Tunable ternary (N, P, B)-doped porous nanocarbons and their catalytic properties for oxygen reduction reaction.
Heteroatom (N, P, and B)-codoped nanocarbons (NPBC) with nanoporous morphology are fabricated via a facile one-step pyrolysis method and exhibit good electrocatalytic activity, durability, and selectivity for the oxygen reduction reaction (ORR) in alkaline media. The ORR activity of NPBC is better than single- (nitrogen-doped carbon (NC)) or dual-doped (nitrogen and phosphorus codoped carbon (NPC) or nitrogen and boron codoped carbon (NBC)) catalysts in terms of onset potential and current density. This synthetic approach is efficient and suitable for large-scale fabrication of metal-free carbon-based catalysts.


The existence of a sticking region in free weight squats.
The aim of this study was to investigate the existence of the sticking region in two legged free weight squats. Fifteen resistance-training males (age 24 ± 4 years, body mass 82 ± 11 kg, body height 179 ± 6 cm) with 6 ± 3 years of resistance-training experience performed 6-RM in free weight squats. The last repetition was analyzed for the existence of a sticking region. Only in 10 out of 15 participants a sticking region was observed. The observed sticking region was much shorter than in the bench press. Furthermore, rectus femoris decreased the EMG activity in contrast to increased EMG activity in biceps femoris around the sticking and surrounding region. No significant change in EMG activity was found for the lateral and medial vastus muscles. It is suggested that a combination of these muscle activity changes could be one of the causes of the existence of the sticking region in free weight squats.


Water and biofilm in drinking water distribution systems in the Netherlands.
To keep the high quality of drinking water in the future for non-chlorinated drinking water systems, knowledge about the variables that most strongly affect this quality is necessary in order to know where to focus on and possibly even change aspects of drinking water production and distribution. Therefore, the aim of this study was to investigate which variables (source of drinking water, growth potential and pipe material type) have the biggest influence on bacterial community composition and biomass concentration of drinking water and biofilm in distribution systems. Ten different distribution systems were sampled for water and biofilm, obtained from four different pipe materials, throughout the Netherlands. The distribution systems are supplied either with drinking water produced from groundwater or surface water, and differ in drinking water quality parameters such as the growth potential. We found a significant relationship for growth potential and ATP concentration in water, but for the ATP in the biofilm none of the parameters showed a significant effect. Furthermore, the source of the drinking water and the pipe material did not significantly affect the ATP concentration in water and biofilm. The bacterial composition of in both water and biofilm was significantly different between distribution systems delivering water with low and high growth potential and between drinking water produced from groundwater or surface water. In contrast, the different pipe materials did not significantly affect composition of biofilm-associated communities. We conclude from these results that the growth potential of the treated water best explains the variation in biomass and bacterial composition in water and biofilm of non-chlorinated drinking water distribution systems followed by the drinking water source, whereas pipe materials seem to be of lesser importance.


S-adenosylhomocysteinase: mechanism of reversible and irreversible inactivation by ATP, cAMP, and 2'-deoxyadenosine.
Homogeneous S-adenosylhomocysteinase (AdoHcyase) from rat liver is a tetrameric enzyme that contains four molecules of tightly bound NAD per mole of enzyme. We report here that incubation of the rat liver enzyme with ATP, Mg2+, and KCl leads to conversion of the active enzyme to an inactive form with release of all enzyme-bound NAD which can be recovered quantitatively by gel filtration. At various concentrations of ATP, the release of NAD corresponds closely with the degree of inactivation, suggesting that the four subunits are equivalent. Hydrolysis of ATP is not required for the inactivation process since nonhydrolyzable ATP analogues can replace ATP in the inactivation process. The ATP-dependent inactivation is fully reversible upon incubation of the inactivated enzyme with NAD. The ATP-dependent inactivation of the enzyme appears to be analogues to the cAMP-dependent inactivation of the enzyme from Dictyostelium discoideum described earlier by Hohman et al. (1985) [Hohman, R. J., Guitton, M. C., & Veron, M. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 4578-4581; Hohman, R. J., Veron, M., & Guitton, M. C. (1985) Curr. Top. Cell. Regul. 26, 233-245] but differs from the irreversible inactivation studied earlier by Abeles et al. (1982) [Abeles, R. H., Fish, S., & Lapinskas, B. (1982) Biochemistry 21, 5557-5562]. These authors have ascribed the time-dependent inactivation that results from incubation of the enzyme with 2'-deoxyadenosine at the C-3' and concluded that AdoHcyase "probably consists of two nonequivalent pairs of subunits".(ABSTRACT TRUNCATED AT 250 WORDS)


Intracranial germinoma in the lateral ventricle with polydipsia and polyuria: a case report and literature review.
Central nervous system germ cell tumors (CNSGCTs) are rare neoplasms which usually develop in the midline structures. They are occasionally involved in off-midline structures of the brain. Here, we report an extremely rare case of an intracranial germinoma in the lateral ventricle. The patient was a 10-year-old boy with a 1-year history of polydipsia and polyuria. Brain magnetic resonance imaging (MRI) showed a relatively homogeneously enhancing lesion in the lateral ventricle, and the posterior pituitary gland was not hyperintense on T1-weighted imaging. Subependymoma was suspected, and tumor removal operation was performed; however, because the intraoperative pathological investigation revealed germinoma, we could only perform partial removal of the tumor. Postoperative histology also confirmed germinoma. Then, the patient received chemotherapy, followed by radiation therapy. MRI showed no recurrence for 6 years after treatment. Intracranial germinoma in the lateral ventricle is extremely rare. The diagnosis is occasionally challenging, especially when the tumors are located in atypical locations. This paper presents a literature review of previously described CNSGCTs of the lateral ventricle to improve awareness of CNSGCTs in atypical locations. We also consider the relationship between imaging findings and clinical manifestations.


Comparison of pregnancy in cattle when non-vitrified and vitrified in vitro-derived embryos are transferred into recipients.
The present study was conducted in cattle to test the null hypothesis that the pregnancy rate of recipient females is similar when in vitro-derived embryos are transferred either fresh (non-vitrified) or after being subjected to vitrification. Cumulus-oocyte complexes, collected twice (6 weeks apart) from 10 donor cows were matured in vitro and inseminated with frozen-thawed sperm from a single proven bull per donor collection. Cleaved embryos were cultured in vitro until day 7 and any resulting blastocysts were graded for stage [early (unexpanded), advanced (expanded, hatching, hatched)] and/or quality and either discarded (poor quality), or, if deemed suitable, transferred fresh or vitrified for later warming and transfer. All blastocysts were transferred singly to oestrus-synchronized cows and pregnancy monitored by transrectal palpation on days 35, 60 and 90. From 20 collections, 818 cumulus-oocyte complexes were aspirated; however, after grading, only 462 (56.5%) were ranked as suitable quality for maturation and insemination. From those 462 complexes inseminated, 363 (78.6%) cleaved during the process and 243 (52.6%) developed to the blastocyst stage with 194 (42.0%) deemed utilizable, of which 85 were vitrified and 109 were transferred fresh. There was a median of 13 (range 0-24) utilizable blastocysts per cow. Of the 109 non-vitrified blastocysts transferred, there were 45 (41.3%) and 41 (37.6%) recipients that were detected to be pregnant on day 35 and day 90, respectively, subsequent to transfer. Thus, an 8.9% abortion rate was observed (4/45). Of the 85 transferred vitrified-warmed blastocysts, 34 were detected to be pregnant (40.0%) on day 35 following transfer, and all pregnancies were maintained at day 90 (0% abortion rate), which was similar to non-vitrified transfers (P > 0.05, Chi-square test). There was no significant difference in pregnancy rate on day 90 in advanced compared to early blastocysts for either the non-vitrified transfers (9/23, 39.1% vs 33/86, 38.3%) or the vitrified transfers (30/72, 41.6% vs 4/13, 30.8%) (P > 0.05 in each case). In summary, these data show that vitrification of in vitro-derived early and advanced blastocysts is a suitable method of cryopreservation of bovine embryos, and, furthermore, that subsequent transfer of all vitrified/warmed blastocysts into recipient females results in pregnancy rates no different to those attained by non-vitrified transfers into recipient females.


Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.
We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic-pituitary-thyroid axis.


Evaluation of muscle force prediction models of the lumbar trunk using surface electromyography.
Optimization-based models for prediction of muscle forces in the lumbar region of the torso are used to estimate the forces acting on spinal motion segments, especially for asymmetric tasks. The objectives of this study were to determine (a) which of four torso model formulations best predicted the electromyographic data, (b) the difference in muscular contribution to spinal compression force for the four models, and (c) the effect of using the lowest possible muscle stress bound in the model formulation. An approach for the investigation of competing optimization model formulations was developed and was illustrated with electromyographic data from static asymmetric loading conditions. This method is based on (a) the choice of experimental conditions in which models predict decidedly different muscle forces, and (b) the ability to ensure that the experimental conditions are such that the minimum number of assumptions about the force-electromyogram relationship must be made in order to choose between competing model predictions. Of the four models analyzed, only the formulation with an objective function that was the sum of cubed muscle stresses predicted the electromyographic data acceptably. The muscular contribution to spinal compression force predicted by these models differed by as much as 160% for some experimental conditions. The use of the lowest possible muscle stress bound does not appear to predict muscle forces that are in agreement with electromyographic data.


Improvements in general health among the elderly: a factor in the rising incidence of hip fractures?
Both hip fracture incidence and life expectancy are known to have increased during the last decades. Seventeen studies of hip fracture incidence from Great Britain and Scandinavia were collected from the literature. It was found that there was a good correlation for both men and women between the incidence of cervical but not trochanteric fractures in the 75-79 year age group and the mean life expectancy at 70 years of age at the time in the country concerned. The increased incidence is probably accounted for partly by the increased lifespan of the infirm. It is, however, suggested that increases in life expectancy among a majority of the elderly also entail better general health at any particular age, and that this may lead to a higher level of physical mobility which raises the risk of falls and fractures.


MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen.
Two isozymes (types 1 and 2) of 5alpha-reductase (5alphaR; EC 184.108.40.206), with differential tissue distribution, catalyze the reduction of testosterone (T) to dihydrotestosterone (DHT) in humans. This study examined sequentially increasing oral doses of MK-386 (4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one), an azasteroid that specifically inhibits the human 5alphaR1 isozyme in vitro. Finasteride, a selective inhibitor of 5alphaR2, was included for comparison. One hundred men were evaluated in a double blind, randomized, placebo-controlled, sequential, increasing dose, parallel group trial. Ten to 20 subjects received MK-386, and 2 to 5 received placebo in each of 6 panels. In 1 panel, 10 subjects received finasteride (5 mg), and 5 received placebo. Treatments were given once daily for 14 days, except in 1 panel in which MK-386 was administered 10 mg twice daily for comparison to 20 mg daily. Serum, sebum, and semen DHT concentrations and serum and sebum T concentrations were measured before and after treatment. The mean changes from baseline on day 14 for serum DHT after placebo and 0.1, 0.5, 5, 20, and 50 mg MK-386 were 6.9%, 4.6%, -2.7%, -1.2%, -14.1% (P < 0.05 vs. placebo), and -22.2% (P < 0.05 vs. placebo), respectively. No significant alterations in serum T were observed after any dose of MK-386. Serum DHT fell 65.8% from the baseline 14 days after finasteride treatment (P < 0.05 vs. placebo). The mean changes from baseline on day 14 in sebum DHT were 5.0%, 3.0%, -25.4% (P < 0.05 vs. placebo), -30.1% (P < 0.05 vs. placebo), and -49.1% (P < 0.05 vs. placebo) for the placebo and 0.5, 5, 20, and 50 mg MK-386 groups, respectively. Finasteride also reduced sebum DHT, but to a lesser extent (- 14.9%; P < 0.05 vs. placebo). Reciprocal increases in sebum T concentration were noted at doses of 5 mg or more of MK-386, but not with finasteride. The mean reduction in semen DHT with 5 mg finasteride was approximately 88% (P < 0.01 vs. placebo); no significant change in semen DHT was noted with 20 or 50 mg MK-386. Serum 3alpha-androstanediol glucuronide values were also reduced after the 20- and 50-mg MK-386 treatments in parallel with the changes in serum DHT. No meaningful changes were observed in serum LH after MK-386 treatment. MK-386 was generally well tolerated by all subjects; reversible aspartate aminotransferase/alanine aminotransferase elevations were observed in two subjects at the 50-mg dose. The differential responses in serum, sebum, and semen DHT concentrations associated with MK-386 and finasteride treatments are consistent with those changes anticipated for selective inhibitors of the human 5alphaR isozymes. Dose-dependent suppression of sebum DHT by a 5alphaR1 inhibitor suggests the potential utility of such compounds in the treatment of acne.


Hypoglycemia in the elderly.
Fifty three elderly hypoglycemic patients seen at Tokyo Metropolitan Geriatric Hospital during last 4 years were reviewed, and these data suggest that clinical characteristics of hypoglycemic patients in the elderly are as follows: 1) Non-diabetics without any hypoglycemic drugs seem to take relatively large part in hypoglycemic patients; 2) malnutrition due to chronic disease, and liver dysfunction may be important predisposing factors in development of hypoglycemia; 3) they are often lacking in adrenergic symptoms and do not tend to present symptoms until their plasma glucose levels decrease at extremely low levels, moreover in such cases, they tend to manifest neuroglycopenia in the beginning of their hypoglycemic attacks. Therefore, it is noteworthy that impaired subjective recognition may increase the risk of hypoglycemia and hypoglycemia should be one of the important considerations in differential diagnosis of stupor and coma in the elderly patients, even though they have not been administered any hypoglycemic agents.


Oral manifestations in a renal osteodystrophy patient - a case report with review of literature.
Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child.


Diagnosis and Treatment of Invasive Aspergillus fumigatus Wound Infection Following Subtotal Colectomy for Perforated Toxic Megacolon in an Immunosuppressed Patient.
Aspergillus is a rare cause of surgical site infection most often seen in immunocompromised patients undergoing cardiac, transplant, ophthalmologic, or burn operations; an unusual case following a colon resection is presented here. The authors report a case of an invasive Aspergillus fumigatus infection following a subtotal colectomy for toxic megacolon. The patient was on antibiotics following the operation and chronic immunosuppression with steroids and infliximab. This was an unusual cause of a postoperative wound infection. This case highlights the importance of early and accurate identification, debridement, and systemic antifungals to prevent widespread infection. With changes in antifungal care over recent years, engaging infectious disease physicians during treatment is recommended.


Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI.
Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models. We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10-7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue. Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.


Interactions between plant-beneficial microorganisms in a consortium: Streptomyces microflavus and Trichoderma harzianum.
The construction of microbial consortia is challenging due to many variables to be controlled, including the cross-compatibility of the selected strains and their additive or synergistic effects on plants. In this work, we investigated the interactions in vitro, in planta, and at the molecular level of two elite biological control agents (BCAs), that is Streptomyces microflavus strain AtB-42 and Trichoderma harzianum strain M10, to understand their attitude to cooperate in a consortium. In vitro, we observed a strong cross-antagonism between AtB-42 and M10 in agar plates due to diffusible metabolites and volatile organic compounds. In liquid co-cultures, M10 hindered the growth of AtB-42 very likely because of secondary metabolites and strong competition for the nutrients. The interaction in the co-culture induced extensive transcriptional reprogramming in both strains, especially in the pathways related to ribosomes, protein synthesis, and oxidoreductase activity, suggesting that each strain recognized the counterpart and activated its defence responses. The metabolome of both strains was also significantly affected. In contrast, in the soil, M10 growth was partially contrasted by AtB-42. The roots of tomato seedlings inoculated with the consortium appeared smaller than the control and single-strain-inoculated plants, indicating that plants diverted some energy from the development to defence activation, as evidenced by the leaf transcriptome. The consortium induced a stronger transcriptional change compared to the single inoculants, as demonstrated by a higher number of differentially expressed genes. Although the cross-antagonism observed in vitro, the two strains exerted a synergistic effect on tomato seedlings by inducing resistance responses stronger than the single inoculants. Our observations pose a question on the usefulness of the sole in vitro assays for selecting BCAs to construct a consortium. In vivo experiments should be preferred, and transcriptomics may greatly help to elucidate the activity of the BCAs beyond the phenotypic effects on the plant.


Endodontic management of a fused mandibular third molar and distomolar: a case report.
Careful management of fused teeth is essential as abnormal morphology can predispose a tooth to caries and periodontal disease. In this paper, a rare case of successful endodontic management of unilateral mandibular third molar fused to a distomolar is reported. Caries was removed from the tooth complex under local anaesthesia. The pulp chambers of the third molar and supernumerary tooth were accessed and the root canals were prepared using rotary instrumentation and copious irrigation with 2.5% sodium hypochlorite. Obturation using the lateral condensation technique with gutta-percha and AH26 sealer was subsequently performed. A 1-year recall showed a good treatment result.


On the Reliability of Wearable Technology: A Tutorial on Measuring Heart Rate and Heart Rate Variability in the Wild.
Wearable sensors are quickly making their way into psychophysiological research, as they allow collecting data outside of a laboratory and for an extended period of time. The present tutorial considers fidelity of physiological measurement with wearable sensors, focusing on reliability. We elaborate on why ensuring reliability for wearables is important and offer statistical tools for assessing wearable reliability for between participants and within-participant designs. The framework offered here is illustrated using several brands of commercially available heart rate sensors. Measurement reliability varied across sensors and, more importantly, across the situations tested, and was highest during sleep. Our hope is that by systematically quantifying measurement reliability, researchers will be able to make informed choices about specific wearable devices and measurement procedures that meet their research goals.


Elevated expression of the EZH2 gene in CALR-mutated patients with primary myelofibrosis.
Primary myelofibrosis (PMF) is one of the BCR/ABL-negative myeloproliferative neoplasms (MPNs), characterized by the diffuse fibrous hyperproliferation, bone marrow osteosclerosis, extramedullary hematopoiesis, and marked splenomegaly. The patients with PMF have an insidious onset, a long duration of clinical course, and the deteriorated quality of life. It has been reported that the CALR gene 9 exon mutations were detected in 25-30% PMF patients, particularly as high as 80% in the JAK2/MPL-negative ones. As the second most common mutation in BCR/ABL-negative MPNs, CALR mutation has been included in the latest World Health Organization (WHO) classification criteria as one of the main diagnostic criteria for both essential thrombocythemia (ET) and PMF. Moreover, the CALR mutations indicated a favorable prognosis, which the mechanism is still under investigation. It was demonstrated that a characterized high expression of EZH2 and SUZ12 in CALR-mutated patients. Taking EZH2 as the research entry point, we initially discussed the mechanism that the CALR-positive patients with PMF exhibited a better prognosis in the current study.


Tracheal intubation of morbidly obese patients: LMA CTrach vs direct laryngoscopy.
LMA CTrach (CT), a modified version of the intubating LMA Fastrach, allows continuous video-endoscopy of the tracheal intubation procedure. We tested the hypothesis that the CT is efficient for tracheal intubation of morbidly obese patients who are at risk of a difficult airway. After Ethics' Committee approval, 104 morbidly obese patients (BMI >35 kg m(-2)) scheduled for bariatric surgery were included in this prospective study. Patients were randomly assigned in two groups: tracheal intubation using direct laryngoscopy (DL) or the CT. Induction of anaesthesia was standardized using sufentanil, propofol and succinylcholine. Characteristics and consequences of airway management were evaluated. Preoperative characteristics of patients and consequences of anaesthesia induction on physiological variables were similar in both groups. Difficulty in facemask ventilation was similar in both groups. Tracheal intubation was successfully carried out with DL and CT. Forty-nine per cent of the patients from the CT group required laryngeal mask manipulation (ventilation and view optimization) resulting in increased duration of tracheal intubation by 57 s as compared with DL. Oxygenation was of better quality in the patients managed with CT than with DL. Blind tracheal intubation was mandatory in eight (17%) patients of the DL group, while tracheal intubation was seen in all patients of the CT group. We demonstrated that the CT was an efficient airway device for ventilation and tracheal intubation in case of a difficult airway in morbidly obese patients.


