Next-Generation Single-Use Ureteroscopes: An In Vitro Comparison.
Single-use ureteroscopes have been gaining popularity in recent years. We compare the optics, deflection, and irrigation flow of two novel single-use flexible ureteroscopes-the YC-FR-A and the NeoFlex-with contemporary reusable and single-use flexible ureteroscopes. Five flexible ureteroscopes, YC-FR-A (YouCare Tech, China), NeoFlex (Neoscope, Inc., USA), LithoVue (Boston Scientific, USA), Flex-Xc (Karl Storz, Germany), and Cobra (Richard Wolf, Germany), were assessed in vitro for image resolution, distortion, field of view, depth of field, color representation, and grayscale imaging. Ureteroscope deflection and irrigation were also compared. The YC-FR-A showed a resolution of 5.04 lines/mm and 4.3% image distortion. NeoFlex showed a resolution of 17.9 lines/mm and 14.0% image distortion. No substantial difference was demonstrated regarding the other optic characteristics between the two. Across all tested ureteroscopes, single-use or reusable, the digital scopes performed best with regard to optics. The YC-FR-A had the greatest deflection at baseline, but lacks two-way deflection. The NeoFlex had comparable deflection at baseline to reusable devices. Both ureteroscopes had substantial loss of deflection with instruments in the working channel. The YC-FR-A had the greatest irrigation rate. The NeoFlex has comparable irrigation to contemporary ureteroscopes. The YouCare single-use fiberoptic flexible ureteroscope and NeoFlex single-use digital flexible ureteroscope perform comparably to current reusable ureteroscopes, possibly making each a viable alternative in the future. Newer YouCare single-use flexible ureteroscopes with a digital platform and two-way deflection may be more competitive, while the NeoFlex devices are undergoing rapid improvement as well. Further testing is necessary to validate the clinical performance and utility of these ureteroscopes, given the wide variety of single-use devices under development.


Reappraisal of the problem of British mariners and sexually transmitted infection.
A detailed appraisal of the British seafarer and his way of life is described and the prevailing management of sexually transmitted disease in the seafarer is outlined. It is shown that the available statistics on the incidence of sexually transmitted disease among seafarers are inadequate. Management at sea and ashore remains generally unsatisfactory. Suggestions are made to improve the management of venereal disease in foreign ports and a simple method is described of managing sexually transmitted disease at sea with trimethoprim/sulphamethoxazole.


Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations.
The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder.


Estimated H-atom anisotropic displacement parameters: a comparison between different methods and with neutron diffraction results.
Anisotropic displacement parameters (ADPs) are compared for H atoms estimated using three recently described procedures, both among themselves and with neutron diffraction results. The results convincingly demonstrate that all methods are capable of giving excellent results for several benchmark systems and identify systematic discrepancies for several atom types. A revised and extended library of internal H-atom mean-square displacements is presented for use with Madsen's SHADE web server [J. Appl. Cryst. (2006), 39, 757-758; http://shade.ki.ku.dk], and the improvement over the original SHADE results is substantial, suggesting that this is now the most readily and widely applicable of the three approximate procedures. Using this new library--SHADE2--it is shown that, in line with expectations, a segmented rigid-body description of the heavy atoms yields only a small improvement in the agreement with neutron results. The SHADE2 library, now incorporated in the SHADE web server, is recommended as a routine procedure for deriving estimates of H-atom ADPs suitable for use in charge-density studies on molecular crystals, and its widespread use should reveal remaining deficiencies and perhaps overcome the inherent bias in the majority of such studies.


Rapid and non-invasive quantification of intramuscular fat content of intact pork cuts.
Having acquired near infrared (NIR) hyperspectral images of intact pork loin samples through an NIR hyperspectral imaging system, the efficiency of a variety of image processing techniques including texture pattern analysis techniques were applied to process hyperspectral images so as to determine the intramuscular fat (IMF) content non-destructively. After the segmentation of region of interest (ROI), the raw spectral, texture-based spectral and textural characteristics of pork images were extracted by spectral averaging and pattern recognition techniques namely Gabor filter and improved gray level co-occurrence matrix (GLCM), respectively. First derivatives of the non-filtered and the Gabor filtered spectra were also investigated. Full waveband partial least squares regression (PLSR) was employed to determine the optimal parameters of Gabor filter and GLCM, and to select optimal wavelengths for IMF prediction. A stepwise procedure was applied to the optimal wavelengths to further optimize them to key wavelengths. Multiple linear regression (MLR) models were built based on the key wavelengths. Mean spectra and the Gabor filtered spectra outperformed GLCM. The best result, represented by correlation coefficients of calibration (Rc), cross validation (Rcv) and prediction (Rp) of 0.89, 0.89, and 0.86, respectively, was achieved using the first derivative of Gabor filtered spectra at 1193 and 1217 nm. To visualize the IMF content in pork, the distribution maps of IMF content in pork were drawn using a mean spectra-based MLR model. These promising results highlight the great potential of NIR hyperspectral imaging for non-destructive prediction of IMF content of intact pork.


An investigation of sites that bind human somatotropin (growth hormone) in the liver of the pregnant rabbit.
The binding of 125I-labelled human somatotropin (growth hormone) to a crude membrane preparation from the liver of pregnant rabbit, and to receptors solubilized from this fraction by Triton X-100, was dependent on time, temperature and receptor concentration. At 4 degrees C a steady state was reached after 20 h, and maximum specific binding (as a percentage of total tracer added) was approx. 50% for both membrane-bound and solubilized receptors. Solubilization did not significantly affect the binding properties of the receptor at low concentrations of Triton X-100 (less than 0.05%, v/v, in the assay tube). However, at higher concentrations (approx. 0.1%, v/v), the detergent lowered the ability of some hormones, for example ovine prolactin, to displace 125I-labelled human somatotropin, but did not affect other hormones such as bovine somatotropin. Some somatogenic hormones, such as bovine somatotropin, and some lactogenic hormones, such as ovine prolactin, displaced 125I-labelled human somatotropin from membrane-bound and solubilized receptor preparations. Furthermore, 85% of 125I-labelled bovine somatotropin was displaced from membrane-bound receptors by ovine prolactin, and 125I-labelled ovine prolactin was almost completely displaced by bovine somatotropin. Scatchard analysis of the binding data for human somatotropin suggested a single class of binding sites in the membrane-bound receptor preparation, with an affinity (Ka) of 1.9 X 10(9) M-1 and a capacity of 1726 fmol/mg of protein; these values were slightly increased by solubilization (Ka = 3.2 X 10(9) M-1, capacity = 2103 fmol/mg of protein). Scatchard analysis of binding to membrane-bound receptors also indicated a single class of high-affinity binding sites for bovine somatotropin (Ka = 4.8 X 10(9) M-1, capacity = 769 fmol/mg) and for ovine prolactin (Ka = 6.1 X 10(9) M-1, capacity = 187 fmol/mg).


Reduced Risk of Alcohol-Induced Pancreatitis With Cannabis Use.
Pancreatitis is an increasingly common clinical condition that causes significant morbidity and mortality. Cannabis use causes conflicting effects on pancreatitis development. We conducted a larger and more detailed assessment of the impact of cannabis use on pancreatitis. We analyzed data from 2012 to 2014 of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample discharge records of patients 18 years and older. We used the International Classification of Disease, Ninth Edition codes, to identify 3 populations: those with gallstones (379,125); abusive alcohol drinkers (762,356); and non-alcohol-non-gallstones users (15,255,464). Each study population was matched for cannabis use record by age, race, and gender, to records without cannabis use. The estimation of the adjusted odds ratio (aOR) of having acute and chronic pancreatitis (AP and CP) made use of conditional logistic models. Concomitant cannabis and abusive alcohol use were associated with reduced incidence of AP and CP (aOR: 0.50 [0.48 to 0.53] and 0.77 [0.71 to 0.84]). Strikingly, for individuals with gallstones, additional cannabis use did not impact the incidence of AP or CP. Among non-alcohol-non-gallstones users, cannabis use was associated with increased incidence of CP, but not AP (1.28 [1.14 to 1.44] and 0.93 [0.86 to 1.01]). Our findings suggest a reduced incidence of only alcohol-associated pancreatitis with cannabis use.


[Preliminary evaluation of inoculation of hepatitis B vaccine in normal adult subjects].
A total of 107 subjects in population without HBsAg, anti-HBs and anti-HBc were inoculated with hepatitis B vaccine in month 0, 1, 6, respectively and followed up for three years. Seven months after the administration of first dose of vaccine response rate of anti-HBs was 94.4%, of which 68.2% had a S/N ratio greater than 10. Three years later the response rate of anti-HBs dropped to 75.7% and the rate of S/N ratio 10 fell to 46.7%, 20 subjects turned negative for anti-HBs and one turned positive for HBsAg. During the same period, of 124 adults who were hepatitis B virus markers negative and were not inoculated, 14 became HBsAg-positive (ALT increased in 3 of them) and 3 turned anti-HBs positive.


