Transplanted gonadotropin-releasing hormone neurons promote pulsatile luteinizing hormone secretion in congenitally hypogonadal (hpg) male mice.
Congenitally hypogonadal (hpg) male mice are unable to synthesize biologically active gonadotropin-releasing hormone (GnRH). Implantation of normal fetal preoptic area tissue containing GnRH neurons into the third ventricle of adult hpg males significantly elevates pituitary levels of luteinizing hormone (LH) and corrects their hypogonadism. In all responding animals, immunoreactive GnRH neurons within the transplant innervate the median eminence of the host. To assess whether gonadal recovery in hpg hosts results from pulsatile secretion of GnRH from grafted neurons, we compared the pattern of variation in plasma LH levels in 19 hpg graft recipients with testicular growth to that of 10 normal adult mice. All animals were castrated prior to receiving an indwelling catheter in the jugular vein. Sequential blood samples were collected (t = 10 min) and assayed for LH. Pulsatile LH secretion was seen in 11 of 19 hpg hosts and in all control mice. While there was great variability between individual animals, measures of baseline LH, LH pulse amplitude and duration, interpulse interval, and LH pulse frequency revealed no difference between hpg graft recipients and normal castrates in their LH pulse pattern. Immunocytochemical analysis of the brain in hpg hosts suggested no correlation between any parameter of pulse activity and individual differences in GnRH cell number or GnRH fiber outgrowth into the median eminence. Sources of variation in LH secretion among graft recipients, and between hpg hosts and normal mice, are discussed. We suggest that transplanted GnRH neurons are capable of integration into a GnRH 'pulse generator' which can support a near-normal pattern of pulsatile LH secretion, leading to testicular growth and steroid production.


Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT.
Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX) in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endothelial cells (HMVECs). Immunofluorescence was used to detect renal endothelial-mesenchymal transition (EndMT); Hematoxylin and Eosin (HE) staining and Masson's Trichrome Staining (MTS) was used to analyze renal fibrosis; CCK-8 was used to evaluate cell viability; Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of miR-101-3p; Western blots were utilized to judge the protein expression levels of EndMT, extracellular matrix and TGF-β1/Smad3 signal pathway. Results: In this study, we first found that the protective effect of DEX on DN was related to EndMT. DEX alleviated kidney fibrosis by inhibiting EndMT in diabetic CD-1 mice. DEX could also inhibit high glucose-induced HMVECs EndMT. Then, we confirmed that miR-101-3p was the regulatory target of DEX. The expression of miR-101-3p was decreased in diabetic CD-1 mice and high glucose-induced HMVECs. After DEX treatment, the miR-101-3p increased, and the inhibition of miR-101-3p could counteract the protective effect of DEX and aggravate the EndMT. Finally, we found that the TGF- β1/Smad3 signal pathway was involved in the protective effect of DEX on DN. DEX inhibited the activation of TGF-β1/Smad3 signal pathway. On the contrary, inhibiting miR-101-3p promoted the expression of TGF-β1/Smad3. Conclusion: DEX protects kidney fibrosis in diabetic mice by targeting miR-101-3p-mediated EndMT.


Lateral canthal surgery in the management of epiphora.
To assess the functional benefit and cosmetic appearance after lateral canthal surgery in the management of epiphora. A case series of 75 eyelids in 52 patients who underwent lateral canthal tightening procedures for epiphora in the Kent & Sussex Hospital (UK) between January 1997 and February 1999. All surgery was performed on a Day Case basis. Patients had between one and three follow-up appointments and all patients were surveyed by telephone in August 1999. The minimum follow-up was six months. All patients demonstrated a successful anatomical result at the time of discharge. Epiphora was cured or greatly reduced in 84% of eyes. Satisfaction with the cosmetic appearance was expressed in 86% of eyes. Transient postoperative tenderness over the lateral orbital rim was the most common complication (63%), in some cases lasting up to eight weeks. Lateral canthal surgery is an effective tool in the management of epiphora, giving good functional and aesthetic results.


Common therapeutic target for both cancer and obesity.
Obesity and cancer are two interrelated conditions of high epidemiological need, with studies showing that obesity is responsible for nearly 25% of the relative contribution to cancer incidence. Given the connection between these conditions, a drug that can operate on both obesity and cancer is highly desirable. Such a drug is accomplishable through the development of potent anti-angiogenesis agents due to the shared underlying role of angiogenesis in the development of both diseases. Prior research has demonstrated a key role of type-2 methionine aminopeptidase (MetAP2) for angiogenesis, which has led to the development of numerous of novel inhibitors. Several irreversible MetAP2 inhibitors have entered clinical trials without great success. Though this lack of success could be attributed to off-target adverse effects, the underlying causes remain unclear. More promising reversible inhibitors have been recently developed with excellent pre-clinical results. However, due to insufficient knowledge of the biological functions of N-terminal protein processing, it is hard to predict whether these novel inhibitors would successfully pass clinical trials and thereby benefit cancer and obesity patients. Significantly more efforts are needed to advance our understanding of the regulation of methionine aminopeptidases and the processes by which they govern the function of proteins.


Comparison of total corneal power measurements obtained with different devices after myopic keratorefractive surgery.
To analyze the differences, agreements, and correlation among total corneal power parameters generated by different instruments after myopic keratorefractive surgery. The prospective cross-sectional study included patients who underwent myopic keratorefractive surgery and received measurements of corneal power 3mo after surgery. Automated keratometer was used for the measurement of simulated keratometry (SimK), swept-source optical coherence tomography (SS-OCT) based biometer for total keratometry (TK), anterior segment-OCT for real keratometry (RK), and Scheimpflug keratometer for the true net power (TNP), the total corneal refractive power (TCRP) and equivalent K-readings (EKR). The differences among these parameters were analyzed, and the agreements and correlation between SimK and other total corneal power parameters were investigated. A total of 70 eyes of 70 patients after myopic keratorefractive surgery were included. The evaluated corneal power parameters were as follows: SimK 38.32±1.93 D, TK 37.54±2.12 D, RK 36.64±2.09 D, TNP 36.56±1.97 D, TCRP 36.70±2.01 D, and EKR 37.55±2.00 D. Pairwise comparison showed that there were significant differences (P<0.001) among all parameters except for between TK and EKR, RK and TNP, RK and TCRP (P=1.000, 1.000, 1.000, respectively). The limits of agreement between SimK and TK, RK, TNP, TCPR, and EKR were 1.08, 1.08, 1.43, 1.48, and 1.73 D, respectively. All parameters showed good correlation with SimK, and the correlation coefficients were 0.995, 0.994, 0.983, 0.982, and 0.975. Among the corneal power parameters after myopic keratorefractive surgery, the value of SimK is the largest, followed by TK and EKR, with TCRP, RK, and TNP being the smallest. The differences among the parameters may be attributable to the different calculation principles. Correct understanding and evaluation of corneal power parameters can provide a theoretical basis for taking advantage of the total corneal power to improve the accuracy of intraocular lens calculation after keratorefractive surgery.


[Early diagnosis and correct treatment of cryptorchism].
Diagnosis in cryptorchidism should be as early as possible for therapeutical purposes and for the achievement of most positive results. Early but also exact diagnosis allows a selective therapy concerning type of procedure and age of performance. Aims of early diagnosis and selected treatment are: prevention of infertility and eventual decrease of androgenic endocrinal function in the adult; prevention of torsion in retractile testis; prevention of trauma in perineal ectopic situation; prevention of cancer especially in cryptorchidism of the adult; prevention of psychogenic defects of the empty scrotum. Those goals can be obtained by different approaches: pharmacological (hormonal stimulation), surgical (orchidopexy) or by their association. If hormonal administration is not suitable or without results surgical approach will be adopted. Which is now the most suitable age for surgery? Testicular damages begin at the second year of life. Therefore operation should be acted in advance. However, up to date international acknowledgement is in favour of surgical management around the fourth year for the advantages of a more mature anatomical situation without reducing quality of results. Purpose of early diagnosis and selective therapy in cryptorchidism is to avoid irreversibility of severe histological alteration able to compromise gonadal, especially germinal, function. It is never to forget that the high level of infertility in cryptorchidism can be depending not only on evident alteration in number, motility and morphology of spermatozoa but also on morphofunctional defects escaping from the routine seminal examination. All that is in tight connection with the intrinsic dysmorphism in cryptorchism where the abnormal position of the testis is only a partial aspect.(ABSTRACT TRUNCATED AT 250 WORDS)


Reverse sural artery flap: caveats for success.
Complex open wounds of the distal third of the leg and ankle remain a reconstructive challenge for the plastic surgeon. In many cases, these wounds are best addressed with a free tissue transfer. Although this group has performed more than 400 free flaps to the leg during the past 6 years, free tissue transfer can be an arduous operation that requires a team approach and substantial donor site morbidity for the patient. In recent years, the authors have favored the reverse sural artery fasciocutaneous flap in 11 patients for its ease of dissection, limited morbidity, and preservation of major vessels to the limb. Caveats for successful performance of the reverse sural artery flap include Doppler evidence of patent peroneal perforators, placement of a lazy T-shape skin paddle over the distal gastrocnemius muscle bellies, inclusion of the lesser saphenous vein to augment venous drainage, and, lastly, careful dissection to provide a wide adipofascial pedicle.


Theoretical studies of binding modes of two covalent inhibitors of cysteine proteases.
Physiological and pathological roles of cysteine proteases make them important targets for inhibitor development. Although highly potent inhibitors of this group of enzymes are known, their major drawback is a lack of sufficient specificity. Two cysteine protease covalent inhibitors, viz. (i) Z-RL-deoxo-V-peptide-epoxysuccinyl hybrid, and (ii) Z-RLVG-methyl-, have been developed and modeled in the catalytic pocket of papain, an archetypal thiol protease. A number of configurations have been generated and relaxed for each system using the AMBER force field. The catalytic pockets S3 and S4 appear rather elusive in view of the observed inhibitors' flexibility. This suggest rather limited chances for the development of selective structure-based inhibitors of thiol proteases, designed to exploit differences in the structure of catalytic pockets of various members of this family.


