Comparison of the diagnostic accuracy of dynamic and static preload indexes to predict fluid responsiveness in mechanically ventilated, isoflurane anesthetized dogs.
To compare the diagnostic accuracy of pulse pressure variation (PPV), stroke volume variation from pulse contour analysis (SVVPCA), plethysmographic variability index (PVI), central venous pressure (CVP) and global end-diastolic volume index measured by transpulmonary thermodilution (GEDVITPTD) to predict fluid responsiveness (FR) in dogs. Prospective study. A group of 40 bitches (13.8-26.8 kg) undergoing ovariohysterectomy. Anesthesia was maintained with isoflurane under volume-controlled ventilation (tidal volume 12 mL kg-1; inspiratory pause during 40% of inspiratory time; inspiration:expiration ratio 1:1.5). Transpulmonary thermodilution cardiac output was recorded through a femoral artery catheter. FR was evaluated by a fluid challenge (lactated Ringer's, 20 mL kg-1 over 15 minutes) administered once (n = 21) or twice (n = 18) before surgery. Individuals were responders if stroke volume index measured by transpulmonary thermodilution increased >15% after the last fluid challenge. Of the 39 animals studied, 21 were responders and 18 were nonresponders. Area under the receiver operating characteristics curve (AUROC) was 0.976, 0.906, 0.868 and 0.821 for PPV, PVI, CVP and SVVPCA, respectively (p < 0.0001 from AUROC = 0.5). GEDVITPTD failed to predict FR (AUROC: 0.660, p = 0.078). Best cut-off thresholds discriminating responders and nonresponders, with respective zones of diagnostic uncertainty (gray zones) were: PPV >16% (15-16%), PVI >11% (10-13%), SVVPCA >10% (9-18%) and CVP ≤1 mmHg (0-3 mmHg). Percentage of animals within gray zone limits was 13% (PPV), 28% (PVI), 51% (SVVPCA) and 67% (CVP). PPV has better diagnostic accuracy to predict FR (conclusive results in nearly 90% of population) than other preload indexes in healthy dogs. When invasive blood pressure is unavailable, PVI will predict FR with reasonable accuracy (conclusive results in approximately 70% of the population). PPV and PVI values above gray zone limits (>16% and >13%, respectively) can reliably predict responders to volume expansion.


The maintenance of stable yield and high genetic diversity in the agricultural heritage torreya tree system.
Understanding how traditional agriculture systems have been maintained would help design sustainable agriculture. In this study, we examined how farmers have used two types of local trees (Torreya grandis) for stable yield and maintaining genetic diversity in the "globally important agricultural heritage torreya tree system". The two type of torreya trees are grafted torreya (GT) tree and non-grafted-torreya (NGT) tree. The GT tree has only female and was used to produced seed yields. The NGT tree has both male and female and was used to support GT tree by providing pollens and rootstocks. We first tested the ratio of GT tree to NGT tree, their age groups, ratio of female trees (including GT and NGT trees) to male, and the flowering period of GT and NGT trees. We then tested seed yields and genetic diversity of GT and NGT trees. We further tested gene flow among NGT trees, and the relationship of gene flow with exchange rates of pollens and seeds. GT and NGT trees (male and female) were planted in a mosaic pattern with a ratio of 4:1 (GT:NGT). In this planting pattern, one NGT male trees provided pollen for 20 female trees of GT and NGT. The trees were classified into four age groups (I = 100-400 years old; II = 400-700 years old; III = 700-1000 years old; and IV = 1000-1300 years old) based on basal diameter. The entire flowering period was longer for NGT trees than for GT trees that ensured GT trees (which lack of males) being exposed to pollens. GT tree had high and stable seed yield that increased with age groups. High genetic diversity has been maintained in both rootstocks of the GT trees and NGT trees. There was a strong gene flow among NGT trees, which positive correlated with the exchange rates of pollens and seeds. Our results suggest that farmers obtain stable seed yields, and maintain high genetic diversity by ingeniously using the local GT tree as yield producer and NGT tree as supporter. These GT and NGT trees together ensure sustainable torreya production.


Relaxation training and guided imagery for an elderly man with bladder cancer: a case report.
Bladder cancer is one of the most common malignancies in elderly patients. This report describes the use of cue-controlled progressive relaxation training and guided imagery with an elderly man who was diagnosed with bladder carcinoma in situ. After 7 therapy sessions over 4 weeks, the posttherapy surgical pathology report showed "no invasive malignancy identified" for urothelial carcinoma in situ. A computed tomography scan showed no incidence of metastatic disease and that the "bladder appeared normal." Although this is a single case report, it should encourage further study and investigation using this alternative therapy for cancer patients.


Glomus tumour of the hand.
We report a series of 18 patients with pain in the thumb or finger tips who were diagnosed as having glomus tumour. Fourteen patients were found to have histopathologically proven glomus tumours, one had a neuroma and three had haemangioma. The duration of symptoms before treatment averaged 1.9 years. Cold-sensitivity and Hildreth's tests have sensitivities of 100% and 77.4% respectively and specificity of 100%. Love's pin test had a sensitivity of 100%. Love's and Hildreth's tests showed 78% accuracy, whereas the cold-sensitivity test was 100% accurate. We used a double-tourniquet technique during dissection and excision of the tumour. None of our patients experienced recurrence of symptoms during the post-operative follow up.


Combination therapy with tumor necrosis factor inhibitors in psoriasis treatment.
Psoriasis is a systemic disease that affects approximately 2% of the US population. Traditional treatment modalities include phototherapy, topical therapy, methotrexate, cyclosporine, and retinoids. Three tumor necrosis factor (TNF) inhibitors have been approved by the US Food and Drug Administration for the treatment of plaque psoriasis: etanercept, infliximab, and adalimumab. The combination of TNF inhibitors with phototherapy and topical and systemic agents may be effective in treating patients who are recalcitrant to monotherapy. We examine clinical trials that evaluated the efficacy and safety of combination treatments with TNF inhibitors. This review elucidates that combination therapy is both effective and well tolerated among patients with refractory psoriasis. Furthermore, combination therapy may allow for reduction of required treatment doses, thereby decreasing the potential for toxicity. It is important to note, however, that the studies reviewed here are limited in the long-term follow-up of patients. We conclude that dermatologists can safely and effectively incorporate combination therapy with TNF inhibitors in the treatment of patients with recalcitrant psoriasis.


Differentiation of the geographical origin of durum wheat semolina samples on the basis of isotopic composition.
The identification of the geographical origin of foods is attracting great interest from consumers and producers since it may be used as a criterion for guaranteeing quality and authenticity. Stable isotope techniques can provide useful information on the origin of food products. The natural abundance isotopic ratios of carbon, oxygen and nitrogen were determined and a comparison made between the isotopic content of samples originating from Italy and those of samples originating from other countries (Canada, Turkey, Australia). A correlation was found between the isotopic composition and geographical origin of the samples. The relationship between isotopic content and the latitude has been confirmed.


Relation of beta-blocker use with frequency of hospitalization for heart failure in patients with left ventricular diastolic dysfunction (from the Heart and Soul Study).
Heart failure (HF) is a common public health problem, and many new cases are now recognized to occur in patients with preserved left ventricular ejection fraction. beta Blockers improve the outcomes of patients with known left ventricular systolic dysfunction, but whether beta blockers provide similar protection among patients with left ventricular diastolic dysfunction is unclear. We studied the association between use of beta blockers and subsequent hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. We evaluated medication use and performed echocardiography at baseline in a prospective cohort of 911 outpatients with known coronary heart disease from the Heart and Soul Study. Hospitalizations for HF were assessed by blinded review of the medical records during an average follow-up of 5.2 years. Of the 911 participants, 118 (13%) had diastolic dysfunction, of whom 2 were lost to follow-up. Of the 116 remaining patients, 19 (25%) of the 77 using beta blockers were hospitalized for HF compared to 16 (41%) of the 39 not using beta blockers (age-adjusted hazard ratio 0.51, 95% confidence interval 0.26 to 1.00; p = 0.05). This association remained after additional adjustment for gender, smoking, history of myocardial infarction, diabetes, and creatinine (hazard ratio 0.46, 95% confidence interval 0.23 to 0.93; p = 0.03). The results were similar after excluding 31 participants with a history of self-reported HF (hazard ratio 0.33, 95% confidence interval 0.13 to 0.86; p = 0.02) and 24 participants with concurrent systolic dysfunction (hazard ratio 0.36, 95% confidence interval 0.14 to 0.89; p = 0.03). In conclusion, the use of beta blockers is associated with a decreased risk of hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease.


Renal colic: new concepts related to pathophysiology, diagnosis and treatment.
To give new insights into the pathophysiology, diagnosis and treatment of acute renal colic caused by a stone disease. Traditional intravenous pyelography is no longer the primary method of investigation in patients with renal colic. If the patient has a history of previous attacks of renal colic and stone disease the recommended diagnostic approach is to start with plain abdominal radiography and ultrasonography together with Doppler ultrasonography. Noncontrast computerized tomography is reserved for unsolved problems. If the patient has no history of stone disease or has atypical clinical presentation it is better to start with noncontrast computerized tomography. Intravenous pyelography is indispensable if an endoscopic or open intervention is required. Magnetic resonance imaging is a promising method of investigation, particularly in pregnant women. Effective pain relief is achieved by the use of opioids, nonsteroidal antiinflammatory drugs or desmopressin. The diagnostic approach to renal colic has recently been changed due to the introduction of new, noninvasive radiologic procedures such as Doppler ultrasonography, noncontrast computerized tomography and magnetic resonance imaging.


