High-order multiband encoding in the heart.
Spatial encoding with multiband selective excitation (e.g., Hadamard encoding) has been restricted to a small number of slices because the RF pulse becomes unacceptably long when more than about eight slices are encoded. In this work, techniques to shorten multiband RF pulses, and thus allow larger numbers of slices, are investigated. A method for applying the techniques while retaining the capability of adaptive slice thickness is outlined. A tradeoff between slice thickness and pulse duration is shown. Simulations and experiments with the shortened pulses confirmed that motion-induced excitation profile blurring and phase accrual were reduced. The connection between gradient hardware limitations, slice thickness, and flow sensitivity is shown. Excitation profiles for encoding 32 contiguous slices of 1-mm thickness were measured experimentally, and the artifact resulting from errors in timing of RF pulse relative to gradient was investigated. A multiband technique for imaging 32 contiguous 2-mm slices, with adaptive slice thickness, was developed and demonstrated for coronary artery imaging in healthy subjects. With the ability to image high numbers of contiguous slices, using relatively short (1-2 ms) RF pulses, multiband encoding has been advanced further toward practical application.


Blood rheology and body composition as determinants of exercise performance in female rugby players.
Athletes involved in rugby are characterized by a very specific pattern of body composition with an unusually important muscle mass. In a preceding study about rugbymen we evidenced that they exhibit a correlation between red blood cell aggregability and the amount of body fat although it remains within a normal range, and that red cell rigidity was correlated to isometric adductor strength. We had the opportunity of studying the relationships among exercise performance, body composition and hemorheology in 19 female rugby players (age 19-26, mean: 24.47 ± 0.67 yr) practising 4 - 10 hr/wk (mean 7.15 ± 0.3) since 1-12 yr (mean 4,05 ± 0,694). VO2max was not related by its own to blood rheology, either hematocrit (r = -0.0717 p = 0.7706) or plasma viscosity (r = 0.0144; p = 0.9533), but other markers of performance exhivited a correlation with red cell rheology. Relationships between fitness and body composition were evidenced. Isometric handgrip strength was negatively correlated to red blood cell aggregability (Myrenne M, r = -0.57839; p = 0.00948 M1 r = -0.58910; p = 0.00795). Adductor isometric strength was negatively correlated to red blood cell aggregability Myrenne M (r = -0.5033; p = 0.0280) but not to M1 (r = -0.4227; p = 0.0714). Fat mass is a major determinant of the maximal oxygen consumption VO2max either measured by a field test (r = -0.766; p = 0.00013) or exercise test (r = -0.575; p = 0.00994) and was also negatively correlated to both handgrip (r = -0.4918; p = 0.0325) and RBC aggregability M (r = -0.57839; p = 0.00948 and M1 r = -0.5891; p = 0.00795). Independently of fat mass, FFM appears to be a determinant of blood viscosity (r = 0.4622; p = 0.0463) due to its correlation with RBC rigidity (r = 0.4781; p = 0.0384). Thus, trained young women exercising 4-10 hr/wk and thus exhibiting a low percentage of body fat exhibit clear relationships between body composition and hemorheology, but fat mass being low, the parameter correlated with blood rheology is in this case fat-free mass, consistent with recent findings indicating that high fat mass in women is sometimes correlated with parameters of the metabolic syndrome such as insulin resistance or inflammation. In addition, parameters quantifying fatness even within such a physiological range are in this sample negatively related with exercise performance.


Complex formation in systems of oppositely charged polyelectrolytes: a molecular dynamics simulation study.
Results of molecular dynamics simulations for systems with two flexible, oppositely charged polymer chains are presented. The lengths N and interaction strength lambda of the chains are varied. We find that the chains remain separated for small values of lambda. For large interaction strengths, i.e., large Bjerrum lengths, we find glasslike structures and order on the length scale of a few monomer diameters. Between these two limits of the interaction strengths, the chains of various lengths collapse into compact complexes that exhibit self-similar structures. The scaling behavior of the radius of gyration is discussed as a function of chain length and interaction strength. In addition, the local structure of the collapsed systems is analyzed and the dependence of the density of the aggregate on the interaction strength is discussed.