A Novel Non-Apoptotic Role of Procaspase-3 in the Regulation of Mitochondrial Biogenesis Activators.
The executioner caspase-3 has been proposed as a pharmacological intervention target to preserve degenerating dopaminergic (DA) neurons because apoptotic mechanisms involving caspase-3 contribute, at least in part, to the loss of DA neurons in patients and experimental models of Parkinson's disease (PD). Here, we determined that genetic intervention of caspase-3 was sufficient to prevent cell death against oxidative stress (OS), accompanied by unexpected severe mitochondrial dysfunction. Specifically, as we expected, caspase-3-deficient DA neuronal cells were very significantly resistant to OS-induced cell death, while the activation of the initiator caspase-9 by OS was preserved. Moreover, detailed phenotypic characterization of caspase-3-deficient DA cells revealed severe mitochondrial dysfunction, including an accumulation of damaged mitochondria with a characteristic swollen structure and broken cristae, reduced membrane potential, increased levels of reactive oxygen species (ROS), and deficits in mitochondrial oxidative phosphorylation (OXPHOS) enzymes. Of great interest, we found that mitochondrial biogenesis was dramatically decreased in caspase-3-deficient DA cells, whereas their capability of mitophagy was normal. In accordance with this observation, caspase-3 gene knock down (KD) resulted in dramatically decreased expression of the key transcriptional activators of mitochondrial biogenesis, such as Tfam and Nrf-1, implicating a non-apoptotic role of procaspase-3 in mitochondrial biogenesis. Therefore, a prolonged anti-apoptotic intervention targeting caspase-3 should be considered with caution due to the potential adverse effects in mitochondria dynamics resulting from a novel potential functional role of procaspase-3 in mitochondrial biogenesis via regulating the expression of mitochondrial biogenesis activators. J. Cell. Biochem. 119: 347-357, 2018. © 2017 Wiley Periodicals, Inc.


Hematopoietic progenitor kinase 1 (HPK1) is required for LFA-1-mediated neutrophil recruitment during the acute inflammatory response.
Recruitment of polymorphonuclear neutrophils (PMNs) to sites of acute inflammation critically depends on β2 integrins (CD11/CD18). Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as an important adaptor protein regulating PMN trafficking downstream of β2 integrins. Here, we show that mAbp1 constitutively co-immunoprecipitated with hematopoietic progenitor kinase 1 (HPK1) in neutrophil-like differentiated HL-60 (dHL-60) cells. HPK1 was enriched at the lamellipodium of polarized dHL-60 cells, where it colocalized with mAbp1 and actin. Functional analysis of PMNs from HPK1-deficient mice showed that HPK1 was critical for CXCL1-induced lymphocyte function-associated antigen 1 (LFA-1)-mediated PMN adhesion to ICAM-1 under flow conditions. Accordingly, CXCL1-mediated induction of high-affinity LFA-1 required HPK1, but macrophage antigen 1 (Mac-1) affinity regulation was independent of HPK1. Intravital microscopy of the mouse cremaster muscle confirmed the defect of CXCL1-induced leukocyte adhesion in HPK1-deficient mice. Furthermore, β2 integrin-mediated post-adhesion processes-adhesion strengthening, spreading, and directed mechanotactic crawling of PMNs under flow conditions-involved HPK1 in vitro and in vivo. Upon intrascrotal administration of tumor necrosis factor α (TNF-α), PMN adhesion and extravasation were severely compromised in HPK1-deficient mice. In summary, our results indicate that HPK1 is critically involved in LFA-1-mediated PMN trafficking during acute inflammation.


Opioids for persistent pain in older adults.
Older adults compose a large portion of patients with persistent pain. Opioid analgesics are widely used to treat acute and persistent pain in cancer and end-of-life care, but their use in other types of persistent pain in older adults is controversial. Clinicians and regulators must work together, balancing the legitimate medical need for opioids while acknowledging increasing opioid misuse and morbidity and mortality related to opioids.


Effects of acetyl-strophanthidin on left ventricular function and ventricular arrhythmias.
Digitalis drugs can suppress ventricular arrhythmias. It is uncertain whether this effect results from improved left ventricular (LV) function. We utilized radionuclide scanning techniques to evaluate changes in LV ejection fraction (EF) after an infusion of acetyl-strophanthidin in 43 patients with frequent ventricular premature beats (VPBs) (44 to 2400/hr). Acetyl-strophanthidin suppressed ventricular arrhythmia in 17 patients, but LVEF increased in only six of these patients (57% to 67%), while it was unaltered in 11 patients (28% to 30%). In 26 patients ventricular arrhythmia was not suppressed. Fifteen of these patients had an increase in LVEF (60% vs 71%), while this was unchanged in 11 patients (27% vs 29%). Thus no correlation was observed between the positive inotropic and antiarrhythmic action of acetyl-strophanthidin on ventricular arrhythmia and LVEF. We conclude that the suppression of VPBs by acetyl-strophanthidin is independent of the drug's effects on LV function. Evidence is reviewed suggesting that the antiarrhythmic effect of acetyl-strophanthidin on ventricular ectopic activity is due to its vagotonic action.


Transitional medicine: will emergency medicine physicians be ready for the growing population of adults with congenital heart disease?
Currently, approximately 85% of children with significant congenital heart problems survive to adolescence and adulthood. This survival rate represents a dramatic improvement in the medical and surgical care of congenital heart disease (CHD) during the last 35 years. Nevertheless, these patients remain at increased risk for significant cardiac problems long after primary interventions are completed. They are more likely than the general population to seek urgent medical care, often in an emergency department setting. They represent a new and growing population of emergency department patients with a specialized set of problems not traditionally part of the training for emergency medicine (EM) physicians. We investigated the current scope and status of training for EM physicians in the immediate management of CHD patients as they grow to adolescence and adulthood. We conducted 2 cross-sectional surveys to assess the current training environment for 2 specific groups: (1) US general EM (GEM) residency programs, and (2) US and Canadian pediatric EM (PEM) fellowship programs. Surveys were mailed to program directors during the summer of 2005. A total of 198 surveys were sent out: 134 to GEM residency directors and 64 to PEM fellowship directors. The response rate overall was 68%, with a 64% response rate from the GEM residency directors and 77% from the PEM fellowship directors. Across all programs, 43% (56/130 respondents) were "unsure" about the existence or location of an adult CHD (ACHD) clinic in their area. When asked to rate the importance of ACHD as a training topic, 40 (85%) of 47 PEM fellowship directors and 62 (74%) of 84 GEM residency directors ranked it as "low priority" or "unnecessary." However, 70 (55%) of 127 respondents were "unsure," "uncomfortable," or "worried" about the ACHD training their trainees receive (PEM, 59%; GEM, 53%). In addition, most program directors (75%) estimated that their trainees care for 5 or fewer ACHD patients annually. There seems to be a mismatch between the growing need for ACHD emergency care and the current state of this topic in both GEM residency and PEM fellowship training programs.


Preoperative concurrent radiation therapy and cisplatinum continuous infusion in IIIa (N2) non small cell lung cancer. A pilot study.
From April 1991 to September 1993, 18 patients affected by a presumed operable IIIa (N2) non small cell lung cancer (NSCLC) with histologically confirmed bulky mediastinal metastases, received preoperative concurrent radiation therapy and continuous infusion of cisplatinum (CDDP). The radiotherapy consisted of 2 Gy given 5 days a week for a total dose of 50 Gy; CDDP was administered by means of a central catheter and a portable pump at the daily dose of 6 mg/m2 given on the same days as the radiation therapy (total dose: 150 mg/m2). Two weeks after the end of the treatment, the patients were reevaluated: 5 patients had either local or distant disease progression, the other 13 were submitted to thoracotomy: 12 received a complete resection and 1 patient underwent only a mediastinal lymphadenectomy, because pneumonectomy was impossible due to lack of respiratory function. No histological evidence of cancer cells was observed in the specimens of 6 patients (33%). Radiological response rate was 61% (11/18); resection rate was 66% (12/18) and complete resection rate was 61% (11/18). There was one postoperative death (5%). The 3 year actuarial survival rate is 63.6% for the patients who received a resection with a median survival time of 18 months. All non operated patients died within one year. Combined preoperative treatment was well tolerated. Better results were achieved in patients with squamous cell carcinoma who had a complete resection following a total tumor sterilization with radio-chemotherapy.


Why a Large-Scale Mode Can Be Essential for Understanding Intracellular Actin Waves.
During the last decade, intracellular actin waves have attracted much attention due to their essential role in various cellular functions, ranging from motility to cytokinesis. Experimental methods have advanced significantly and can capture the dynamics of actin waves over a large range of spatio-temporal scales. However, the corresponding coarse-grained theory mostly avoids the full complexity of this multi-scale phenomenon. In this perspective, we focus on a minimal continuum model of activator-inhibitor type and highlight the qualitative role of mass conservation, which is typically overlooked. Specifically, our interest is to connect between the mathematical mechanisms of pattern formation in the presence of a large-scale mode, due to mass conservation, and distinct behaviors of actin waves.


Proportions of sewage sludge in the production and quality of Malpighia emarginata DC. seedlings.
Sewage sludge (SS) has nutritional contents and has been implemented in the cultivation of seedlings. This study aimed to evaluate the quality of Malpighia emarginata DC. seedlings produced in different substrates with SS. Treatments were implemented with the addition of SS, and after 180 days seedling the characteristics were measured: aerial part and root system length, stem base diameter, number of leaves, fresh and dry mass of aerial part and root, and total biomass. The Dickson Quality Index (DQI) was calculated and the macro and micronutrient content of the aerial part and root. The accumulation of macronutrients in the root system followed the order of N>K>P>Ca>Mg>S, and aerial part of N>Ca>K>P>Mg>S, in the two vegetative structures N and S were in lower concentration. For micronutrients, the accumulation in the root system occurred with Fe>Zn>Mn>Cu>B, and aerial part with Fe>Mn>Zn>B>Cu. It was noted that in the two vegetative structures the Fe content was more concentrated. The use of SS in the substrate formulation proved effective in obtaining viable seedlings for field planting, being recommended the treatment with 60% SS + 40% organic compost.