Deciphering the Molecular Signature of Human Hyalocytes in Relation to Other Innate Immune Cell Populations.
Hyalocytes are the tissue-resident innate immune cell population of the vitreous body with important functions in health and vitreoretinal disease. The purpose of this study is to gain new insights into the biology and function of human hyalocytes in comparison to other innate immune cells. The present study applies fluorescence-activated cell sorting and RNA sequencing to compare the transcriptional profiles of human hyalocytes, retinal microglia (rMG) and classical, intermediate, and non-classical monocytes isolated from the same patients. Immunohistochemistry was applied for morphological characterization of human hyalocytes. Pairwise analysis indicates distinct differences between hyalocytes and monocytes, whereas a high degree of similarity to rMG is apparent, with comparable expression levels of established microglia markers, such as TREM2, P2RY12, and TMEM119. Among the top expressed genes in hyalocytes, SPP1, CD74, and C3, were significantly upregulated when compared with monocytes. Despite the high level of similarity of hyalocytes and rMG, ten highly expressed genes in hyalocytes compared to microglia were identified, among them FOS, DUSP1, and EGR2. This study reveals a high degree of similarity between hyalocytes and retinal microglia. Nevertheless, hyalocytes exhibit some expression differences that may adapt them to the specific needs of the vitreous and provide the basis for deciphering the multiple roles of this fascinating cell population in health and vitreoretinal diseases.


[The present situation and countermeasures of Uighur medicine compound].
Uighur medicine compound, which created and used by Uighur nationality, is under the guidance of the Uighur medical theory system of herbal formula and dialectical use of minority nationality conventional medicines. In recent years, Uighur medicine attracted more and more attention of people which have used and were using it. Combining the history of Uighur medicine, this article summarizes the Uighur resources, medicinal materials, drugs preparation, ancient documents, and the establishment of the clinical evaluation system and so on, and then analyzes the status quo and the existing problems in Uighur medicine compound research and industry. On this basis, we put forward countermeasures and suggestions for the development of Uighur medicine.


Assessment of the primary stability of root analog zirconia implants designed using cone beam computed tomography software by means of the Periotest® device: An ex vivo study. A preliminary report.
The implant primary stability is a fundamental prerequisite for a success of osseointegration process which determines the prosthetic reconstruction time. The aim of the present study was to assess the quality and precision of modern conical bone computer tomography (CBCT) software in preparing root analog zirconia implants (RAZIs) by measuring its primary stability by means of the Periotest device. Thirteen pig jaws with proper erupted first premolar (P1) teeth were used in the study. The CBCT examination was conducted in the area of the P1 tooth in each mandible. The 3-dimensional (3D) view of each tooth was designed from CBCT scan. The created 3D images were used to prepare root analog zirconia implants milled from a medical-grade zirconia block by means of laboratory milling. The RAZIs and titanium implants were placed into an alveolar socket after the tooth had been removed. The primary stability of the teeth before their extraction (G1), RAZIs (G2) and titanium implants (G3) were checked by Periotest devices. The mean results in PTV were: 15.9, 3.35, 12.7 for G1, G2 and G3 group, respectively. RAZIs during immediate loading achieved a significantly higher primary stability (lower Periotest value) as compared to the teeth and implants. The modern CBCT device allows us to design a precise image of an extracted tooth for the purpose of manufacturing a root analog implant. The additional feature of the surgical protocol using RAZI is the possibility of avoiding the augmentation procedure, which reduces the whole cost of the treatment.


Polyamine transport system mediates agmatine transport in mammalian cells.
Agmatine is a biogenic amine with the capacity to regulate a number of nonreceptor-mediated functions in mammalian cells, including intracellular polyamine content and nitric oxide generation. We observed avid incorporation of agmatine into several mammalian cell lines and herein characterize agmatine transport in mammalian cells. In transformed NIH/3T3 cells, agmatine uptake is energy dependent with a saturable component indicative of carrier-mediated transport. Transport displays an apparent Michaelis-Menten constant of 2.5 microM and a maximal velocity of 280 pmol x min(-1) x mg(-1) protein and requires a membrane potential across the plasma membrane for uptake. Competition with polyamines, but not cationic molecules that utilize the y+ system transporter, suppresses agmatine uptake. Altering polyamine transporter activity results in parallel changes in polyamine and agmatine uptake. Furthermore, agmatine uptake is abrogated in a polyamine transport-deficient human carcinoma cell line. These lines of evidence demonstrate that agmatine utilizes, and is dependent on, the polyamine transporter for cellular uptake. The fact that this transport system is associated with proliferation could be of consequence to the antiproliferative effects of agmatine.


Changes in kidney function during the menopausal transition: the Study of Women's Health Across the Nation (SWAN) - Michigan site.
The aim of the study was to examine changes in kidney function during the menopausal transition (MT) and associations with levels of sex hormones (follicle stimulating hormone [FSH], sex hormone binding globulin [SHBG], estradiol, and testosterone). We used data from the Michigan site of Study of the Women's Health Across the Nation, a longitudinal study of the MT. For this analysis, we included women who had at least one creatinine measure before the final menstrual period (FMP) and at least one creatinine measure after the FMP (n = 101 women with 440 observations). To determine whether the declines in estimated glomerular filtration rate (eGFR) remained constant during the MT, we used local weighted regression curves to fit eGFR estimates. We examined the association between sex hormones and eGFR with longitudinal mixed models adjusting for baseline age, day of menstrual cycle, and time from FMP. At baseline, women had a mean age of 45.4 ± 2.5 years; 54% were African-American and 46% were white. Although eGFR declined significantly over time, declines were linear, consistent with declines in eGFR due to age alone rather than the MT. Total testosterone, estradiol, ratio of testosterone:estradiol, and free androgen index were not significantly associated with eGFR, whereas lower FSH (-0.039, 95% confidence interval [CI] -0.067 to -0.012) and higher SHBG (0.050, 95% CI 0.004-0.096) were associated with higher eGFR. Kidney function declines during the MT. Although associated with levels of FSH and SHBG, the rate of decline in eGFR is consistent with what would be expected of age alone.


Staging: the key to rational management of lung cancer.
Staging is the quantitative assessment of malignant disease and allows logical groupings of patients with a similar extent of disease for prognostic, therapeutic, and analytic purposes. In bronchogenic carcinoma a stage is assigned based on size, location, and the extent of invasion of the primary tumor, as well as the presence of any regional or metastatic disease. Selecting the most appropriate treatment for a patient with bronchogenic carcinoma depends on precise staging. The extent of local invasion and presence of metastatic disease will determine the likelihood of complete resection and possible cure. Careful assessment of the history, blood chemistry, radiographic studies, bronchoscopy, mediastinoscopy, and exploration (thoracotomy) are all important staging tools. Routine radionuclide scans have no useful role when there is no clinical or laboratory evidence of metastases. The T status of a tumor is best judged by bronchoscopy and at thoracotomy. Thoracic surgeons must be familiar with the techniques available to determine T status intraoperatively and use this information when planning resection. Computed tomography of the chest has fallen short in predicting direct invasion of the mediastinum and chest wall. Cervical and anterior mediastinoscopy remain important tools in determining operability. Intraoperative assessment of node involvement determines the extent of resection and likelihood of cure.


Competency-based student self-assessment on a surgery rotation.
Although self-assessment is an essential component of self-directed adult learning, few data exist regarding the ability of medical students to perform this important task. Therefore, the purpose of this study was to evaluate the ability of medical students to perform self-assessment during a third-year surgery clerkship. Sixty-eight (34 male, 34 female) third-year medical students assessed their progress at the midpoint of an 8-week surgery clerkship using an 11-item, competency-based evaluation. Students compared perceptions of their performance with a faculty member's assessment using the identical evaluation form. Male students tended to overestimate their midclerkship performance compared with faculty formative and summative evaluations (3.31 +/- 0.03 vs 3.23 +/- 0.03 and 3.28 +/- 0.03) although this did not reach statistical significance. Female students significantly underestimated their midclerkship performance compared with faculty formative and summative evaluations (3.06 +/- 0.03 vs 3.40 +/- 0.03 and 3.45 +/- 0.03, P < 0.05 vs faculty evaluations). Preclerkship academic performance (first- and second-year grade point averages and NBME Part 1 scores) was not predictive of student self-assessment. Finally, women statistically outperformed men on the surgery clerkship (86.6% +/- 0.75 vs 83.2% +/- 1.20, P < 0.05 vs male students). Female students tend to underestimate their midclerkship performance compared with male students on a surgery rotation. Despite lower self-assessment, female students actually outperform male students. Women may underreport their capabilities when compared with men as a result of gender differences in socialization. These gender differences in self-assessment may be important to recognize when faculty provide feedback to students.


[The venous thromboembolic disease].
Venous thromboembolic disease (VTD) is a frequent medical problem. The VTD includes deep vein thrombosis (DVT), the posthrombotic syndrome (PTS) and pulmonary embolism (PE). The generation of a thrombus in the venous system, is caused by several abnormalities that induce the loss of the most important characteristic of the blood, the liquid state. DVT is due to the formation of a thrombus. Main causes for thrombus formation are thrombophilias which may be classified as primary and secondary. All thrombophilias may affect the homeostasis favoring a hypercoagulable state. In the XIX Century, Virchow classified all the causes of hypercoagulable states as follows: due to stasis of the venous blood flow, due to damage of the endothelium an a hypercoagulable clinical condition. Several risk factors for VTD has been described, during the hospitalization to both, medical and surgical conditions. Among the last, orthopedic and vascular surgery of the legs. Although nearly 50 % of DVTs are asymptomatic and 3 % of the patients with VTD develop PE and 30 % of them die. Thromboprophylaxis is the main strategy to prevent and to diminish the incidence of DVT and its complications. Thromboprophylaxis is useful to improve the quality of life of the patients at risk and it is an effective economical strategy for health care institutions.


Hypericin hydroquinone: potential as a red-far red photosensitizer?
Hypericin hydroquinone is the product of two-electron reduction of hypericin (quinone), a potent phenanthroperylenequinone photosensitizer. In contrast to the quinone, the hydroquinone exhibits strong absorbance in the far-red spectral region. Herein we provide initial evidence on the potential of hypericin hydroquinone as a far-red photosensitizer.