Process of change during social skills training with preadolescents and its relation to treatment outcome.
Videotaped excerpts of treatment sessions from a recent intervention study were examined to explore the changes occurring during social skills training and their relation to treatment outcome. 27 unpopular preadolescents who showed few conversational skills during pretreatment observations engaged in cooperative activities with 2 socially accepted classmates for 10 half-hour sessions. Half of these triads received coaching in conversational skills, while the others received nonspecific adult support during these activities. The quality of social interactions among triad members was evaluated during the sixth and tenth sessions. Children who received social skills training displayed more conversational skills and received more positive peer support during treatment than children who did not receive coaching. Coached children increased skill performance over time while noncoached children did not change. Furthermore, both conversational skills displayed and positive peer responses received during treatment sessions were positively related to treatment outcome.


Cancer incidence and surveillance strategies in individuals with RASopathies.
RASopathies are a set of clinical syndromes that have molecular and clinical overlap. Genetically, these syndromes are defined by germline pathogenic variants in RAS/MAPK pathway genes resulting in activation of this pathway. Clinically, their common molecular signature leads to comparable phenotypes, including cardiac anomalies, neurologic disorders and notably, elevated cancer risk. Cancer risk in individuals with RASopathies has been estimated from retrospective reviews and cohort studies. For example, in Costello syndrome, cancer incidence is significantly elevated over the general population, largely due to solid tumors. In some forms of Noonan syndrome, cancer risk is also elevated over the general population and is enriched for hematologic malignancies. Thus, cancer surveillance guidelines have been developed to monitor for the occurrence of such cancers in individuals with some RASopathies. These include abdominal ultrasound and urinalyses for individuals with Costello syndrome, while complete blood counts and splenic examination are recommended in Noonan syndrome. Improved cancer risk estimates and refinement of surveillance recommendations will improve the care of individuals with RASopathies.


DNA sequence of the yeast transketolase gene.
Transketolase (EC 126.96.36.199) is the enzyme that, together with aldolase, forms a reversible link between the glycolytic and pentose phosphate pathways. We have cloned and sequenced the transketolase gene from yeast (Saccharomyces cerevisiae). This is the first transketolase gene of the pentose phosphate shunt to be sequenced from any source. The molecular mass of the proposed translated protein is 73,976 daltons, in good agreement with the observed molecular mass of about 75,000 daltons. The 5'-nontranslated region of the gene is similar to other yeast genes. There is no evidence of 5'-splice junctions or branch points in the sequence. The 3'-nontranslated region contains the polyadenylation signal (AATAAA), 80 base pairs downstream from the termination codon. A high degree of homology is found between yeast transketolase and dihydroxyacetone synthase (formaldehyde transketolase) from the yeast Hansenula polymorpha. The overall sequence identity between these two proteins is 37%, with four regions of much greater similarity. The regions from amino acid residues 98-131, 157-182, 410-433, and 474-489 have sequence identities of 74%, 66%, 83%, and 82%, respectively. One of these regions (157-182) includes a possible thiamin pyrophosphate (TPP) binding domain, and another (410-433) may contain the catalytic domain.


Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.
Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. K a and V d parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., *2/*2, *2/*3, *2/*5, *3/*5, and *3/*8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of k e across different genotypes. Conclusions The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.


Peanut leaf inspired multifunctional surfaces.
Nature has long served as a source of inspiration for scientists and engineers to design and construct multifunctional artificial materials. The lotus and the peanut are two typical plants living in the aquatic and the arid (or semiarid) habitats, respectively, which have evolved different optimized solutions to survive. For the lotus leaf, an air layer is formed between its surface and water, exhibiting a discontinuous three-phase contact line, which resulted in the low adhesive superhydrophobic self-cleaning effect to avoid the leaf decomposition. In contrast to the lotus leaf, the peanut leaf shows high-adhesive superhydrophobicity, arising from the formation of the quasi-continuous and discontinuous three-phase contact line at the microscale and nanoscale, respectively, which provides a new avenue for the fabrication of high adhesive superhydrophobic materials. Further, this high adhesive and superhydrophobic peanut leaf is proved to be efficient in fog capture. Inspired by the peanut leaf, multifunctional surfaces with structural similarity to the natural peanut leaf are prepared, exhibiting simultaneous superhydrophobicity and high adhesion towards water.


Robotics in Spine Surgery: A Technical Overview and Review of Key Concepts.
The use of robotic systems to aid in surgical procedures has greatly increased over the past decade. Fields such as general surgery, urology, and gynecology have widely adopted robotic surgery as part of everyday practice. The use of robotic systems in the field of spine surgery has recently begun to be explored. Surgical procedures involving the spine often require fixation via pedicle screw placement, which is a task that may be augmented by the use of robotic technology. There is little margin for error with pedicle screw placement, because screw malposition may lead to serious complications, such as neurologic or vascular injury. Robotic systems must provide a degree of accuracy comparable to that of already-established methods of screw placement, including free-hand, fluoroscopically assisted, and computed tomography-assisted screw placement. In the past several years, reports have cataloged early results that show the robotic systems are associated with equivalent accuracy and decreased radiation exposure compared with other methods of screw placement. However, the literature is still lacking with regard to long-term outcomes with these systems. This report provides a technical overview of robotics in spine surgery based on experience at a single institution using the ExcelsiusGPS (Globus Medical; Audobon, PA, USA) robotic system for pedicle screw fixation. The current state of the field with regard to salient issues in robotics and future directions for robotics in spinal surgery are also discussed.


Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia.
More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2K/H-2D) and for CD45. Cells that did not stain positively for H-2K/H-2D and CD45 were sorted as the germ cell-enriched fraction. The sorted germ cell-enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia.


Effect of V2-receptor-mediated changes on inner medullary blood flow induced by AVP.
We have previously shown that arginine vasopressin (AVP) in physiological amounts reduces inner medullary blood flow and that the mechanism of this decrease is at least in part mediated by the vasopressor (V1-receptor) action of AVP. To determine whether the antidiuretic action of AVP (V2-receptor) also contributes to the reduction in inner medullary blood flow, we determined capillary blood flow (QVR) in individual descending vasa recta (DVR) and ascending vasa recta (AVR) using fluorescence videomicroscopy in the exposed renal papilla of the anesthetized rat. Three groups of chronically water-diuretic rats were studied in three consecutive periods: control (period 1), experimental (period 2), and recovery (period 3). Group I rats (designated the AVP group) received AVP, 45 ng X h-1 X kg body wt-1; group II (AVP + V2-inhibitor), AVP plus its specific antidiuretic antagonist d(CH2)5[D-Ile2,Thr4]AVP; and group III (V2-inhibitor), the antagonist alone, respectively, in the experimental period 2. Only group I rats concentrated their urine, urine osmolality (Uosmol) = 499 +/- 48 mosmol/kgH2O, whereas urine remained hypotonic throughout in groups II and III. In group I, QVR in DVR and AVR decreased in period 2; but in groups II and III, QVR tended to increase. These results suggest that the AVP-induced decrease in papillary vasa recta blood flow is in part mediated by its antidiuretic V2-receptor as well as by its vasopressor (V1-receptor). They also suggest that the rate of urinary flow in the medullary collecting ducts is a determinant of inner medullary blood flow.


PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial-mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy.
Human head and neck squamous cell carcinoma (HNSCC) is usually treated with chemoradiotherapy, but the therapeutic efficacy could be hampered by intrinsic radioresistance and early relapse. Repeated administrations of rhenium-188 (188Re)-conjugated radiopharmaceutical has been reported to escalate the radiation doses for better control of advanced human cancers. Here we found that high dosage of 188Re-liposome, the liposome-encapsulated 188Re nanoparticles exhibited significant killing effects on HNSCC FaDu cells and SAS cells but not on OECM-1 cells. To investigate the biological and pharmaceutical responses of high 188Re-liposomal dosage in vivo, repeated doses of 188Re-liposome was injected into the orthotopic tumor model. FaDu cells harboring luciferase reporter genes were implanted in the buccal positions of nude mice followed by intravenous injection of 188Re-liposome. The Cerenkov luminescence imaging (CLI) was performed to demonstrate an increased accumulation of 188Re-liposome in the tumor lesion of nude mice with repeated doses compared to a single dose. Repeated doses also enhanced tumor growth delay and elongated the survival of tumor-bearing mice. These observations were associated with significant loss of Ki-67 proliferative marker and epithelial-mesenchymal transition (EMT) markers in excised tumor cells. The body weights of mice were not significantly changed using different doses of 188Re-liposome, yet repeated doses led to lower blood counts than a single dose. Furthermore, the pharmacokinetic analysis showed that the internal circulation of repeated 188Re-liposomal therapy was elongated. The biodistribution analysis also demonstrated that accumulations of 188Re-liposome in tumor lesions and bone marrow were increased using repeated doses. The absorbed dose of repeated doses over a single dose was about twofold estimated for a 1 g tumor. Together, these data suggest that the radiopharmacotherapy of 188Re-liposome can enhance tumor suppression, survival extension, and internal circulation without acute toxicity using repeated administrations.