Effect of biologically active substances derived from hydrobionts of the Pacific Ocean on parameters of lipid metabolism during experimental hypercholesterolemia.
We studied the effect of biologically active substances derived from hydrobionts, namely maristim (natural product from sea urchin roe) and fucolam (polysaccharides of fucoidan and calcium alginate from brown algae) on blood biochemistry in the mouse model of nutritional hypercholesterolemia. Maristim and fucolam are found to be capable to normalize the levels of the major indicators of lipid and carbohydrate metabolism and aminotransferase enzyme activity in terms of atherogenic load. Correction action of biologically active substances is more expressed in combined application. Identified experimentally normalizing effects of maristim and on lipid and carbohydrate metabolism allow us to recommend the further study in clinical trials of these biologically active substances and based on them additives.


Response and adaptation by plants to flooding stress.
Stress on plants imposed by flooding of the soil and deeper submergence constitutes one of the major abiotic constraints on growth, species' distribution and agricultural productivity. Flooding stress is also a strong driver of adaptive evolution. This has resulted in a wide range of biochemical, molecular and morphological adaptations that sanction growth and reproductive success under episodic or permanently flooded conditions that are highly damaging to the majority of plant species. However, even seemingly poorly adapted species possess some short-term resilience that is important for overall success of these plants in various habitats. The papers contained in this Special Issue address these topics and emphasize molecular, biochemical and developmental processes that impact on flooding tolerance. Most of the articles are based on lectures given to the 8th Conference of the International Society for Plant Anaerobiosis (ISPA), held at the University of Western Australia, Perth, 20-24 September, 2004. Reviews and research papers are presented from the leading laboratories currently working on plant responses to flooding stress.


Modeling for the optimal biodegradation of toxic wastewater in a discontinuous reactor.
The degradation of toxic compounds in Sequencing Batch Reactors (SBRs) poses inhibition problems. Time Optimal Control (TOC) methods may be used to avoid such inhibition thus exploiting the maximum capabilities of this class of reactors. Biomass and substrate online measurements, however, are usually unavailable for wastewater applications, so TOC must use only related variables as dissolved oxygen and volume. Although the standard mathematical model to describe the reaction phase of SBRs is good enough for explaining its general behavior in uncontrolled batch mode, better details are needed to model its dynamics when the reactor operates near the maximum degradation rate zone, as when TOC is used. In this paper two improvements to the model are suggested: to include the sensor delay effects and to modify the classical Haldane curve in a piecewise manner. These modifications offer a good solution for a reasonable complexification tradeoff. Additionally, a new way to look at the Haldane K-parameters (micro(o),K(I),K(S)) is described, the S-parameters (micro*,S*,S(m)). These parameters do have a clear physical meaning and, unlike the K-parameters, allow for the statistical treatment to find a single model to fit data from multiple experiments.


Total Synthesis and Structural Determination of the Dimeric Tetrahydroxanthone Ascherxanthone A.
The first total synthesis of the dimeric tetrahydroxanthone ascherxanthone A has been accomplished. This synthetic strategy features (1) enantioselective intramolecular allylic C-H oxidation to construct a core chiral chromane, (2) intramolecular aldol reaction/dehydration to form the enone group, and (3) intermolecular Suzuki-Miyaura coupling to connect two monomeric tetrahydroxanthones. This synthetic work allowed us to determine the axial chirality of the 2,2'-biaryl C-C bond and the absolute configuration of the ascherxanthone A. This approach should facilitate the preparation of derivatives and structurally related natural products for medicinal studies.


Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis.
The metabolic fibroblast growth factors (FGFs), FGF1, FGF15/19, and FGF21 differ from classic FGFs in that they modulate energy homeostasis in response to fluctuating nutrient availability. These unique mediators of metabolism regulate a number of physiological processes which contribute to their potent pharmacological properties. Administration of pharmacological doses of these FGFs causes weight loss, increases energy expenditure, and improves carbohydrate and lipid metabolism in obese animal models. However, many questions remain regarding the precise molecular and physiological mechanisms governing the effects of individual metabolic FGFs. Here we review the metabolic actions of FGF1, FGF15/19, and FGF21 while providing insights into their pharmacological effects by examining known biological functions.


A Preliminary Study of Antibiotic Resistance Genes in Domestic Honey Produced in China.
Antibiotic resistance genes (ARGs) are emerging contaminants that pose a health risk to humans worldwide. Little information on ARGs in bee honey is available. This study profiles ARGs in bee honey samples produced in China, the biggest producer in the world. Of 317 known ARGs encoding resistance to 8 classes of antibiotics, 212 were found in collected honey samples by a real-time quantitative polymerase chain reaction approach. Occurrence frequencies of genes providing resistance to FCA (fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol) and aminoglycosides were 21.0% and 18.5%, respectively. Frequencies of genes encoding efflux pumps were 42.5% and those of destructase genes 36.6%, indicating that these two mechanisms were predominant for resistance. Nine plasmid-mediated quinolone resistance genes were detected. Of the nine transposase genes known to be involved in antibiotic resistance, eight were found in the samples examined, with tnpA-4, tnpA-5, and tnpA-6 being more abundant. The abundance of the transposase genes was associated with genes conferring resistance to tetracyclines (r = 0.648, p < 0.01), macrolide-lincosamide-streptogramin B (r = 0.642, p < 0.01), FCA (r = 0.517, p < 0.01), and aminoglycosides (r = 0.401, 0.01 < p < 0.05). This is the first study on the abundance and diversity of ARGs in Chinese bee honey products. These findings suggest that bee honey may be a significant source of ARGs that might pose threat to public health. Further research is required to collect more samples in diverse geographic regions in China to make a more comprehensive judgment of ARG in bee honey.


[Establishing the types of Dienes compatibility in clinical Proteus mirabilis strains].
The aim of the study was to use the Dienes phenomenon for the differentiation of Proteus mirabilis strains isolated from urine by the method of making possible their typing. The subject of the study were 351 strains of Proteus mirabilis obtained from the laboratory of the Institute of Pediatrics, Medical Academy in Lódź. For establishing of the compatibility type 18 indicator strains were taken, each of them had action antagonistic towards all other ones. The results were read according to the presence or absence of the demarcation line between indicator strains and the studied strain. Out of 351 strains in 190 (54%) the reactions were compatible with one or more indicator strains. They were classified into 30 Dienes compatibility types. In the view of the simplicity and easy performance the method can be used in every microbiological laboratory.


Shared Decision-Making in Acute Surgical Illness: The Surgeon's Perspective.
Surgical patients increasingly have more comorbidities and are of an older age, complicating surgical decision-making in emergent situations. Little is known about surgeons' perceptions of shared decision-making in these settings. Twenty semi-structured interviews were conducted with practicing surgeons at 2 large academic medical centers. Thirteen questions and 2 case vignettes were used to assess perceptions of decision-making, considerations when deciding whether to offer to operate, and communication patterns with patients and families. Thematic analysis revealed 6 major themes: responsibility for the decision to operate, perceived futility, surgeon judgment, surgeon introspection, pressure to operate, and costs of the operation. Perceived futility was universally considered a contraindication to surgical intervention. However, the challenge of defining futility led participants to emphasize the importance of patients' self-determined risk-to-benefit analysis when considering surgical intervention. More experienced surgeons reported greater comfort with communicating to patients that a condition was not amenable to an operation and reserved the right to refuse to operate. Due to external pressures and uncertainty, some providers err on the side of operative intervention, despite suspected futility. Greater experience allows surgeons to withstand external pressures, be confident in their assessments of perceived futility, and guide patients and their families away from additional interventions.


Sulfur-Doped Mesoporous Carbon Nitride with an Ordered Porous Structure for Sodium-Ion Batteries.
Mesoporous carbon nitride (MCN) with well-ordered porous structures is a promising anode material for secondary ion batteries owing to their unique physico- and electrochemical properties. However, the practical application of these MCNs in sodium-ion batteries (SIBs) is still limited because of their confined interlayer distance, which results in restricted accommodation of Na ions inside the lattice. Here, we report on the synthesis of highly ordered sulfur-doped MCN (S-MCN) through a hard template approach by employing dithiooxamide (DTO) as a single molecular precursor containing carbon, nitrogen, and sulfur elements. The interlayer distance of carbon nitride is significantly expanded upon the introduction of larger S ions on the MCN lattice, which enables high capability of Na ion accommodation. We also demonstrate through the first-principles density functional theory calculation that the present S-MCN is highly optimized not only for the chemical structure but also for uptaking abundant Na ions with high adsorption energy. The specific discharge capacity of SIBs appears to be remarkably enhanced for S-MCN (304.2 mA h g-1) compared to the nonporous S-CN (167.9 mA h g-1) and g-C3N4 (5.4 mA h g-1), highlighting the pivotal roles of the highly ordered mesoporous structure and S-doping in enhancing the electrochemical functionality of carbon nitride as an anode material for SIBs.


Circadian rhythms from flies to human.
In this era of jet travel, our body 'remembers' the previous time zone, such that when we travel, our sleep wake pattern, mental alertness, eating habits and many other physiological processes temporarily suffer the consequences of time displacement until we adjust to the new time zone. Although the existence of a circadian clock in humans had been postulated for decades, an understanding of the molecular mechanisms has required the full complement of research tools. To gain the initial insights into circadian mechanisms, researchers turned to genetically tractable model organisms such as Drosophila.


Site of Preference Energy and Selective Uptake of Transition-Metal Ions from a Magma.
Results of absorption spectra measurements on silicate glasses of various compositions indicate that ions of the first transition-metal series are present in tetrahedral and octahedral sites in silicate melts (glasses). The fractionation patterns observed for transition-metal ions between magmas and silicate minerals can be interpreted according to crystal field theory in terms of octahedral "site preference energies" of transition ions in crystal lattices.


Current practice and attitudes of Australian obstetricians toward population-based carrier screening for inherited conditions.
An anonymous survey of Australian Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted with the aim of understanding current practice and attitudes toward population-based carrier screening for inherited conditions in the setting of routine pregnancy care. Of 1,121 Fellows invited to complete the online questionnaire by e-mail, 237 (21%) responded, and of these 156 were practicing obstetricians and completed the whole survey. Of the respondents, 83% expressed support for population-based carrier screening for at least some conditions, with 97% supporting carrier screening for β-thalassaemia, and 83% supporting carrier screening for cystic fibrosis (CF). A small proportion of obstetricians reported offering carrier screening as part of routine pregnancy care (20% for β-thalassaemia, 8% for CF, 5% for fragile X syndrome, and 2% for spinal muscular atrophy). The main practical barriers identified for screening were cost, time constraints, and availability of supporting services. Addressing these issues is crucial for the successful implementation of population-based carrier screening programs in Australia and internationally.