Changes in receptor activator of nuclear factor-kappaB, and its ligand, osteoprotegerin, bone-type alkaline phosphatase, and tartrate-resistant acid phosphatase in ovariectomized rats.
We investigated time-course changes in the expression of receptor activator of nuclear factor-kappaB (RANK), its ligand (RANKL), osteoprotegerin (OPG), bone-type alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRAP) in ovariectomized (OVX) rats. Samples of sera and coccyges were used for analysis of the enzyme activities and expression levels of proteins and mRNAs, and an immunohistochemical analysis was also performed. Serum BAP activity increased to 158.6% of the pre-operation value at 1 week after OVX, and then decreased to 38.7% at 8 weeks after OVX. On the other hand, the serum TRAP activity increased to 130.9% of the pre-operation level at 1 week after OVX, and was maintained at a high level, compared with the pre-operation level. The patterns of BAP and TRAP activity in the coccyges specimens were similar to those seen in the sera. The expression profiles of TRAP, RANK, and RANKL proteins in the coccyx specimens were similar to the pattern of serum TRAP activity, while the profiles of the BAP and OPG proteins were similar to the pattern of serum BAP activity in OVX rats. The changes in the mRNA expression levels of the osteogenic proteins were similar to those for protein expression. These biochemical changes in OVX rats were confirmed by immunohistochemical studies. Our results suggest that not only osteoclastogenesis accelerated but also osteoblastogenesis transiently increased during the early phase of osteoporosis.


[The effectiveness of using semipermeable membrane in preterm infants to reduce transepidermal losses].
An investigation was made on the effectiveness of using semipermeable membrane on the skin of preterm infants on the evolution of weight loss and blood glucose values, water share, urine specific gravity and sodium. This is an experimental study, of the randomized clinical trial type, carried out from March to August 2008 in the Neonatal Intensive Care Unit of the Teaching Maternity Assis Chateaubriand (TMAC) in the city of Fortaleza-Ceará. The sample consisted of 42 preterm infants. The data were presented in tables and charts. In the application of the semipermeable membrane, the preterm infants of the intervention group (IG) had a decrease in the sodium levels and the daily flow demands, they also presented fewer hyperglycemia episodes and the urinary density was kept within normal patterns. The semipermeable membrane is, in fact, an effective therapeutic resource to minimize transepidermal water losses.


Effect of Exogenous Putrescine, Spermidine, and Spermine on K Uptake and H Extrusion through Plasmamembrane in Maize Root Segments.
The action of exogenous polyamines (putrescine, spermidine, and spermine) on ;washing' and fusicoccin-stimulated K(+) uptake and H(+) extrusion through the plasmamembrane in maize (Zea mays L., hybrid line Plenus S 516) root apical segments was studied. The results showed that polyamines inhibit the washing-stimulated K(+) influx and H(+) extrusion without interfering with K(+) uptake and H(+) extrusion stimulated by fusicoccin. Spermidine appeared to be the most effective in inhibiting K(+) uptake and H(+) extrusion while putrescine showed a smaller inhibiting action with respect to the others. The analysis of kinetic constants indicated that the polyamines behave as competitive inhibitors with respect to K(+).


Molecular and biochemical effects of a kola nut extract on androgen receptor-mediated pathways.
The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea "Bizzy," using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI(50)) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC(50)) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.


Growth of immature Chironomus calligraphus in laboratory conditions.
Chironomidae larvae are important macroinvertebrates in limnic environments, but little knowledge exists about their biometrics development characteristics. This study aims to describe the immature Chironomus calligraphus Goeldi, 1905 under laboratory conditions by the accomplishment of thirteen egg masses from eggs eclosion to adults emergency, at controlled room temperature (25ºC) and photoperiod (12-12h). Larvae were feed ad libitum with "Alcon Basic - MEP 200 Complex" fish food and commercial dehydrated Spirulina. The postures had a mean length of 9 ± 1 mm (n = 13) and 348 ± 66 eggs. The brownish colored eggs with elliptical shape had length of 160.3 ± 17.7 µm (n = 130), being arranged as an organized string in a pseudo spiral form. The time duration from the first to the four instars were three, four, four and eight days, and the average length of a cephalic capsule to each one of the instars (66.3 ± 12.3 µm, 102.9 ± 22.1 µm, 159 ± 24.6 µm, 249.2 ± 29.7 µm, n = 456) were significantly different (ANOVA, p < 0.001). The Dyar's Rule showed a constant growth rate, r = 1.5. Our results demonstrated that C. calligraphus is a species with short life cycle, low mortality rate, food adaptability, fast larval growth and easily maintained at laboratory, factors that allowed the use of this native species as a tool for ecotoxicological tests.


Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury.
Embryonic heart is characterized of rapidly dividing cardiomyocytes required to build a working myocardium. Cardiomyocytes retain some proliferative capacity in the neonates but lose it in adulthood. Consequently, a number of signaling hubs including microRNAs are altered during cardiac development that adversely impacts regenerative potential of cardiac tissue. Embryonic stem cell cycle miRs are a class of microRNAs exclusively expressed during developmental stages; however, their effect on cardiomyocyte proliferation and heart function in adult myocardium has not been studied previously. To determine whether transient reintroduction of embryonic stem cell cycle miR-294 promotes cardiomyocyte cell cycle reentry enhancing cardiac repair after myocardial injury. miR-294 is expressed in the heart during development, prenatal stages, lost in the neonate, and adult heart confirmed by qRT-PCR and in situ hybridization. Neonatal ventricular myocytes treated with miR-294 showed elevated expression of Ki67, p-histone H3, and Aurora B confirmed by immunocytochemistry compared with control cells. miR-294 enhanced oxidative phosphorylation and glycolysis in Neonatal ventricular myocytes measured by seahorse assay. Mechanistically, miR-294 represses Wee1 leading to increased activity of the cyclin B1/CDK1 complex confirmed by qRT-PCR and immunoblot analysis. Next, a doxycycline-inducible AAV9-miR-294 vector was delivered to mice for activating miR-294 in myocytes for 14 days continuously after myocardial infarction. miR-294-treated mice significantly improved left ventricular functions together with decreased infarct size and apoptosis 8 weeks after MI. Myocyte cell cycle reentry increased in miR-294 hearts analyzed by Ki67, pH3, and AurB (Aurora B kinase) expression parallel to increased small myocyte number in the heart. Isolated adult myocytes from miR-294 hearts showed increased 5-ethynyl-2'-deoxyuridine+ cells and upregulation of cell cycle markers and miR-294 targets 8 weeks after MI. Ectopic transient expression of miR-294 recapitulates developmental signaling and phenotype in cardiomyocytes promoting cell cycle reentry that leads to augmented cardiac function in mice after myocardial infarction.


Tethered cord in children: a clinical classification with urodynamic correlation.
Tethered cord was classified based on clinical presentation and correlated with urodynamic and uroradiographic findings. A total of 54 children underwent cord untethering from 1993 through 2000. Preoperative magnetic resonance imaging, fluorourodynamics and renal ultrasound were performed in all cases, and postoperative (mean 16 months) fluorourodynamics was done in 33. The conus was at L-2 or lower, with or without a thickened filum in 51 patients and 3 older children with voiding dysfunction had normal cords. Children were classified into group 1-19 with orthopedic deformities (scoliosis or lower limb abnormalities, group 2-16 with cutaneous back lesions, group 3-13 with voiding dysfunction (VD) or urinary tract infection without cutaneous lesions and group 4-6 with associated syndromes. In group 1, 3 patients (16%) had preoperative hyperreflexia (HR) which improved postoperatively in 2, HR developed in 1, none had hydronephrosis or reflux (VUR), 5 (26%) had voiding dysfunction (VD) and 4 improved postoperatively. In group 2, 4 patients (25%) had preoperative HR and all improved postoperatively, and 5 (31%) had VUR and 2 improved postoperatively. In group 3, 11 patients (85%) had HR and 2 (15%) were areflexic preoperatively and 6 (areflexic 1, HR 5) improved postoperatively, 3 (23%) had VUR and 2 improved postoperatively, and 7 (54%) had improved VD but 5 (71%) were on anticholinergics. All 3 patients with VD/normal cords had preoperative HR, and 1 improved, 1 had preoperative VUR which resolved and 1 clinically improved but was on anticholinergics. In group 4, 5 patients (83%) had HR and 2 improved, 2 (33%) had VUR and both improved, and 3 (50%) had VD and 1 improved. Older children who present with orthopedic problems have rare neurourological abnormalities many of which resolve after surgery. Similarly, infants who are diagnosed early with a cutaneous back lesion can have urodynamic abnormalities, which also have a high rate of resolution. Older children who present with VD have the highest incidence of urodynamic abnormalities. While many seem improved clinically after surgery, they require anticholinergics. All patients with VATER's syndrome should be evaluated prospectively for tethered cord.


Probiotic Properties of Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041 Show Potential to Counteract Functional Gastrointestinal Disorders in an Observational Pilot Trial in Infants.
Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041-isolated from healthy children's feces-in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to in silico analyses. No virulence factors were detected for any strain and only the non-transferable erm(49) gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of B. longum KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. In vitro characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens' inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of B. longum KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains B. longum KABP042 and P. pentosaceus KABP041, and of their potential to treat pediatric FGIDs. Clinical Trial Registration: [www.ClinicalTrials.gov], [identifier NCT04944628].


A Langevin-Based Model With Moving Posturographic Target to Quantify Postural Control.
Falls are a major concern of public health, particularly for older adults, as the consequences of falls include serious injuries and death. Therefore, the understanding and evaluation of postural control is considered key, as its deterioration is an important risk factor predisposing to falls. In this work we introduce a new Langevin-based model, local recall, that integrates the information from both the center of pressure (CoP) and the center of mass (CoM) trajectories, and compare its accuracy to a previously proposed model that only uses the CoP. Nine healthy young participants were studied under quiet bipedal standing conditions with eyes either open or closed, while standing on either a rigid surface or a foam. We show that the local recall model produces significantly more accurate prediction than its counterpart, regardless of the eyes and surface conditions, and we replicate these results using another publicly available human dataset. Additionally, we show that parameters estimated using the local recall model are correlated with the quality of postural control, providing a promising method to evaluate static balance. These results suggest that this approach might be interesting to further extend our understanding of the underlying mechanisms of postural control in quiet stance.