[Personalized approach to working up an early motor rehabilitation program for children with vertebral column and spinal cord injury, taking into account exercise tolerance].
The relevance of rehabilitation of children with vertebral column and spinal cord injury (VCSCI) is due to the steady growth in the number of such patients. The mandatory conditions for early motor rehabilitation are to size efforts, to exclude fatigue and overtraining, and to gradually increase loads. The priority tasks of drawing up an individual motor program are to determine the rehabilitation abilities of a child and his/her willingness to perform the proposed load. To investigate whether the motor rehabilitation program can be personalized for children with severe VCSCI on the basis of estimation of exercise tolerance. The investigation enrolled 25 patients with VCSCI (12 people with superior paraparesis or inferior paraplegia and 13 with inferior paraparesis or inferior paraplegia); their mean age was 12.1±5.0 years. An individual active motor rehabilitation program was worked out for all the patients according to the results of exercise tolerance testing. The latter was performed using ergospirometry to determine the maximum oxygen consumption (VO2 max) and the time to reach the anaerobic threshold. After a rehabilitation cycle, all the patients showed an increase in VO2 max and time to reach the anaerobic threshold. The obtained results about the increase in VO2 max with active exercises and the expansion of the aerobic corridor in both patient groups suggest that the exercise tolerance was enhanced due to increases in muscle strength and total body endurance. By the end of the rehabilitation cycle, all the patients displayed an increase in the motor density of exercises to 29.2±4.3 (64.9%) of the 45 min. Passive load decreased to 15.8±4.3 (35.1%) min. Assessment of the individual capabilities of a patient allows one to personalize the motor rehabilitation program. Ergospirometry is a technique to monitor the adequacy of the proposed program.


Effect of feed supplementation with zinc glycine chelate and zinc sulfate on cytokine and immunoglobulin gene expression profiles in chicken intestinal tissue.
The aim of the study was to evaluate the effect of inorganic and organic forms of Zn on the expression of cytokines (IL-2, TNF-α, IFN-γ, IL-12, IL-17, IL-4, IL-10, and TGF-β) and immunoglobulins (IgA and IgG) in the tissues of the small intestine (jejunum and ileum) of broiler chickens. In the experiment, 90 broiler chickens were divided into 4 experimental groups and a control group, with 18 birds each. The birds received Zn supplements in inorganic form with and without phytase (ZnSO4 and ZnSO4 + F), and in organic form with glycine, with and without phytase (Zn-Gly and Zn-Gly + F). The total rearing period was 42 days. Quantitative real-time (RT)-PCR was used to measure the expression of the cytokines and immunoglobulins. The differences between the results obtained for the control and experimental groups, between the groups receiving ZnSO4 and Zn-Gly, and between groups ZnSO4-F and Zn-Gly-F were analyzed statistically. High relative expression of IL-2 was observed for the chickens in the groups receiving ZnSO4-F, Zn-Gly, and Zn-Gly-F on d 42 in comparison to the control group. High relative expression of TNF-α, IL-12, and IL-17 was noted in the group that received ZnSO4 + F. High expression of IgG, IgA, IL-4, TGF-β, and IL-10 was noted in the groups of chickens that received feed supplemented with Zn-Gly and Zn-Gly + F chelates on d 42 of the study in comparison to the control group. In conclusion, supplementation with Zn-Gly chelates can ensure Th1 and Th2 balance during the immune response in the gut-associated lymphoid tissue (GALT), and, by increasing IgA and IgG expression, also can stimulate potentiation of the immune response involved in passive protection of the body from infection. In contrast, the use of inorganic forms of Zn, in the form of sulfates, can induce local inflammatory processes in the intestines, which, in the case of long-term supplementation, lead to the development of infections.