[Prerequest for increasing cure rate of cancer by chemotherapy].
Cancer chemotherapy is now the major modality to increase cure rate of cancer. In the past two decades systemic chemotherapy markedly improved the curability of several advanced malignancies in both adults and children. Several other cancers are also considered as curable by adjuvant setting. As for the low response group we must continue comprehensive approaches to improve response rate and duration. The knowledges of newer cancer biology provide us many ideas and targets of chemotherapy. The fundamental difficulties lie in cancer treatment are tumor side heterogeneity and host side individuality. Heterogeneity is now interpreted as the results of gene-instability and multi-oncogene involvement is of current interests. Thus in order to overcome these difficulties pharmacology-directed chemotherapy is now indispensable.


Levels of di-(2-ethylhexyl)phthalate and total phthalate esters in milk, cream, butter and cheese.
Di-(2-ethylhexyl)phthalate (DEHP) and total phthalate ester plasticizer levels were determined in milk, cream, butter and cheese samples from a variety of sources from three European countries (UK, Norway and Spain). Samples of milk (from Norway) obtained at various stages during collection, transportation and packaging operations showed no apparent trends in phthalate contamination with total phthalate levels (expressed as DEHP equivalents) in the raw milk of between 0.12 and 0.28 mg/kg. On processing the DEHP was concentrated in the cream at levels up to 1.93 mg/kg, whereas low fat milk contained from < 0.01 to 0.07 mg/kg. Retail dairy products (from Spain) were contaminated with < 0.01-0.55 mg/kg DEHP with a maximum total phthalate level of 3.0 mg/kg in cream samples. UK pooled milk samples from doorstep delivery (obtained from different regions of the country) contained low levels of DEHP (< 0.01-0.09 mg/kg) and total phthalate (0.06-0.32 mg/kg). Retail UK samples of cheese, butter and other fatty products varied considerably in their levels of contamination, the highest being cheese samples containing 17 mg/kg of DEHP and 114 mg/kg total phthalate. However, the majority of samples contained 0.6-3.0 mg/kg DEHP and 4-20 mg/kg total phthalate. UK cream samples contained levels of 0.2-2.7 mg/kg DEHP and 1.8-19.0 mg/kg total phthalate. The level found in these products was too high to have resulted solely from milk by concentration in the fat phase and must therefore have arisen in other ways.


Oncocytic liver cell adenoma.
A 46-year-old woman underwent right hepatic lobectomy for the removal of a solitary liver tumour from a non-cirrhotic liver. The macroscopic and light microscopic features were those of a liver cell adenoma but the cells appeared oncocytic. Electron microscopy confirmed the numerous mitochondria characteristic of oncocytes. The difficulty of distinguishing oncocytic liver cell adenoma from fibrolamellar hepatocellular carcinoma is discussed.


Detecting water quality patterns in New Hampshire's estuaries using National Coastal Assessment probability-based survey data.
Between 2000 and 2006, the New Hampshire Department of Environmental Services and the University of New Hampshire collected water quality samples at 25 to 40 stations per year in a 56.5-km(2) estuary as part of the Environmental Protection Agency's National Coastal Assessment program. Due to the high density of stations, probabilistic statistics for the estuary could be calculated with low uncertainty. The proportions of the estuary exceeding thresholds in each year were calculated for temperature, salinity, dissolved oxygen, chlorophyll a, nitrogen as nitrate and nitrite, nitrogen as ammonium, phosphorus as orthophosphate, total suspended solids, and fecal coliform bacteria. These values were tested for trends over time and correlations with climate variables. The same statistical tests were applied to monthly grab sample data from a representative station in the estuary. The outcomes of the statistical tests on the two datasets were compared to determine if they provided similar information to coastal managers. Trends and correlations were equally likely to be detected using the probability-based data and the fixed station data, but the results were different for the two datasets. The differences were likely due to the distributed nature of the probability-based sampling design, which places stations in all sections of the estuary. In addition, expressing the probabilistic datasets as estimated proportions reduced variability in volatile parameters, such as bacteria, relative to the grab sample dataset. It will be important to develop tools to rectify trends from probability-based surveys with fixed station monitoring to provide clear information to managers.


Menopause: an important milestone in women's health.
Menopause, a natural process in a woman's life, is defined as the cessation of menstrual period for 12 consecutive months. In Singapore, the average age of natural menopause is 49 years of age. We discuss the challenges faced by menopausal women and provide an example of a holistic approach to the management of women during this important stage of their lives.


Tritiated thymidine uptake in pig skin. Comparison of in vivo and in vitro techniques.
Tritiated thymidine (3HT) was used in one of three ways to label deoxyribonucleic acid replication in epidermal cells of miniature swine: (1) the radioactive material was injected intracutaneously in vivo; (2) the radioactive material was injected intracutaneously into biopsy specimens and the specimens incubated in vitro in Eagle's medium, or (3) uninjected biopsy specimens were incubated in Eagle's medium with added 3HT. The first two methods yielded the same proportions of labeled cells with uniform distribution of labeled cells. The third method resulted in labeling of cells mainly at the periphery of the biopsy specimens. The advantages of the in vitro over the in vivo technique of injection of 3HT includes the fact that injecting a biopsy specimen avoids the problems of large amounts of radioactive waste disposal in animal studies or the legal and ethical problems of tracer studies in humans.


Bridging the distance: bibliographic instruction for remote library users.
Electronic information resources are proliferating, library collections are increasingly accessible via the Internet, and the number of end users who access library resources remotely is on the rise. Changes in user behavior drives a corresponding change in the way instructional programs must be delivered to meet the needs of remote library users. This paper discusses some technologies currently available for remote instruction, assesses their use, and offers views on future trends.


Ground-based measurements of leaf area index: a review of methods, instruments and current controversies.
Leaf area index (LAI) is the total one-sided area of leaf tissue per unit ground surface area. It is a key parameter in ecophysiology, especially for scaling up the gas exchange from leaf to canopy level. It characterizes the canopy-atmosphere interface, where most of the energy fluxes exchange. It is also one of the most difficult to quantify properly, owing to large spatial and temporal variability. Many methods have been developed to quantify LAI from the ground and some of them are also suitable for describing other structural parameters of the canopy. This paper reviews the direct and indirect methods, the required instruments, their advantages, disadvantages and accuracy of the results. Analysis of the literature shows that most cross-validations between direct and indirect methods have pointed to a significant underestimation of LAI with the latter techniques, especially in forest stands. The two main causes for the discrepancy, clumping and contribution of stem and branches, are discussed and some recent theoretical or technical solutions are presented as potential improvements to reduce bias or discrepancies. The accuracy, sampling strategy and spatial validity of the LAI measurements have to be assessed for quality assurance of both the measurement and the modelling purposes of all the LAI-dependent ecophysiological and biophysical processes of canopies.


Exon skipping of cathepsin B: mitochondrial targeting of a lysosomal peptidase provokes cell death.
The alternatively spliced messenger RNA of the human cysteine peptidase cathepsin B missing exons 2 and 3 encodes a truncated form of the enzyme lacking the signal peptide and part of the inhibitory propeptide. This deletion results in a new N-terminal leader sequence characteristic of proteins predestined for transport into mitochondria. We determined enzyme targeting to intracellular organelles by transfecting HeLa cells with constructs containing segments of variable length of the N terminus of truncated cathepsin B fused to green fluorescent protein. Co-localization of the constructs with mitochondria and the endoplasmic reticulum was probed with specific markers. None of the chimeric products were found in the endoplasmic reticulum, showing that truncated cathepsin B is misrouted from its regular biosynthetic pathway and forced to enter the mitochondria instead of lysosomes as its final destination. The first 20 amino acids of the new N terminus were necessary and sufficient for mitochondrial targeting, but only cells expressing the complete truncated cathepsin B sequence died by nuclear fragmentation. This new and unexpected behavior draws attention to an additional extralysosomal role for a cysteine peptidase with several recognized important pathophysiological functions. Mitochondrial targeting of cathepsin B may have significant consequences on cell life in pathological or physiological situations characterized by excessive transcription of the cathepsin B message lacking exons 2 and 3, as observed for instance in osteoarthritic cartilage.


Contrast enhanced ultrasound (CEUS) - an unique monitoring technique to assess microvascularization after buried flap transplantation.
Incidence of patients requiring complex soft tissue or osseous reconstruction has dramatically increased. However most of the monitoring systems have limitations in tissue penetration and are not able to detect microvascular complications after transplantation of so-called buried-flaps, that have no contact to the surface.Aim of the study was to assess contrast enhanced ultrasound (CEUS) as monitoring tool after buried flap transplantations. 20 patients were examined after buried flap transplantation using CEUS. Quantitative perfusion analysis (TIC) was performed with an integrated perfusion software using stored cine-loops. Two perfusion-parameters, time to PEAK (TtoPk) and area under the curve (Area), were evaluated using TIC analysis. Minor complications were observed in 3 patients. In these patients a delayed contrast agent wash-in and wash-out was observed. Additionally the perfusion values TtoPk (sec.) and Area (relative Units) were clearly different in the patients with minor complications: TtoPk: 32.0 sec; Area 425.5 rU (without complication), TtoPk: 38.6 sec.; Area: 18.3 rU (wound healing disturbance) and TtoPk: 14.4 sec.; Area: 105.9 rU (hematoma). As CEUS can assess microvascularization almost depth-independent, CEUS is an unique method to assess global flap perfusion after buried flap transplantation.


BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease region between D21S55 and MX1 on chromosome 21.
Chromosome 21 is a model for the study of human chromosomal aneuploidy, and the construction of its physical and transcriptional maps is a necessary step in understanding the molecular basis of aneuploidy-dependent phenotypes. To identify the gene(s) responsible for Down syndrome congenital heart disease (DS-CHD), we constructed a physical map of the D21S55 to MX1 region. A bacterial artificial chromosome (BAC) library was screened using several YACs spanning the interval, and a P1-derived artificial chromosome (PAC) library was screened using radiolabeled STS PCR products and whole BACs in gap-filling initiatives. FISH confirmed the location of all BAC and PAC clones to 21q22.2-q22.3. Overlaps were established using clone-to-clone Southerns and 24 new STSs, generated from the direct sequencing of BAC and PAC ends, along with 35 preexisting STSs. Approximately 3.5 Mb of the 4- to 5-Mb D21S55 to MX1 interval is covered in 85 BACs and 24 PACs, representing fourfold coverage within the contigs. These BAC and PAC contigs are valuable reagents for isolating the genes for DS-CHD.


Characterization of HeLa cells persistently infected with influenza virus B/Lee/40 with respect to telomerase activity and apoptosis.
The purpose of this study was to examine telomerase activity and apoptotic changes in HeLa cells persistently infected with influenza viruses B/Lee/40 (He/Le cells). He/Le cells were established as described previously [Intervirology 2002;45:67-70], and passaged twice a week. The existence of influenza virus genes was monitored by the reverse transcription polymerase chain reaction (RT-PCR). Telomerase activities in He/Le cells were assayed by Telochaser (stretch PCR method). Apoptotic changes in He/Le cells were examined using the Apoptotic DNA Ladder Kit and the In situ Cell Death Detection Kit, Fluorescence. In He/Le cells, (1) all eight influenza virus genes were detected by RT-PCR until 62 days post infection (p.i.); (2) only nucleoprotein gene remained detectable until 120 days p.i.; (3) telomerase activity of He/Le cells normalized to those of uninfected HeLa cells was remarkably decreased (16-55% of control) during the persistence of influenza and recovered up to 80% of control on day 168 p.i. when no influenza virus gene was detected by RT-PCR, and (4) no apoptotic changes were detected despite the continuous existence of influenza virus genes. In He/Le cells, telomerase activity was suppressed exclusively during the persistence of influenza, and no apoptotic changes were detected.


Solitary thyroid gland metastasis from rectal cancer: A case report and review of the literature.
Metastatic carcinoma of the thyroid gland is a rare encounter in clinical practice, but autopsy series showed that it is not so rare. Thyroid metastasis from colorectal cancer (CRC) is rare and has a poor prognosis. We herein report a rare case of solitary thyroid metastasis from rectal cancer combined with needle tract implantation after fine-needle aspiration (FNA) of the thyroid nodule and review the relevant literature. A 54-year-old woman with a history of TNM stage III CRC presented a 1.3 cm × 1.0 cm mass in the left thyroid gland. FNA and histological examination of the left thyroid lobe surgical specimen confirmed the diagnosis of isolated metastatic adenocarcinoma from the rectum. Needle tract implantation was observed in the neck 11 mo after the FNA examination. The 2.5-cm seeding lesion was successfully removed by surgery, and the patient recovered well. The literature relevant to this clinical condition, the diagnostic workup, spread pathway, and surgical management of these rare lesions is reviewed. For a patient with a thyroid mass and a history of CRC, metastatic thyroid carcinoma should be considered even if the patient has no evidence of other organ metastasis from CRC. FNA cytological examination of the thyroid mass is useful in the differential diagnosis between primary thyroid disease and metastatic thyroid carcinoma. Thyroid lobectomy of the gland containing the metastatic tumor is suggested in patients with metastatic carcinoma of the thyroid.


Atherogenic risk in obese and in diabetic children.
By a complex biochemical, immunologic, morphohistochemical and ultrastructural study, carried out on a group of 42 obese and 38 diabetic children, comparatively with 12 normal controls, the authors arrive at conclusions which prove that obesity and diabetes mellitus carry great atherogenic risk factors. Even though the intimate atherogenesis mechanism is not perfectly known, the abnormal values of insulinemia, lipidemia and cortisolemia are certainly involved in this process. In diabetes mellitus the immunologic factor is also involved. Microangiopathy in diabetes mellitus and capillary lesions in the adipose tissue of obese children may also represent atherogenic risk factors. An efficient prophylaxis in atherosclerosis must therefore begin in childhood.


Threshold for thermal ionization of an aluminum surface by pulsed megagauss magnetic field.
The first measurement of the threshold for thermal ionization of the surface of thick metal by pulsed magnetic field (B) is reported. Thick aluminum-with depth greater than the magnetic skin layer-was pulsed with partial differential B/ partial differential t from 30-80 MG/micros. Novel loads avoided nonthermal plasma (from electron avalanche, or energetic particles or photons from arcs). Thermal plasma forms from 6061-alloy aluminum when the surface magnetic field reaches 2.2 MG, in qualitative agreement with numerical simulation results by Garanin et al. [J. Appl. Mech. Tech. Phys. 46, 153 (2005)].


Can we consider medical residents as shift workers?
Although medical residents are characterized by long working hours, night shifts and high levels of work load, it is unclear if their work schedule can be classified as shift work, or if it has a similar impact on residents' well-being. The present paper compared the profile of complaints about sleep or daytime functioning of medical residents to that of rotating shift workers and day workers, of similar ages. Sixty-one residents (aged: 32.2 +/- 2.2 years), after 2 years of residency, participated in the study. The two control groups with a similar age range (26-40 years) were chosen, and included 94 rotating shift workers and 146 day workers. All subjects completed self-administered questionnaires on their sleep habits, and their sleep-wake cycle was monitored by a wrist-worn actigraph. Ten percent of the residents complained about difficulties falling asleep, 34% complained about morning tiredness, 14% complained about mid-sleep awakening, and 20% about prolonged fatigue. The residents slept significantly less than the day workers, and their sleep efficiency was significantly higher. When examining their subjective complaints profile, residents complained more than day workers and their answers were more similar to those of rotating shift workers, therefore they can be considered to be characterized as shift workers.


Case Report: Prenatal Diagnosis and Treatment of Fetal Autoimmune-Associated First-Degree Atrioventricular Block: First Report From China.
Background: The rapid progression from fetal first-degree atrioventricular block (AVB) to third-degree AVB had been reported. However, how to define fetal first-degree AVB with proper technique and the necessity of the treatment in utero for fetal autoimmune-associated first-degree AVB are still controversial. Purpose: To explore the diagnosis and the effect of treatment for fetal first-degree AVB. Cases Presentation: Four pregnant women with positive autoantibodies anti-SSA/Ro were admitted into our hospital with complaints of rapid prolonged atrioventricular (AV) intervals of their fetuses. Fetal AV intervals were re-measured by tissue Doppler imaging (TDI) from the onset of atrial contraction to ventricular systole (Aa-Sa), which were 170 ms (case 1-twin A), 160 ms (case 1-twin B), 163 ms (case 2) and 172 ms (case 3) and 170 ms (case 4), respectively. The histories of medication usage or infection during gestation were denied. Amniotic fluid genetic screenings and virological tests were negative in all cases. No structural cardiac disorders were found and the cardiovascular profile scores were 10 for each fetus. Oral dexamethasone (initial dose of 4.5 mg daily) and hydroxychloroquine (200 mg bid) plus weekly follow-up surveillance were suggested. The dosage of dexamethasone was adjusted according to the changes of the AV intervals and fetal development of biparietal diameters (BPD) and femur lengths (FL). All fetal AV intervals were controlled well. Maternal and fetal adverse effects were noted as diabetes in 1 mother and growth retardation in all fetuses. All fetuses were delivered via cesarean section at 35+4, 37, 38, and 37+1 gestational weeks, with 10 scores of Apgar score. Postnatally, positive anti-SSA/Ro was found in all neonates. However, there were no clinical or laboratory evidence of neonatal lupus syndrome. No abnormal signs were found on postnatal electrocardiogram and echocardiography for all neonates. With a follow-up of 8-53 months, there was no progression of disease and all infants demonstrated normal physical, mental, and motor development. Conclusion: Prenatal treatment for fetal autoimmune-associated first-degree AVB could be an alternative. Strict surveillance and timely adjustment of the treatment according to the conditions of the mother and the fetus are indicated. Further studies are necessary to prove our concept.


Implications of regression analysis and correlational data between subtests of the WISC-R and the PPVT-R for a delinquent population.
Computed correlations between the subscales of the Wechsler Intelligence Scales for Children-Revised (WISC-R) and the Peabody Picture Vocabulary Test-Revised (PPVT-R) using as a sample 72 adjudicated male delinquents aged 13-10 to 16-11. Significant relationships at the .0001 level were obtained for 10 subtests with only one, Object Assembly, computed at the .001 level. A forward selection multiple regression analysis resulted in six subtests of the WISC-R correlating to the PPVT-R with a R2 value of .78. The significance and the implications of this relationship for the juvenile delinquent population were discussed.


The onset of NIDDM and its relationship to clinical diagnosis in Egyptian adults.
The onset of diabetes relative to clinical diagnosis was estimated in Egyptians with non-insulin-dependent diabetes mellitus (NIDDM) based on the relationship between retinopathy and duration of diabetes. Between July 1992 and October 1993 the Diabetes in Egypt (DIE) Project performed a cross-sectional, population-based survey with clinical and laboratory follow-up to describe the prevalence of microvascular, neuropathic, and macrovascular complications among Egyptians > or = 20 years of age with diagnosed diabetes, previously undiagnosed diabetes, impaired glucose tolerance, and normal glucose tolerance. The sample of persons with diabetes diagnosed prior to the survey had medical examinations which included a dilated eye examination and retinal photographs. Generalized linear models were used to relate the probability of retinopathy to duration of diabetes. Among 218 persons with diabetes diagnosed prior to the DIE project, 87 (40%) had diabetic retinopathy. The onset of retinopathy was estimated to occur 2.6 years (p = 0.04) prior to clinical diagnosis. The estimated annual incidence of retinopathy was 5% and the estimated prevalence at the time of clinical diagnosis of diabetes was 12%. On the basis of reports that retinopathy does not occur until approximately 5 years after the development of diabetes, the onset of NIDDM was estimated to occur 7.6 years prior to its clinical diagnosis. This estimate of the onset of NIDDM in Egyptians is comparable to other estimates reported for US and Australian populations.


