurotoxicity.
The immunosuppressive management of liver transplant recipients suffering early calcineurin inhibitor-induced neurotoxicity is a challenge in daily clinical practice. We have assessed the use of everolimus as the main immunosuppressant in patients presenting severe neurotoxicity in the early post-transplantation period. From October 1988 to October 2012, 10 patients in our center received everolimus because of severe neurotoxicity in the 1st 3 months after transplantation. We analyzed several variables associated with this treatment, including patient characteristics, time from liver transplantation to conversion to everolimus, immunosuppression regimens before and after conversion, treatment efficacy, adverse events, and discontinuation after conversion. Median follow-up after conversion to everolimus was 27 months (range, 1-63 mo). Neurotoxic events were: akinetic mutism in 4 patients, repeated convulsions in 3, cerebrovascular accident in 1, Guillain-Barré syndrome in 1, and disabling tremor in 1. Treatment with calcineurin inhibitors was discontinued in all patients. Post-conversion regimens consisted of everolimus plus mycophenolate mofetil (MMF) plus steroids in 7 patients, everolimus plus MMF in 1, everolimus plus steroids in 1, and everolimus alone in 1. Liver function was maintained for ≥1 month in all patients except 1, who presented a severe rejection that was treated with steroid bolus and Neoral cyclosporine. Neurologic function was fully recovered in 8 patients. In 1 patient with akinetic mutism and another with convulsions, tacrolimus was reintroduced at 2 months and 1 month, respectively, after resolution of the neurotoxic event. Everolimus is feasible and effective as the main immunosuppressant in patients suffering severe neurotoxicity during the 1st 3 months after transplantation. It allows neurologic function to be recovered while maintaining adequate liver function.


Depressive symptoms in patients with coronary artery disease.
To assess the presence of depressive symptoms in patients with coronary artery disease in the preoperative period for coronary artery bypass surgery (CABG) in Aracaju, Sergipe, Brazil. A cross-sectional study with 63 hospitalized patients prior to CABG. Two instruments were used for data collection; one for the sociodemographic and clinical characteristics, and the other to evaluate the presence of depressive symptoms, Beck Depression Inventory (BDI). The mean age was 58 years; most were male (60.3%); with a partner (81%) low educational level (71.4% attended school through elementary school). Among the patients, 36.5% were classified with dysphoria, and 25.4% had some degree of depression (6.3% mild, 17.5% moderate, and 1.6% severe). The group of patients with lower educational level presented higher depressive symptoms. Six of every ten patients with coronary artery disease showed dysphoria or some degree of depression. The results of this study can support the planning of nursing care for patients before and after CABG, as well as the development of public health policies to ensure complete, quality care for these patients, understanding depression as a variable that can interfere with recovery after cardiac surgery.


Painless legs and moving toes: a syndrome related to painful legs and moving toes?
The syndrome of painful legs and moving toes consists of continuous or semicontinuous involuntary writhing movements of the toes associated with pain in the affected extremity. We report a 57-year-old man with a 33-year history of painless and semicontinuous involuntary movements of the toes of the left foot similar to those seen in painful legs and moving toes. There was no family history of movement disorder. The history and physical examination were negative for significant trauma, radiculopathy, or peripheral neuropathy. There were no other neurological findings or involuntary movements. It is unlikely that the involuntary movements were precipitated by neuroleptics or psychosis. CT scan of the head; EEG, CT, and MRI scans of the lumbosacral spine; and EMG and nerve conduction studies of the legs showed no significant abnormalities except for a predominant cocontraction of the left foot flexors and extensors at 0.6-1.2 Hz in a pattern sometimes seen in painful legs and moving toes. We conclude that there is a condition clinically and electrophysiologically similar to painful legs and moving toes that we call painless legs and moving toes, the etiology of which remains undetermined.