Redox/Near-Infrared Dual-Responsive Hollow Mesoporous Organosilica Nanoparticles for Pesticide Smart Delivery.
Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.


Treatment with iron of patients with heart failure with and without anemia.
Iron deficiency is a common cause of anemia in otherwise healthy individuals and plays an important role in the development of anemia within the heart failure patient population. Iron-deficient heart failure patients experience worse symptoms and are less exercise tolerant than those without iron deficiency. These symptoms may occur even before clinical anemia is evident. This article reviews studies of the benefits of the use of intravenous iron to treat iron deficiency in anemic and nonanemic heart failure patients and an overview of the physiology and pathophysiology of iron metabolism in chronic heart failure.


Variation in fracture rates by country may not be explained by differences in bone mass.
It is unclear whether the high fracture incidence in Sweden compared with other countries is related to low bone mass. We present and compare bone mineral density (BMD, g/cm(2)) at the femoral neck in a mainly osteoporotic referral population consisting of 2,031 men and 6,932 women with that of previous population-based cohorts. BMD measurements were collected at a single study center in Sweden, and data on validated hip fractures were collected from the corresponding health-care district and the cohort investigated. The BMD values of our cohort were similar to those of population-based cohorts from other countries. In contrast, the total incidence of hip fractures in 80-year-old women and men in the health-care district where our BMD measurements were performed was high (1.8% and 0.9%, respectively). The correlation between age and BMD was more negative in men aged 20-49 years than in women of the same age group (-0.011 vs. -0.006 g/cm(2) yearly, P < 0.001). In contrast, at 50-80 years of age, more negative regression coefficients were seen in women (-0.007 vs. -0.004 g/cm(2) yearly, P < 0.001 for comparison). In conclusion, a low BMD may not be the key factor explaining Sweden's comparatively high fracture incidence. In our cross-sectional data, age trends in BMD at the femoral neck differ between men and women. It would be highly interesting to further study the underlying causes of the global variations in fracture incidence rates.


[Determination of elements of hypericum perforatum L. in Xinjiang by microwave digestion-ICP-AES].
Sample digestion by microwave is of some merits: simple, rapid, saving agents, nonpollution and being easy digested. HNO3-HClO4 (5:1) was used as a microwave digestion agent. A direct method is reported for the determination of Fe, Ca, Mg, Zn, Mn, Cu, Na, K, Ba, Al, Pb and Cr in Hypericum perforatum L. in Xinjiang by inductively coupled plasma atomic emission spectrometry(ICP-AES). The selection of digestion conditions of the technique is described. The recoveries for these elements were 93.2%-103.0%, and the relative standard deviation (RSD) of the twelve samples were 0.4%-2.9%. According to standard sample GBW07602 bush twigs and leaves, the authors checked the method for accuracy and precision. The results were found to be basically consistent with the reference values. It was proved that the method features satisfactory precision and accuracy. The method was applied to the determination of plant materials with good agreement.


Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up.
To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed. Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity. Median follow-up was 80.5 months (range, 60-98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy-seven percent of the patients were satisfied with their cosmetic results. Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.


Microbiological assay for estimating salivary concentrations of the cariostatic antibiotic Actinobolin.
A logarithmic-ratio microbiological assay has been developed for the estimation of concentrations of actinobolin (or inhibitory equivalents) in human saliva. The utility of this assay has been demonstrated by presenting data that show concentrations of this antibiotic (or inhibitory equivalents) detected in saliva or saline after incubation at 37 C for periods as long as 6 hr. The results of some statistical analyses of the assay data have been included.


Valuing whole complex lives: Young adults' experiences of recovery-related principles in mental healthcare in the United States.
One in five young adults (aged 18-25 years) in the United States experiences a past year mental disorder, commonly including depression or anxiety. Yet, 1.5 million each year do not receive needed mental health services and are unlikely, in general, to seek formal mental healthcare. We aimed to inform the development of a novel programme for young adult mental health by first eliciting their positive and negative prior experiences with mental health providers. Four focus groups with 19 young adults (aged 19-26 years) recruited from the community and with moderate to severe depression and/or anxiety were conducted in 2018 in a western US state. Participants' prior experiences with services/providers were elicited along six pre-defined recovery-related concepts: feeling listened to and validated, inclusivity, full information and consent, hope and optimism, connectedness, and change. Focus groups were audio-recorded, transcribed verbatim and uploaded into NVivo version 12 software. Two independent coders used deductive thematic analysis to identify patterned responses. Feeling listened to and validated appeared as a cornerstone of other recovery concepts. Participants discussed past negative experiences with psychiatrists and regret for being put on medications in their teenage years without information or options. Hope and optimism were low because of a general focus by professionals to address immediate symptom-based issues, rather than on improving their overall lives. Service providers' focus on medication-taking, and other one-size-fits-all tools, was interpreted as lacking a sincere desire to help. Young adults were particularly sensitive to inauthentic interactions and superficial strategies, which left them craving care that incorporated their whole lives, acknowledged biopsychosocial interconnections and prioritised improving their lives over 'feeling better' in a given moment. Mental health providers should consider developing programmes that shift focus away from an exclusively medical understanding of distress and towards holistic, educational or relational approaches that value body, mind, self-exploration and authentic connection.


Singular spectrum analysis improves analysis of local field potentials from macaque V1 in active fixation task.
Local field potentials (LFPs) represent the relatively slow varying components of the neural signal, and their analysis is instrumental in understanding normal brain function. To be properly analyzed, this signal needs to be separated in its fundamental frequency bands. Recent studies have shown that empirical mode decomposition (EMD) can be exploited to pre-process LFP recordings in order to achieve a proper separation. However, depending on the analyzed signal, EMD is known to generate components that may cover a too wide frequency range to be considered as narrow banded. As an alternative, we present here an improved version of the singular spectrum analysis (SSA) algorithm, validated by numerical simulations, and applied to LFP recordings in V1 of a macaque monkey exposed to simple visual stimuli. The components generated by the improved SSA algorithm are shown to be more meaningful than those generated by EMD, paving the way for its use in LFP analysis.


Life before and beyond blistering: The role of collagen XVII in epidermal physiology.
Type XVII collagen (COL17) is a transmembranous protein that is mainly expressed in the epidermal basal keratinocytes. Epidermal-dermal attachment requires COL17 expression at the hemidesmosomes of the epidermal basement membrane zone because congenital COL17 deficiency leads to junctional epidermolysis bullosa and acquired autoimmunity to COL17 induces bullous pemphigoid. Recently, in addition to facilitating epidermal-dermal attachment, COL17 has been reported to serve as a niche for hair follicle stem cells, to regulate proliferation in the interfollicular epidermis and to be present along the non-hemidesmosomal plasma membrane of epidermal basal keratinocytes. This review focuses on the physiological properties of COL17 in the epidermis, its role in maintaining stem cells and its association with signalling pathways. We propose possible solutions to unanswered questions in this field.


Commercial versus synthesized polymers for soil erosion control and growth of Chinese cabbage.
Soil erosion leads to environmental degradation and reduces soil productivity. The use of anionic polyacrylamide (PAM) and synthesized biopolymer (BP) using lignin, corn starch, acrylamide, and acrylic acid were tested to evaluate soil erosion, water quality, and growth of Chinese cabbage (Brassica campestris L.). Each treatment of PAM and BP was applied at 200 kg ha(-1) to loamy sand soil and subjected to a slope of 36% with a 20 mm h(-1) simulated rainfall. Application of BP decreased soil pH compared to the untreated check (CK); however, the soil pH was not altered with PAM. The decrease in pH might most likely be due to availability of anionic sites to be protonated on soils having pH >6 and soil buffering capacity. Both PAM and BP applications may not induce eutrophication with stable levels of total contents of N and P. With PAM and BP, the average values of suspended soil (SS) and turbidity were reduced by up to 96.0 and 99.9%, respectively, compared to CK. Reduction of SS can be attributed to increasing soil stability and shear strength by clay flocculation. There was no toxicity effects resulting from germination tests and the dry weight was increased by 17.7% (vs. CK) when PAM and BP were applied. These results are attributed to increases in water retention and plant-available water. The use of polymeric soil amendments is an environmentally friendly way to mitigate soil erosion and nonpoint source pollution.


Natural history of anterior knee pain: a 14- to 20-year follow-up of nonoperative management.
We describe a consecutive series of girls with idiopathic anterior knee pain in adolescence and who were treated nonoperatively. At a mean follow-up of 16 years, 22% had no pain, 71% thought that their symptoms were better than at presentation, 88% used analgesics rarely or not at all, and 90% continued to participate regularly in sports. Nevertheless, about one in four of the patients continued to have significant symptoms for < or = 20 years after presentation. No features were identified that predicted those patients in whom symptoms would persist. We conclude that surgical treatment of idiopathic anterior knee pain in adolescents is not justified until a procedure has been shown to provide a better outcome than that reported here or until a way has been found to distinguish the few patients who will not get better spontaneously from the majority who will.