Employment equality legislation, 3 March 1988.
On 1 April 1988, new employment equality legislation came into effect in Israel. The new legislation outlaws discrimination at work on the grounds of sex, marital status, and parenthood with respect to recruitment, terms of employment, promotion, vocational training, retraining, dismissal, and severance pay. Under the legislation, 1) employers may not cause prejudice to workers who allege discrimination, help others to do so, or decline sexual advances by a direct or indirect supervisor; 2) the burden of proof in discrimination claims against an employer is on the employer if the worker can show that requirements set by the employer have been met; 3) company managers and co-owners in a partnership are personally liable for violations on the part of the employer if the firm has over six workers unless they prove that the offense was committed without their knowledge or that they had taken all appropriate measures to prevent it; and 4) no special rights given to women by law, collective agreement, or other work contract are to be considered discrimination. The legislation establishes a Public Council to advise the Minister of Labour and Social Affairs on implementing and publicizing the legislation. It also allows a father to receive the following work benefits that were previously restricted to mothers: 1) leave of absence to care for a sick child and 2) statutory leave and statutory entitlement to severance pay for resigning to care for a newborn or adopted baby if the father is the sole guardian or if the mother renounces her right because she is working.


[Eustachian orifice malignant melanoma: a case report].
The patient, a 52 year old male was admitted to the hospital, because of right hearing loss before three months. Six months ago; the patient had the right former group sinusitis and nasal polyps, and had the right former group sinus open and polypectomy operation outside the hospital. The surgery was uneventful and the postoperative dressing was done. He has no history of tinnitus, earache, ear pus, epistaxis, headache, dizziness. Physical examination on admission shows the right external auditory canal was clean, tympanic membrane integrity, pale yellow, mild depression, and poorly eardrum movement. The electronic nasopharyngoscopy show a black mass in the edge of the anterior lip of the right eustachian tube. The mass has a smooth surface, and only seen partly. Nasopharynx magnetic resonance shows in the right pharyngeal orifice visible there was a round short T2 node, maximum diameter of 13 mm, the border was clear. The parapharyngeal space had been compressed which close to the right eustachian tube torus. After the scan enhanced, the lesions was strengthened. The pure tone audiometry shows right mild conduction deafness, and the acoustic impedance showing right type B tympanogram curve. Eardrum puncture extracted got about 0.2 ml yellow liquid. Otitis media with effusion is considered. A biopsy is taken by means of the nasal endoscopic. The pathology report is the right eustachian orifice malignant melanoma. The immunohistochemical examination (Horton-Magath-Brown 45) showed a positive reaction.


Validating self-report measures of pain and function in patients undergoing hip or knee arthroplasty.
To investigate the factorial and construct validity of a four-item pain intensity scale, the P4, in patients awaiting primary total hip or knee arthroplasty secondary to osteoarthritis. A construct validation design was applied to a sample of convenience of 117 patients (mean age 65.6 [SD = 11.2] years) at their preoperative visit. All patients completed the P4 and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Exploratory and confirmatory factor analyses were used to examine the factorial structure of the P4 and WOMAC. To evaluate construct validity, we examined the correlation between the P4 and WOMAC pain sub-scales and the ability of the P4 to differentiate between patients awaiting hip and knee replacement. Two distinct factors consistent with the themes of pain and function were identified with P4 and WOMAC physical function items, but not with the WOMAC pain and physical function items. The P4 correlates more with the WOMAC pain scores (r = 0.67) than with the WOMAC physical function scores (r = 0.60). The P4's validity was supported in this patient group. The use of the P4 with the WOMAC physical function sub-scale provides a more distinct assessment of pain and function than the WOMAC pain and physical function scales.