Pregnancy outcome after laser vaporization of the cervix.
Treatment of cervical intraepithelial neoplasia (CIN) with cold knife or CO2-laser conization is associated with obstetrical problems in subsequent pregnancies. Little is published about pregnancy outcome after laser vaporization of the uterine cervix. The aim of this study was to determine the risk of preterm delivery and low birth weight in pregnancies following this kind of treatment. Two hundred and thirty-six women who during the 11 year period 1982 to 1992 underwent laser vaporization of the uterine cervix and after treatment gave birth were included in this study. For each case two controls matched for parity, age (-/+ 3 years) and year of delivery were identified. The material was analyzed as a matched cohort study. No relationship was found between laser vaporization and preterm delivery or low birth weight. Medial gestational length was in both groups 40 weeks (range 3142 weeks among cases and 2842 weeks among controls). Mean birth weight was 3428 g (range 1370 to 6130 g) among cases and 3407 (range 672 to 5470 g) among controls. Laser vaporization of the uterine cervix does not influence the outcome of subsequent pregnancy.


Prospective evaluation of clinically relevant type B hyperlactatemia in dogs with cancer.
Cancer is considered a cause of type B hyperlactatemia in dogs. However, studies evaluating cancer as a cause of clinically relevant type B hyperlactatemia (>2.5 mmol/L) are lacking. Cancer cells have a higher lactate production because of increased aerobic glycolysis, known as the "Warburg effect." The mechanisms through which aerobic glycolysis occurs are not well elucidated, but neoplasia may cause type B hyperlactatemia via this process. To determine if malignant tumors of dogs are associated with clinically relevant type B hyperlactatemia (>2.5 mmol/L). Thirty-seven client-owned dogs with malignant tumors: 22 with hematopoietic and 15 with solid tumors. Histology was used to confirm the diagnosis (cytology was considered adequate for diagnosis of lymphoma). Confounding conditions associated with hyperlactatemia were excluded. Lactate measurements were immediately performed on free-flow jugular whole blood samples using the LactatePro analyzer. All dogs had lactate concentrations<2.5 mmol/L. Mean blood lactate concentration was 1.09 mmol/L. Mean blood lactate concentrations for solid and hematopoietic tumors were 0.95 and 1.19 mmol/L, respectively. Dogs with lymphoma (n=18) had a mean blood lactate concentration of 1.15 mmol/L. Malignant tumors were not considered a cause of clinically relevant type B hyperlactatemia. Therefore, cancer-related type B hyperlactatemia in dogs is uncommon, and hyperlactatemia should prompt careful investigation for causes other than cancer.


Role of acrylates in the development of contact dermatitis in diabetic patients-A Polish dermatology tertiary centre experience.
In recent years, an increasing number of contact dermatitis cases triggered by acrylates contained in diabetes medical devices have been reported. Acrylates seem to play a major role in the development of irritant contact dermatitis and allergic contact dermatitis (ACD) in diabetic patients. To study a group of patients with contact dermatitis caused by diabetes medical devices with a focus on acrylates as possible allergens responsible for contact dermatitis. Fifteen patients with diabetes mellitus type 1 and contact dermatitis from diabetic devices were patch tested to 25 acrylate allergens. Three patients (20%) reacted to the following allergens: three patients reacted to isobornyl acrylate (IBOA) and one of them additionally to 2-hydroxyethyl acrylate (2-HEA); results were of clinical relevance. All three patients were using insulin pumps and glucose sensors (GS)-in one patient contact dermatitis was towards the insulin pump and the GS, in one patient only towards the insulin pump and in one patient only towards the GS. Twelve patients (80%) did not show any skin reaction towards the allergens tested. A majority of diabetic patients showed no reactions towards any acrylate allergen tested; yet, the presence of untested allergens must be kept in mind. IBOA proved to be a cause of ACD in diabetes patients. 2-HEA might be another culprit allergen, but its presence in the devices must first be confirmed.


Pathogens detected in the faeces of children with diarrhoea in a Sydney hospital.
During a 54-week period, faecal samples taken from 350 children under 5 years of age, who were admitted with acute diarrhoea to the infectious diseases ward of a Sydney hospital, were examined for pathogens. Rotavirus was detected as the sole agent in the specimens of 58 patients (16.6%), enteroviruses in those of 26 patients (7.4%), salmonellae in those of 19 patients (5.4%) and Campylobacter jejuni in those of 15 patients (4.3%). Shigellae were not detected. The results are discussed and, in view of the changing patterns of infection, it is suggested that there is a continuing need for research into the causes of enteritis in Australia.