A Mixed Method Review of Tobacco Cessation for the Cardiopulmonary Rehabilitation Clinician.
To systematically survey the literature, describe the current tobacco science, and perform a mixed method review of randomized control trials of tobacco research in the cardiopulmonary population. Mixed method review was conducted on major resource databases. Inclusion criteria were English language with a minimum follow-up of 6 months, published between January 1, 2007, and June 30, 2016; adult smokers ≥18 years of age with cardiovascular and/or pulmonary disease; initiation of subject recruitment from hospital or community; tobacco cessation (TC) as the main aim of the study; biometric validation of smoking status; first-line TC medications; and nonpharmacological treatments. The pooling of the 10 studies through forest plot analysis revealed the effect of tobacco continuous abstinence rates significant at 3, 6, and 12 months (total OR = 3.73; 95% CI, 2.58-5.38). Also, tobacco point prevalence rates of TC treatments demonstrated overall effects that were significant at the different end points (total OR = 2.63; 95% CI, 1.90-3.64). In both cases, the higher ORs were found in the 3 months end point. Most successful interventions consisted of a combination of pharmacological and nonpharmacological therapy (predominantly counseling). The evidence continues to support the recommended first-line TC pharmacotherapy and nonpharmacological practices published in the 2008 national guidelines. Implications for cardiopulmonary rehabilitation clinicians are discussed.


Circulating endothelial progenitor cells decrease in infants with bronchopulmonary dysplasia and increase after inhaled nitric oxide.
Impairment of endothelial progenitor cells (EPCs) has been shown to contribute to the development of bronchopulmonary dysplasia (BPD). In the current study, the relationship between EPC changes of after birth and the development of BPD was investigated, and the effects of inhaled nitric oxide (iNO) on EPCs were evaluated. Sixty infants with a gestational age of less than 32 weeks and a birth weight of less than 1500 g were studied. NO was administered to infants who were receiving mechanical ventilation or CPAP for at least 2 days between the ages of 7 and 21 days. EPC level was determined by flow cytometry at birth, 7, 21 and 28 days of age and 36 weeks' postmenstrual age (PMA), before and after the iNO treatment. Plasma concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and granulocyte-macrophage colony-stimulating factor were determined via immunochemical assay. Twenty-five neonates developed BPD, 35 neonates survived and did not develop BPD. EPC level was decreased on day 7 and 21 in infants who later developed BPD compared with infants that did not develop BPD. From birth to 21 days of age, BPD infants had a persistently lower VEGF concentration compared with non-BPD infants. No difference was found between the two groups at day 28 or 36 weeks PMA. In infants that later developed BPD, iNO raised the KDR(+)CD133(+) and CD34(+)KDR(+)CD133(+) EPC numbers along with increasing the level of plasma VEGF. EPC level was reduced at 7 days of age in infants with BPD, and iNO increased the EPC number along with increasing the level of VEGF. Further studies are needed to elucidate the mechanism leading to the decrease of EPCs in infants with BPD and to investigate the role of iNO treatment in the prevention of BPD.


Family Dynamics and the Alzheimer's Disease Experience.
Using constructivist grounded theory, this study explored how family groups respond to Alzheimer's disease in its early stages. Seven family units (N = 22) participated in a series of 26 longitudinal interviews and 14 other family caregivers took part in three focus groups at a later stage for refinement and verification of the findings. Data analysis revealed four types of family dynamics: close dynamics at the start that were maintained throughout the experience, close dynamics at the start which became conflicting, conflicting dynamics at the start which remained problematic, and conflicting dynamic at the start which became closer over time. Factors such as prior relationships and family history, motivation to care, family organization, communication, and the family vision for future shaped the development of these dynamics. This theory of family dynamics in Alzheimer's disease has the potential to inform the development of more adequate early interventions for families living with the illness.


[Interdisciplinary Application of Smart Technology in Psychiatric Care].
The popularization of smart technology is a global phenomenon. The increasing ubiquity of smartphones offers the potential to apply smart technology in areas such as healthcare and behavioral change interventions. Mobile health services may enhance the effectiveness and resolve the shortcomings of traditional medical services, which cannot continuously and instantly track changes in disease symptoms. The popularity of mobile phones has led to the emergence of mobile health applications. Mobile health applications use active and passive methods to collect data and transmit information. Studies have confirmed the feasibility and acceptance of these applications in assessing and detecting diseases and in mental health interventions. In this article, the limitations of traditional psychiatric medical diagnosis and the opportunity to develop mobile health using information and communication technology are discussed, and related empirical research on using smart technology to evaluate and detect symptoms is explored using the example of bipolar disorders. In addition, the benefits and future prospects of onset alert and the development of healthcare models for action are highlighted. In the future, we look forward to developing mobile health applications that meet the needs of healthcare in Taiwan. Furthermore, we recommend more research and investment in related fields to accumulate more extensive empirical evidence.


Analysis of variation in charges and prices paid for vaginal and caesarean section births: a cross-sectional study.
To examine the between-hospital variation of charges and discounted prices for uncomplicated vaginal and caesarean section deliveries, and to determine the institutional and market-level characteristics that influence adjusted charges. Using data from the California Office of Statewide Health Planning and Development (OSHPD), we conducted a cross-sectional study of all privately insured patients admitted to California hospitals in 2011 for uncomplicated vaginal delivery (diagnosis-related group (DRG) 775) or uncomplicated caesarean section (DRG 766). Hospital charges and discounted prices adjusted for each patient's clinical and demographic characteristics. We analysed 76 766 vaginal deliveries and 32 660 caesarean sections in California in 2011. After adjusting for patient demographic and clinical characteristics, we found that the average California woman could be charged as little as US$3296 or as much as US$37 227 for a vaginal delivery, and US$8312-US$70 908 for a caesarean section depending on which hospital she was admitted to. The discounted prices were, on an average, 37% of the charges. We found that hospitals in markets with middling competition had significantly lower adjusted charges for vaginal deliveries, while hospitals with higher wage indices and casemixes, as well as for-profit hospitals, had higher adjusted charges. Hospitals in markets with higher uninsurance rates charged significantly less for caesarean sections, while for-profit hospitals and hospitals with higher wage indices charged more. However, the institutional and market-level factors included in our models explained only 35-36% of the between-hospital variation in charges. These results indicate that charges and discounted prices for two common, relatively homogeneous diagnosis groups-uncomplicated vaginal delivery and caesarean section-vary widely between hospitals and are not well explained by observable patient or hospital characteristics.


CUL-4A is critical for early embryonic development.
Ubiquitin-mediated degradation targets cell cycle regulators for proteolysis. Much of the ubiquitin pathway's substrate specificity is conferred by E3 ubiquitin ligases, and cullins are core components of some E3s. CUL-4A encodes one of six mammalian cullins and is amplified and/or overexpressed in breast cancer, which suggests a role in regulating cell cycle progression. To examine CUL-4A's physiologic function, we generated a CUL-4A deletion mutation in mice. No viable CUL-4A(-/-) pups and no homozygous mutant embryos as early as 7.5 days postcoitum (dpc) were recovered. However, CUL-4A(-/-) blastocysts are viable, hatch, form an inner cell mass and trophectoderm, and implant (roughly 4.5 dpc), indicating that CUL-4A(-/-) embryos die between 4.5 and 7.5 dpc. Despite 87% similarity between the Cul-4A and Cul-4B cullins, the CUL-4A(-/-) lethal phenotype indicates that CUL-4A has one or more distinct function(s). Surprisingly, 44% fewer heterozygous pups were recovered than expected by Mendelian genetics, indicating that many heterozygous embryos also die during gestation due to haploinsufficiency. Taken together, our findings indicate that appropriate CUL-4A expression is critical for early embryonic development.


Sarcocystis infection in the white-tailed deer (Odocoileus virginianus) in Montana: intensity and description of Sarcocystis odoi n sp.
Sarcocystis infection was diagnosed in 27 of 36 (75%) samples of meat from white-tailed deer (Odocoileus virginianus) in Montana. Two structurally distinct thin- and thick-walled sarcocysts were found in the white-tailed deer; the thin-walled sarcocysts were those of S odocoileocanis. A new name, S odoi, was proposed for the thick-walled sarcocysts. Sarcocysts of S odoi were up to 1,050 microns long and 260 microns wide and contained a 6.5- to 12-microns thick wall. The ultrastructure of sarcocysts of S odocoileocanis was compared with that of S odoi. A cat fed meat containing thin- and thick-walled sarcocysts shed oocysts and sporocysts 24 days later. The sporocysts in the cat's feces were 13.3 X 9.6 microns and probably belonged to S odoi.