Impact of history of mental disorders on short-term mortality among hospitalized patients with sepsis: A population-based cohort study.
Mental disorders are associated with markedly reduced life expectancy, in part due to an increased risk of death due to infection, likely reflecting sepsis-associated mortality. Patients with mental disorders are at an increased risk of sepsis, but data on the prognostic impact of mental disorders in sepsis are sparse, showing conflicting findings. We used statewide data to identify hospitalizations aged ≥18 years with sepsis in Texas during 2014-2017. Mental disorders, including mood, anxiety, psychosis, and personality disorders were identified using Clinical Classification Software codes. Multilevel, multivariable logistic regression with propensity adjustment (primary model), with propensity score matching, and multivariable logistic regression as alternative models, were used to estimate the association between mental disorders and short-term mortality (defined as in-hospital mortality or discharge to hospice). Additional models were fitted for sensitivity analyses and to estimate the prognostic associations of individual categories of mental disorders. Among 283,025 hospitalizations with sepsis, 56,904 (20.1%) had mental disorders. Hospitalizations with vs without mental disorders were younger (age 18-44 years 12.2% vs 10.6%), more commonly white (61.0% vs 49.8%), with lower burden of comorbidities (mean [SD] Deyo comorbidity index 2.53 [2.27] vs 2.73 [2.47]), and with lower need for organ support (mechanical ventilation 32.8% vs 36.0%); p<0.0001 for all comparisons. Crude short-term mortality among sepsis hospitalizations with and without mental disorders was 25.0% vs 32.8%, respectively. On adjusted analyses, mental disorders remained associated with lower odds of short-term mortality (adjusted odds ratio 0.792 [95% CI 0.772-0.812]). This finding was consistent on the alternative modeling approaches, sensitivity analyses, and examination of individual categories of mental disorders. Mental disorders were associated, unexpectedly, with markedly lower risk of short-term mortality in sepsis. Further studies to examine the mechanisms underlying these findings may inform future efforts to improve sepsis outcomes.


The internal dynamics of international migration systems.
"In this paper I provide a conceptualization of international migration networks, which can be used to identify and integrate the internal components of migration systems, and formalize the relationships in an analytic model of the internal network dynamic. With the use of the operationalized model, and microlevel and macrolevel data for guestworkers in Germany during the period 1970 to 1989, we can empirically test the relative influence of internal network variables versus external forces on the attraction of immigrants over time. The empirical results suggest that--as the system matures--network variables have an increasing impact on the attraction of immigrants, while the impact of economic factors declines. The research is concluded with a series of simulations that further highlight the internal dynamic of international migration systems."


Etiology, diagnosis, and demographic analysis of maxillofacial trauma in elderly persons: A 10-year investigation.
The aim of this study was to investigate etiologies and diagnoses of maxillofacial trauma in emergency services in Brazil over a period of 10 years. Additionally, associations among sex, age, accident location, and dependent variables were analyzed. Understanding the epidemiology of trauma and the physiology of aging is important in maintaining health and bettering service for the elderly population. The primary mode of investigation was analysis of medical records from 2003 to 2013. These researchers recorded the diagnosis and etiology of the trauma, the location where the accident occurred, and the sex and age of the participants. Variable categories were compared using Chi-squared distribution, and logistic regression was used to analyze the associated factors. Of the 677 individuals analyzed, the female sex was predominant (57.61%) and the most prevalent age ranges were between 60 and 69 years (40.18%) and between 70 and 79 years (35.16%). Chi-squared distribution showed that men suffered more fractures (18.47%, p = 0.028) and women suffered more contusions (21.54%, p = 0.028). With regard to the various etiologies related to the traumas, traffic accidents (17.77%, p < 0.001) and aggression (17.42%, p < 0.001) were more frequent in males, and falls (83.03%, p < 0.001) were more frequent in females. The primary etiologies for maxillofacial trauma in the elderly population were falls, and the primary diagnoses were fractures. A deeper understanding of the physiological changes associated with aging, and preventive action to reduce falls, traffic accidents, and aggression in this population could be beneficial with regard to quality of life for elderly persons.


Measurement properties of a multicultural weight-specific quality-of-life instrument for children and adolescents.
To evaluate the psychometric properties of a new multicultural weight-specific quality-of-life (QOL) measure for children and adolescents-Youth Quality-of-Life Instrument-Weight module (YQOL-W). Twenty-five candidate items were administered to 443 children and adolescents between 11 and 18 years of age, of whom 53% were female, 33% were white, 30% were African American and 37% were Mexican American. Thirty-four percent had a healthy body mass index (BMI), 20% were overweight and 46% were obese. Twenty-one of the original 25 candidate items were retained in the final instrument. Exploratory and confirmatory factor analyses (CFA) resulted in a one-factor (21 items, alpha = 0.97) and a three-factor model including a Self factor (4 items, alpha = 0.90), a Social factor (11 items, alpha = 0.95) and an Environment factor (5 items, alpha = 0.90). CFA found the three-factor model had better model fit (P < 0.05). Both the one-factor and three-factor scores were negatively correlated with BMI and the Children's Depression Inventory and positively correlated with generic quality of life, all at the P < 0.05 level. The 1-week test-retest intra-class correlation coefficients were 0.73 for Social, 0.71 for Self, 0.73 Environment and 0.77 for the one-factor model. The YQOL-W shows good reliability and validity for assessing weight-specific QOL in children and adolescents.


Precise Chemodynamic Therapy of Cancer by Trifunctional Bacterium-Based Nanozymes.
Chemodynamic therapy (CDT) destroys cancer cells by converting H2O2 or O2 into reactive oxygen species (ROS), but its therapeutic efficacy is restricted by the antioxidant capacity of tumor. Previous solutions focused on strengthening the nanodrugs with the ability to increase ROS production or weaken the antioxidant capacity of cancer cells. Conversely, we here develop a mild nanodrug with negligible side effects. Specifically, the Au@Pt nanozyme decorated on a bacterial surface (Bac-Au@Pt) is reported to achieve precise CDT. Due to the tumor targeting ability of bacteria and catalytic property of Au@Pt nanozyme under acidic conditions, this nanosystem can release ROS to tumor cells effectively. In addition, the interferon gamma released by T cells specifically decreases the intracellular reductants in tumor cells, while having no obvious effect on normal cells. Therefore, a low dose of Bac-Au@Pt achieves a satisfactory therapeutic efficacy to tumor cells and is nontoxic to normal cells even at their acidic components. This nanosystem enables CDT and immunotherapy to mutually benefit and improve by each other, providing a promising strategy to achieve high anticancer efficacy even with a low dose usage.


Effects of multi-dimensional social capital on mental health of children in poverty: An empirical study in Mainland China.
Using the data of 1314 underprivileged children in Xiushui, China, this study adopted an ecological framework to explore how social capital embedded in family, peer, school, and community interplay and affect the mental health of poor children. Structural equation modeling was employed to verify the hypothesized model. The results demonstrated that higher levels of family, peer, and school social capital were all associated with better mental health outcomes of children in poverty. Moreover, family, peer, and school social capital fully mediated the effect of community social capital on children's mental health. Theoretical and practical implications were discussed.


Determination and prediction of the digestible and metabolisable energy content of barley for growing pigs based on chemical composition.
This experiment was conducted to define the sources of variation determining the energy content of barley and to develop a practical method to predict the digestible energy (DE) and metabolisable energy (ME) content of individual barley samples. The 19 barley samples used in this study were diverse varieties grown in different regions. The feeding experiment used 57 barrows (initial body weight 31.5 ± 3.2 kg) and was conducted over two consecutive periods (n = 6 per treatment) using a completely randomised design. During each period, the pigs were placed in metabolic crates for a 5-d total collection of faeces and urine following a 10-d adaptation to the diets. Among the barley samples, on dry matter (DM) basis the levels of neutral detergent fibre, acid detergent fibre (ADF), crude protein and starch ranged from 16.1% to 38.9%, 3.9% to 9.6%, 10.1% to 16.8% and 43.5% to 57.9%, respectively. The mean determined DE and ME contents amounted to 14.7 and 14.4 MJ/kg DM and varied among the samples by 1.85 MJ (13.6%) and 1.78 MJ (13.3%), respectively. The ADF fraction accounted for 73% and 76% of the total variation in the DE and ME content, respectively. It revealed that for prediction of the DE and ME contents in barley, equations had the best fit when the analysed contents of ADF, neutral detergent fibre and gross energy were used for calculation (R2 = 0.92). On the basis of the developed equations, the DE and ME contents of barley of different origin can be predicted with an acceptable accuracy when used as feed for growing pigs.


Role of Phenolic Inhibitors in Peroxidase-mediated Degradation of Indole-3-acetic Acid.
7-Hydroxy-2,3-dihydrobenzofuran derivatives, metabolites of a carbamate insecticide carbofuran, and five other phenolic inhibitors of indoleacetic acid (IAA) oxidase interfered with IAA-induced spectral change in the Soret band of horseradish peroxidase (HRP). The onset of IAA degradation required transformed HRP intermediates. The inhibitors, when added before IAA, protected HRP from reacting with IAA, thus preventing formation of highly reactive enzyme intermediates, and consequently, IAA degradation. When added after IAA, the inhibitors quickly reversed the IAA-induced spectral change of HRP and inhibited further IAA degradation.The phenolic inhibitors differed in stability and reactivity. 7-Hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran, 3,7-dihydroxy-2,2-dimethyl-2,3-dihydrobenzofuran, catechol, protocatechuic acid, caffeic acid, ferulic acid, and scopoletin belonged to one group which produced only a temporary inhibition to IAA-induced spectral change of HRP and IAA degradation since the inhibitors were metabolized in the reaction. The length of the lag was dependent on the IAA, inhibitor, and enzyme concentrations. 3-Keto-7-hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran and 3-keto-carbofuran belonged to the other group which produced a persistent inhibition.Degradation of IAA required both the heme group and apoprotein of HRP. Reconstituted enzyme from bovine hemin and apoprotein or HRP after unfolding by urea or guanidine treatment were inhibited by the inhibitors in a way similar to the native HRP. The inhibition was reversible by higher concentrations of IAA, but the plot of 1/v versus 1/s and 1/v versus i were curvilinear, reflecting the complex nature of a competitive inhibition.