Acute Photobiomodulation by LED Does Not Alter Muscle Fatigue and Cycling Performance.
The purpose of the present study was to investigate the ergogenic effects of two doses of photobiomodulation therapy (PBMT) in comparison to placebo on markers of respiratory and muscle activity, blood acid-base, ion and lactate concentrations, indicators of muscle fatigue (global, central, and peripheral), and time to exhaustion in severe-intensity cycling. Two separate studies were performed, both in a pseudorandomized and balanced, crossover design. In study 1, 14 male recreational cyclists completed three constant-load, severe-intensity cycling bouts that were duration matched. The PBMT (18 × 38 cm array with 200 diodes) treatments occurred before bouts at 260, 130, or 0 J (placebo) doses. EMG activity of selected lower limb musculature was assessed during each bout. Maximal voluntary contractions of knee extension with peripheral nerve stimulations and EMG activity evaluation of vastus lateralis was also performed before and after cycling. In study 2, 13 recreational cyclists performed three bouts of constant-load, severe-intensity cycling until exhaustion, preceded by PBMT as detailed previously. Blood lactate concentrations, respiratory responses, EMG activity, and capillary gasometry aspects were monitored. In both studies, there were no interactions effects (time-condition) on the EMG activity, which was displayed as root mean square (P ≥ 0.168) and median frequency (P ≥ 0.055) during cycling. In study 1, there were no interaction effects on the indicators of muscle fatigue after exercise (P ≥ 0.130). In study 2, there were no differences on time to exhaustion (P = 0.353) and no interaction effects among the physiological responses monitored (P ≥ 0.082). Based on our findings, the PBMT at 260- and 130-J doses does not have a beneficial effect on muscle fatigue, cycling performance, metabolic parameters, and muscle activity in male recreational cyclists.


Impact of biosolids and wastewater effluent application to agricultural land on corticosterone content in lettuce plants.
We studied corticosterone occurrence in lettuce plants grown on three biosolids amended soils under irrigation with either tap water or secondary wastewater effluent. Corticosterone was examined as it has possible implications for human health. It is a major glucocorticoid, and as such has an effect on regulation of metabolism, immune functions and stress response. The plants were grown in 220-L lysimeters packed with 3 soils which represent a wide range of physicochemical properties. Lettuce was grown in cycles (two in summer and two in winter) during 3 years, and in every spring season the sludges were re-applied. Corticosterone was quantified using ELISA and LCMS, and was found in the biosolids, tap water, wastewater effluent and lettuce plants. The respective ranges of concentrations were: 11-92 ng g(-1), 0.5-1.6 ng L(-1), 4.2-4.7 ng L(-1); and 1-900 ng g(-1) dry weight. A positive relationship was found between corticosterone concentrations in winter-grown lettuces and the plants fresh weight. The corticosterone content of the plants did not correspond with either the type of irrigation water or the biosolids type and rate of application or the soil properties.


Cord blood transplantation for cure of HIV infections.
HIV infection has not been cured by antiretroviral drugs or gene therapy, but it has been cured by a hematopoietic cell transplantation (HCT) that was performed for a patient with acute myeloid leukemia and HIV infection using peripheral blood stem cells from an adult donor homozygous for CCR5-Δ32 (CCR5-Δ32/Δ32). HIV has remained undetectable more than 6 years after discontinuation of antiretroviral therapy. However, this approach cannot be readily generalized because of the low prevalence of the CCR5-Δ32 allele and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients, as when bone marrow or peripheral blood stem cell transplants are performed. In contrast, cord blood (CB) transplants require less stringent HLA matching. CB units are being screened to develop an inventory of cryopreserved homozygous CCR5-Δ32 units available for HCT. One hundred eighty homozygous CCR5-Δ32 units have been identified, and 300 units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA-matched unit with a minimal cell dose of ≥2.5 × 10(7) total nucleated cells (TNC) per kilogram and for white adults a 27.9% probability. With a minimal cell dose requirement of ≥1 × 10(7) TNC per kilogram, the corresponding projected probabilities are 85.6% and 82.1%. CB transplantation does not require as stringent an HLA match between donor and recipient as bone marrow or peripheral blood HCTs, and HCT using cord bloods from donors homozygous for CCR5-Δ32 is, at the present time, the only feasible means of treatment of reasonable numbers of patients who are infected with HIV.


Effects of prostaglandin E1 and indomethacin on the stimulation-evoked overflow of 3H-noradrenaline from guinea-pig taenia.
Prostaglandin E1 (5.8 X 10(-8) M) markedly and reversibly reduced the stimulation-evoked overflow of total tritium, while it had no effects on basal outflow. Indomethacin (8.4 X 10(-6) M) increased the stimulation-evoked overflow of total tritium at low frequencies (2--5 HZ), while it had no effect at high frequencies of stimulation (more than 10 HZ). It was concluded that endogenous prostaglandin E1 also plays a regulatory role in adrenergic inhibitory neurotransmission by inhibiting the noradrenaline release from adrenergic nerve terminals of the guinea-pig taenia caecum.


Recent advances in microfluidic cell sorting techniques based on both physical and biochemical principles.
Microfluidic technologies for isolating cells of interest from a heterogeneous sample have attracted great attentions, due to the advantages of less sample consumption, simple operating procedure, and high separation accuracy. According to the working principles, the microfluidic cell sorting techniques can be categorized into biochemical (labeled) and physical (label-free) methods. However, the inherent drawbacks of each type of method may somehow influence the popularization of these cell sorting techniques. Using the multiple complementary isolation principles is a promising strategy to overcome this problem, therefore there appears to be a continuing trend to integrate two or more sorting methods together. In this review, we focus on the recent advances in microfluidic cell sorting techniques relied on both physical and biochemical principles, with emphasis on the mechanisms of cell separation. The biochemical cell sorting techniques enhanced by physical principles and the physical cell sorting techniques enhanced by biochemical principles, are first introduced. Then, we highlight on-chip magnetic-activated cell sorting, on-chip fluorescence-activated cell sorting, multi-step cell sorting and multi-principle cell sorting techniques, which are based on both physical and biochemical separation mechanisms. Finally, the challenges and future perspectives of the integrated microfluidics for cell sorting are discussed.


[Detection of microcalcifications in digital mammograms based on dual-threshold].
Breast cancer is one of the main cancers leading to women mortality in the world. Since the causes are still obscure, the microcalcification clusters are the primary indicators of breast cancer, and the detection is of importance to the prevention and treatment of the disease. Microcalcifications appear in the small clusters of a few pixels and as spots which are slightly brighter than their backgrounds. It becomes a challenge to detect all the microcalcifications. This paper presents an approach for detecting microcalcifications in digital mammograms employing a dual-threshold method developed from LoG edge detection. Two thresholds are proposed in our method based on two additional criterions. Experimental results show that the proposed method can locate the microcalcifications exactly in mammogram as well as restrain the contours produced by the noises.


Spontaneous retroperitoneal hemorrhage caused by segmental arterial mediolysis.
Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal hemorrhage can be caused by tumors, such as renal cell carcinoma and angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is segmental arterial mediolysis. Although computed tomography is used for the diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires angiography, with pathologic confirmation for a definitive diagnosis.


High rate otoacoustic emissions.
One of the practical problems of testing young children using evoked otoacoustic emissions (EOAEs) is that there is a need for the child to be quiet for a period of a minute or so. To achieve this can mean test periods of 10 min or longer. A new application of maximum length sequences (MLSs) to EOAEs is described that enables the test to be performed in a few seconds or less. Data from adults and neonates obtained at stimulation rates up to 840 clicks/s are presented and compared with conventionally derived emissions and the implications and applications of this new method are assessed.


Stepwise Growth of Fullerene Nanoparticles through Guest Exchange of γ-Cyclodextrin Complexes in Water.
Stepwise growth of fullerene nanoparticles (nCx ; x=60 or 70) was performed through guest exchange of a γ-cyclodextrin (γ-CD) complex. Fullerenes bicapped by γ-CD were mixed with presynthesized nCx in the presence of poly(ethylene glycol) (PEG) in water. Fullerenes expelled from the γ-CD hosts by PEG were piled on the original nCx , resulting in growth of nCx . This process could be repeated and the size of nCx increased according to the number of growth steps. The growth of fullerene nanoparticles was confirmed by UV/Vis absorption spectroscopy, dynamic light scattering measurements, and TEM observations. The stepwise growth method also enabled the preparation of C60 /C70 core/shell fullerene nanoparticles, which had the ability to photogenerate active oxygen, 1 O2 .


Mean-field and anomalous behavior on a small-world network.
We consider various equilibrium statistical mechanics models with combined short- and long-range interactions and identify the crossover to mean-field behavior, finding anomalous scaling in the width of the mean-field region, as well as in the mean-field amplitudes. We then show that this model enables us, in many cases, to determine the universal critical properties of systems on a small-world network. Finally, we consider nonequilibrium processes.


A quantitative approach to the choice of number of samples for percentile estimation in bootstrap and visual predictive check analyses.
Understanding the uncertainty in parameter estimates or in derived secondary variables is important in all data analysis activities. In pharmacometrics, this is often done based on the standard errors from the variance-covariance matrix of the estimates. Confidence intervals derived in this way are by definition symmetrical, which may lead to implausible outcomes, and will require translation to generate uncertainties in derived variables. An often-used alternative is numerical percentile estimation by, for example, nonparametric bootstraps to circumvent these issues. Visual predictive checks (VPCs), which is a commonly used model diagnostic tool in pharmacometric analyses, also rely on the estimation of percentiles through numerical approaches. Given the cost in terms of run times and processing times for these methods, it is important to consider the trade-off between the number of bootstrap samples or simulated data sets in the VPCs, to the increase in precision related to a large number of bootstrap samples or simulated data sets. The objective with this tutorial is to provide a quantitative framework for assessing the precision in estimated percentile limits in bootstrap and visual predictive checks analyses to facilitate an informed choice of confidence interval width, number of bootstrap samples/simulated data sets, and required level of precision.