[The b chromosome polymorphism in Armenian and Turkey populations of the grasshopper Eyprepocnemis plorans plorans (Charpentier) (Orthoptera, Acrididae, Eyprepocnemidinae)].
Karyotype analysis of the grasshopper Eyprepocnemis plorans samples derived from Armenian and Turkey populations was performed using C-banding technique. Chromosome polymorphism was associated only with B chromosomes that were revealed in all studied populations. Six new B chromosome morphotypes were described. Four morphotypes were found only in Armenian populations. One morphotype was revealed only in Turkey populations. One B chromosome morphotype was present in Armenian and Turkey populations. B chromosomes derived from Asian populations consisted mostly from C-positive regions. In some of the B chromosomes small C-negative regions were also registered. Morphotypes of the B chromosomes derived from Armenian and Turkey populations drastically differed from the B chromosomes described in the Iberian Peninsula and North African populations. In contrast to the B chromosomes from Armenian and Turkey populations the B chromosomes from Spain populations contained C-positive and C-negative regions alternated in their arms.


Covid-19 pandemic and spillover effects in stock markets: A financial network approach.
This paper examines the impact of the COVID-19 pandemic on 51 major stock markets, both emerging and developed. We isolated the countries susceptible to shock transmissions, and evaluated countries with immunity, during the lockdown. Specifically, using dependence dynamics and network analysis on a bivariate basis, we identify volatility and contagion risk among stock markets during the COVID-19 pandemic. The empirical findings add to the existing body of literature, given that previous work has not placed emphasis on network topologic metrics when it comes to financial networks, specifically during the COVID-19. The evidence shows instant financial contagion a result of the lockdown and the spread of the novel coronavirus. The methodological framework outlines important information for investors and policymakers on using financial networks to improve portfolio selection, by placing an emphasis on assets according to centrality.


Gustatory thalamus lesions in the rat: II. Aversive and appetitive taste conditioning.
The learning capacities of rats with electrolytic lesions of the gustatory thalamus (GT) were investigated in 3 experiments. In Experiment 1, the presence of a taste cue failed to overshadow odor aversion learning in the lesioned rats, yet these same animals acquired normal taste and odor aversions. Thalamic lesions had no discernible effect on the acquisition of a conditioned flavor preference in Experiment 2. Finally, GT lesions completely reversed the anticipatory contrast effect shown by control subjects in Experiment 3. These results suggest that damage to the GT spares taste detection and recognition and simple associative learning but interferes with learning that involves more complex gustatory information processing.


Hemolytic uremic syndrome associated with clopidogrel: a case report.
Clopidogrel and ticlopidine are antiplatelet agents used in the treatment of patients with cerebrovascular and peripheral vascular disease and to reduce the risk for thrombosis in patients undergoing coronary artery stenting. Ticlopidine has been reported to have major hematologic adverse effects, including neutropenia and thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (HUS). Clopidogrel, an analogue of ticlopidine, was developed because it did not show bone marrow toxic effects in either tissue culture or animal models. In human studies, to date, clopidogrel has been associated with a low incidence of severe neutropenia and no reported cases of thrombotic thrombocytopenic purpura or HUS. For these reasons, clopidogrel has been increasingly used in place of ticlopidine after coronary artery stenting. We report a case of clopidogrel-associated HUS. This observation implicates clopidogrel as a possible causative agent in HUS.


The Ross operation: initial Israeli experience.
The need for aortic valve replacement in children and young adults poses a special problem to cardiologists and surgeons. Replacing the sick aortic valve with the patient's pulmonary valve as described by Ross has proven to be a good option in this special age group. To review our initial experience in order to assess the short-term results. From January 1996 to June 1999, 40 patients (age 8 months to 41 years) underwent aortic valve replacement with pulmonary autograft. Indications for surgery were congenital aortic valve disease in 30 patients, bacterial endocarditis in 5, rheumatic fever in 3, and complex left ventricular outflow tract obstruction in 3. Trans-esophageal echocardiography was performed preoperatively and post-bypass in all patients, and transthoracic echocardiography was done prior to discharge and on follow-up. There was no preoperative or late mortality. All patients remain in functional class I (New York Heart Association) and are free of complications and medication. None showed progression of autograft insufficiency or LVOT obstruction. Homograft insufficiency in the pulmonary position has progressed from mild to moderate in one patient, and three developed mild homograft stenosis. The Ross procedure can be performed with good results in the young population and is considered an elegant surgical alternative to prosthetic values and homografts.


Methodology for linking Ryan White HIV/AIDS Program Services Report (RSR) client level data over multiple years.
The Health Resources and Services Administration's (HRSA), HIV/AIDS Bureau (HAB) is responsible for leading the nation's efforts to provide health care, medications, and support services to low-income people living with HIV through the Ryan White HIV/AIDS Program (RWHAP). The RWHAP funds and coordinates with cities, states, and local community-based organizations to deliver efficient and effective HIV care, treatment, and support services for over half a million vulnerable people living with HIV (PLWH) and their families in the United States. The annual RWHAP Services Report (RSR) is an important source of information for monitoring RWHAP's progress towards National HIV/AIDS Strategy goals. Since 2010, HRSA HAB has used the annual client-level RSR data to monitor program-related outcomes, conduct program evaluations, understand service provision, and conduct extensive analysis on disparities in viral suppression and retention in HIV care. HRSA HAB receives annual RSR submissions from RWHAP recipients and sub-recipients. However, the de-identified nature of the data limits HRSA HAB's ability to expand beyond year-to-year analyses and conduct additional analyses to evaluate outcomes for clients who are seen in multiple years. The current paper describes the development and validation of a method to link RSR client-level records across multiple data years. Using seven RSR reporting years of data (2010 to 2016), we applied a Fellegi-Sunter (F-S) linkage model that used client demographic characteristics and their providers' geographic locations to calculate matching weights for each record pair based on estimated agreement and disagreement conditional probabilities across RSR years. To validate our methodology, we conducted an internal sample review and external validation to assess the level of accuracy of the linkage, and the extent to which the linked data set corresponds accurately to clinical records of individual clients. The linkage result yielded 70 to 80 percent year-to-year client carry-over rate over seven years of the RSR data; 96 percent linkage ratio from the internal sample review and 79.9 to 94.2 percent of provider network client carry- over rate per year from the external validation. This methodology addresses a gap in data analysis capabilities by allowing HRSA HAB to link RWHAP clients across reporting years. Despite weak identifying information and lack of continuity of service reporting, the longitudinal linkage improves HRSA HAB's ability to evaluate the patterns of viral suppression and monitor service utilization over time for individuals who receive services in multiple years. These analyses will support future analytic activities in understanding the impact and outcomes of the RWHAP, and will assist HRSA HAB in monitoring progress toward meeting National HIV/AIDS Strategy goals. For those looking for ways to assess health services data, the F-S unsupervised method combining weak identifying attributes and geographic proximity offers practical solutions to the problem of linking de-identified information about individuals across multiple years and improving longitudinal research.


Antifibrogenic Influence of Mentha piperita L. Essential Oil against CCl4-Induced Liver Fibrosis in Rats.
Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-β1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.


Semi-parametric estimates of population accuracy and bias of predictions of breeding values and future phenotypes using the LR method.
Cross-validation tools are used increasingly to validate and compare genetic evaluation methods but analytical properties of cross-validation methods are rarely described. There is also a lack of cross-validation tools for complex problems such as prediction of indirect effects (e.g. maternal effects) or for breeding schemes with small progeny group sizes. We derive the expected value of several quadratic forms by comparing genetic evaluations including "partial" and "whole" data. We propose statistics that compare genetic evaluations including "partial" and "whole" data based on differences in means, covariance, and correlation, and term the use of these statistics "method LR" (from linear regression). Contrary to common belief, the regression of true on estimated breeding values is (on expectation) lower than 1 for small or related validation sets, due to family structures. For validation sets that are sufficiently large, we show that these statistics yield estimators of bias, slope or dispersion, and population accuracy for estimated breeding values. Similar results hold for prediction of future phenotypes although we show that estimates of bias, slope or dispersion using prediction of future phenotypes are sensitive to incorrect heritabilities or precorrection for fixed effects. We present an example for a set of 2111 Brahman beef cattle for which, in repeated partitioning of the data into training and validation sets, there is very good agreement of statistics of method LR with prediction of future phenotypes. Analytical properties of cross-validation measures are presented. We present a new method named LR for cross-validation that is automatic, easy to use, and which yields the quantities of interest. The method compares predictions based on partial and whole data, which results in estimates of accuracy and biases. Prediction of observed records may yield biased results due to precorrection or use of incorrect heritabilities.