MicroRNA-454-3p inhibits cervical cancer cell invasion and migration by targeting c-Met.
Increasing evidence has demonstrated that microRNAs (miRNAs) have a crucial role in the initiation and progression of tumors. The present study aimed to investigate the expression and the role of miRNA-454-3p in human cervical cancer. Human cervical cancer cells were transfected with miRNA-454-3p mimics or negative control miRNA. MTT, Transwell and wound healing assays were performed to investigate the effects of miRNA-454-3p overexpression on cell proliferation, invasion and migration, respectively. The results indicated that miRNA-454-3p was down-regulated in human cervical cancer cell lines, while its ectopic overexpression significantly inhibited their proliferation, migration and invasion. Furthermore, a luciferase reporter assay confirmed that c-met was a novel target of miRNA-454-3p in HeLa cells. In conclusion, the results of the present study suggested that miRNA-454-3p exhibits significant tumor-suppressive effects in cervical cancer by targeting c-met, and may be a potential means of treating cervical cancer.


Circulatory effects of gastrointestinal hormones and related peptides.
Circulatory effects of gastrointestinal hormones and related peptides are surveyed. Only experiments using low peptide dosages, non-extensive surgery and intravenous infusions give relevant data in this field. Glucagon, secretin, vasoactive intestinal peptide, gastrin, cholecystokinin, Substance P and Somatostatin are vasoactive within the splanchnic area, each fraction in a specific pattern.


[Quantitative variation of total alkaloids contents in Dendrobium officinale].
To investigate the total alkaloid content and find out the variation of total alkaloids content in Dendrobium officinale with different germplasms and harvesting ages with the aim of providing scientific basis for the authenticity identification and the breeding of D. officinale. Forty one samples with 1-3 ages were collected from cultivated fields of Zhejiang and Yunnan provinces and 11 samples were collected from markets. The total alkaloid contents of samples were determined using acid-dye colorimetry method. The determined total alkaloid contents in D. officinale ranged 0.0190%-0.0430%. The averages of total alkaloid contents were 0.0253%, 0.0270% and 0.0326% in 1-year-old, 2-year-old and 3-year-old samples of Zhejiang province, respectively. The average of total alkaloid content was 0.034 3% in 1-year-old samples of Yunnan province. The total alkaloid content of D. officinale with different germplasms and physiological ages existed significant discrepancy, and it increased with the growth of ages. The total alkaloid content of cultivated D. officinale in Yunnan province was higher than that in samples from Zhejiang province. But the authentic D. officinale had certain range of total alkaloid content. Samples whose total alkaloids content divagates from this range must be counterfeit; Samples whose total alkaloid content is in this range still need to combines with other active chemical groups like polysaccharides content to identify the authenticity and quality of medicinal materials.


Knock-in mouse lines expressing either mitochondrial or microsomal CYP1A1: differing responses to dietary benzo[a]pyrene as proof of principle.
In the past, CYP1A1 protein was known to be located in the endoplasmic reticulum (ER; microsomes). More recently, CYP1A1 was shown also to be targeted to the inner mitochondrial membrane; mitochondrial import is dependent on NH(2)-terminal processing that exposes a cryptic targeting signal. It is interesting that microsomal and mitochondrial CYP1A1 enzymes exhibit different substrate specificities, electron donors, and inducer properties. To understand the physiological functions of microsomal versus mitochondrial CYP1A1, we have generated three knock-in lines by altering the CYP1A1 NH(2) terminus. Cyp1a1(mtt/mtt) mice encode an NH(2)-terminal 31-amino acid-truncated protein, deleting the ER-targeting signal and exposing the cryptic mitochondrial-targeting signal. Cyp1a1(mtp/mtp) mice encode a protein carrying L7N and L17N mutations; this mutant lacks the signal recognition particle (SRP)-binding site and subsequent ER-targeting, but requires proteolysis by a cytosolic peptidase for mitochondrial import. Cyp1a1(mc/mc) mice encode a microsomal protein having R34D and K39I mutations, which abolish the mitochondrial targeting signal. After dioxin or beta-naphthoflavone treatment of these mouse lines, the CYP1A1 protein was shown to be located in the mitochondria of the Cyp1a1(mtp/mtp) and Cyp1a1(mtt/mtt) lines and in microsomes of the Cyp1a1(mc/mc) line. To test for differences in function, we compared the response to dietary benzo[a]pyrene (BaP). After 18 days of daily oral BaP, wild-type and Cyp1a1(mc/mc) mice were completely protected, whereas Cyp1a1(-/-) and Cyp1a1(mtp/mtp) mice showed striking toxicity and compensatory up-regulation of CYP1A2 and CYP1B1 mRNA in several tissues. Our data support the likelihood that it is the microsomal rather than mitochondrial CYP1A1 enzyme that protects against oral BaP toxicity.