Photodissociation of [Ar-N2]+ induced by near-IR femtosecond laser fields by ion-trap time-of-flight mass spectrometry.
Photodissociation of [Ar-N2]+ induced by a near-IR (800 nm) femtosecond laser pulse is investigated using ion-trap time-of-flight mass spectrometry. The intra-complex charge transfer proceeding in the course of the decomposition of the electronically excited Ar+(2P3/2)⋯N2(X1Σg +), prepared by the photoexcitation of the electronic ground Ar(1S0)⋯N2 +(X2Σg +), is probed by the ion yields of Ar+ and N2 +. The yield ratio γ of N2 + with respect to the sum of the yields of Ar+ and N2 + is determined to be γ = 0.62, which is much larger than γ ∼ 0.2 determined before when the photodissociation is induced by a nano-second laser pulse in the shorter wavelength region between 270 and 650 nm. This enhancement of γ at 800 nm and the dependence of γ on the excitation wavelength are interpreted by numerical simulations, in which the adiabatic population transfer from Ar+(2P3/2)⋯N2(X1Σg +) to Ar(1S0)⋯N2 +(X2Σg +) at the avoided crossings is accompanied by the vibrational excitation in the N2 +(X2Σg +) moiety followed by the intra-complex vibrational energy transfer from the N2 +(X2Σg +) moiety to the intra-complex vibrational mode leading to the dissociation.


[Ligneous conjunctivitis: a case report].
We report a case of ligneous conjunctivitis in a young patient and we describe the clinical findings and the histological aspects of the lesions, which allows us to sum up the treatment of this rare disorder. We recommend the use of topical ciclosporine, heparin, and corticosteroids. To conclude we analyse the different way in which the disease can evolue.


A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome.
To determine the underlying genetic cause of Axenfeld-Rieger syndrome (ARS) in a three-generation family. ARS is a multisystem, autosomal dominant disorder characterized by specific ocular and non-ocular anomalies sometimes caused by mutations in the transcription factor gene, PITX2. The three coding exons of the PITX2 gene, i.e., exons 2, 3, and 4, in affected and unaffected subjects were amplified by polymerase chain reaction (PCR) and sequenced. The PCR products of exon 4 were subcloned and sequenced to confirm the nature of the mutation. A deletion of thymine (T) 1261 was identified, creating a frameshift mutation in codon 227. This change is predicted to create 11 novel amino acids downstream, followed by premature truncation of the protein. This mutation highlights the functional importance of a conserved 14-amino acid sequence at the C-terminus of the protein thought to be important in repressing DNA binding and in protein-protein interactions.


Cytoskeletal dissociation of ezrin during renal anoxia: role in microvillar injury.
The association/dissociation of ezrin, a microvillar membrane-cytoskeleton linker, was studied to search for the initial step leading to anoxia-induced brush-border breakdown in a rabbit proximal tubule suspension. Electron microscopy studies display time-dependent damage to the microvilli during anoxia; immunoblots demonstrate the dissociation of ezrin from the cytoskeleton, reflected by the significant decrease in Triton X-100-insoluble ezrin from control (91%) to 39% after 30 min. Simultaneously, Triton X-100-soluble and extracellular ezrin increased with no change in total ezrin, Triton X-100 solubility of actin, or total intracellular protein. Parallel immunocytochemistry studies show diffusion of ezrin from the brush border, where ezrin is highly colocalized with F-actin during normoxia into the cytoplasm. Thirty minutes of reoxygenation following 30 min of anoxia causes recovery of the microvillar structure and reassociation of ezrin to the cytoskeleton and the brush border. Application of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (4 mM) or inhibition of intracellular calpain or calcineurin do not prevent the dissociation of ezrin during anoxia. We conclude that ezrin-cytoskeletal dissociation may initiate microvillar breakdown during anoxia via calcium-independent mechanisms.


Tuning Ordered Pattern of Pd Species through Controlled Block Copolymer Self-Assembly.
We report a method for the preparation of ordered patterns of Pd species on a substrate based on the use of polystyrene-block-poly(ethylene oxide) copolymer (PS-b-PEO) templates and selective inclusion of palladium (Pd) species in the PEO domains. PS-b-PEO samples of different total molecular masses self-assemble in a cylindrical microphase-separated morphology, in which vertically aligned PEO cylinders, with different diameters depending on the molecular mass, are organized in a hexagonal array of different lateral spacings. The cylindrical nanostructure is maintained after the selective inclusion of Pd species (Pd acetate and Pd nanoparticles (NPs) after reduction of Pd ions of the salt) in the PEO cylinders so that the characteristic sizes (diameters and lateral spacings) of the included Pd species are tuned by the characteristic sizes of the block copolymer (BCP) template, which are regulated by molecular mass. Treatment of nanocomposites at elevated temperatures in air removes the polymer matrix and leads to the formation of arrays of palladium oxide (PdO) NPs covering a solid support. The patterns of PdO NPs are characterized by different particle diameters and gap distances, mirroring the patterns and characteristic nanodimensions of the parent BCPs used as templates.


Drug-induced immune thrombocytopenia due to moxifloxacin.
A 39-year-old woman with 1 day of oral petechiae, leg ecchymoses and epistaxis was found to have isolated thrombocytopenia. She had recently completed a 10-day course of moxifloxacin for an upper respiratory infection. On further questioning, she had developed thrombocytopenia 2 years earlier after a treatment course with moxifloxacin. After ruling out other causes, drug-induced immune thrombocytopenia due to moxifloxacin was diagnosed. Her platelets returned to normal range 15 days after finishing the medication.


Beating-heart on-pump coronary artery bypass grafting vs. off-pump coronary artery bypass grafting: a systematic review and meta-analysis.
Beating-heart on-pump coronary artery bypass grafting (CABG), otherwise known as BH-ONCAB, can reduce myocardial injury by preserving native coronary blood flow while maintaining hemodynamic stability by the effective support of cardiopulmonary bypass (CPB). This study aimed to identify whether BH-ONCAB confers a survival, mortality, or morbidity benefit over off-pump CABG (OPCAB). A systematic literature review identified 18 studies incorporating 5,615 patients (1,548 BH-ONCAB and 4,067 OPCAB cases) who satisfied the inclusion criteria. Outcome measures were meta-analyzed using random-effects modeling. Between-study heterogeneity was investigated through quality assessment and risk of bias analysis. The results demonstrated comparable early mortality and long-term survival between BH-ONCAB and OPCAB coronary revascularization with no significant statistical differences. The incidences of stroke, renal failure, blood loss, and arrhythmias were significantly higher in patients who underwent BH-ONCAB than patients who underwent OPCAB. However, BH-ONCAB conferred lower rates of incomplete revascularization and greater numbers of distal anastomoses. BH-ONCAB is a safe and comparable alternative to OPCAB in terms of early mortality and late survival. BH-ONCAB may confer particular advantages in preventing incomplete revascularization and allowing more distal anastomoses compared to OPCAB. However, BH-ONCAB was associated with more postoperative complications due to the use of CPB. Future work should focus on larger matched studies and multicenter randomized controlled trials to optimize our surgical revascularization strategies.


Factors Associated with Lesion Recurrence Following Cervical Conization.
To investigate the factors influencing lesion recurrence during the follow-up after cervical conization and evaluate the clinical value of human papillomavirus (HPV) testing and thinprep cytology test (TCT) in postoperative follow-up patients undergoing cervical conization. A total of 289 patients with cervical lesions who underwent primary cervical conization at our hospital between January 1, 2018, and December 31, 2019, were included in this study. TCT, HPV testing, and colposcopy were performed every 6 months for a follow-up period of 3 years. Based on the follow-up results, the patients were divided into recurrence and non-recurrence groups. The basic and colposcopic data of the two groups were analyzed to identify factors influencing lesion recurrence. Additionally, the clinical value of HPV testing and TCT in postoperative follow-up and recurrence diagnosis of patients undergoing cervical conization was assessed. The recurrence group showed significantly higher age of onset, concurrent rate of other chronic diseases, and parity, as well as a markedly lower barrier contraceptive rate compared to the non-recurrence group, with statistically significant differences (P < .05). In the recurrence group, the type III transformation zone (TZ) predominated (59.26%), which significantly differed from the non-recurrence group (P < .05). The detection rates of abnormal TCT findings and HPV infections in postoperative reexaminations were significantly higher in the recurrence group compared to the non-recurrence group (P < .05), whereas no significant differences were observed between the two groups before cervical conization (P > .05). Among the recurrence group (n = 54), 52 cases (96.3%) had HPV infections, and 29 cases (53.7%) had abnormal TCT findings, with a significantly higher detection rate for HPV infections (P < .05). The area under the receiver operating characteristic (ROC) curve (AUC) for HPV testing, TCT, and combined HPV testing with TCT after cervical conization were 0.861, 0.712, and 0.882, respectively. These results indicate that HPV testing alone performs similarly to combined HPV testing with TCT and significantly outperforms TCT alone in predicting lesion recurrence after cervical conization. Factors influencing lesion recurrence after cervical conization include patient age, barrier contraceptive rate, concurrent rate of other chronic diseases, parity, and type of transformation zone. HPV testing alone is more sensitive and accurate than TCT in predicting lesion recurrence during postoperative follow-up of patients undergoing cervical conization. This finding can reduce missed diagnoses and provide a significant theoretical basis for postoperative follow-up of patients undergoing cervical conization.


Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with Quantitative Biochemical Measures of Aβ42 but not Aβ40.
Amyloid imaging demonstrates the in vivo presence of amyloid-β (Aβ) deposits in the aging human brain but it is still unknown which structural forms and modifications of Aβ are detected. In Alzheimer's disease, most amyloid deposits are predominantly composed of Aβ ending at amino acid residues Val40 or Ala42. It has been reported that Aβ40 is largely restricted to neuritic plaques while Aβ42 may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment while diffuse plaques may be the initial type of Aβ deposited. Whether PET amyloid ligands such as florbetapir-18F (Amyvid) are partially or wholly selective for brain deposits of Aβ40 or Aβ42 is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against Aβ40 and Aβ42. Spearman's univariable correlations were significant for both Aβ40 and Aβ42, but were much stronger for Aβ42. Multiple linear regression showed significance only for Aβ42. These results suggest that florbetapir binds only weakly, if at all, to Aβ40. This may be in part due to the higher likelihood for Aβ42 to be present in a β-pleated sheet tertiary structure, or to differences between Aβ40 and Aβ42 in β-pleated sheet tertiary or quaternary structure.


Effects of Pedalo® training on balance and fall risk in stroke patients.
[Purpose] This study sought to examine the effects of Pedalo® training on balance and fall risk in stroke patients. [Subjects and Methods] Thirty-one subjects with stroke were recruited and randomly allocated into two groups: the Pedalo® group (n=15) and the Treadmill group (n=16). The Pedalo® group performed conventional physical therapy program with Pedalo® training for 30 minutes, five times a week, for 8 weeks, while the Treadmill group conducted conventional physical therapy programs and treadmill gait training for 30 minutes, five times a week, for 8 weeks. [Results] After intervention, both groups showed a significant improvement in balance. A significant greater balance improvement was found in the Pedalo® group compared to the Treadmill group. Also, a significant reduction in risk of fall was seen in both group but this reduction was not significantly different between the two groups. [Conclusion] Pedalo® training may be used to improve balance and reduce fall risk in stroke patients.


Modeling and spectral simulation of matrix-isolated molecules by density functional calculations: a case study on formic acid dimer.
The supermolecule approach has been used to model molecules embedded in solid argon matrix, wherein interaction between the guest and the host atoms in the first solvation shell is evaluated with the use of density functional calculations. Structural stability and simulated spectra have been obtained for formic acid dimer (FAD)-Ar(n) (n = 21-26) clusters. The calculations at the B971∕6-31++G(3df,3pd) level have shown that the tetrasubstitutional site on Ar(111) plane is likely to incorporate FAD most stably, in view of consistency with the matrix shifts available experimentally.


The mouse Edr2 (Mph2) gene has two forms of mRNA encoding 90- and 36-kDa polypeptides.
The vertebrate Polycomb Group (PcG) genes encode proteins that form large multimeric and chromatin-associated complexes implicated in the stable repression of developmentally essential genes. Here we have isolated a 2.5-kb cDNA for Edr2, a mouse homolog of the Drosophila PcG gene Ph, although it was originally identified as a 3.8-kb cDNA. However, little is known about molecular basis of the 3.8-kb cDNA. Genomic and RNA analyses have shown that Edr2 locates on Chromosome 4 as a single copy gene and is transcribed into at least two transcript isoforms about 3.0 and 4.4 kb in length, most likely corresponding to the 2.5- and 3.8-kb cDNAs, respectively. The largest open reading frames in the 2.5- and 3.8-kb cDNAs encode 36- and 90-kDa polypeptides, respectively. The 36-kDa protein is a truncated form lacking of the N-terminal region of the 90-kDa protein. Interestingly, it has been demonstrated that the 3.0-kb mRNA accumulates at a much higher level than the 3.8-kb mRNA in mouse embryos and mature tissues. Immunostaining assay of mammalian cells has shown that the 36-kDa form tagged with HA colocalizes with the other PcG protein Mel18 in nuclei, suggesting that the smaller protein is capable of forming maltimeric complex with other PcG proteins. Therefore, the 36-kDa protein might function generally as a PcG protein.


[A clinical and epidemiological profile of ocular emergencies in a reference emergency center].
To evaluate epidemiological aspects of eye injuries in a reference emergency center. The study had two surveys: in the first (A) victims of ocular trauma where 1,483 patients admitted along 2003 had their epidemiological data analyzed and the second (B), where 133 patients had clinical aspects and risk and protective factors analyzed by a standard questionnaire between May and June 2004. In survey A, most patients were males (1,314 or 89%). Ocular surface foreign body was the most frequent occurrence with 863 (58%) cases. In survey B it was shown that ocular protection was used only by 17% (22) patients. The accidents occurred more frequently at the workplace 70% (93), followed by the home (22%). In survey B, 34% of the patients had previous accidents. The profile of patients victims of ocular trauma shows that there is a higher frequency of males and accidents involving cornea foreign body. The use of protective glasses is incipient and recurrence of this lesion is considerable. A preventive and educational strategy among the population with special focus on workplaces and homes is necessary to reduce ocular trauma occurrence.


Baohuoside I suppresses invasion of cervical and breast cancer cells through the downregulation of CXCR4 chemokine receptor expression.
More than 90 percent of cancer-mediated deaths are due to metastasis, but the mechanisms that control metastasis remain poorly understood. Thus, the therapy targeting this process has been challenged constantly, but no therapy has yet been approved. CXC chemokine receptor 4 (CXCR4), a Gi protein-coupled receptor for the CXC chemokine ligand (CXCL) 12/stromal cell derived factor (SDF) 1α, is known to be expressed in various tumors. Recently, the CXCL12/CXCR4 axis has emerged as a key mediator of tumor metastasis; therefore, the possibility that identification of CXCR4 inhibitors can be a promising strategy for abrogating metastasis has been considered. In this report, we investigate baohuoside I, a component of Epimedium koreanum, as a regulator of CXCR4 expression as well as function in cervical cancer and breast cancer cells. We observed that baohuoside I downregulated CXCR4 expression in a dose- and time-dependent manner in HeLa cells. Treatment with a pharmacological proteasome and lysosomal inhibitors did not have a substantial effect on baohuoside I's ability to suppress CXCR4 expression. When we investigated the molecular mechanism of action, it was observed that the suppression of CXCR4 expression occurred at the level of mRNA. The decrease in the level of CXCR4 expression caused by baohuoside I was correlated with inhibition of the CXCL12-induced invasion of both cervical and breast cancer cells. Overall, our results show that baohuoside I exerts its antimetastatic effect through the downregulation of CXCR4 expression and, thus, has the potential to play a role in the suppression of cancer metastasis.


Considerations for national public health leadership in advancing sexual health.
Nations across the globe face significant public heath challenges in optimizing sexual health, including reducing human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), sexually transmitted infections (STIs), unintended pregnancies, and sexual violence, and mitigating the associated adverse social and economic impacts. In response, some countries have implemented national strategies and other efforts focused on promoting more holistic and integrated approaches for addressing these syndemics. This article describes opportunities for national leadership to use a more holistic approach to improve the sexual health of individuals and communities.


Brain Imaging in Patients With Dementia Visiting U.S. Emergency Departments.
OBJECTIVE. This article aimed to assess changing use of brain imaging tests among patients with Alzheimer disease and vascular dementia who visited U.S. emergency departments (EDs) between 2006 and 2014. MATERIALS AND METHODS. Using the largest publicly available all-payer ED database, the Nationwide Emergency Department Sample, we identified a weighted cohort of 427,705 individuals with Alzheimer disease and 33,743 individuals with vascular dementia who visited U.S. EDs between 2006 and 2014. Logistic regression analyses were performed to identify factors associated with use. RESULTS. Between 2006 and 2014, ED visits among patients with Alzheimer disease and vascular dementia declined by 24.7% and 20.3%, respectively. However, there was a significant increase in utilization rates of head CT (from 4.4% to 11.1% in patients with Alzheimer disease and from 1.5% to 2.9% in patients with vascular dementia) and brain MRI (from 0.04% to 0.5% in patients with Alzheimer disease and 0.0% to 0.1% in those with vascular dementia) in the same time period. Among patients with Alzheimer disease, age, median income in patient ZIP code, day of the week of the ED visit, hospital teaching status, and hospital geographic region were significant predictors of imaging use. Among patients with vascular dementia, insurance type and hospital classification (urban vs rural) were significant predictors of imaging use. CONCLUSION. Despite declining ED visits, ED brain imaging in patients with Alzheimer disease and vascular dementia has increased. Various patient-specific and hospital-specific factors contribute to differential utilization rates.


Efficacy of ketogenic diet in CDKL5-related epilepsy: a single arm meta-analysis.
Drug-resistant epilepsy is one of the most important features of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. The ketogenic diet (KD) may be effective for patients with CDKL5-related epilepsy, but there is little high-quality evidence to confirm the efficacy. This meta-analysis investigated the efficacy and safety of KD in CDKL5-related epilepsy. The PubMed, Embase, Web of Science, Cochrane Library, WanFang, CNKI and VIP databases were searched for relevant studies published up to January 1, 2022. Two reviewers independently screened the literature according to inclusion and exclusion criteria and evaluated the bias risk of the included studies. Meta-analysis was performed using Review Manager 5.3 software. A total of 12 retrospective studies involving 193 patients met the inclusion criteria. Meta-analysis revealed that the definite responder rate to KD in the treatment of CDKL5-related epilepsy was 18.0% [95% CI (0.07, 0.67)], with no statistical heterogeneity among studies (I2 = 0%, P = 0.45). The clinical responder rate was 50.5% [95% CI (0.75, 1.39)], and there was no statistical heterogeneity among all studies (I2 = 46%, P = 0.05). Subgroup analysis showed that there was no significant difference in the clinical responder rate between the two groups with seizure onset age before and after 1 month (P = 0.14). Only one study mentioned adverse reactions, and the incidence of adverse reactions was 78.3% (18/23). Constipation and vomiting were the main manifestations, implying a high incidence of gastrointestinal adverse reactions. The definite responder rate to KD in CDKL5-related epilepsy was 18%, and the gastrointestinal adverse reactions were probably common in these patients. All the studies included in the meta-analysis were retrospective, and most of them had small sample sizes. Additional high-quality studies are needed to confirm the efficacy and tolerance of KD in CDKL5-related epilepsy.