Melatonin: A hypothesis for Kawasaki disease treatment.
Kawasaki disease (KD) is the most common cause of acquired heart disease with unknown etiology among children in developed countries. Acute inflammation of the vasculature, genetic susceptibility and immunopathogenesis based on a transmittable and infectious origin, are the pathologic events involved in the early inflammatory etiology and progression of this disease. However, the exact causes of KD remain unknown. Current proposed recommendations include three therapy lines; firstly, an initial standard therapy with intravenous immunoglobulin (IVIG) followed by aspirin. Secondly, in cases of high risk of coronary lesions, the adjunctive therapy with corticosteroid is commonly considered. Thirdly, in KD patients refractory to the previous therapies, tumor necrosis factor (TNF-α) antagonists are being used to modulate pro-inflammatory cytokines. In view of this status quo, our starting hypothesis is that the ubiquitous and non-toxic neurohormone melatonin could be of critical importance in developing novel adjuvant therapies against KD, as it occurs with a plethora of other diseases. Considering its pleiotropic properties, particularly its antiinflammatory and immunoregulatory capacities, melatonin should be of great therapeutic interest for helping to control the main pathologic features of KD patients. In addition, this multifunctional indole has a safe pharmacological profile, enhancing the therapeutic activity of several drugs and reducing their possible side effects. Consequently, melatonińs actions to manage KD need to be tested in further clinical studies.


Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants.
The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospective double-blind randomized controlled trial among "high risk" infants with family history of atopy among first-degree relatives. The incidence of atopic eczema, wheezing, rhinitis, gastrointestinal symptoms, and colic was noted and serum IgE antibodies to milk were estimated. Seventy-two infants were recruited into each of the following groups: cow milk whey hydrolysate formula (NAN/HA), conventional cow milk formula (Similac), soy-based formula (Isomil), and exclusive breast feeding for greater than or equal to 4 months. The number of infants who exited for reasons other than atopy and were excluded from analysis were 4, 5, 4, and 12 in the four groups, respectively. The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA, 24 of 67 infants fed Similac, 25 of 68 infants fed Isomil, and 12 of 60 breast-fed infants. Among symptomatic infants, skin prick test to milk proteins was positive in four out of five infants fed NAN/HA, 16 of 24 fed Similac, 2 of 25 fed Isomil, and 7 of 12 breast-fed. IgE antibodies to milk were found in 2 of 68, 9 of 67, 0 of 68, and 6 of 60 infants in the four groups, respectively. It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants.(ABSTRACT TRUNCATED AT 250 WORDS)


Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner.
Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR(-/-)). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner.


Understanding the dynamics of information technology implementation: a study of clinical information systems.
Health care institutions are considering a variety of emerging information technologies (ITs) in the hope of increasing efficiency, reducing costs, re-engineering work processes, and improving quality of care. The recent, rapid advances made in the use of innovative ITs in the health care field can present a plethora of problems to the administrative staff. Perhaps the most pressing of these concerns is the ability of today's hospitals to effectively create and utilize computer-based information systems. IT implementation has long been of great interest for information systems researchers. This branch of information system study seeks to identify those factors that are integral to optimizing the usage of IT. For example, researchers have advised practitioners that managerial support, high quality system design, commitment to advancing with the field, and extensive project planning are all key elements of successful system. In sum, previous research has produced a set of managerial proscriptions which, taken as a whole, constitute the "ideal" way to implement an IT system. Yet despite these normative principles and proscriptions, many health care institutions continue to find their attempts to make use of IT fraught with difficulty. Therefore, the objective of this study is to broaden and edify our understanding of IT implementation. More specifically, we seek to dispel the myth of the "ideal" system setup by exploring some of the alternative systems in use. We wish to investigate how and why the components of these alternative systems interact to produce utilization success (or failure). The study investigates the establishment and subsequent use of three clinical information systems (CIS) in a large tertiary care teaching hospital. The first case study is that of the hospital-wide implementation of a computer system that allows physicians to sign their medical records electronically. The second case examines the use of an electronic patient chart used to support the work of a variety of clinicians. Finally, we study a nursing assessment system used by two groups of nurses (intensive care unit and resuscitation unit) at a state-of-the-art, newly established Trauma Center. Qualitative was gathered through semi-structured interviews with people involved in the implementation process as well as a sample of user representatives. More than 90 interviews were conducted over a period of six months. Observational data completed our qualitative assessment. Quantitative evidence was gathered through questionnaires administered to a small sample of key informants. Three techniques of qualitative data analysis are being used in combination, namely, coding, analytical memos and displays. Data analysis is still in its infancy at this point. Regarding its relevance to the role of the administrator, this study will allow general and health care management as well as IT professionals to gain insight into the dynamics of the implementation of innovative technologies. In other words, results from this study will provide clear and relevant answers to the questions of how and why the outcome of the information system project is influenced by the way in which the technology is introduced.


Little evidence for late-onset ADHD in a longitudinal sample of women.
Individuals with late-onset symptoms of attention-deficit/hyperactivity disorder (ADHD) are presenting to providers at increasing rates. Recent birth-cohort studies reveal evidence for late-onset ADHD, but conclusions are challenged by measurement methods as well as presence of participant impairment and psychiatric comorbidities. We examined the occurrence of late-onset ADHD in a small but thoroughly investigated group of diverse (47% white) women followed from childhood to adulthood. From a larger, 16-year longitudinal study, a subsample of young women without childhood ADHD (N = 87) was assessed at four time points between childhood and adulthood via a multimethod, multiinformant approach. We used a stepped diagnostic procedure to identify those who initially met symptom criteria for ADHD after childhood and then evaluated them for remaining DSM ADHD diagnostic criteria, including impairment, cross-situational symptoms, and comorbid diagnoses. Of 87 participants, 17 met ADHD symptom criteria after childhood. Fifteen showed no evidence of childhood onset, 10 showed clear evidence of impairment, and nine had cross-situational symptoms. Of these nine, all but one showed clinically significant co-occurring or preexisting psychiatric diagnoses and/or substance use that might account for ADHD symptoms. Although 19.5% of women from our subsample without childhood ADHD met symptom criteria for ADHD during adolescence/adulthood, only one showed the needed combination of impairment and cross-situational symptoms without significant co-occurring mental health problems. It is possible that uncomplicated cases of adult ADHD do arise, yet we find little supporting evidence herein. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Inferring Cell Subtypes and LncRNA Function by a Cell-Specific CeRNA Network in Breast Cancer.
Single-cell RNA sequencing is a powerful tool to explore the heterogeneity of breast cancer. The identification of the cell subtype that responds to estrogen has profound significance in breast cancer research and treatment. The transcriptional regulation of estrogen is an intricate network involving crosstalk between protein-coding and non-coding RNAs, which is still largely unknown, particularly at the single cell level. Therefore, we proposed a novel strategy to specify cell subtypes based on a cell-specific ceRNA network (CCN). The CCN was constructed by integrating a cell-specific RNA-RNA co-expression network (RCN) with an existing ceRNA network. The cell-specific RCN was built based on single cell expression profiles with predefined reference cells. Heterogeneous cell subtypes were inferred by enriching RNAs in CCN to the estrogen response hallmark. Edge biomarkers were identified in the early estrogen response subtype. Topological analysis revealed that NEAT1 was a hub lncRNA for the early response subtype, and its ceRNAs could predict patient survival. Another hub lncRNA, DLEU2, could potentially be involved in GPCR signaling, based on CCN. The CCN method that we proposed here facilitates the inference of cell subtypes from a network perspective and explores the function of hub lncRNAs, which are promising targets for RNA-based therapeutics.


Parathyroid hormone-related protein-stanniocalcin antagonism in regulation of bicarbonate secretion and calcium precipitation in a marine fish intestine.
Bicarbonate secretion in the intestine (duodenum) of marine fish has been suggested to play a major role in regulation of calcium availability for uptake. However, while the end process may lead to carbonate precipitation, regulation of transport of calcium and/or bicarbonate may actually result in fine-tuning of calcium availability for transport. To test this hypothesis, sea bream (Sparus auratus) duodenal preparations were mounted in Ussing-type chambers and the effect of parathyroid hormone-related protein (PTHrP) and stanniocalcin 1 (STC 1) on the control of intestinal bicarbonate secretion and calcium transport was analyzed. As expected, PTHrP increased net calcium uptake, as a result of an increase of calcium uptake without changes in calcium efflux. In contrast, purified sea bream STC 1 caused a minor decrease of calcium uptake and a two- to threefold increase in calcium efflux. As a result, STC 1 was able to invert the calcium flux from net calcium uptake to net calcium loss, which is in keeping with its known actions as a hypocalcemic factor. Furthermore, both PTHrP and STC 1 regulate intestinal bicarbonate secretion. PTHrP increased calcium uptake and simultaneously reduced the single factor that induces calcium precipitation, bicarbonate secretion. In contrast, STC 1, while reversing the calcium net flux to make it secretory, promoted intestinal bicarbonate secretion, both actions directed to decrease the calcium gradient across the epithelium and promote immobilization in the form of bicarbonate in the intestinal lumen. Together our results provide robust evidence to support an antagonistic action of PTHrP and STC 1 in the fine control of movements of both calcium and bicarbonate in the intestine of seawater fish.