Indirect immunofluorescence test in New World leishmaniasis: serological and clinical relationship.
The indirect immunofluorescence test (IF) for anti-Leishmania antibodies (IgG and IgM) was performed with sera from the following groups of individuals: 214 cutaneous leishmaniasis patients, 28 healthy subjects with positive Montenegro's skin test (MST), 29 healthy subjects with negative MST and 16 visceral leishmaniasis patients. The first four groups came from a suburban area of Rio de Janeiro (Jacarepaguá) where cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis is endemic. It was observed that IF-IgM titers were significantly higher amongst the cutaneous leishmaniasis patients with less than four months of disease as compared to those with longer periods and that IF-IgG titers were significantly higher in patients with multiple lesions as compared to those with single lesions. The visceral leishmaniasis patients had IF-IgG titers significantly higher than those from cutaneous leishmaniasis patients. A group of 28 individuals selected amongst the 214 cutaneous leishmaniasis patients had their IF-titers (IgG and IgM) compared to those of the two control groups of healthy subjects from the endemic area, respectively with positive and negative MST. Significantly higher titers of IF-IgG and IF-IgM were found in the group with active disease. The same group of patients showed IF-IgG titers significantly lower at the end of the antimonial therapy than those observed during this treatment.


Effects of Fourier-plane amplitude and phase errors on image reconstruction. I. Small amplitude errors.
The effects of Fourier-plane, or spectral, amplitude and phase errors on reconstructed images are studied in terms of the expected mean square error in the image. The relationship between the variance of amplitude and phase errors and the expected mean square error is derived for small amplitude errors and arbitrarily large phase errors. This allows "equivalent" amplitude and phase errors to be defined. The effects of large amplitude errors are discussed in general terms. Simulations are used to verify these relationships, and the effects of spectral amplitude and phase errors on reconstructed images are compared.


The management of non-insulin-dependent diabetes mellitus.
Non-insulin-dependent diabetes mellitus afflicts ten million Americans (half of whom are undiagnosed) and often is diagnosed only because of its complications. When diagnosed, it is generally treated inadequately. The key to appropriate management is an evaluation of each patient's pathophysiology by careful physical and laboratory examinations. A clear understanding of the therapeutic actions of diet, exercise, sulfonylurea agents, and the new insulins permits the physician to design a specific treatment regimen that can restore normal or near-normal glycemic and lipid control, overcome insulin resistance, and prevent, delay, or slow the course of complications that result from the toxic effects of hyperglycemia.


MicroRNA: an important regulator in acute myeloid leukemia.
MicroRNAs (miRNAs) are a general class of endogenous non-coding RNAs with a length of 22 nucleotides, widely existing in diverse species and playing important roles in malignancies initiation and progression. MiRNAs are essential to many in vivo biological processes such as cell proliferation, apoptosis, immune response, and tumorigenesis. Significant progress till date has been made in understanding the roles of microRNAs in normal hematopoiesis and hematopoietic malignant diseases. In this review, we summarize the particular signatures of microRNAs in acute myeloid leukemia (AML) patients with specific karyotype and the clinical significance of microRNAs in early diagnosis and treatment. MicroRNAs hypermethylation was also proved to correlate with the pathogenesis of AML. However, the target genes and exact pathways of microRNAs participating in these processes are still unknown and more efforts need to be made in the near future.