Associations between various attended automated office blood pressure estimations and all-cause and cardiovascular mortality: Minhang study.
The method of evaluating office blood pressure (OBP) varies greatly among different guidelines. We performed a cohort study to compare the association of various directly transferred attended automated OBP (AOBP) estimations with all-cause and cardiovascular mortalities. Overall, 475 181 sets of OBPs from 35 622 participants aged 35 years or older were extracted from the electronic health record of the Xinzhuang town hospital in the Minhang District, Shanghai, China. Each set of OBPs contained three consecutive AOBPs that were transferred directly to the electronic health record. The mean of three OBPs, mean of the last two OBPs, and alternative average OBP were calculated. The difference between the first and average OBPs changed along with the calendar month, and it was highest in December (5.3/2.1 mmHg) and lowest in July (3.8/2.0 mmHg). The subjects older than 80 years of age displayed the largest discrepancy in the blood pressure control rate according to the first OBP or average OBP (12.1%). During the 3.9-year follow-up, 1055 deaths occurred. The alternative average SBP was associated with both all-cause [hazard ratio: 1.07, 95% confidence interval (CI): 1.04-1.11] and cardiovascular (hazard ratio: 1.17, 95% CI: 1.11-1.23) mortalities. The uncontrolled alternative average OBP remained significantly associated with an increasing risk of all-cause (hazard ratio: 1.24, 95% CI: 1.09-1.40) and cardiovascular (hazard ratio: 1.53, 95% CI: 1.25-1.86) mortality, but not the average of the last two or mean of three readings. We observed an obvious discrepancy in the OBP level and OBP control rate according to different AOBP estimations. The alternative average OBP seemed to be more powerful in predicting both all-cause and cardiovascular mortalities than the average of the last two or mean of three readings.


Beta 2-adrenoceptor induced increase of plasma insulin levels in man: evidence of direct and indirect B-cell stimulation and liver effects.
Beta 2-Adrenoceptor stimulation is known to increase plasma levels of insulin in man. To study the mechanism behind this increase, plasma insulin, plasma C-peptide, and blood glucose responses to the beta 2-adrenoceptor agonist terbutaline were investigated in healthy humans. Terbutaline (125 micrograms i.v.) induced an increase in plasma levels of C-peptide from 0.68 +/- 0.11-0.90 +/- 0.14 nmol/l after 2 min (p less than 0.05) (n = 10). Likewise, plasma insulin concentrations increased, from 0.16 +/- 0.05-0.30 +/- 0.08 nmol/l (p less than 0.02). 20 min after terbutaline injection, plasma levels of C-peptide were 0.98 +/- 0.26 nmol/l and of insulin were 0.21 +/- 0.05 nmol/l. Calculations of the minute to minute increase of plasma levels of C-peptide and insulin during the 20 min after terbutaline injection, revealed that plasma insulin increased during the first 2 min by 59 +/- 8% of the increase of plasma C-peptide, and during the third and fourth min by 44 +/- 12% of the increase of plasma C-peptide; the difference being the liver extraction of insulin. In contrast, during min 4-10 after terbutaline injection, plasma insulin levels increased more than did plasma C-peptide levels, indicating that terbutaline inhibits the liver extraction of insulin. Blood glucose levels did not change during the first 4 min after terbutaline injection. During min 6-10 after terbutaline administration, blood glucose increased, from 4.94 +/- 0.24-5.42 +/- 0.25 mmol/l (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Naturalistic nursing.
Where nurse education aims to provide an overarching intellectual framework, this paper argues that it should be the framework of naturalism. After an exposition of the chief features of naturalism and its relationship to science and morality, the paper describes naturalistic nursing, contrasting it with some other perspectives. There follows a defence of naturalism and naturalistic nursing against several objections, including those concerning spirituality, religion, meaning, morality, and alternative sources of knowledge. The paper ends with some of the advantages of the naturalistic approach.


Cerebrospinal Fluid Shunting Complications in Children.
Although cerebrospinal fluid (CSF) shunt placement is the most common procedure performed by pediatric neurosurgeons, shunts remain among the most failure-prone life-sustaining medical devices implanted in modern medical practice. This article provides an overview of the mechanisms of CSF shunt failure for the 3 most commonly employed definitive CSF shunts in the practice of pediatric neurosurgery: ventriculoperitoneal, ventriculopleural, and ventriculoatrial. The text has been partitioned into the broad modes of shunt failure: obstruction, infection, mechanical shunt failure, overdrainage, and distal catheter site-specific failures. Clinical management strategies for the various modes of shunt failure are discussed as are research efforts directed towards reducing shunt complication rates. As it is unlikely that CSF shunting will become an obsolete procedure in the foreseeable future, it is incumbent on the pediatric neurosurgery community to maintain focused efforts to improve our understanding of and management strategies for shunt failure and shunt-related morbidity.


Metabolite profiling to discriminate different species and genus from thistles in Korea using liquid chromatography with quadrupole time-of-flight mass spectrometry.
This study was designed to classify and identify closely related thistle species in the genus Cirsium, as well as Carduus and Cephalonoplos species, which are also thistles. The comprehensive and untargeted metabolite profiles of nine Korean thistles were determined using ultra high performance liquid chromatography combined with hybrid quadrupole time-of-flight mass spectrometry. The difference in metabolite profiles among species was explored using principal component analysis and hierarchical clustering analysis. The significantly different metabolites (Bonferroni-corrected P-value < 0.001) were used to construct a partial least squares discriminant analysis model to predict the species of thistle. Nine species were successfully classified using a partial least squares discriminant analysis model and confirmed using a cross-validation method. Species with similar features were grouped based on unique patterns in variable clusters. The present study suggests that liquid chromatography with quadrupole time-of-flight mass spectrometry untargeted metabolomic profiling with chemometric analysis is an efficient and powerful tool for discriminating between different species of medicinal herbs.


Effects of intraduodenal amylase, lipase, trypsin, and bile on pancreatic enzyme secretion in the rat.
The effect of duodenal infusion of trypsin, amylase, lipase and bile on pancreatic enzyme secretion was studied in conscious rats surgically prepared with bile-pancreatic fistulae. Trypsin infusion resulted in a depression of the secretory volume and protein and trypsinogen output. All these effects were reversed after additional infusion of trypsin inhibitor. Infusion of amylase or lipase in doses comparable to those of trypsin did not influence the secretory volume, protein or enzyme output. Likewise, intraduodenal bile infusion to rats with diverted bile-pancreatic juice did not change these parameters; also in rats with trypsin reinfused into the duodenum, bile infusion was without effect.


Inhibition of SDF-1 receptors CXCR4 and CXCR7 attenuates acute pulmonary inflammation via the adenosine A2B-receptor on blood cells.
Acute pulmonary inflammation is characterized by migration of polymorphonuclear neutrophils into the different compartments of the lung. Recent studies showed evidence that the chemokine stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 influence migration of immune cells and their activity was linked to adenosine concentrations. We investigated the particular role of CXCR4- and CXCR7-inhibition and the potential link to the adenosine A2B-receptor, which plays an important anti-inflammatory role in the lung. After LPS-inhalation for 45 minutes, administration of the CXCR4-inhibitor (AMD3100) decreased transendothelial and transepithelial migration, whereas CXCR7-antagonism influenced epithelial migration exclusively. In A2B-/- mice, no anti-inflammatory effects were detectible through either one of the agents. Using chimeric mice, we identified A2B on hematopoietic cells to be crucial for these anti-inflammatory effects of CXCR4/7-inhibition. Both inhibitors decreased TNFα, IL6, CXCL1 and CXCL2/3 levels in the bronchoalveolar lavage of wild type mice, while not influencing the chemokine release in A2B-/- mice. Inflammation augmented the expression of both receptors and their inhibition increased A2B-levels upon inflammation. In vitro assays with human epithelium/endothelium confirmed our in vivo findings. During inflammation, inhibition of CXCR4- and CXCR7-receptors prevented microvascular permeability in wild type but not in A2B-/- mice, highlighting the pivotal role of an active A2B-receptor in this setting. The combination of both inhibitors had a synergistic effect in preventing capillary leakage. In conclusion, we determined the pivotal role of CXCR4- and CXCR7-inhibition in acute pulmonary inflammation, which depended on A2B-receptor signalling.


6-Alpha-glucosyltransferase and 3-alpha-isomaltosyltransferase from Bacillus globisporus N75.
A bacterial strain, Bacillus globisporus N75, produced two glycosyltransferases, 6-alpha-glucosyltransferase (6GT) and 3-alpha-isomaltosyltransferase (IMT), jointly catalyzing formation of cyclo-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1--> (CTS) from alpha-1,4-glucan. The N75 enzymes produced CTS from dextrin in a 43.8% yield at the reaction temperature of 50 degrees C, which was 10 degrees C higher than a critical temperature of CTS-forming by the enzymes from B. globisporus C11. The optimum temperatures for 6GT and IMT reactions were 55 degrees C and 50 degrees C, respectively. The thermal stability of both enzymes was 45 degrees C under the condition at pH 6.0 for 60 min. The genes for 6GT and IMT were cloned from the genomic DNA of N75. The amino acid sequences deduced from the 6GT and IMT genes showed 82% and 85% identities, respectively, to the sequences of the enzymes from C11. CTS yield was decreased by high concentrations of the substrate. It was found that the reaction yield was improved by adding cyclomaltodextrin glucanotransferase (CGTase). We demonstrated mass-production of CTS from starch by using the N75 enzymes and CGTase.