The angiotensin II type 1 receptor blocker losartan attenuates bioprosthetic valve leaflet calcification in a rabbit intravascular implant model.
There is evidence that angiotensin II type I receptor blocker (ARB) could reduce structural valve deterioration. However, the anticalcification effect on the bioprosthetic heart valve (BHV) has not been investigated. Thus, we investigated the effects of losartan (an ARB) on calcification of implanted bovine pericardial tissue in a rabbit intravascular implant model. A total of 16 male New Zealand White rabbits (20 weeks old, 2.98-3.34 kg) were used in this study. Commercially available BHV leaflet of bovine pericardium was trimmed to the shape of a 3-mm triangle and implanted to both external jugular veins of the rabbit. The ARB group (n = 8) was given 25 mg/kg of powdered losartan daily until 6 weeks after surgery by direct administration in the buccal pouch of the animals. The control group (n = 8) was given 5 ml of normal saline by the same method. After 6 weeks, quantitative calcium determination, histological evaluation and western blot analysis of interleukin-6 (IL-6), osteopontin and bone morphogenetic protein 2 (BMP-2) were performed to investigate the mechanisms of the anticalcification effect of losartan. No deaths or complications such as infection or haematoma were recorded during the experiment. All animals were euthanized on the planned date. The calcium measurement level in the ARB group (2.28 ± 0.65 mg/g) was significantly lower than that in the control group (3.68 ± 1.00 mg/g) (P = 0.0092). Immunohistochemistry analyses revealed that BMP-2-positive reactions were significantly attenuated in the ARB group. Western blot analysis showed that losartan suppressed the expression of IL-6, osteopontin and BMP-2. Our results indicate that losartan significantly attenuates postimplant degenerative calcification of a bovine pericardial bioprosthesis in a rabbit intravascular implant model. Further studies are required to assess the effects of ARBs on BHV tissue in orthotopic implantations using a large animal model.


[Mechanisms of chronic stress influence on the brain hemodynamic in persons with employment-related chronic stress].
To discuss the mechanisms by which chronic psychosocial stress (CPSS) affects the parameters of cerebral blood flow. One hundred and sixty locomotive machinists (LM) and machinist assistants (MA), whose profession is rated as one of the most stressful, were enrolled in this study. The control group consisted of 100 healthy volunteers. The activity of the stressor system was assessed by the levels of stress hormones in serum (ACTH, cortisol, adrenaline). The functional state of the endothelium was assessed by secretion of nitric oxide and endothelin-1. Doppler ultrasound was used to measure the linear velocity of blood flow in the cerebral vessels, the size of the intima-media complex of the common carotid artery, and the results of the endothelium-dependent vasodilation. Blood pressure was monitored daily. The action of CPSS is accompanied by the persistent increase in the serum cortisol levels. This process contributes to the development of vasoconstriction with the initiation of endothelial dysfunction with impaired production of nitric oxide and increased secretion of endothelin-1 and the formation of arterial hypertension. With progression of these processes, there is a decrease in cerebral blood flow. The observed increase in the size of the intima-media complex of the common carotid artery correlates with the severity of arterial hypertension and endothelial dysfunction. CPSS leads to a decrease in cerebral blood flow and subsequent development of endothelial dysfunction and arterial hypertension, which are related to high levels of stress hormones circulating in the blood. These processes lead to functional failure of the vascular endothelium.


The evolutionary origin of a complex scrambled gene.
Some species of ciliates undergo massive DNA elimination and genome rearrangement to construct gene-sized "chromosomes" in their somatic nucleus. An example is the extensively scrambled DNA polymerase alpha gene that is broken into 48 pieces and distributed over two unlinked loci in Stylonychia. To understand the emergence of this complex phenomenon during evolution, we examined DNA polymerase alpha genes in several earlier diverging species, representing evolutionary intermediates. Mapping these data onto an evolutionary tree suggests that this gene became extensively fragmented and scrambled over evolutionary time through a series of steps, each leading to greater complexity. Our results also suggest a possible mechanism for intron loss by deletion of intron sequences as DNA during development of the somatic nucleus.


Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population.
The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. 230 (13.9%) patients proved to have stage I-II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease.


[Treatment of acute pulmonary hemorrhage in a patient with pulmonary atresia and ventricular septal defect by coil embolization of a systemico-pulmonary collateral artery].
Pulmonary hemorrhage due to rupture of pulmonary arteries causes significant morbidity and mortality in the natural history of older patients with pulmonary atresia and ventricular septal defect. The only therapeutical option for patients with persisting pulmonary hemorrhage was surgical resection of the involved pulmonary segments. In this case report we describe the successful termination of an acute pulmonary hemorrhage in a 9-year-old patient by coil-embolization of a systemicopulmonary collateral artery, which provided additional blood supply to the left upper-lobe segments. The hemorrhage ceased within 24 h and has not recurred during a follow-up period of 7 months. In our opinion, the success of the embolization can be attributed to a reduction of the perfusion pressure and a normalization of the arterial blood flow in the affected lung segments.


A proteomic investigation of apple fruit during ripening and in response to ethylene treatment.
A proteomic approach employing a two dimensional electrophoresis (2-DE) technique with SYPRO Ruby, a fluorescent stain with improved sensitivity and quantitative accuracy, was performed to separate the total proteins from apple fruit at different stages of ripening and senescence. After imaging and statistical analyses were performed on 2340 spots, a total of 316 spots, or approximately 13.5% of the total protein population, was found to be significantly changed in this study. Of the 316 proteins, 219 spots were only present at a specific ripening stage, while 97 spots were significantly different (p<0.05) throughout fruit ripening and in response to ethylene treatment. From 316 candidate spots, 221 proteins were further identified by liquid chromatography and mass spectrometry analysis with protein sequence and express sequence tag (EST) data searching. Analysis and identification of proteins revealed that apple fruit ripening is associated with increase of abundance of many proteins with functions such as ethylene production, antioxidation and redox, carbohydrate metabolism, oxidative stress, energy, and defense response. Ethylene treatment increased a group of unique proteins that were not present during normal fruit ripening and have not been previously reported. It also reduced some proteins involved in primary metabolism, including those of the last few steps of the glycolytic pathway. This study demonstrated the complexity and dynamic changes of protein profiles of apple fruit during ripening and in response to exogenous ethylene treatment. Identifying and tracking protein changes may allow us to better understand the mechanism of ripening in climacteric fruit. Postharvest physiology and biochemistry has been conducted on apple fruit for many years. Ethylene plays an important role in ripening and senescence in many climacteric fruit. However, little information is available at the proteome level to investigate fruit ripening and effect of ethylene treatment. The significance of this paper is that it is the first study employing 2-DE and fluorescent dye in the investigation of the apple fruit ripening and influence of ethylene treatment. It reveals some significant biological changes in association with these events and demonstrates significant changed proteins under these conditions. Therefore, our study links the biological events with proteomic information and provides detailed peptide information on all identified proteins. Through the function analysis, those significantly changed proteins are also analyzed. These findings from this paper provide not only proteome information on fruit ripening, but also pave the ground for further quantitative studies using SMR to investigate certain proteins and pathways under the hypothesis involved in fruit ripening. This article is part of a Special Issue entitled: Translational Plant Proteomics.


Fold recognition insights into function of herpes ICP4 protein.
ICP4 is an important factor regulating the life cycle of HSV1. This conserved protein has several molecular functions, including activation of expression of viral late gene transcripts and inhibition of immediate early genes. Although ICP4 and its Alphaherpesvirinae homologs (eg.: IE62 of VZV) have been subjects of various molecular studies, a complete view of their molecular function is lacking. Here we present the results of fold recognition and molecular modelling of ICP4 functional domains. The performed state-of-the-art bioinformatic fold recognition analysis identified a dual helix-turn-helix motif as a binding module of repressor activities (so called region 2 domain). The mapping of distant homology identified that a segment responsible for activation of late gene promoters (region 4) exhibits folding of uracil DNA glycosylase (UDG), but seems to be a non-functional homolog of UDG. Potential implications of the results are discussed.


Giant coronary artery aneurysms in an infant with Kawasaki disease: Evaluation by echocardiography and computed tomographic angiography.
Kawasaki disease (KD) is a vasculitis that affects medium-sized arteries and can lead to coronary artery aneurysms. KD should be considered in any infant presenting with prolonged fever. Delaying treatment beyond Day 10 of fever portends a high risk of coronary artery aneurysms. Echocardiography is often necessary to diagnose KD in young infants who frequently present without classic physical examination findings. We report on a case of KD with giant aneurysms in a 2-month-old infant. A combination of transthoracic echocardiography and CT angiography was utilized in the diagnosis as well as in the management of this infant.


A universal, rapid, and inexpensive method for genomic DNA isolation from the whole blood of mammals and birds.
There is no 'one' procedure for extracting DNA from the whole blood of both mammals and birds, since each species has a unique property that require different methods to release its own DNA. Therefore, to obtain genomic DNA, a universal, rapid, and noncostly method was developed. A very simple biological basis is followed in this procedure, in which, when the blood is placed in water, it rapidly enters the RBCs by osmosis and causes cells to burst by hemolysis. The validity of extracting genomic DNA was confirmed by several molecular biological experiments. It was found that this method provides an efficient and versatile alternative for extracting bulk amounts of highly-qualified DNA from the blood of a wide range of species. This is the first manuscript that describes use of distilled water as the only eliminator of RBCs among all other known DNA extraction techniques.


Effects of green tea extract administration on the pharmacokinetics of clozapine in rats.
The pharmacokinetic interaction between clozapine, an atypical antipsychotic with metabolic complications, including weight gain, and green tea consumption has not been evaluated, although green tea is responsible for beneficial effects, including weight reduction, and is widely consumed in the world. Commercial green tea extract (175 mg kg(-1)) or saline was administered orally for 4 days before the oral administration of clozapine (20 mg kg(-1) ) to rats. Plasma concentrations of clozapine were measured up to 5 h after clozapine administration, and then hepatic CYP1A2 expression and activity were determined. There was no significant difference in the elimination half-life of clozapine between the green tea extract and saline groups. However, the time to reach peak concentration (T(max)) was significantly increased by green tea extract. The mean total area under the plasma concentration-time curve (AUC(0-infinity)) and maximal peak plasma concentration (C(max)) of clozapine in the green tea extract group were significantly lower than those of controls. Green tea extract induced a approximately 2-fold increase in hepatic CYP1A2 levels, while the activity increased slightly (by 10% of control). Because of this reduction in AUC and T(max) of clozapine by green tea extract pretreatment, we suggest that both the rate and amount of absorption of clozapine may be reduced by green tea extract, although the hepatic elimination phase may not be significantly altered. Therefore, the clinical implications of the effects of green tea on the bioavailability of clozapine in patients should be further evaluated.