Invasive Propionibacterium acnes infections in a non-selective patient cohort: clinical manifestations, management and outcome.
An increasing number of reports suggest that Propionibacterium acnes can cause serious invasive infections. Currently, only limited data exist regarding the spectrum of invasive P. acnes infections. We conducted a non-selective cohort study at a tertiary hospital in the UK over a 9-year-period (2003-2012) investigating clinical manifestations, risk factors, management, and outcome of invasive P. acnes infections. Forty-nine cases were identified; the majority were neurosurgical infections and orthopaedic infections (n = 28 and n = 15 respectively). Only 2 cases had no predisposing factors; all neurosurgical and 93.3 % of orthopaedic cases had a history of previous surgery and/or trauma. Foreign material was in situ at the infection site in 59.3 % and 80.0 % of neurosurgical and orthopaedic cases respectively. All neurosurgical and orthopaedic cases required one or more surgical interventions to treat P. acnes infection, with or without concomitant antibiotic therapy; the duration of antibiotic therapy was significantly longer in the group of orthopaedic cases (median 53 vs 19 days; p = 0.0025). All tested P. acnes isolates were susceptible to penicillin, ampicillin and chloramphenicol; only 1 was clindamycin-resistant. Neurosurgical and orthopaedic infections account for the majority of invasive P. acnes infections. Most cases have predisposing factors, including previous surgery and/or trauma; spontaneous infections are rare. Foreign material is commonly present at the site of infection, indicating that the pathogenesis of invasive P. acnes infections likely involves biofilm formation. Since invasive P. acnes infections are associated with considerable morbidity, further studies are needed to establish effective prevention and optimal treatment strategies.


Advancing primary care to promote equitable health: implications for China.
China is a country with vast regional differences and uneven economic development, which have led to widening gaps between the rich and poor in terms of access to healthcare, quality of care, and health outcomes. China's healthcare reform efforts must be tailored to the needs and resources of each region and community. Building and strengthening primary care within the Chinese health care system is one way to effectively address health challenges. This paper begins by outlining the concept of primary care, including key definitions and measurements. Next, results from a number of studies will demonstrate that primary care characteristics are associated with savings in medical costs, improvements in health outcomes and reductions in health disparities. This paper concludes with recommendations for China on successfully incorporating a primary care model into its national health policy, including bolstering the primary care workforce, addressing medical financing structures, recognizing the importance of evidence-based medicine, and looking to case studies from countries that have successfully implemented health reform.


Evaluating a murine model of endometritis using uterine isolates of Escherichia coli from postpartum buffalo.
Ascending infection of the uterus with Gram-negative bacteria is responsible for postpartum endometritis in cattle and buffalo and can adversely affect fertility. Development of a laboratory animal model for bovine endometritis would facilitate the understanding of the pathogenesis as it is difficult to conduct controlled experimentation in the native host. In the present study, 30 virgin Swiss Albino mice (5-8 weeks old) were used to evaluate the pathogenic potential of Escherichia coli, isolated from the normally calved postpartum buffalo to induce endometritis. Mice in the diestrus phase of the estrous cycle were randomly allotted to one of the following four intravaginal inoculation (100 μL) treatments: EG (experimental group)-1: sterile normal saline; EG-2, -3 and -4: E. coli@ 1.5 × 104, 105 and 106 CFU/ml, respectively. The animals were then scarified 36 h post-inoculation to study gross and microscopical lesions. Gross changes were confined to EG-4. Acute endometritis was recorded in 50% of the EG-3 and 66.7% of the EG-4. The rate of acute endometritis development was significantly higher in EG-4 (P<0.05) as compared to the other groups. The present study demonstrated that the animal model for bubaline endometritis can be developed in mice by intravaginal inoculation of E.coli@ 1.5 × 106 CFU/ml at diestrus. Ease of intravaginal inoculation, apparent absence of systemic involvement and high infective rate are the advantages of the model over other studies.