Specifying the neural basis of the spacing effect with multivariate ERP.
The spacing effect refers to the finding that, given a fixed amount of study time, a longer interval between study repetitions improves long-term retention (e.g., Cepeda et al., 2006; Ebbinghaus, 1885/1967; Melton, 1970). Although the spacing effect is a robust and reliable finding in the memory literature, its cognitive and neural mechanisms remain unclear. We used event-related potentials (ERPs) to investigate the neural correlates of the spacing effect in the context of the study-phase retrieval hypothesis, which posits that repeated exposure of an item serves as a reminder of one's previous experience with the item, thereby promoting long-term retention. ERPs were recorded from 30 healthy young adults as they studied pairs of words under three levels of lag, corresponding to 0, 4, or 12 intervening pairs between the first and second occurrences of a target pair. We used two study-phase tasks that differed in the degree of retrieval that was required. During the test phase, participants were tested on paired-associate recall. The results demonstrated a significant effect of spacing on memory performance. However, the effect of encoding task and the interaction between encoding task and spacing were not significant. The results of the partial least squares analyses, which are not constrained by time window or electrode selection, revealed a spacing effect on the ERP data for both study-phase tasks; this effect occurred late in the epoch and was most salient over the centro-parietal scalp region. The results add to the literature on the neural correlates of the spacing effect by providing a more comprehensive account compared to past ERP findings that were focused on testing specific ERP components. They also call for further investigation on the various theoretical accounts of the spacing effect.


Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitment to the plasma membrane in KK-Ay mice.
For over 4000 years, liquorice has been one of the most frequently employed botanicals as a traditional herbal medicine. Although previous reports have found that liquorice flavonoids possess various health beneficial effects, the underlying mechanism responsible for the anti-diabetic effect of liquorice flavonoids remains unclear. The present study demonstrates that liquorice flavonoid oil (LFO) improves type 2 diabetes mellitus through GLUT4 translocation to the plasma membrane by activating both the adenosine monophosphate-activated protein kinase (AMPK) pathway and Akt pathway in muscle of KK-Ay mice. Furthermore, LFO lowered postprandial hyperglycaemia in a human study. These results indicate that LFO may exert a therapeutic effect on metabolic disorders, such as diabetes and hyperglycaemia, by modulating glucose metabolism through AMPK- and insulin-dependent pathways in skeletal muscle.


Volunteer-led physical activity interventions to improve health outcomes for community-dwelling older people: a systematic review.
Physical activity (PA) is important for older people to maintain functional independence and healthy ageing. There is strong evidence to support the benefits of physical activity interventions on the health outcomes of older adults. Nonetheless, innovative approaches are needed to ensure that these interventions are practical and sustainable. This systematic review explores the effectiveness of volunteer-led PA interventions in improving health outcomes for community-dwelling older people. Five databases (MEDLINE, Embase, CINAHL, PEDro, Cochrane library) were systematically searched for studies using trained volunteers to deliver PA interventions for community-dwelling older people aged ≥ 65 years. Meta-analysis was not conducted due to included study heterogeneity. Twelve papers describing eight studies (five papers reported different outcomes from the same study) were included in the review. All eight studies included strength and balance exercises and frequency of PA ranged from weekly to three times a week. Volunteer-led exercises led to improvements in functional status measured using the short physical performance battery, timed up and go test, Barthel Index, single leg stand, step touch test, chair stand test, and functional reach. Frailty status identified by grip strength measurement or the use of long-term care insurance improved with volunteer-led exercises. Interventions led to improvement in fear of falls and maintained or improved the quality of life. The impact on PA levels were mixed. Limited evidence suggests that volunteer-led PA interventions that include resistance exercise training, can improve outcomes of community-dwelling older adults including functional status, frailty status, and reduction in fear of falls. More high-quality RCTs are needed to investigate the effects of volunteer-led PA interventions among older people.


Characterization of Genes Encoding Key Enzymes Involved in Anthocyanin Metabolism of Kiwifruit during Storage Period.
'Hongyang' is a red fleshed kiwifruit with high anthocyanin content. In this study, we mainly investigated effects of different temperatures (25 and 0°C) on anthocyanin biosynthesis in harvested kiwifruit, and characterized the genes encoding key enzymes involved in anthocyanin metabolism, as well as evaluated the mode of the action, by which low temperature regulates anthocyanin accumulation in 'Hongyang' kiwifruit during storage period. The results showed that low temperature could effectively enhance the anthocyanin accumulation of kiwifruit in the end of storage period (90 days), which related to the increase in mRNA levels of ANS1, ANS2, DRF1, DRF2, and UGFT2. Moreover, the transcript abundance of MYBA1-1 and MYB5-1, the genes encoding an important component of MYB-bHLH-WD40 (MBW) complex, was up-regulated, possibly contributing to the induction of specific anthocyanin biosynthesis genes under the low temperature. To further investigate the roles of AcMYB5-1/5-2/A1-1 in regulation of anthocyanin biosynthesis, genes encoding the three transcription factors were transiently transformed in Nicotiana benthamiana leaves. Overexpression of AcMYB5-1/5-2/A1-1 activated the gene expression of NtANS and NtDFR in tobacco. Our results suggested that low temperature storage could stimulate the anthocyanin accumulation in harvested kiwifruit via regulating several structural and regulatory genes involved in anthocyanin biosynthesis.