FTO Promotes Adipogenesis through Inhibition of the Wnt/β-catenin Signaling Pathway in Porcine Intramuscular Preadipocytes.
Numerous studies have demonstrated that FTO plays an important role in adipogenesis. Herein, we designed a small interfering RNA targeting FTO to knock down its endogenous expression and investigated its effects on the proliferation and differentiation of porcine intramuscular preadipocytes. Its possible mechanism was also investigated. We showed that FTO silencing significantly decreased the level of phospho-Histone H3 protein and inhibited the proliferation of porcine intramuscular preadipocytes. In addition, the expressions of peroxisome proliferators-activated receptor γ (PPARγ) and CAAT/enhancer binding protein (C/EBPα) were down-regulated, but the expression of β-catenin was up-regulated, by FTO silencing. Of specific interest here was that LiCl, a Wnt/β-catenin signaling specific activator, attenuated the FTO-induced upregulation of PPARγ and downregulation of β-catenin. Collectively, our data demonstrated that FTO silence decreased the proliferation and differentiation of porcine intramuscular preadipocytes, and FTO affects the porcine intramuscular preadipocytes differentiation might be via Wnt/β-catenin signaling pathway.


[Transurethral incision of the prostate].
Transurethral incision of the prostate (TUIP) is performed by a knife-shaped electrode in the folds between the lateral and middle lobe of the prostate roughly at numbers 5 and 7 of the dial from the neck of the urinary bladder in the direction towards the colliculus seminalis. In the course of five years TUIP was indicated in 87 patients--with so-called minimal benign prostatic hyperplasia (less tissue than 10 g). The operation accounted for 13.6% of operations performed on account of benign prostatic hyperplasia. Forty-four of 57 checked patients (77.2%) reported subjective improvement of complaints after TUIP and had no complaints, in five the condition was unaltered and in eight the subjective symptoms were more severe. Transurethral incision of the prostate is technically less pretentious than transurethral resection of the prostate.


Raman study of the polybenzimidazole-phosphoric acid interactions in membranes for fuel cells.
Poly(2,5-benzimidazole) (AB-PBI) membranes are investigated by studying the FT-Raman signals due to the benzimidazole ring vibration together with the C-C and C-H out-of- and in-plane ring deformations. By immersion in aqueous ortho-phosphoric acid for different time periods, membranes with various doping degrees, i.e. different molar fractions of acid, are prepared. The chemical-physical interactions between polymer and acid are studied through band shifting and intensity change of diagnostic peaks in the 500-2000 cm(-1) spectral range. The formation of hydrogen bonding networks surrounding the polymer seems to be the main reason for the observed interactions. Only if the AB-PBI polymer is highly doped, the Raman spectra show an additional signal, which can be attributed to the presence of free phosphoric acid molecules in the polymer network. For low and intermediate doping degrees no evidence for free phosphoric acid molecules can be seen in the spectra. The extent of the polymer-phosphoric acid interactions in the doped membrane material is reinvestigated after a period of one month and the stability discussed. Our results provide insight into the role of phosphoric acid as a medium in the conductivity mechanism in polybenzimidazole.


Performance of the BBraun perfusor space syringe driver under hyperbaric conditions.
The BBraun Perfusor Space™ syringe driver is already in use by ambulance services and retrieval teams but has not previously been assessed for hyperbaric chamber use. Pump flow accuracy was tested at rates between 1 and 40 ml· h⁻¹ using three different brands of 50 ml syringe. Function of the occlusion alarms was assessed using the same syringes. The hyperbaric profile involved pressurisation to 284 kPa at 30 kPa· min⁻¹, 30 min at 284 kPa and decompression at 30 kPa· min⁻¹. Output was recorded from differences in weight of collection containers. A single device was tested. Performance was highly dependent on the syringe type used, with two of the three 50 ml syringes used demonstrating 'stiction' at both low and high occlusion pressure alarm settings, most marked during pressurisation. On decompression from 284 kPa all syringes alarmed at significantly lower pressures. Because of the stiction problems only the flow measurements for the BBrown Omni¬ x 50 ml syringes are reported. At a pressure of 284 kPa, the difference between programmed and delivered rates was within the manufacturer's specification of 10%: at 40 ml· h⁻¹ (median variation 1.25%, IQR 0.5-1.7%), 10 ml· h⁻¹ (8.6%, IQR 8-9.2%), 5 ml· h⁻¹ (-8.8%, IQR - 1.6-8.8%) and 1 ml· h⁻¹ (-4%, IQR 4-12%). Pressurisation was associated with significantly lower flow rates whilst decompression was associated with significantly increased rates. Limited testing at 405 kPa was also within the manufacturer's specifications. A BBraun Infusor Space syringe driver performed within acceptable performance criteria but is highly dependent on syringe type and flow rates. The potential for the device to under deliver on pressurisation and over deliver on depressurisation, however, suggests vigilance and appropriate rate adjustments may be necessary during these phases.


Career progression of men and women doctors in the UK NHS: a questionnaire study of the UK medical qualifiers of 1993 in 2010/2011.
To report the career progression of a cohort of UK medical graduates in mid-career, comparing men and women. Postal and questionnaire survey conducted in 2010/2011, with comparisons with earlier surveys. UK. In total, 2507 responding UK medical graduates of 1993. Doctors' career specialties, grade, work location and working pattern in 2010/2011 and equivalent data in earlier years. The respondents represented 72% of the contactable cohort; 90% were working in UK medicine and 7% in medicine outside the UK; 87% were in the UK NHS (87% of men and 86% of women). Of doctors in the NHS, 70.6% of men and 52.0% of women were in the hospital specialties and the great majority of the others were in general practice. Within hospital specialties, a higher percentage of men than women were in surgery, and a higher percentage of women than men were in paediatrics, obstetrics and gynaecology, clinical oncology, pathology and psychiatry. In the NHS, 63% of women and 8% of men were working less-than-full-time (in general practice, 19% of men and 83% of women; and in hospital specialties, 3% of men and 46% of women). Among doctors who had always worked full-time, 94% of men and 87% of women GPs were GP principals; in hospital practice, 96% of men and 93% of women had reached consultant level. The 1993 graduates show a continuing high level of commitment to the NHS. Gender differences in seniority lessened considerably when comparing doctors who had always worked full-time.


Femtosecond coherent Raman spectroscopy and its application to porphyrins.
The results on femtosecond time-resolved coherent anti-Stokes Raman scattering (CARS) experiments for the analysis and control of ground state vibrational dynamics of porphyrin systems are briefly reviewed. By detecting the spectrum of the transient CARS signal, a detailed mapping of the dynamics initiated by the stimulated Raman pump process is achieved. The method yields the dephasing behavior and spectral information of the investigated system at the same time. The different contributions to the ground state vibrational dynamics are selected by changing the direction of the CARS signal analyzer in the polarization arrangement used.


Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation.
Dorsoventral (D/V) patterning in Drosophila oogenesis is initiated by the transmission of a TGF-alpha-like ligand, Gurken (Grk), from the oocyte to the anterodorsal follicle cells, activating the EGF receptor (Egfr) signaling pathway. The zinc-finger transcription factor CF2 is a negative regulator of the rhomboid (rho) gene that encodes an essential membrane-bound component of the dorsalizing pathway. Expression of CF2 itself is negatively regulated by the activated Egfr. In this report, we demonstrate that CF2 is the target of down-regulation by the MAPK kinase cascade, and that this down-regulation is independent of the Rho function. These results suggest that D/V patterning involves a two-step signaling process: the initial Egfr signal, which represses CF2 and induces rho expression; and the subsequent Egfr + Rho signal, which determines the dorsal cell fates. Furthermore, we show that CF2 down-regulation occurs at the post-translational level through a mechanism involving coupled cytoplasmic retention and degradation.


Transcranial direct current stimulation (tDCS) to improve naming ability in post-stroke aphasia: A critical review.
Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation tool that can be used to influence cortical brain activity to induce measurable behavioral changes. Although there is growing evidence that tDCS combined with behavioural language therapy could boost language recovery in patients with post-stroke aphasia, there is great variability in patient characteristics, treatment protocols, and outcome measures in these studies that poses challenges for analyzing the evidence. The purpose of this study is to critically analyze the methodological rigor of the evidence regarding the use of tDCS for post-stroke anomia. This critical review was conducted by searching four databases (MEDLINE, EMBase, PsycINFO, and CINAHL). Nineteen studies fully met the inclusion criteria. Three critical appraisal tools and Robey and Schultz's (1998) five- phase model for conducting clinical outcome research were adopted to evaluate and analyze the current level of evidence. Methodological issues of the studies were also identified. The current level of evidence for using tDCS for anomia is at the pre-efficacy level with emerging evidence at the efficacy level. Lack of proper evaluation of carry-over effects in cross-over studies, lack of or unclear randomization, allocation concealment, and incomplete data handling were the main methodological issues that could threaten the validity of the tDCS for anomia studies. Several methodological issues have been identified in pre-efficacy studies that pose challenges in determining whether tDCS is a beneficial adjunct to behavioral aphasia therapy. Future studies need to improve the quality of the methods used to investigate the effect of tDCS for anomia.


Regulation of apicomplexan microfilament dynamics by a minimal set of actin-binding proteins.
Efficient and rapid host cell invasion is a prerequisite for an intracellular parasitic life style. Pathogens typically induce receptor-mediated endocytosis and hijack the force-transducing system of a host cell to gain access to a replication-competent niche. In striking contrast, apicomplexan parasites such as Plasmodium, the causative agent of malaria, and the human and animal pathogens Toxoplasma and Cryptosporidium employ their own actomyosin motor machinery to propel themselves into prospective host cells. Understanding the regulation and dynamics of actin-based motility of these parasites is therefore central to understanding their pathogenesis. The parasite genomes harbour surprisingly few potential actin-regulatory proteins indicating that a basic repertoire meets the requirements to regulate actin dynamics. In this article, we summarize our current knowledge of Plasmodium microfilament dynamics and describe its potential players.