[Mental health of elderly and old people when using a complete dry dental prosthesis: myth or reality?]
The study studied the ratio of 17 adults with complete loss of teeth and using complete removable acrylic dentures, to the disease, taking into account the degree of stability of dentures during chewing. To determine the type of patient's attitude toward the disease, a clinical test method was used to determine the type of attitude towards the disease, in which the clinical-psychological typology of patients' attitude to 'illness' was realized, which provides the possibility of determining one of the twelve types of response. It was found that when using complete removable dentures, regardless of age and sex, the types of attitude towards the disease were more often noted, with a marked disadaptive behavior with a predominantly intrapsychic orientation of the response to the disease, which was manifested by characteristic reactions such as irritable weakness, anxious, depressed, oppressed state. The use of the cream to fix the removable dental prostheses Corega allowed to improve the stability of complete removable dentures, to eliminate the pronounced phenomena of mental disadaptation, and to create realistic treatment settings for patients, to help restore social ties.


Nature of the light-induced h efflux and na uptake in cyanobacteria.
We investigated the nature of the light-induced, sodium-dependent acidification of the medium and the uptake of sodium by Synechococcus. The rate of acidification (net H(+) efflux) was strongly and specifically stimulated by sodium. The rates of acidification and sodium uptake were strongly affected by the pH of the medium; the optimal pH for both processes being in the alkaline pH range. Net proton efflux was severely inhibited by inhibitors of adenosine triphosphatase activity, energy transfer, and photosynthetic electron transport, but was not affected by the presence of inorganic carbon (C(i)). Light and C(i) stimulated the uptake of sodium, but the stimulation by C(i) was observed only when C(i) was present at the time sodium was provided. Amiloride, a potent inhibitor of Na(+)/H(+) antiport and Na(+) channels, stimulated the rate of acidification but inhibited the rate of sodium uptake. It is suggested that acidification might stem from the activity of a light dependent proton excreting adenosine triphosphatase, while sodium transport seems to be mediated by both Na(+)/H(+) antiport and Na(+) uniport.


Organizational characteristics of Brain Injury Clubhouse Model programs.
We provide an overview of the Clubhouse Model and the history and development of Brain Injury Clubhouses. We describe organizational-level characteristics associated with eight Brain Injury Clubhouses to address gaps in the literature and inform future studies or program development. A electronic survey, the Clubhouse Profile Questionnaire (CPQ) was tailored for Brain Injury Clubhouses. The CPQ gathers program-level data that can be used to identify active ingredients of Clubhouses, understand best practices, examine, and evaluate program characteristics. The brain injury version of the CPQ was administered to a sample of eight Clubhouses affiliated with the International Brain Injury Clubhouse Association as part of a project designed to gather data on Clubhouse program characteristics and describe sociodemographic characteristics of people served by Brain Injury Clubhouses. CPQ data from eight Brain Injury Clubhouses was analyzed. Brain Injury Clubhouse programs in this sample served approximately 17 members per day. There was wide variability in the size, funding and funding mechanisms, and length of operation of Brain Injury Clubhouses in this study. Findings suggest that Brain Injury Clubhouses offer a wide range of services and supports. Additional research on the impact of Brain Injury Clubhouses is needed.


Assessment of pelvic floor function: a series of simple tests in nulliparous women.
The aim of the study was to assess normal ranges, variations, test-retest reliability and correlations between tests for a battery of simple, minimally invasive tests of pelvic floor function in nulliparous asymptomatic women. Women were recruited by advertisement and underwent dipstick urinalysis, simple cystometrics, provocative tests for incontinence, Q-tip test and surface electromyography with acrylic plug electrodes. Subjects were retested at a later date. Nineteen subjects underwent initial testing and 12 were retested. A wide range of normal values was obtained. Cystometric measures of first and strong urge to void the maximum bladder capacity, Q-tip test and rectal perineometry had significant correlations between the two visits. There were no significant between-test correlation coefficients. It was concluded that the simple tests used demonstrate a mixed ability to follow pelvic floor function longitudinally.