Retinal function and structure in Ant1-deficient mice.
Mutations in ANT, a mitochondrial ATP transporter, are typically associated with myopathy. Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology. RT-PCR was used to confirm Ant1 expression in retinas of wild-type (WT) or Ant1(-/-) mice. Full-field ERGs were used to test retinal function under dark- and light-adapted conditions and the recovery of the photoresponse to a bright flash. Using histologic methods, the authors assessed the retinal location of ANT and ANT1-β-gal reporter protein, mitochondrial activity with cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) staining, retinal layer thickness, and bipolar cell types using Chx10 and recoverin. Ant1(-/-) mice had supernormal ERG b-waves under both dark- and light-adapted conditions. X-Gal staining was detected in a subset of cells within the inner retina. The following characteristics were normal in Ant1(-/-) mice compared with age-matched WT mice: recovery of the photoresponse, COX and SDH activity, retinal morphology, and bipolar cell morphology. The presence of ANT1 in a subset of inner retinal cells accompanied by supernormal ERG responses suggests that ANT1 may be localized to hyperpolarizing bipolar cells. However, the immunohistochemical techniques used here did not show any differences in bipolar cells. Moderate functional changes coupled with a lack of detectable morphologic changes suggest that ANT1 is not essential for ATP transport in the retina.


[A new look at platelets and microparticles, including their role in haemostatic disorders and progression of neoplastic disease].
Platelets (PLT) are the smallest yet highly reactive components of the circulatory system. Microvesicles (platelet-derived microvesicles - PMV), also known as microparticles or microplatelets (platelet-derived microparticles - PMP), are released from platelets upon stimulation by thrombin, collagen or others platelet agonists. Both PLT and PMP play a role in haemostasis and mediate signal transmission between cells, especially cancer cells, thus modulating their functions. Moreover, these two platelet populations participate in transcellular exchange of information, affect immune responses and angiogenesis, which may facilitate tumour growth and development of distant metastases. Their role in tumour progression has been recognized, but the mechanism of their action remains still unclear. Assessment of PMP as a diagnostic and prognostic marker in various disorders is currently a subject of intense investigation.


Assessing enablement in clinical practice: a systematic review of available instruments.
Enablement is an intervention by which the health care provider recognizes, promotes and enhances patients' ability to control their health and life. An abundant health literature suggests that enablement is associated with good outcomes. In this review, we aimed at identifying and comparing instruments that assess enablement in the health care context. We conducted a systematic literature review using Medline, Embase, Cochrane, Cinahl and PsycINFO databases, 1980 through March 2009, with specific search strategy for each database. Citations were included if they reported: (1) development and/or validation of an instrument; (2) evaluation of enablement in a health care context; and (3) quantitative results following administration of the instrument. The quality of each main retained citation was assessed using a modified version of the Standards for Reporting of Diagnostic Accuracy. Of 3135 citations identified, 53 were retrieved for detailed evaluation. Four articles were included. Two instruments were found: the Patient Empowerment Scale (PES) and the Empowering Speech Practices Scale (ESPS). Both instruments assessed enablement in hospital setting, one from the inpatient's perspective (PES) and the other from both perspectives (ESPS). Two instruments assess enablement in hospital setting. No instrument is currently available to assess enablement in an ambulatory care context.


Nd:YAG laser penetration into cast titanium and gold alloy with different surface preparations.
This study investigated the effect of surface preparation on the Nd:YAG laser penetration into cast titanium and gold alloy. Cast blocks of each metal were given four different surface preparations: (i) coloured with black marker; (ii) air-abraded with 50 microm Al2O3; (iii) ground with SiC points and (iv) polished with 1 microm Al2O3 (mirror-polished). Two blocks with each of the surface preparations were abutted and laser-welded at their interface using the voltages of 210-260 V in increments of 10 V. After the welded blocks were mechanically separated, the laser penetration was measured using computer graphics. Regardless of the surface preparation, an increase in voltage increased the laser penetration for both metals. The laser penetration into titanium prepared with black marker and air-abrasion was significantly deeper than into the titanium ground with SiC points and mirror-polished. Although there were no statistical differences in penetration among the surface preparations for the gold alloy, the penetration in the mirror-polished specimens was shallower than any of the other preparation methods at higher voltages of 240-260 V. The results obtained in this study suggested that broken metal frameworks with finished surfaces should be painted with black marker or air-abraded before laser welding.


Channel formation by FhaC, the outer membrane protein involved in the secretion of the Bordetella pertussis filamentous hemagglutinin.
Many virulence factors of pathogenic microorganisms are presented at the cell surface. However, protein secretion across the outer membrane of Gram-negative bacteria remains poorly understood. Here we used the extremely efficient secretion of the Bordetella pertussis filamentous hemagglutinin (FHA) to decipher this process. FHA secretion requires a single specific accessory protein, FhaC, the prototype of a family of proteins necessary for the extracellular localization of various virulence proteins in Gram-negative bacteria. We show that FhaC is heat-modifiable and localized in the outer membrane. Circular dichroism spectra indicated that FhaC is rich in beta-strands, in agreement with structural predictions for this protein. We further demonstrated that FhaC forms pores in artificial membranes, as evidenced by single-channel conductance measurements through planar lipid bilayers, as well as by liposome swelling assays and patch-clamp experiments using proteoliposomes. Single-channel conductance appeared to fluctuate very fast, suggesting that the FhaC channels frequently assume a closed conformation. We thus propose that FhaC forms a specific beta-barrel channel in the outer membrane for the outward translocation of FHA.


Toward clarification of the doctor of nursing practice degree.
The doctor of nursing practice (DNP) degree has been recommended by the American Association of College of Nursing (AACN) as the terminal degree in nursing practice by 2015 (AACN, 2004). However, confusion regarding this degree still exists. To promote understanding of this degree, the pertinent history of doctoral education in nursing is reviewed. In addition, a clear definition of the degree, including the competencies of the DNP degree, is provided. A comparison of the PhD in nursing and the DNP degree is also reviewed to provide further clarification. DNP graduates may engage in various roles such as leadership, health policy advocate, and scholarship. These roles will be reviewed as well as the relevant issues associated with this degree such as use of the title "Dr.," educating others about the degree, faculty shortages, and program enrollment. Finally, the implications for emergency nursing regarding the DNP degree are discussed.


Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms.
Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers. Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity (LOH) was evaluated for ACVR2 and ACVR1, and ACVR2 promoter methylation by methylation-specific PCR and bisulfite sequencing and chromosomal instability (CIN) phenotype via fluorescent LOH analysis of 3 duplicate markers. ACVR2 promoter methylation and ACVR2 expression were assessed in colon cancer cell lines via qPCR and IP-Western blots. Re-expression of ACVR2 after demethylation with 5-aza-2'-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathological criteria. Of 51 MSS colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. No somatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (p<0.001) and ACVR2 promoter hypermethylation (p<0.05). ACVR2 LOH, but not promoter hypermethylation, correlated with CIN status. In colon cancer cell lines with fully methylated ACVR2 promoter, loss of ACVR2 mRNA and protein expression was restored with 5-Aza treatment. Loss of ACVR2 was associated with an increase in primary colon cancer volume (p<0.05). Only a small percentage of MSS colon cancers lose expression of activin signaling members. ACVR2 loss occurs through LOH and ACVR2 promoter hypermethylation, revealing distinct mechanisms for ACVR2 inactivation in both MSI and MSS subtypes of colon cancer.


The hypoxic inducible stress response as a target for cancer drug discovery.
All solid tumors experience some degree of hypoxia. The response to the stress of hypoxia is mediated in large part by the hypoxia inducible factor-1 (HIF-1) transcription factor that increases the expression of a variety of genes that allow the tumor to survive and grow in the hostile hypoxic environment. Increased tumor HIF-1 has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis. This has lead to the current interest in HIF-1 as a cancer drug target. HIF-1 activity in tumors depends on the availability of the HIF-1alpha subunit, the levels of which increase under hypoxic conditions or through the activation of oncogenes and/or inactivation of tumor-suppressor genes. HIF-1alpha level and HIF-1 activity are regulated by multiple pathways involving transcription, translation, post-translational modification, and the interaction with other transcription factors. A number of agents have been reported to block HIF-1 activity, acting on all of these mechanisms. Not all of the agents have been shown to block tumor HIF-1 activity in vivo. Some have shown marked HIF-1 inhibition and anti-tumor activity. There are agents already, or soon to be, tested in the clinic as anti-tumor inhibitors of HIF-1. The challenges will be to determine whether the effects of these agents that are seen is due to HIF-1 inhibition and to identify which patients are most likely to benefit from treatment with HIF-1 inhibitors.


Potassium transport in two tomato species : lycopersicon esculentum and lycopersicon cheesmanii.
The commercial tomato, lycopersicon esculentum Mill. cv Walter, and its wild relative, Lycopersicon cheesmanii ssp. minor (Hook.) C.H. Mull., were grown for 30 days under controlled conditions and in solution culture varying in its content of Na(+) and K(+). Subsequently, (86)Rb-labeled K(+) uptake and distribution were studied. From all solutions, ;Walter' consistently absorbed (86)Rb-labeled K(+) at a higher rate in micromoles per gram fresh weight per 30 minutes than L. cheesmanii. L. cheesmanii distributed a greater proportion of the absorbed K(+) from its root to its shoot. When 0.6 millimolar NaNO(3) replaced 0.6 millimolar KNO(3) in the pretreatment solution, intact plants of both genotypes followed a similar pattern as when they were pretreated with K(+) only, but a greater percentage of the absorbed K(+) remained in the roots. Leaf slices of L. cheesmanii plants deprived of K(+) for 6 days showed a greater rate of K(+) uptake than did slices from ;Walter' plants pretreated the same way. Stem slices of L. cheesmanii, however, had a lower uptake rate than did those of ;Walter'. Both leaf and stem slices of ;Walter' plants, pretreated 6 days with 0.6 millimolar NaNO(3) substituting for 0.6 millimolar KNO(3) in their growth medium, had greater rates of (86)Rb-labeled K(+) uptake from 0.5 and 20 millimolar KCl solutions than did slices of L. cheesmanii. These marked differences in patterns of ion uptake and translocation indicate that these genotypes of tomato have evolved different mechanisms to deal with K(+) and Na(+) in their environments.