Evaluation of the oxygen delivery ability of PEG-hemoglobin in Sprague-Dawley rats during hemodilution.
Polyethylene glycol (PEG) conjugation allows bovine hemoglobin (Hb) to retain its oxygen delivery capability while increasing its plasma expansion capacity. To determine whether PEG-Hb's ability to sustain life is due to its oxygen delivery capability rather than its plasma expansion capacity, Sprague-Dawley rats were exchange-transfused up to an 85% hematocrit reduction with either PEG-Hb, PEG-50%-methemoglobin (PEG-mHb), PEG-carbon monoxide hemoglobin (PEG-COHb) or PEG-human serum albumin (PEG-HSA). Survival and respiratory rates were monitored during the exchange transfusion, at five minutes, 24 hours and 48 hours post operative. Rats surviving 14 days were evaluated for hematology, blood chemistry and histopathology. Rats infused with PEG-Hb had a survival rate of 100% during the transfusion and 79% at 24 hours, as compared to 24 hour survival rates of 30% for PEG-mHb, and 0% for both PEG-COHb and PEG-HSA. PEG-Hb treated rats that survived the 2 week observation period had normal hematological and blood chemistry levels and no significant morphological effects. Therefore, this study demonstrates that PEG-Hb can sustain life while similar plasma expansion agents with less oxygen delivery capability are not as effective.


Artificial Enzyme-based Logic Operations to Mimic an Intracellular Enzyme-participated Redox Balance System.
Owing to the biocatalytic properties of artificial enzymes and the redox characteristic of glutathione, a colorimetric and resettable biological operation was successfully designed to mimic enzyme-participated redox balance in living systems. As one promising candidate of a natural enzyme, artificial enzyme possesses many advantages and has been used in numerous fields. Similar to natural enzymes, communications are also present between different artificial enzymes. With the assistance of four artificial enzymes, three simple biological logic gates were fabricated to help us deepen the understanding of communications between artificial enzymes. In the presence of glutathione, the system could be easily reset without any complicated procedures. We prospect that this work may push forward the exploration of communications between different artificial enzymes and the design of novel artificial enzyme-based biological gates or nanodevices. We hope that our mimic system may help us further understand the functioning of complex biological pathways in biological systems.


Synthesis and characterization of NBD-PS: a fluorescent analog of cerebroside arylsulfatase A deficiency disorders.
N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]psychosine sulfate (NBD-PS), a fluorescent analog of cerebroside sulfate (CS), was synthesized and tested as an alternative to the radiolabeled forms of CS used for assaying arylsulfatase A (ASA) in its physiological role as a cerebroside sulfate sulfohydrolase. NBD-PS simulates the natural substrate for ASA. Protocols have been developed for its use in differentiating low enzyme activities in diagnostic samples. Hydrolysis of NBD-PS is specific for ASA and optimal assay parameters were identical to those determined for CS. Differentiations between each of the major phenotypes for ASA activity were possible in the set of samples tested. One particular advantage was the ability to discriminate between individuals exhibiting arylsulfatase A pseudodeficiency and the truly deficient individuals with metachromatic leukodystrophy. Differential diagnosis was possible with fibroblast extracts by an assay that is more sensitive than procedures employing radioisotopes. Reaction products may be analyzed quantitatively by HPLC, or semiquantitatively with TLC. NBD-PS provides a simpler, safer, and more cost-effective means of performing natural substrate enzyme assays for ASA. Phenotyping with the fluorescence assay is an effective alternative to the laborious radioactive CS preparations and tissue culture loading studies that have previously been necessary.


Kinetic mechanism of human class IV alcohol dehydrogenase functioning as retinol dehydrogenase.
Molecular genetic studies have indicated that alcohol dehydrogenase may be involved in the synthesis of retinoic acid, a hormonal molecule regulating diverse cellular functions at the transcriptional level. Class IV alcohol dehydrogenase (ADH) has been reported to be the most efficient enzyme catalyzing oxidation of retinol in human ADH family. Initial velocity, product inhibition, and dead-end inhibition experiments were performed with the recombinant human class IV ADH to elucidate kinetic mechanism with all-trans-retinol and all-trans-retinal as natural substrates. Fluorescence quenching was titrated in formation of the binary and abortive ternary enzyme complexes. The minimal mechanism deduced from steady-state kinetic and equilibrium binding studies is best described as an asymmetric rapid equilibrium random mechanism with two dead-end ternary complexes for retinol oxidation and a rapid equilibrium ordered mechanism with one dead-end ternary complex for retinal reduction, a unique mechanistic form for zinc-containing ADHs in the medium chain dehydrogenase/reductase superfamily. Dissociation constants for the binary complexes as well as the productive and abortive ternary complexes determined from different experimental approaches are in reasonable agreement. Kinetic isotope effect studies suggest rate-limiting isomerization of the central ternary complexes in both reaction directions. The potential interference of retinol metabolism by ethanol through the ADH pathway may play a significant role in the pathogenesis of fetal alcohol syndrome and alcohol-related upper digestive tract cancer.


Leukocyte and lymphocyte subsets after a short pharmacological stress by intravenous epinephrine and hydrocortisone in healthy humans.
Nine healthy volunteers received epinephrine and hydrocortisone intravenously in order to assess the typical acute response to a brief stress, of leukocyte and lymphocyte subsets, acute phase reactants and lymphocyte reactivity to T and B mitogens. At 10 min., all leukocyte subsets were increased, especially mononuclear cells. At 1 hour, moderate lymphopenia and monocytopenia occurred. At 6 hours, neutrophilia and eosinopenia were observed. During the lymphocytic early wave, all the lymphocyte subset counts increased, particularly T-suppressive/cytotoxic and natural killer cells. As a consequence, the percentage of T cells decreased and the CD4/CD8 ratio fell. No changes in acute phase reactants occurred over the 24 hours of the study. All leukocyte and lymphocyte subsets were normalized and mitogen reactivity was unchanged 24 hours after the stress. These typical shifts in leukocyte subsets could probe the adrenocortical and medullary response to an environmental stressor.


Regulation of chondrosarcoma metabolism by cyclic adenosine 3'5'-monophosphate.
The in vitro effects of cyclic AMP on amino acid transport and synthesis of macromolecules in the Swarm rat chondrosarcoma were investigated using the cyclic AMP analogue, N6-monobutyryl cyclic AMP (MBcAMP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (MIX). Amino acid transport was assessed by measuring alpha-amino-[1-14C]isobutyrate (AIB) uptake. The synthesis of macromolecules was estimated by measuring radiolabeled precursor incorporation into total proteins, proteoglycan, and RNA. MBcAMP stimulated [14C]AIB uptake, [3H]uridine transport, and UTP formation. MBcAMP inhibited 35SO4 and [3H]leucine incorporation into proteoglycan and stimulated [3H]uridine incorporation into RNA. MIX elevated endogenous cyclic AMP levels in the Swarm rat chondrosarcoma and mimicked the effects of MBcAMP on AIB transport and radiolabeled precursor incorporation into macromolecules. For comparative purposes, the effects of MBcAMP on AIB uptake and macromolecule synthesis in rat costal cartilage segments were investigated. MBcAMP and MIX stimulated AIB uptake by costal cartilage segments, inhibited [3H]leucine incorporation into total protein and 35SO4 incorporation into proteoglycan, and had no effect on [3H]uridine incorporation into RNA.


The effect of halogen hetero-atoms on the vapor pressures and thermodynamics of polycyclic aromatic compounds measured via the Knudsen effusion technique.
Knowledge of vapor pressures of high molar mass organics is essential to predicting their behavior in combustion systems as well as their fate and transport within the environment. This study involved polycyclic aromatic compounds (PACs) containing halogen hetero-atoms, including bromine and chlorine. The vapor pressures of eight PACs, ranging in molar mass from (212-336) g.mol(-1), were measured using the isothermal Knudsen Effusion technique over the temperature range of (296-408) K. These compounds included those with few or no data available in the literature, namely: 1,4-dibromonaphthalene; 5-bromoacenaphthene; 9-bromoanthracene; 1,5-dibromoanthracene; 9,10-dibromoanthracene; 2-chloroanthracene; 9,10-dichloroanthracene and 1-bromopyrene. Enthalpies of sublimation of these compounds were determined via application of the Clausius-Clapeyron equation. An analysis is presented on the effects of the addition of halogen hetero-atoms to pure polycyclic aromatic hydrocarbons using these data as well as available literature data. As expected, the addition of halogens onto these PACs increases their enthalpies of sublimation and decreases their vapor pressures as compared to the parent compounds.


Application of the presentation-assimilation-discussion class in oral pathology teaching.
The presentation-assimilation-discussion (PAD) class is a novel teaching method in which half the class time is allocated for the instructor's presentation and the other half for student's assimilation and discussion. This study evaluates and compares the teaching outcomes of the PAD class and traditional lecture-based method in oral pathology courses in School of Stomatology, Kunming Medical University. The experimental and control groups included 88 undergraduates from Class 2017 and 72 undergraduates from Class 2016, respectively. The PAD method was applied on the experimental group in 2019, whereas the traditional lecture-based method was applied on the control group in 2018. The two groups' teaching outcomes were compared using final theory tests, biopsy diagnostic tests, and questionnaires. The Mann-Whitney U-test and independent-sample t-test were adopted for statistical analysis. In five multiple-choice questions examining the same knowledge point from final theory tests, the distribution of the final scores showed a statistically significant difference between the two groups (p < 0.05). In the biopsy diagnostic tests, the experimental group scored higher than the control group (p < 0.05). In the questionnaires, there was no statistically significant difference for the "enhancing knowledge mastery" item (p > 0.05). However, the experimental group showed significant superiority in the remaining nine items (p < 0.05). [Correction added on August 30, 2021, after first online publication: The data value p was corrected in the last sentence of result section.] CONCLUSIONS: Compared with the traditional lecture-based teaching, the PAD class stimulated a passion for learning among students and results in improved teaching outcomes. Therefore, the application of PAD class in oral pathology teaching should be recommended.


A neural network applied to criminal psychological profiling: an Italian initiative.
The author presents a brief discussion of criminal profiling followed by an introduction to the Italian Neural Network for Psychological Criminal Profiling (NNPCP) project. This project, based on a so-called neural network and data mining, is an innovative technique being developed with the intention of extending criminal profiling to single serious crimes through the use of a computerized database.