IL-33 and Soluble ST2 Are Associated With Recurrent Spontaneous Abortion in Early Pregnancy.
Normal pregnancy is related to the successful transition from type 1 cellular immunity to type 2 cellular immunity. Therefore, this study aimed to investigate whether there is abnormal expression of cytokines in the process of inducing Recurrent spontaneous abortion (RSA). Interleukin (IL)-33 is a new member of the IL-1 family, and ST2, as IL-33's receptor, induced the production of type 2 cytokines. In this study, blood samples were collected from 19 non-pregnant women of normal childbearing age, 28 normal pregnant women, and 33 women with RSA. The serum concentrations of IL-33 and ST2 were detected by flow cytometry. Our results showed that the serum concentrations of IL-33 and ST2 in the RSA group were significantly higher than those in the healthy control group (IL-33: P < 0.05; ST2: P < 0.0001), and IL-33 and ST2 had a higher level in the process of RSA predictive value. In addition, this study initially found that the serum concentrations of IL-33 and ST2 were not significantly correlated with the number of weeks of pregnancy, and there was a lower correlation between IL-33 and ST2 during RSA. This result may be related to the small number of cases. This study is the first time to correlate the changes in serum concentrations of IL-33 and ST2 with RSA, which may be a novel biomarker for the prediction and treatment of RSA.


Housestaff and attending physician knowledge of and attitude towards an EMR on the eve of implementation.
A variety of factors determine the successful implementation of clinical information systems such as EMR's. A major determinant of implementation success is clinical users' acceptance and willingness to use the system. Previous studies have looked at communicating with and addressing physician concerns during and post-implementation of an EMR. Our qualitative study looked at communicating with and addressing concerns of physician (housestaff and attending) users on prior to (eve of) EMR implementation as well as determining the preferred means of communication.


Combined First-Principles Calculations of Electron-Electron and Electron-Phonon Self-Energies in Condensed Systems.
We present a method to efficiently combine the computation of electron-electron and electron-phonon self-energies, which enables the evaluation of electron-phonon coupling at the G0W0 level of theory for systems with hundreds of atoms. In addition, our approach, which is a generalization of a method recently proposed for molecules [J. Chem. Theory Comput. 2018, 14, 6269-6275], enables the inclusion of nonadiabatic and temperature effects at no additional computational cost. We present results for diamond and defects in diamond and discuss the importance of numerically accurate G0W0 band structures to obtain robust predictions of zero point renormalization (ZPR) of band gaps, and of the inclusion of nonadiabatic effects to accurately compute the ZPR of defect states in the band gap.


Enhanced recovery pathways in pancreatic surgery: State of the art.
Pancreatic surgery is being offered to an increasing number of patients every year. Although postoperative outcomes have significantly improved in the last decades, even in high-volume centers patients still experience significant postoperative morbidity and full recovery after surgery takes longer than we think. In recent years, enhanced recovery pathways incorporating a large number of evidence-based perioperative interventions have proved to be beneficial in terms of improved postoperative outcomes, and accelerated patient recovery in the context of gastrointestinal, genitourinary and orthopedic surgery. The role of these pathways for pancreatic surgery is still unclear as high-quality randomized controlled trials are lacking. To date, non-randomized studies have shown that care pathways for pancreaticoduodenectomy and distal pancreatectomy are safe with no difference in postoperative morbidity, leading to early discharge and no increase in hospital readmissions. Hospital costs are reduced due to better organization of care and resource utilization. However, further research is needed to clarify the effect of enhanced recovery pathways on patient recovery and post-discharge outcomes following pancreatic resection. Future studies should be prospective and follow recent recommendations for the design and reporting of enhanced recovery pathways.


Lorenz Heister and the challenge of trepanation: a neurosurgical case study from the 18th century.
In the 18th century, medical practice was essentially based on communication. Cranial trepanation, however, was usually performed on an unconscious person. Here the dialogue ceased. It was the only operation which had to be attempted without the positive consent of the patient. Thus trepanation challenged the surgeon's skill not only with its intricate surgical practice, but also with its unusual social setting. The present paper illustrates possible ways out of the "trap of trepanation" by interweaving two points of view. On the one hand, a general account is given on the basis of surgical publications written by Lorenz Heister and his contemporaries. On the other, the unpublished sources of the Heister correspondence serve to reconstruct the case of Heinrich Wilhelm Bachmann, a German merchant who fell victim to a traffic accident and underwent trepanation in 1753. The case study shows how the physician in charge counterbalanced the patient's inability to communicate by strengthening the remaining network of professionals, and ultimately confirming his decisions by use of the post-mortem.