Crystallization and preliminary X-ray crystallographic analysis of the probable tRNA-modification GTPase (TrmE) from Staphylococcus aureus.
Probable tRNA-modification GTPase (TrmE) is a guanine nucleotide-binding protein that is conserved between bacteria and humans. GTPase hydrolyzes GTP and plays a pivotal role in signalling pathways. In this study, TrmE from Staphylococcus aureus was overexpressed in Escherichia coli. The enzyme was found to crystallize at 295 K when ammonium sulfate was used as a precipitant. X-ray diffraction data were collected to 2.9 A resolution from the crystallized enzyme using synchrotron radiation. The crystal was found to belong to the cubic space group I23, with unit-cell parameters a = b = c = 229.47 A, alpha = beta = gamma = 90 degrees . The crystal is likely to contain four monomers in the asymmetric unit, with a corresponding V(M) of 2.4 A(3) Da(-1) and a solvent content of 50%.


Impact of diseases and pests on premature fruit drop in sweet orange orchards in São Paulo state citrus belt, Brazil.
Despite technical improvements in the citrus chain and leadership in orange production achieved in the past decades, premature fruit drop remains a major component of crop loss in São Paulo state citrus belt, the largest sweet orange production area in the world. The present study aimed to determine, during five consecutive seasons, the impact of the diseases and pests on premature fruit drop in the orange belt. Fruit drop due to the main diseases and pests averaged approximately 11.0%, which corresponded to approximately 63% of the annual fruit drop. The average fruit drop rate due to fruit borer and fruit flies combined was 4.0%, Huanglongbing (HLB) 3.3%, black spot 2.6%, leprosis 1.0% and citrus canker 0.3%. The average amount of fruit drop (million 40.8 kg boxes) and value of crop losses (million US$ dollars), in five seasons, were 12.7 and 66.2 for fruit borer/fruit flies, 11.0 and 57.9 for HLB, 8.1 and 42.2 for black spot, 3.1 and 15.6 for leprosis, and 0.9 and 4.9 for citrus canker, respectively. Fruit borer and fruit flies (combined), HLB, black spot, leprosis and citrus canker are, in this order, the main diseases and pests in the orange belt of São Paulo state. All of these causes significantly increased the overall fruit drop rate in the evaluated seasons. The results will contribute to the development of the Brazilian citrus industry, while showing to other citrus-growing regions the potential that diseases and pests have to jeopardize production. © 2022 Society of Chemical Industry.


Experience and mentoring requirements for competence in new/inexperienced paramedics.
A paramedic may be unprepared to practice alone or with an inexperienced partner immediately following completion of training. Emergency medical services systems have not generally set standards to ensure that a newly-licensed paramedic is competent to practice alone. Many other trades and professions, including health care providers, require many hours of mentoring or apprenticeship prior to working in an unsupervised environment. This paper summarizes mentoring requirements for other clinical professions and reviews studies from the out-of-hospital and hospital literature that demonstrate a positive correlation between experience and outcome and/or competence. The author recommends specific benchmarking and supervision by a training officer or an experienced paramedic to ensure competence in new and inexperienced paramedics.


Neuropathic Pain in Acute and Subacute Neuropathies: A Systematic Review.
Neuropathic pain (NP) is a common symptom caused by lesions or diseases of the somatosensory nervous system. Acute/subacute peripheral neuropathies (APN) are rare, however can be particularly painful. The aim of this systematic review was to estimate the incidence of NP in APN and overview the various etiologies of such neuropathies. Systematic review. Medline search. We hand-searched Medline for observational studies published between 1995 and 2017. Our search strategy identified 1,400 papers. Of these, 70 met our inclusion criteria and were included in this review. Out of a total of 2,341 patients, 1,139 patients were diagnosed with NP (pooled incidence of NP 48.7%). In Guillain-Barré syndrome (GBS), the commonest cause of APN, the pooled estimate of NP was 34.8%. Other causes of painful APN include immune-mediated, vasculitic, metabolic, nutritional, toxic, paraneoplastic, and infectious. An important limitation was that GBS accounted for the majority of patients with APN, as such the calculated incidence reflected mainly this disease entity. Another important limitation was that very few studies targeted primarily NP. Thus, it is highly likely that observational studies reporting NP were missed. Finally there could always be a publication bias due to underreporting and gray literature. NP is a cardinal manifestation of APN. The use of validated diagnostic tools and accepted diagnostic criteria of NP is recommended for both clinical and research purposes. Neuropathic, pain, acute, subacute, neuropathy, polyneuropathy, frequency, incidence.


Toxicity of gold nanoparticles functionalized with cationic and anionic side chains.
The structure and properties of gold nanoparticles make them useful for a wide array of biological application. Toxicity, however, has been observed at high concentrations using these systems. MTT, hemolysis, and bacterial viability assays were used to explore differential toxicity among the cell types used, using 2 nm core particles. These studies show that cationic particles are moderately toxic, whereas anionic particles are quite nontoxic. Concentration-dependent lysis mediated by initial electrostatic binding was observed in dye release studies using lipid vesicles, providing the probable mechanism for observed toxicity with the cationic MMPCs.


The Effect of Age on Dengue Presentation and the Diagnostic Accuracy of the 2015 Pan American Health Organization Case Criteria in a Puerto Rican Cohort.
We evaluated dengue presentation by age, the performance of the 2015 Pan American Health Organization (PAHO) case criteria in identifying dengue cases, and variables to improve specificity. Patients with fever ≤7 days (N = 10 408) were recruited from 2 emergency departments from May 2012 through December 2015. Serum samples were tested for dengue, chikungunya, and nasopharyngeal swabs for respiratory viruses. Smoothing splines assessed differences in the frequencies of signs/symptoms by age. Least absolute shrinkage and selection operator regressions identified the variables that best predicted dengue. Among 985 dengue cases, children aged <5 years were least likely to have leukopenia, but most likely to have rash and petechiae. Adults had the highest odds of aches/pains and headaches/retro-orbital pain. The 2015 PAHO criteria had sensitivity of 93% and specificity of 25%. Specificity could be improved by requiring at least 2 of the following criteria: vomiting/nausea, petechiae, rash, or leukopenia (specificity 68%, sensitivity 71%) or by using 2015 PAHO criteria plus either (1) aspartate aminotransferase >50 IU/L or platelet count <100 000 platelets/μL (specificity 81%, sensitivity 56%) or (2) itchy skin or absence of rhinorrhea or cough (specificity 51%, sensitivity 82%). The 2015 PAHO dengue case criteria had excellent sensitivity but poor specificity. This can be improved by adding signs/symptoms associated with dengue diagnosis.


Tissue Inhibitor of Metalloproteinases-1 Overexpression Mediates Chemoresistance in Triple-Negative Breast Cancer Cells.
Triple-negative breast cancer (TNBC) is among the most aggressive breast cancer subtypes. Despite being initially responsive to chemotherapy, patients develop drug-resistant and metastatic tumors. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a secreted protein with a tumor suppressor function due to its anti-proteolytic activity. Nevertheless, evidence indicates that TIMP-1 binds to the CD63 receptor and activates noncanonical oncogenic signaling in several cancers, but its role in mediating TNBC chemoresistance is still largely unexplored. Here, we show that mesenchymal-like TNBC cells express TIMP-1, whose levels are further increased in cells generated to be resistant to cisplatin (Cis-Pt-R) and doxorubicin (Dox-R). Moreover, public dataset analyses indicate that high TIMP-1 levels are associated with a worse prognosis in TNBC subjected to chemotherapy. Knock-down of TIMP-1 in both Cis-Pt-R and Dox-R cells reverses their resistance by inhibiting AKT activation. Consistently, TNBC cells exposed to recombinant TIMP-1 or TIMP-1-enriched media from chemoresistant cells, acquire resistance to both cisplatin and doxorubicin. Importantly, released TIMP-1 reassociates with plasma membrane by binding to CD63 and, in the absence of CD63 expression, TIMP-1-mediated chemoresistance is blocked. Thus, our results identify TIMP-1 as a new biomarker of TNBC chemoresistance and lay the groundwork for evaluating whether blockade of TIMP-1 signal is a viable treatment strategy.


Spontaneous Deposition of Prussian Blue on Multi-Walled Carbon Nanotubes and the Application in an Amperometric Biosensor.
A simple method has been developed for the spontaneous deposition of Prussian blue (PB) particles from a solution containing only ferricyanide ions onto conducting substrates such as indium tin oxide glass, glassy carbon disk and carbon nanotube (CNT) materials. Formation of PB deposits was confirmed by ultraviolet-visible absorption spectrometry and electrochemical techniques. The surface morphology of the PB particles deposited on the substrates was examined by atomic force microscopy and scanning electron microscopy. CNT/PB composite modified glassy carbon electrodes exhibited an electrocatalytic property for hydrogen peroxide reduction. These modified electrodes exhibited a high sensitivity for electrocatalytic reduction of hydrogen peroxide at -0.05 V (vs. Ag|AgCl), probably due to the synergistic effect of CNT with PB. Then, CNT/PB modified electrodes were further developed as amperometric glucose biosensors. These biosensors offered a linear response to glucose concentration from 0.1 to 0.9 mM with good selectivity, high sensitivity of 0.102 A M-¹ cm-2 and short response time (within 2 s) at a negative operation potential of -0.05 V (vs. Ag|AgCl). The detection limit was estimated to be 0.01 mM at a signal-to-noise ratio of 3.