Factors influencing hydroquinone degradation in aqueous solution using a modified microelectrolysis method.
The discharge of hydroquinone (HQ), an important chemical raw material, to natural waters poses different ecological threats to aquatic organisms. In this study, we investigated the removal performance of traditional and modified microelectrolysis methods in aqueous solutions. The traditional microelectrolysis packing was modified by adding manganese (Mn), zinc (Zn), and copper (Cu) powder as additives. The factors affecting the removal performance of HQ, such as catalytic metal type, mass fraction of additive, reaction time, and initial pH, were examined. The results showed that the Mn modified packing exhibited the best performance compared to Zn and Cu powder. The removal rate of HQ using Mn modified packing can reach 94% after 4 h. In addition, 9% of Mn packing has a higher removal rate than other mass fractions. The acidic solution pH shows a more favorable degradation than a neutral and alkaline solution. The intermediates of HQ degradation by modified microelectrolysis were identified and then the pathway of HQ degradation was proposed. Our result indicates that Mn as catalytic metal holds promising potential to enhance HQ removal in water using the microelectrolysis method.


Multidisciplinary approach to enhancing provider well-being in a metropolitan medical group in the United States.
Physician burnout refers to depersonalization, emotional exhaustion, and a sense of lower personal accomplishment. Affecting approximately 50% of physicians in the United States, physician burnout negatively impacts both the physician and patient. Over a 3-year-period, this prospective study evaluated the multidisciplinary approach to decreasing provider burnout and improving provider well-being in our metropolitan community. A multidisciplinary Well-Being Task Force was established at our Institution in 2017 to assess the myriad factors that may play a role in provider burnout and offer solutions to mitigate the stressors that may lead to decreased provider well-being. Four multifaceted strategies were implemented: (1) provider engagement & growth; (2) workflow/office efficiencies; (3) relationship building; and (4) communication. Providers at our Institution took the Mayo Clinic's well-being index survey on 3 occasions over 3 years. Their scores were compared to those of providers nationally at baseline and at 1 and 2 years after implementing organizational and individualized techniques to enhance provider well-being. Lower well-being index scores reflected better well-being. The average overall well-being index scores of our Institution's providers decreased from 1.76 at baseline to 1.32 2 years later compared to an increase in well-being index scores of physicians nationally (1.73 to 1.85). Both male and female providers' average well-being index scores at our Institution decreased over the 3 years of this study, from 1.72 to 1.58 for males and 1.78 to 1.21 for females, while physicians' scores nationally increased for both genders. The average well-being index scores were highest for providers at our Institution who graduated from medical school less than 5 years earlier (2.0) and who graduated 15-24 years earlier (2.3), whereas the average lowest scores were observed in providers who graduated ≥25 years earlier (1.37). Obstetricians/gynecologists and internal medicine physicians had the highest average well-being index scores (2.48 and 2.4, respectively) compared to other medical specialties. The turnover rate of our Institution's providers was 5.6% in 2017 and 3.9% in 2019, reflecting a 30% decrease. This study serves as a model to reduce provider burnout and enhance well-being through both organizational and individual interventions.


Does physiological hyperarousal enhance error rates among insomnia sufferers?
To examine the association between physiological hyperarousal and response accuracy on reaction time tasks among individuals with insomnia. This study was conducted at affiliated Veterans Administration (VA) and academic medical centers using a matched-group, cross-sectional research design. Eighty-nine individuals (48 women) with primary insomnia, PI (MAge = 49.8 ± 17.2 y) and 95 individuals (48 women) who were well-screened normal sleepers, NS (MAge = 46.9 ± 17.0 y). Participants underwent 3 nights of polysomnography followed by daytime testing with a four-trial Multiple Sleep Latency Test (MSLT). Before each MSLT nap, they rated their sleepiness and completed computer-administered reaction time tasks. The mean number of correct and error responses made by each participant across testing trials served as dependent measures. The PI and NS groups were each subdivided into alert (e.g., MSLT mean onset latency > 8 min) and sleepy (e.g., MSLT mean onset latency ≤ 8 min) subgroups to allow for testing the main and interaction effects of participant type and level of alertness. Alert participants had longer MSLT latencies than sleepy participants (12.7 versus 5.4 min), yet both alert and sleepy individuals with PI reported greater sleepiness than NS. Alert participants also showed lower sleep efficiencies (83.5% versus 86.2%, P = 0.03), suggesting 24-h physiological hyperarousal particularly in the PI group. Individuals with PI had fewer correct responses on performance testing than did NS, whereas a significant group × alertness interaction (P = 0.0013) showed greater error rates among alert individuals with PI (mean = 4.5 ± 3.6 errors per trial) than among alert NS (mean = 2.6 ± 1.9 errors per trial). Physiological hyperarousal in insomnia may lead to more apparent daytime alertness yet dispose individuals with insomnia to higher error rates on tasks requiring their attention.


Prescribing. Keys to maximizing benefit while avoiding adverse drug effects.
When prescribing for older patients, some physicians are overly cautious, and this strategy can result in a less than optimal treatment outcome. The reluctance to treat aggressively is understandable because the geriatric population is susceptible to adverse drug reactions. The key to maximizing therapy lies in individualizing it as much as possible. There are a number of steps physicians can take to ensure that their patients are not being undertreated. These steps include regular reevaluations of dosages and plasma drug concentrations, recognition and understanding of drug side effects, and avoidance of certain agents. Close monitoring allows physicians to minimize risks, maximize benefits, and get the most out of what modern medications can do to help older patients.


Canadian adolescent mothers' perceptions of influences on breastfeeding decisions: a qualitative descriptive study.
There is increased recognition of the importance of breastfeeding at a national level as evidenced by the increased number of Canadian mothers initiating breastfeeding. However, adolescent mothers (<19 years), compared to all other mothers, have lower rates of breastfeeding initiation and duration. The purpose of this study was to examine the facilitating influences and barriers to initiating, and continuing breastfeeding, as perceived by adolescent mothers in Durham Region, Ontario, Canada. The principles of interpretive description guided this qualitative study. A purposeful, homogenous sample of 16 adolescent mothers (15-19 years) were recruited to complete individual, semi-structured, face-to-face interviews. Conventional content analysis was used to code data, identify concepts and synthesize them into overall themes. Adolescent mothers in this study expressed that the decision to breastfeed was made prenatally and while partner and family member opinions about breastfeeding initiation were influential, the decision was made independently. Mothers were primarily motivated to initiate breastfeeding due to the health benefits for the infant. Lower breastfeeding duration rates were found among mothers who decided to only "try" breastfeeding when compared to the mothers who committed to breastfeeding. Influences on continued breastfeeding included: 1) the impact of breastfeeding on social and intimate relationships; 2) the availability of social support; 3) the physical demands of breastfeeding; 4) mothers' knowledge of breastfeeding practices and benefits; and 5) mothers' perceived sense of comfort in breastfeeding. The results of this study provide health care providers new conceptual insight and understanding of the factors that influence adolescents' decisions to "try" breastfeeding and to continue providing breastmilk to their infants. Professional implications drawn from this study include active engagement of adolescents in the pre and postnatal periods, including early assessment of potential barriers surrounding breastfeeding decisions. This early professional interaction highlights the professional as a form of support, and allows for sharing of evidence-informed breastfeeding information and practical breastfeeding skills. Inclusion of adolescents' positive social support networks should be emphasized in professional breastfeeding support. Motivational interviewing is a promising prenatal strategy to influence behavior change and reduce ambivalence in decision-making about breastfeeding, creating opportunities for health care providers to tailor interventions.


Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.
In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity.


On the relation between ocular torsion and visual perception of line orientation.
A recent study by Poljac et al. [Poljac, E., Lankheet, M. J. M., & van den Berg, A. (2005). Perceptual compensation for eye torsion. Vision Research, 45(4), 485-496] concluded that there was complete perceptual compensation for ocular torsion, although they did not directly measure ocular torsion. Using a similar eccentric-gaze paradigm to induce changes in torsion, which were directly measured, we found inconsistent torsional eye movements at eccentric fixation, and also failed to detect a significant relationship between ocular torsion and the perception of line orientation. We then used a stimulus known to induce large changes in ocular torsion: on-centre yaw rotation. This stimulus induced a consistent change in the torsional position of the eye which positively correlated to subjects' visual perception of horizontal.