Actinomyces odontolyticus infection 3 months post-robotic-assisted laparoscopic prostatectomy.
Actinomyces odontolyticus infection is a rare bacterial infection with only 46 cases reported from its discovery in 1958. This case highlights an immunocompetent patient who presented with an infected lymphocele and bacteraemia following a robotic-assisted laparoscopic prostatectomy and extended pelvic lymph node dissection 3 months previously. He was treated for a fever of unclear origin initially using amoxicillin, gentamicin and metronidazole. Subsequently, he was found to have an infected lymphocele, which required surgical drainage. He was discharged 19 days after admission with three times daily oral amoxicillin which is to be continued for 6-12 months. This case highlights the need for effective communication between the laboratory and medical teams, and the importance of prompt source control.


Student and staff experiences of attendance monitoring in undergraduate obstetrics and gynecology: a cross-sectional survey.
Despite the widespread introduction of active learning strategies to engage students across modern medical curricula, student attendance and attendance monitoring remain a challenging issue for medical educators. In addition, there is little published evidence available to medical educators regarding the use of attendance monitoring systems. The aim of this study was to evaluate the opinions of students and staff about the use of a paper-based student logbook to record student attendance across all clinical and classroom-based learning activities within an undergraduate clinical rotation in obstetrics and gynecology (OBGYN). Each student undertaking the clinical rotation in OBGYN was required to complete a paper-based logbook in a booklet format that listed every clinical and classroom-based activity that the student was expected to attend. A cross-sectional survey evaluating the acceptability, practicality, and effect on access to learning opportunities of using the logbook was undertaken. The survey was conducted among all medical students who completed their OBGYN rotation over a full academic year and staff who taught on the program. The response rate was 87% (n=128/147) among students and 80% (n=8/10) among staff. Monitoring attendance was widely acceptable to students (n=107/128, 84%) and staff (n=8/8, 100%). Most students (n=95/128, 74%) and staff (n=7/8, 88%) recommended that attendance should be mandatory during rotations. Almost all staff felt that attendance should contribute toward academic credit (n=7/8, 88%), but students were divided (n=73/128, 57%). Students (n=94/128, 73%) and staff (n=6/8, 75%) reported that the use of the logbook to record attendance with tutor signatures was a satisfactory system, although students questioned the need for recording attendance at every classroom-based activity. Most students felt that the logbook facilitated access to learning experiences during the rotation (n=90/128, 71%). Staff felt that the process of signing logbooks improved their interaction with students (n=6/8, 75%). The survey showed that the use of a paper-based logbook to record medical student attendance with tutor signatures across all clinical and classroom-based learning activities was acceptable and practical for students and staff and was felt to facilitate access to learning opportunities. The study provides medical educators with evidence to support monitoring of attendance within clinical rotations.


Automated lung sound analysis for detecting pulmonary abnormalities.
Identification of pulmonary diseases comprises of accurate auscultation as well as elaborate and expensive pulmonary function tests. Prior arts have shown that pulmonary diseases lead to abnormal lung sounds such as wheezes and crackles. This paper introduces novel spectral and spectrogram features, which are further refined by Maximal Information Coefficient, leading to the classification of healthy and abnormal lung sounds. A balanced lung sound dataset, consisting of publicly available data and data collected with a low-cost in-house digital stethoscope are used. The performance of the classifier is validated over several randomly selected non-overlapping training and validation samples and tested on separate subjects for two separate test cases: (a) overlapping and (b) non-overlapping data sources in training and testing. The results reveal that the proposed method sustains an accuracy of 80% even for non-overlapping data sources in training and testing.


Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate.
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to cutaneous human beta-papillomavirus infections causing persistent flat warts or pityriasis versicolor-like lesions. This generalized verrucous skin disorder resembles generalized verrucosis, but these 2 conditions are distinguished by differences in clinical manifestation and the human papillomavirus types involved. A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 (EVER1) and TMC8 (EVER2) determine susceptibility to this disorder; however, they have not solved all EV cases fully. These deficiencies account for 75% of affected individuals, leaving a substantial number of patients without an underlying genetic cause. Recently, it has been revealed that mutations in additional genes (RHOH, MST-1, CORO1A, and IL-7) result in extensive human beta-papillomavirus replication and therefore manifest with an EV-like phenotype. The term "acquired EV" is used to describe an EV-like phenotype that develops in immunocompromised hosts, and the introduction of this entity further aggravates the confusion. Reevaluation of these entities is warranted. Here, we review the available data on this issue, provide up to date information on the major characteristics that differentiate between these seemingly clinically similar disorders, and highlight the different mechanisms involved in each disorder.


Analysis of long term care in the context of social and health services in social institutional facilities in Slovakia.
Long-term care for people with chronic illnesses and disabilities present an urgent challenge around the world. Existing systems of care, which typically rely on unpaid family members, are not by themselves enough to meet growing demands. This analysis includes survey on the structure of services provided in selected social facilities in Slovakia. The survey on structure of provided services includes social facilities providing services to the target groups involved in this analysis: Elderly people in retirement age; Disabled and chronically ill citizens in working age. For data collection from social facilities we used questionnaire method. The data were obtained from the managements of these facilities (n=405). In social facilities, the age range of clients was 76-85 years (31%); the length of stay of a patient in a social facility was in 36% patients 11 years and longer. The most frequently performed activities in employees were related to services and activities (31%) and social care (30%). For 52% social facilities is waiting time 1 year and longer. The length of stay of patient in social facilities is affected in 83% by combination of health and social problems and as to the diagnosis structure the most prevalent conditions are ischemic heart diseases, heart attack, hypertension (39%), locomotor disease (36%). In 2006 the budget resources of social facilities were in 72% contributions from the state budget. Long-term care is closely interlinked with other programmes and systems, which can reduce the need for long-term care or which complement it.


Solution structure of the ribosome-binding domain of E. coli translation initiation factor IF3. Homology with the U1A protein of the eukaryotic spliceosome.
Initiation of translation in prokaryotes requires the formation of a complex between the messenger RNA, the 30 S ribosomal subunit and the initiator tRNA(fMet). Initiation factor IF3 binds to the 30 S ribosomal subunit and proof-reads the initiation complex, thereby ensuring the accuracy of this step. IF3 also plays a pleiotropic role in the regulation of translation, as a result of differential influences exerted on the levels of the initiation of translation of genes or groups of genes. IF3 is composed of two independent domain or roughly identical sizes. We have expressed and purified the C-terminal domain of E. coli IF3 and shown that it retains both the 30 S particle binding and 70 S ribosome dissociating activities of the native protein. We have obtained 1H and 15N NMR resonance assignments and its 3D solution structure was calculated using 551 restraints. It is composed of a mixed beta-sheet backed by two alpha-helices. It shows a striking resemblance to the U1A small nuclear ribonucleoprotein structure, which binds to the U1 snRNA in the eukaryotic spliceosome. This suggests a convergent evolution process for these two proteins that are associated with ribonucleoproteic complexes.


Contribution of off-road tests to predicting on-road performance: a critical review of tests.
Driving is an essential activity of daily living. Because it is easily disrupted by illness or injury, it is a common subject of occupational therapy assessment. Assessments of driving are critically important and carry legal implications for therapists. A full occupational therapy assessment comprising both off- and on-road testing is time and labour intensive and therefore expensive. Off-road tests are used to inform on-road assessments, and, if they have sufficient sensitivity and specificity they may replace an on-road assessment for some clients. The twofold purpose of this article is to compare and critique off-road tests to predict driving performance and to determine if any is sufficiently accurate to identify drivers who do not require an on-road assessment. We reviewed tests commonly used by researchers to predict driving capacity (i) that have been used in research since 2000 and (ii) for which sensitivity and specificity had been (or could be) calculated. We compared the tests on five characteristics: diagnostic makeup of samples, sample sizes, outcome measures, sensitivity and specificity and potential for use as a supplement to on-road assessment or to identify drivers for whom an on-road assessment is not necessary. No gold standard off-road test exists for predicting on road performance. DriveSafe/DriveAware and SMC Tests had the highest reported sensitivity and specificity. Thus, with further research, one or both may be found to predict on-road performance accurately and to minimise the need for on road assessment. Several other tests are a useful supplement to on-road testing.


[Digestive system diseases and style of nutrition among secondary school students].
In the paper there was examined 246 pupils from secondary school. The auditorial survey including 23 questions was drawn up. The questions referred to digestive diseases occurrence among members of family, pupils under the survey, their style of nutrition, financial status of their family. It was interesting how kind of food, keeping regular hours, behaviour during eating is connected with frequency of digestive disease occurrence. 14.5% of pupils suffered from alimentary tract diseases especially constipation and peptic ulcer. A large percentage (46.2%) do not eat regularly, and 85% is in a hurry, doing something else during eating. 39.4% of examined use spices, ketchup, mustard every time, 17.5% do not eat vegetables, fruit at all, 45.9% eat sweets every day. Before leaving for school 45.9% pupils do not even eat breakfast. 69.1% of subjects claimed that stress is a reason of occurence their digestive disorders. In the paper abnormal style of nutrition is more frequent among pupils complaining of digestive system diseases.