Hypoplastic left heart syndrome - unresolved issues.
Hypoplastic left heart syndrome (HLHS) is one of the most challenging congenital heart defects. At present, it is expected that - at best - 70% of newborns with HLHS will reach adulthood. This review addresses the problems of right ventricular (RV) failure and insufficient growth of pulmonary vasculature in these patients. In order to further improve long-term prognosis translational research to control RV function, growth of pulmonary arteries and progress in chronic circulatory support are clearly needed to provide a further improvement for adults with HLHS.


[Level and trend of cardiovascular disease mortality in China from 2002 to 2016].
Objective: To investigate the level and trend of cardiovascular disease mortality in China from 2002 to 2016. Methods: Using data of China Health Statistics Yearbook (2003-2012) and China's Health and Family Planning Statistical Yearbook (2013-2017),we calculated the age-standardized mortality rates (ASMR) in China. Joinpoint regression model was employed to estimate the annual percent change (APC) and average annual percent change (AAPC) of cardiovascular disease ASMR. Results: (1)The ASMR of cardiovascular disease were 225.65/100 thousands, 242.74/100 thousands, 214.63/100 thousands, 240.97/100 thousands, 195.24/100 thousands, 201.50/100 thousands, 208.83/100 thousands, 248.44/100 thousands, 261.38/100 thousands, 231.98/100 thousands, 210.25/100 thousands, 237.80/100 thousands, 235.21/100 thousands, 237.58/100 thousands,and 237.25/100 thousands from 2002 to 2016, and there was no significant difference in ASMR of cardiovascular disease (AAPC=0.2%, P>0.05) . The ASMR of chronic rheumatic heart disease decreased significantly (AAPC=-4.5%,P<0.05). There were no significant differences in ASMR of cerebrovascular disease, hypertensive heart disease, and ischemic heart disease (AAPC=0, P>0.05; AAPC=2.0%, P>0.05; AAPC=4.3%, P>0.05, respectively). (2) There were no significant differences in ASMR of cardiovascular disease from 2002 to 2016 in city and country (AAPC=-0.7%, P>0.05; AAPC=0.8%, P>0.05, respectively). The ASMR of chronic rheumatic heart disease decreased significantly in city and rural area (AAPC=-4.4%, P<0.05; AAPC=-4.6%, P<0.05, respectively). (3) There were no significant differences in ASMR of cardiovascular disease from 2002 to 2016 in male and female (AAPC=-0.3%,P>0.05; AAPC=-0.2%,P>0.05,respectively). The ASMR of chronic rheumatic heart disease decreased significantly in female (AAPC=-4.2%, P<0.05). The ASMR of ischemic heart disease increased significantly in male and female (AAPC=4.7%,P<0.05; AAPC=5.2%,P<0.05,respectively). (4) The ASMR of cardiovascular disease showed a significant upward trend in residents aged 15 to 34 from 2002 to 2016 (AAPC=3.1, P<0.05). There were no significant differences in ASMR of cardiovascular disease in residents aged 35 to 64 and ≥65 (AAPC=-0.1%, P>0.05; AAPC=-0.2%, P>0.05, respectively). Conclusion: The ASMR of cardiovascular disease in China remains stable during 2002 to 2016, and the ASMR of cardiovascular disease shows upward trend among young people.


Modeling evolution of crosstalk in noisy signal transduction networks.
Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.


A comparison of similarity measures for digital subtraction radiography.
Subtraction is useful in detecting small changes in sequentially acquired radiographs. Even if the imaging geometry is constant, radiographs must be registered after their digitization. To compare different algorithms for image registration and to register digital X-rays themselves, various similarity measures have been proposed. This study compares eight mathematical similarity standards using 172 radiographs acquired in different, but exactly known projection. Whenever the computation time is a critical factor, e.g. registering images using methods similar to correlation techniques, the entropy of the subtraction image's histogram function (EHDI) is found to be the best similarity standard. If not, e.g. comparative assessing different image registration techniques, the cross covariance coefficient (CCC) is appropriate.


Elimination of Mother-to-Child Transmission of HIV - Thailand.
Thailand experienced a generalized human immunodeficiency virus (HIV) epidemic during the 1990s. HIV prevalence among pregnant women was 2.0% and the mother-to-child transmission (MTCT) rate was >20% (1-3). In June 2016, Thailand became the first country in Asia to validate the elimination of MTCT by meeting World Health Organization (WHO) targets. Because Thailand's experience implementing a successful prevention of MTCT program might be instructive for other countries, Thailand's prevention of MTCT interventions, outcomes, factors that contributed to success, and challenges that remain were reviewed. Thailand's national prevention of MTCT program has evolved with prevention science from national implementation of short course zidovudine (AZT) in 2000 to lifelong highly active antiretroviral therapy regardless of CD4 count (WHO option B+) in 2014 (1). By 2015, HIV prevalence among pregnant women had decreased to 0.6% and the MTCT rate to 1.9% (the elimination of MTCT target is <2% for nonbreastfeeding populations) (4). A strong public health infrastructure, committed political leadership, government funding, engagement of multiple partners, and a robust monitoring system allowed Thailand to achieve this important public health milestone.


What influences medical students to pursue careers in obstetrics and gynecology?
The purpose of this study was to identify factors that influence medical students to choose of obstetrics/gynecology as a career specialty. A Web-based survey of medical students was conducted that included demographics, desire to enter the obstetrics and gynecology specialty, factors that influence selection of the obstetrics and gynecology specialty, perceptions about the obstetrics and gynecology specialty, and incidents of encouragement and discouragement toward entering the obstetrics and gynecology specialty. Analysis included parametric and nonparametric testing. Fifty-one percent of the students (n=205) returned the survey: 131 women (64%) and 72 men (35%); 2 respondents did not specify gender. Various factors influenced a medical student to pursue a career in obstetrics and gynecology, which revealed some specific areas of significant difference between genders, particularly in relation to lifestyle issues and practice trends. This study amplifies the importance of understanding the role of student gender when exploring the obstetrics and gynecology specialty as a career choice. Appreciating factors that influence decisions to enter the obstetrics and gynecology specialty provides opportunities to impact the experiences and decisions of students toward considering the obstetrics and gynecology specialty as a career choice.


Stimulus-Responsive Regulation of Enzyme Activity for One-Step and Multi-Step Syntheses.
Multi-step biocatalytic reactions have gained increasing importance in recent years because the combination of different enzymes enables the synthesis of a broad variety of industrially relevant products. However, the more enzymes combined, the more crucial it is to avoid cross-reactivity in these cascade reactions and thus achieve high product yields and high purities. The selective control of enzyme activity, i.e., remote on-/off-switching of enzymes, might be a suitable tool to avoid the formation of unwanted by-products in multi-enzyme reactions. This review compiles a range of methods that are known to modulate enzyme activity in a stimulus-responsive manner. It focuses predominantly on in vitro systems and is subdivided into reversible and irreversible enzyme activity control. Furthermore, a discussion section provides indications as to which factors should be considered when designing and choosing activity control systems for biocatalysis. Finally, an outlook is given regarding the future prospects of the field.


Virtual microfluidics for digital quantification and single-cell sequencing.
We have developed hydrogel-based virtual microfluidics as a simple and robust alternative to complex engineered microfluidic systems for the compartmentalization of nucleic acid amplification reactions. We applied in-gel digital multiple displacement amplification (dMDA) to purified DNA templates, cultured bacterial cells and human microbiome samples in the virtual microfluidics system, and demonstrated whole-genome sequencing of single-cell MDA products with excellent coverage uniformity and markedly reduced chimerism compared with products of liquid MDA reactions.


Development and evaluation of loop-mediated isothermal amplification (LAMP) for rapid detection of Clonorchis sinensis from its first intermediate hosts, freshwater snails.
Clonorchiasis, caused by Clonorchis sinensis, is a key foodborne zoonosis, which is mainly found in China, Korea and Vietnam. Detection of this parasite from the second intermediate host, the freshwater fish is the common method for epidemiological surveys of this parasite, but is time consuming, labour intensive and easily leads to misdiagnosis. In this study, we have developed a rapid, sensitive and reliable molecular method for the diagnosis of C. sinensis from its first intermediate hosts, freshwater snails, based on a loop-mediated isothermal amplification (LAMP) method. The specific amplified fragment from genomic DNA of C. sinensis did not cross-react with those from other relevant trematodes and a range of hosts (freshwater fish, shrimps and snails) of C. sinensis living in similar environments. The detection limit of the LAMP method was as low as 10 fg which was 1000 times more sensitive than conventional PCR, which was also demonstrated by successful application to field samples. These results show that the LAMP method is a more sensitive tool than conventional PCR for the detection of C. sinensis infection in the first intermediate hosts and, due to a simpler protocol, is an ideal molecular method for field-based epidemiological surveys of this parasite.


Impact and control of protozoan parasites in maricultured fishes.
Aquaculture, including both freshwater and marine production, has on a world scale exhibited one of the highest growth rates within animal protein production during recent decades and is expected to expand further at the same rate within the next 10 years. Control of diseases is one of the most prominent challenges if this production goal is to be reached. Apart from viral, bacterial, fungal and metazoan infections it has been documented that protozoan parasites affect health and welfare and thereby production of fish in marine aquaculture. Representatives within the main protozoan groups such as amoebae, dinoflagellates, kinetoplastid flagellates, diplomonadid flagellates, apicomplexans, microsporidians and ciliates have been shown to cause severe morbidity and mortality among farmed fish. Well studied examples are Neoparamoeba perurans, Amyloodinium ocellatum, Spironucleus salmonicida, Ichthyobodo necator, Cryptobia salmositica, Loma salmonae, Cryptocaryon irritans, Miamiensis avidus and Trichodina jadranica. The present report provides details on the parasites' biology and impact on productivity and evaluates tools for diagnosis, control and management. Special emphasis is placed on antiprotozoan immune responses in fish and a strategy for development of vaccines is presented.


Analysis of a naturally occurring K99+ enterotoxigenic Escherichia coli strain that fails to produce K99.
A spontaneously occurring field isolate of enterotoxigenic Escherichia coli that was genotypically K99+ but phenotypically K99- was analyzed for the reason that it did not express K99. The defect, which was cis active, was located within an area 5' to the first gene required for K99 biogenesis and was the result of the deletion of a single base pair.