Substrate uptake and subcellular compartmentation of anoxic cholesterol catabolism in Sterolibacterium denitrificans.
Cholesterol catabolism by actinobacteria has been extensively studied. In contrast, the uptake and catabolism of cholesterol by Gram-negative species are poorly understood. Here, we investigated microbial cholesterol catabolism at the subcellular level. (13)C metabolomic analysis revealed that anaerobically grown Sterolibacterium denitrificans, a β-proteobacterium, adopts an oxygenase-independent pathway to degrade cholesterol. S. denitrificans cells did not produce biosurfactants upon growth on cholesterol and exhibited high cell surface hydrophobicity. Moreover, S. denitrificans did not produce extracellular catabolic enzymes to transform cholesterol. Accordingly, S. denitrificans accessed cholesterol by direction adhesion. Cholesterol is imported through the outer membrane via a putative FadL-like transport system, which is induced by neutral sterols. The outer membrane steroid transporter is able to selectively import various C27 sterols into the periplasm. S. denitrificans spheroplasts exhibited a significantly higher efficiency in cholest-4-en-3-one-26-oic acid uptake than in cholesterol uptake. We separated S. denitrificans proteins into four fractions, namely the outer membrane, periplasm, inner membrane, and cytoplasm, and we observed the individual catabolic reactions within them. Our data indicated that, in the periplasm, various periplasmic and peripheral membrane enzymes transform cholesterol into cholest-4-en-3-one-26-oic acid. The C27 acidic steroid is then transported into the cytoplasm, in which side-chain degradation and the subsequent sterane cleavage occur. This study sheds light into microbial cholesterol metabolism under anoxic conditions.


Paclitaxel administered by a 1-hour infusion: A phase I-II trial comparing two schedules.
Paclitaxel is currently administered by prolonged intravenous infusion primarily because of severe hypersensitivity reactions that occurred with rapid infusions during early clinical trails. This phase I-II study evaluates the feasibility of 1-hour paclitaxel administration and compares the toxicity and efficacy of two different 1-hour infusion schedules. One hundred sixty-four patients with advanced, refractory cancer were randomized to receive one of two paclitaxel schedules: a 1-hour infusion or a 3-day, divided dose schedule, each daily dose administered by 1-hour infusion. The first 60 patients received a total paclitaxel dose of 135 mg/m2, and the remaining 104 patients received 200 mg/m2. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Cytokines were not routinely used. No serious hypersensitivity reactions occurred in 620 courses of paclitaxel. Both doses were well tolerated; grade 3 or 4 leukopenia was produced in 22% of courses at 135 mg/m2 and 23% of courses at 200 mg/m2. Both schedules were well tolerated, but grade 3 and 4 leukopenia was more common with the 3-day schedule when paclitaxel 200 mg/m2 was administered. Myalagias were more common with the 1-day schedule. Major responses occurred in 35 of 153 evaluable patients (23%). Response rates in ovarian, breast, and non-small cell lung cancer were 45%, 33%, and 25%, respectively. At the 200 mg/m2 dose, 11 of 36 patients (31%) with non-small cell lung cancer responded, including 6 of 16 who had received previous chemotherapy. No major difference in response rates was observed when the 1-day and 3-day schedules were compared. Paclitaxel can be safely administered by 1-hour infusion in an outpatient setting. A dose of 200 mg/m2 is well tolerated without the use of cytokines. Both schedules are well tolerated; however, the 3-day schedule produces more leukopenia when a 200 mg/m2 dose is administered. Antitumor activity was seen with both doses and schedules. Administration of paclitaxel over 1-hour is less toxic, easier, and less expensive than are prolonged infusions, and deserves continued investigation.