Consecutive Infections With Influenza A and B Virus in Children During the 2014-2015 Seasonal Influenza Epidemic.
In a retrospective analysis of the test results for 647 patients with laboratory-confirmed influenza, we identified 13 children with influenza A virus infection who were subsequently infected with influenza B virus after a mean interval of 50 days. None of these children were considered immunodeficient or had an increased frequency of infections. Our data provide novel information in showing that consecutive infection with influenza A and B viruses can occur during a regular influenza season in immune-competent children and that a preceding influenza A virus infection may not provide cross-protection against influenza B virus infection.


Prokaryotic Expression and Serodiagnostic Potential of Glyceraldehyde-3-Phosphate Dehydrogenase and Thioredoxin Peroxidase from Baylisascaris schroederi.
Baylisascaris schroederi, a roundworm parasite of giant pandas, badly affects the health of its hosts. Diagnosis of this disease currently depends mainly on sedimentation floatation and Polymerase Chain Reaction (PCR) methods to detect the eggs. However, neither of these methods is suitable for diagnosis of early-stage panda baylisascariasis and no information on early diagnosis of this disease is available so far. Therefore, to develop an effective serologic diagnostic method, this study produced recombinant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and thioredoxin peroxidase (Tpx) proteins from B. schroederi using a prokaryotic expression system. We determined the immunological characteristics of these proteins and their location in the parasite. Indirect enzyme-linked immunosorbent assays (ELISAs) were established to detect B. schroederi infection in giant pandas based on GAPDH and Tpx respectively. The open reading frame of the GAPDH gene (1083 bp) encoded a 39 kDa protein, while the predicted molecular weight of Tpx (588 bp) was 21.6 kDa. Western-blotting analysis revealed that both recombinant proteins could be recognized with positive serum of pandas infected with B. schroederi. Immunohistochemical staining showed that the endogenous GAPDH of B. schroederi was widely distributed in the worm while Tpx was mainly localized in the muscle, eggs, gut wall, uterus wall and hypodermis. Serological tests showed that the GAPDH-based indirect ELISA had a sensitivity of 95.83% and specificity of 100%, while the test using Tpx as the antigen had sensitivity of 75% and specificity of 91.7%. Thus, B. schroederi Tpx is unsuitable as a diagnostic antigen for baylisascariasis, but B. schroederi GAPDH is a good candidate diagnostic antigen for B. schroederi in pandas.


Neutron diffraction experiment with the Y116S variant of transthyretin using iBIX at J-PARC: application of a new integration method.
Transthyretin (TTR) is one of more than 30 amyloidogenic proteins, and the amyloid fibrils found in patients afflicted with ATTR amyloidosis are composed of this protein. Wild-type TTR amyloids accumulate in the heart in senile systemic amyloidosis (SSA). ATTR amyloidosis occurs at a much younger age than SSA, and the affected individuals carry a TTR mutant. The naturally occurring amyloidogenic Y116S TTR variant forms more amyloid fibrils than wild-type TTR. Thus, the Y116S mutation reduces the stability of the TTR structure. A neutron diffraction experiment on Y116S TTR was performed to elucidate the mechanism of the changes in structural stability between Y116S variant and wild-type TTR through structural comparison. Large crystals of the Y116S variant were grown under optimal crystallization conditions, and a single 2.4 mm3 crystal was ultimately obtained. This crystal was subjected to time-of-flight (TOF) neutron diffraction using the IBARAKI biological crystal diffractometer (iBIX) at the Japan Proton Accelerator Research Complex, Tokai, Japan (J-PARC). A full data set for neutron structure analysis was obtained in 14 days at an operational accelerator power of 500 kW. A new integration method was developed and showed improved data statistics; the new method was applied to the reduction of the TOF diffraction data from the Y116S variant. Data reduction was completed and the integrated intensities of the Bragg reflections were obtained at 1.9 Å resolution for structure refinement. Moreover, X-ray diffraction data at 1.4 Å resolution were obtained for joint neutron-X-ray refinement.


High levels of mercury and low levels of persistent organic pollutants in a tropical seabird in French Guiana, the Magnificent frigatebird, Fregata magnificens.
In the present study, trace elements and persistent organic pollutants (POPs) were quantified from Magnificent frigatebirds (Fregata magnificens) breeding at a southern Atlantic island. Stable isotope ratio of carbon (δ(13)C) and nitrogen (δ(15)N) were also measured to infer the role of foraging habitat on the contamination. For another group from the same colony, GPS tracks were recorded to identify potential foraging areas where the birds may get contaminated. Fourteen trace elements were targeted as well as a total of 40 individual POPs, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The concentration of Hg in the blood was up to 6 times higher in adults (5.81 ± 1.27 μg g(-1) dw.) than in nestlings (0.99 ± 0.23 μg g(-1) dw.). A similar pattern was found for POPs. ∑PCBs was the prevalent group both in adults (median 673, range 336-2801 pg g(-1) ww.) and nestlings (median 41, range 19-232 pg g(-1) ww.), followed by the sum of dichlorodiphenyltrichloroethanes and metabolites (∑DDTs), showing a median value of 220 (range 75-2342 pg g(-1) ww.) in adults and 25 (range 13-206 pg g(-1) ww.) in nestlings. The isotope data suggested that the accumulation of trace elements and POPs between adults and nestlings could be due to parental foraging in two different areas during incubation and chick rearing, respectively, or due to a shift in the feeding strategies along the breeding season. In conclusion, our work showed high Hg concentration in frigatebirds compared to non-contaminated seabird populations, while other trace elements showed lower values within the expected range in other seabird species. Finally, POP exposure was found generally lower than that previously measured in other seabird species.


Human umbilical cord blood-derived CD34-positive endothelial progenitor cells stimulate osteoblastic differentiation of cultured human periosteal-derived osteoblasts.
The aim of this study was to examine the effects of human umbilical cord blood-derived CD34-positive endothelial progenitor cells (CD34+ EPCs) on osteoblastic differentiation of cultured human periosteal-derived osteoblasts (POs). CD34+ cells from human umbilical cord blood were sorted to purify more EPCs in characterization. These sorted cells showed CD31, VE-cadherin, and KDR expression as well as CD34 expression and formed typical tubes in Matrigel. These sorted cells were referred to as human cord blood-derived CD34+ EPCs. In in vivo bone formation using a miniature pig model, the newly formed bone was clearly examined in defects filled with polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffolds containing either human umbilical cord blood-derived CD34+ EPCs and POs or human umbilical vein endothelial cells (HUVEC) and POs; however, the new bone had the greatest density in the defect treated with CD34+ EPCs and POs. Osteoblastic phenotypes of cultured human POs using ALP activity and von Kossa staining were also more clearly found in CD34+ EPC-conditioned medium than CD34-negative (CD34-) cell-conditioned medium, whereas HUVEC-conditioned medium had an intermediate effect. PCR array for common cytokines and growth factors showed that the secretion of interleukin (IL)-1β was significantly higher in CD34+ EPCs than in HUVEC, followed by level in CD34- cells. In addition, IL-1β also potently and dose dependently increased ALP activity and mineralization of POs in culture. These results suggest that human umbilical cord blood-derived CD34+ EPCs stimulates osteoblastic differentiation of cultured human POs. The functional role of human umbilical cord blood-derived CD34+ EPCs in increasing the osteogenic phenotypes of cultured human POs may depend on IL-1β secreted from human umbilical cord blood-derived CD34+ EPCs.


[Chronic bony instability of the elbow joint].
The high stability of the elbow joint is provided by the congruent articular surfaces in combination with soft tissue stabilizers. The main osseous contributor of elbow stability is the coronoid, which is therefore referred to as a primary stabilizer. The radial head as a secondary stabilizer together with the medial collateral ligament assures valgus stability and together with the coronoid it assures posterolateral stability. Insufficiency of the osseous stabilizers may lead to difficulties in the treatment of chronic dislocation and complex instability. Thereby reconstruction of the osseous constraints of the elbow joint is not performed in isolation from addressing insufficient soft-tissue stabilizers. Bony stabilizers and reconstructional procedures are discussed in this review.


[A patient of ADEM with central and peripheral conduction block improved with ultra-high-dose methylprednisolone].
A patient with exanthem and fever showed progressive disturbance of consciousness and flaccid quadriplegia predominantly in the lower extremities. Antibiotics, aciclovir, high-dose methylprednisolone (1 g/day for 3 consecutive days) and IVIG (400 mg/kg/day for 5 consecutive days) were not effective. Nerve conduction study and SEP in the lower extremities showed peripheral and central conduction block. EEG showed irregular sharp and slow waves predominantly in the left hemisphere. ABR and SEP in the upper extremities were normal. Consecutive studies of cranial and spinal MRIs showed no abnormalities. A diagnosis of acute disseminated encephalomyelitis (ADEM) was made. We started administration of ultra-high-dose methylprednisolone (5.4 mg/kg/h for 47 hours), the dose for acute spinal cord injury based on the randomized controlled trial of The Third National Acute Spinal Cord Injury Study in the USA. After this, she regained consciousness and the quadriplegia improved. The abnormalities in the electrophysiological studies also normalized. It is thought that the neuroprotective mechanism of ultra-high-dose methylprednisolone could be attributed to its inhibition of lipid peroxidation, secondary, ischemia, energy failure and so on. If the usual treatment is not effective for severe encephalomyelitis cases, we can consider the administration of ultra-high-dose methylprednisolone as one of the new treatment options.


Broadband/multiband absorption through surface plasmon engineering in graphene-wrapped nanospheres.
In this paper, a thin film constructed by a periodic assembly of graphene-wrapped particles with spherical geometry has been proposed as a polarization-insensitive reconfigurable perfect absorber. The performance of the proposed structure is based on the cooperative excitation of the quadrupole localized surface plasmons on graphene shells. By sweeping the quality of graphene shells, it is recognized that the low-quality graphene material is the best choice for the absorber design. Moreover, the effect of graphene chemical potential and periodicity of the particles on the absorptivity of the structure is investigated. The physical mechanism of performance is clarified by investigating the excited localized surface plasmon resonances. In addition, the angle-independent behavior up to around 60 degrees for both transverse electric (TE) and transverse magnetic (TM) waves is proved. Interestingly, by engineering the substrate height, our proposed absorber exhibits dynamic broadband performance due to the impedance matching and multiband absorption by enhancing the Fabry-Perot resonances of a micrometer-sized substrate. The possibility of attaining a similar static broadband response by stacking multiple layers is also proved. Our proposed sub-wavelength absorber can be suitable for novel optoelectronic devices due to its simple geometry.