Outcomes from an outpatient smoking-cessation clinic.
To determine the success of an outpatient smoking-cessation clinic by assessing smoking abstinence rates and factors associated with lower abstinence rates. We also sought to determine whether smoking abstinence rates differed among various smoking-cessation products. Patients were referred by primary care providers to a pharmacist-managed smoking-cessation clinic. Patients received tailored behavioral counseling, educational materials, and drug therapy consisting of sustained-release (SR) bupropion; nicotine patch, inhaler, or nasal spray; or combination therapy. Patients were monitored by phone or clinic visit for 6 months, if possible. Outcomes assessed were abstinence (both point prevalence and continuous abstinence) and adverse effects. Patients lost to follow-up were assumed to be smoking. Over 2 years, 198 patients were enrolled in the program. At the initial visit, 35.4% received the patch, 32.8% bupropion SR, 18.2% a combination of patch plus inhaler, 9.6% inhaler alone, and fewer than 5% other therapies. At 6 weeks, a statistically significant difference was observed in continuous abstinence rates between the nicotine patch versus bupropion SR groups (22.9% vs 7.7%, p=0.02) and between the combination patch-inhaler versus bupropion SR groups (25% vs 7.7%, p=0.02). However, this difference was not significant beyond the 6-week visit. A trend toward higher abstinence rates was noted at 6 weeks in the nicotine patch-inhaler versus the other treatment groups, possibly suggesting the need for more intense treatment regimens with combination therapy. Point prevalence abstinence rates after 12 weeks were 18.6%, 15.4%, 22.2% and 21.1% respectively, for the patch, bupropion SR, patchinhaler, and inhaler alone treatment groups. The corresponding continuous abstinence rates were 10.0%, 3.1%, 11.1%, and 10.5%. Although statistically significant differences between products were noted at 6 weeks, no sustained difference in smoking abstinence rates was observed between products. At 6 months, point prevalence and continuous abstinence rates were small, but the decline in success noted over time and the limited overall success rates are consistent with rates for the United States. Our findings suggest that when smokers are assisted in quitting, initial contact as well as follow-up evaluation and monitoring must be intense and sustained to increase the likelihood of successful abstinence. Tobacco dependence is clearly a chronic condition warranting repeated treatment and monitoring until continuous abstinence is achieved.


Revival of Krebs-Ringer balanced salt solution for the investigation of polymorphonuclear leukocytes and Pseudomonas aeruginosa biofilm interaction.
To study the interaction between aggregating bacteria and polymorphonuclear leukocytes (PMNs) in vitro, the chosen medium must favor both the isolated PMNs and the bacteria. To investigate the best-suited medium for the in vitro survival of isolated unactivated human PMNs, we compared three different mammalian cell media: Krebs-Ringer balanced salt solution (BSS), Hanks' BSS (HBSS) and Roswell Park Memorial Institute (RPMI) 1640. The death of PMNs was estimated by the release of lactate dehydrogenase activity. Furthermore, two types of serum, human (HS) and fetal bovine (FBS), were compared at different concentrations (0%, 2%, 5%, 10%) and at three different time points (2, 4, 20 h). We show that Krebs-Ringer BSS prolonged the survival of PMNs compared to HBSS and RPMI 1640 and that the addition of 10% FBS significantly enhanced the long-term survival (20 h) compared to HS. Furthermore, we observed aggregation of Pseudomonas aeruginosa when grown in the presence of either a mixture of histones, histone H3, arginine or lysine. In this study, we show that the use of Krebs-Ringer BSS is highly relevant for the study of the interaction of bacteria and PMNs in relation to novel treatment strategies of biofilm infections due to the reproduction of bacterial aggregation as seen in chronic bacterial infections.


Human Escherichia coli strains of different geographical and time source: bacteriocin types and their gene sequences are population-specific.
Bacteriocin production was tested in two sets of Escherichia coli strains: one isolated in 1978 from healthy children of rubber tree tappers and Indians in Amazonia, Brazil (n = 35), and the second one isolated in 2004 from healthy adult volunteers in the Moravia region, Czech Republic (n = 53). Although the occurrence of bacteriocin production was rather similar in both groups (54.3% and 43.4% respectively), the spectra of bacteriocin-encoding determinants in both groups were different. Altogether, 12 different bacteriocin-encoding determinants were found among the tested strains. The occurrence of colicin E1- and Y-genes was higher (P = 0.02 and P = 0.009 respectively) while the occurrence of microcin V gene was lower (P = 0.02) among Amazonian strains compared with Moravian strains. The colicin-encoding determinants of colicins Ia, M, Y and E1 were amplified from Amazonian and Moravian producer strains and sequenced, as were chromosomal 16S rRNA, gyrB and tonB genes. While sequence alignments of chromosomal loci revealed no clusters with respect to geographical origin of strains, the colicin-encoding genes were very similar among the strains of each origin but different between the two geographic groups.


F-waves--physiology and clinical uses.
F-waves are low amplitude responses produced by antidromic activation of motoneurons. They may not appear after each stimulus and are inherently variable in latency, amplitude, and configuration. Meaningful analysis of F-waves requires an appreciation of these characteristics of F-waves as well as an understanding of their physiology. These features of F-waves as well as their physiology are reviewed. This is important since F-waves are one of the most frequently used studies in clinical neurophysiology and much of the controversies surrounding the use of F-waves relates to a failure to adequately consider the requirements of F-wave analysis. These requirements include the number of F-waves that need to be recorded, the parameters that should be evaluated, and the muscle from which the F-waves are recorded. If analyzed correctly, current reports would indicate that F-waves are the most sensitive and reliable nerve conduction study for evaluating polyneuropathies, can be abnormal in focal proximal nerve dysfunction, can be at least as sensitive as needle electromyography for defining lumbosacral radiculopathies, and can provide a meaningful physiological window into disorders of the central nervous system. Reports supporting these statements and their clinical relevance are discussed.


Clinical efficacy of two forms of intravenous iron--saccharated ferric oxide and cideferron--for iron deficiency anemia.
Over 90% of iron deficiency anemia cases are due to iron deficiency associated with depletion of stored iron or inadequate intake. Parenteral iron supplementation is an important part of the management of anemia, and some kinds of intravenous iron are used. However, few studies have evaluated the clinical efficacy of these drugs. The purpose of this study was to compare and assess the clinical efficacy of two types of intravenous iron injection, saccharated ferric oxide (SFO) and cideferron (CF). Medical records were obtained for 91 unrelated Japanese anemia patients treated with SFO (n = 37) or CF (n = 54) from May 2005 to May 2010 at Gunma University Hospital. Patients treated with blood transfusion, erythropoietin or oral iron were excluded. Hemoglobin (Hb) values measured on day 0, 7 and 14 were used to assess the efficacy of intravenous irons. A significant increase was observed in the mean Hb value by day 14 of administration in both the CF group and SFO group, and the mean Hb increase due to administration of CF for 7 days was comparable to that of SFO for 14 days. Age and sex did not affect improvement of Hb value. CF is fast acting and highly effective compared with SFO for the treatment of iron deficiency anemia. The use of CF may shorten a therapeutic period for iron deficiency anemia, and CF may be feasible for reducing the hospitalization period.


Trauma and personality correlates in long-term pediatric cancer survivors.
To explore the relationship between PTSD and trauma-spectrum symptoms, including personality and functional correlates, in long term pediatric cancer survivors (N = 40), we assessed these constructs with a structured interview for PTSD, a clinical interview, and self-report questionnaires. Thirty-five out of 40 participants (88%) currently met at least one trauma symptom at a functionally significant level. These survivors demonstrate high levels of restraint and low levels of distress, representative of a repressive adaptive style. After more than 5 years since treatment completion, the relatively high levels of current trauma-spectrum symptoms may reflect the long-term deleterious impact of childhood cancer.


The amide rotational barrier in isonicotinamide: Dynamic NMR and ab initio studies.
We report use of dynamic nuclear magnetic resonance (NMR) to measure the amide rotational barrier in isonicotinamide. A significant challenge to obtaining good transition rates from dynamic NMR data is suppression of errors due to inherent line widths associated with transverse relaxation. We address this challenge with a fitting procedure that incorporates transverse relaxation over the temperature range of interest simply and reliably. The fitting model is nonlinear in only one of the fit parameters, namely, the activation enthalpy. This reduces parameter estimation to solution of a single transcendental equation, which avoids both a fine search over a multidimensional parameter space and extrapolation of a "limiting line width" solely from slow-exchange data. The activation enthalpy Delta H++ measured for isonicotinamide, +14.1 +/- 0.2 kcal/mol, falls between those of its regioisomers picolinamide and nicotinamide, which were reported in an earlier study. In that study, ab initio calculations of the rotational barriers helped to discern the relative importance of steric, electronic, and hydrogen-bonding effects in this biochemically significant combination of pyridine-ring and carboxamide moieties. A direct comparison between isonicotinamide and nicotinamide, where steric and hydrogen-bonding effects differ only slightly, permits a closer study of electronic considerations.


In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens.
The pleuromutilin antibiotic lefamulin demonstrated in vitro activity against the most relevant bacterial pathogens causing sexually transmitted infections (STI), including Chlamydia trachomatis (MIC50/90, 0.02/0.04 mg/liter; n = 15), susceptible and multidrug-resistant Mycoplasma genitalium (MIC range, 0.002 to 0.063 mg/liter; n = 6), and susceptible and resistant Neisseria gonorrhoeae (MIC50/90, 0.12/0.5 mg/liter; n = 25). The results suggest that lefamulin could be a promising first-line antibiotic for the treatment of STI, particularly in populations with high rates of resistance to standard-of-care antibiotics.