Mechanisms of agonism and inverse agonism at serotonin 5-HT1A receptors.
Mechanisms of agonist and inverse agonist action at the serotonin 5-HT1A receptor have been studied using the modulation of guanosine 5'-O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS) binding in membranes of Chinese hamster ovary (CHO) cells expressing the receptor (CHO-5-HTA1A cells). A range of agonists increased [35S]GTPgammaS binding with different potencies and to different maximal extents, whereas two compounds, methiothepin and spiperone, inhibited both agonist-stimulated and basal [5S]GTPgammaS binding, thus exhibiting inverse agonism. Potencies of agonists to stimulate [35S]GTPgammaS binding in membranes from CHO-5-HT1A cells were reduced by adding increasing concentrations of GDP to assays, whereas changes in sodium ion concentration did not affect agonist potency. The maximal effect of the agonists was increased by increasing sodium ion concentrations. The affinities of agonists in ligand binding assays were unaffected by changes in sodium ion concentration. Increasing GDP in the assays of the inverse agonists increased potency for spiperone to inhibit [35S]GTPgammaS binding and had no effect for methiothepin, in agreement with the sensitivity of these compounds to guanine nucleotides in ligand binding assays. Potencies for these inverse agonists were unaffected by changes in sodium ion concentration. These data were simulated using the extended ternary complex model. These simulations showed that the data obtained with agonists were consistent with these compounds achieving agonism by stabilising the ternary complex. For inverse agonists, the simulations showed that the mechanism for spiperone may be to stabilise forms of the receptor uncoupled from G proteins. Methiothepin, however, probably does not alter the equilibrium distribution of different receptor species; rather, this inverse agonist may stabilise an inactive form of the receptor that can still couple to G protein.


The use of electrochemically activated saline as a uterine instillation in pony mares.
Twelve pony mares were randomly assigned to either a control or a treatment group and inseminated with fresh, raw semen from a single stallion of known fertility in a cross-over trial design. Pregnancy was diagnosed by transrectal ultrasound 12-14 days post-ovulation and then terminated by administration of a luteolytic dose of cloprostenol. Treatment mares received a uterine instillation of 100 ml of electrochemically activated (ECA) saline 4-12 hours post-insemination. Control mares received no treatment post-insemination. Per cycle pregnancy rate was 58.3 % in the control group and 50 % in the treatment group. There was no statistical difference (P = 1.000) in pregnancy rate between the 2 groups. The principles of ECA and applications of ECA saline are discussed.


H3N2 canine influenza virus and Enterococcus faecalis coinfection in dogs in China.
In May 2017, 17 dogs in a German Shepherd breeding kennel in northern China developed respiratory clinical signs. The owner treated the dogs with an intravenous injection of Shuang-Huang-lian, a traditional Chinese medicine, and azithromycin. The respiratory signs improved 3 days post-treatment, however, cysts were observed in the necks of eight dogs, and three of them died in the following 2 days. Quantitative real-time PCR was used to detect canine influenza virus (CIV). All of the dogs in this kennel were positive and the remaining 14 dogs had seroconverted. Two of the dogs were taken to the China Agricultural University Veterinary Teaching Hospital for further examination. Two strains of influenza virus (A/canine/Beijing/0512-133/2017 and A/canine/Beijing/0512-137/2017) isolated from the nasal swabs of these dogs were sequenced and identified as avian-origin H3N2 CIV. For the two dogs admitted to the hospital, hematology showed mild inflammation and radiograph results indicated pneumonia. Cyst fluid was plated for bacterial culture and bacterial 16 s rRNA gene PCR was performed, followed by Sanger sequencing. The results indicated an Enterococcus faecalis infection. Antimicrobial susceptibility tests were performed and dogs were treated with enrofloxacin. All 14 remaining dogs recovered within 16 days. Coinfection of H3N2 CIV and Enterococcus faecalis was detected in dogs, which has not been reported previously. Our results highlight that CIV infection might promote the secondary infection of opportunistic bacteria and cause more severe and complicated clinical outcomes.


Design, challenge, and promise of stimuli-responsive nanoantibiotics.
Over the past few years, there have been calls for novel antimicrobials to combat the rise of drug-resistant bacteria. While some promising new discoveries have met this call, it is not nearly enough. The major problem is that although these new promising antimicrobials serve as a short-term solution, they lack the potential to provide a long-term solution. The conventional method of creating new antibiotics relies heavily on the discovery of an antimicrobial compound from another microbe. This paradigm of development is flawed due to the fact that microbes can easily transfer a resistant mechanism if faced with an environmental pressure. Furthermore, there has been some evidence to indicate that the environment of the microbe can provide a hint as to their virulence. Because of this, the use of materials with antimicrobial properties has been garnering interest. Nanoantibiotics, (nAbts), provide a new way to circumvent the current paradigm of antimicrobial discovery and presents a novel mechanism of attack not found in microbes yet; which may lead to a longer-term solution against drug-resistance formation. This allows for environment-specific activation and efficacy of the nAbts but may also open up and create new design methods for various applications. These nAbts provide promise, but there is still ample work to be done in their development. This review looks at possible ways of improving and optimizing nAbts by making them stimuli-responsive, then consider the challenges ahead, and industrial applications.Graphical abstractA graphic detailing how the current paradigm of antibiotic discovery can be circumvented by the use of nanoantibiotics.


The population challenge in Africa and the prospects for the African Development Bank's intervention.
"The paper advocates that unchecked population growth may lead to serious social and economic burdens in developing countries in general, and particularly in Africa.... The theoretical stand advocated here is that population and development are intimately linked and strongly influence each other. Therefore, an attempt to foster economic growth and hopefully improve the standard of living of the people without taking into consideration the population factor would be as illusory as an attempt to control population without involving economic variables." Using this perspective, the author examines prospects for the African Development Bank's intervention in the population sector. (SUMMARY IN FRE)


Three-dimensional magnetic resonance rendering imaging of lumbosacral radiculography in the diagnosis of symptomatic extraforaminal disc herniation with or without foraminal extension.
Retrospective analysis of lumbosacral radiculography using 3-dimensional (3D) magnetic resonance (MR) rendering in patients with extraforaminal disc herniation. To investigate the significance of lumbosacral radiculography as depicted by 3D MR rendering in the diagnosis of symptomatic extraforaminal disc herniation with or without foraminal extension. Given that accurate evaluation of the extraforaminal zones on routine axial and sagittal images is difficult, extraforaminal disc herniations tend to be sometimes overlooked. In addition, oblique coronal images along intervertebral foramina and MR myelography may not clearly demonstrate a detailed full view of nerve root changes. Furthermore, the detection of the morphologic changes of the nerve root is very important for the diagnosis of symptomatic extraforaminal disc herniation. Thus, a useful method for evaluating the nerve root in order to diagnose symptomatic extraforaminal disc herniation is required. Twenty-four patients with extraforaminal and combined (extraforaminal with foraminal) lumbar disc herniations were included in this study. Conventional spin-echo sequence and 3D coronal fast-field echo sequences with selective water excitation by using the principles of the selective excitation technique (Proset imaging) were acquired. Indentation and swelling of the nerve roots and dorsal root ganglion (DRG) in the symptomatic sides and levels were evaluated on the basis of 3D MR rendering images of the lumbar spine. The tilting angle of the nerve root in the symptomatic side was compared with those in the asymptomatic contralateral side again on the basis of the 3D MR rendering images. Dorsal root ganglion indentation without swelling of the nerve roots was found in 7 patients whereas that with swelling of the nerve roots was observed in 6 patients. Swelling of the entire segment of the nerve from nerve root to spinal nerve (n = 9) or only the spinal nerve (n = 2) was observed in 11 patients. Compared with the contralateral nerve root, 7 patients exhibited a tilting angle abnormality of the ipsilateral nerve root. Based on lumbosacral radiculography through 3D MR rendering, important findings related to the diagnosis of symptomatic extraforaminal disc herniation include swelling of DRG and/or nerve roots and DRG indentation. Ultimately, 3D MR lumbosacral radiculography is a very useful method in the diagnosis of the symptomatic extraforaminal disc herniation.


Genetic markers for urine haptoglobin is associated with decline in renal function in type 2 diabetes in East Asians.
Urine haptoglobin (uHP) level prospectively predicts diabetic kidney disease (DKD) progression. Here, we aim to identify genetic determinants of uHP level and evaluate association with renal function in East Asians (EA) with type 2 diabetes (T2D). Genome-wide association study (GWAS) among 805 [236 Chinese (discovery) and 569 (57 Malay and 512 Chinese) (validation)] found that rs75444904/kgp16506790 variant was robustly associated with uHP level (MetaP = 1.21 × 10-60). rs75444904 correlates well with plasma HP protein levels and multimerization in EA but was not in perfect LD (r2 = 0.911 in Chinese, r2 = 0.536 in Malay) and is monomorphic in Europeans (1000 G data). Conditional probability analysis indicated weakening of effects but residual significant associations between rs75444904 and uHP when adjusted on HP structural variant (MetaP = 8.22 × 10-7). The rs75444904 variant was associated with DKD progression (OR = 1.77, P = 0.014) independent of traditional risk factors. In an additional validation-cohort of EA (410 end-stage renal disease (ESRD) cases and 1308 controls), rs75444904 was associated with ESRD (OR = 1.22, P = 0.036). Furthermore, increased risk of DKD progression (OR = 2.09, P = 0.007) with elevated uHP level through Mendelian randomisation analysis provide support for potential causal role of uHP in DKD progression in EA. However, further replication of our findings in larger study populations is warranted.