[Mini-invasive approach in the treatment of acute necrotizing pancreatitis].
The study aims to evaluate the efficacy of percutaneous necrosectomy performed under ultrasound control and endoscopic necrosectomy trough secondary sinus track (ENTSST) using nephroscope and cystoscope. Puncture of fluid collections in the pancreas was performed under ultrasonographic control to 23 patients with acute necrotizing pancreatitis (ANP). ENTSST using nephroscope and cystoscope was performed to 47 patients after open or percutaneous necrosectomy and persistent sepsis (without satellite collection of CT). Seventeen (74%) patients treated with percutaneous necrosectomy recovered without open surgery. Two of this group died. The average hospital stay was 42 days. Twenty-three patients required an average of two (from 1 to 4) ENTSST. Based on our initial results we believe that the percutaneous necrosectomy and ENTSST in well selected patients might be the better choice than the open necrosectomy and postoperative lavage. Common solution of these methods has not been reached yet.


Piroxicam encapsulated in liposomes: characterization and in vivo evaluation of topical anti-inflammatory effect.
Liposomes of soya phosphatidylcholine, cholesterol, and stearylamine (molar ratio 6/3/1) and 0.1% alpha-tocopherol were prepared by the extrusion of multilamellar vesicles through 0.2-micron polycarbonate membrane. Liposomes were characterized by electron transmission microscopy, and the mean structure diameter was 278 nm. The encapsulation efficiency obtained was 12.73%. The topical anti-inflammatory effect was evaluated in vivo by the cotton pellet granuloma method. We analyzed free piroxicam at 4 mg/kg, piroxicam encapsulated in liposomes added to 1.5% hydroxyethylcellulose (HEC) gel at 1.6 mg/kg, and piroxicam encapsulated in liposomes added to HEC gel at 4 mg/kg; the inhibition of inflammation obtained was 21.1%, 32.8%, and 47.4%, respectively. These results showed that the encapsulation of piroxicam produced an increase of topical anti-inflammatory effect, suggesting that the inhibition of inflammation can be obtained with lower drug concentrations.


[Attitudes of Norwegian physicians to homeopathy. A questionnaire among 2 019 physicians on their cooperation with homeopathy specialists].
This study presents Norwegian doctors' attitudes concerning co-operation with homeopaths, their advice to patients who want to try homeopathic treatment and for which diseases, if any, they might be positive to homeopathic treatment. The Norwegian Medical Association made a randomised, stratified sample consisting of 2,019 Norwegian doctors below the age of 71. The study was made questionnaire-based and a total of 1,434 doctors (71%) replied. 7% of the doctors have or wish to have patient-associated collaboration with homeopaths. 32% would give positive advice to patients who expressed a desire to try homeopathic treatment, while 50%, owing to insufficient knowledge, would not give advice. Doctors educated abroad are more positive to homeopathic treatment than doctors educated in Norway are. 50% of Norwegian doctors tend to be positive to homeopathic treatment for one or more specific conditions. Anxiety, migraine and hayfever are the conditions most often mentioned. Male senior doctors are the least positive to homeopathic treatment for all of the listed conditions. Patients who would like to try homeopathic treatment after consultation with a doctor should consult a female general practitioner who has studied abroad.


Ovariectomy Alters Gene Expression of the Hippocampal Formation in Middle-Aged Rats.
Ovarian hormones regulate the transcriptome of the hippocampus and modulate its functions. During menopause this complex signaling declines, leading to impaired learning and memory. This study was undertaken to clarify the effects of long-term, surgical ovariectomy (OVX) on the rat hippocampal transcriptome. At age of 13 months, intact control and ovariectomized groups were formed. All animals were killed 5 weeks after gonadectomy; hippocampal formations were dissected and processed for transcriptome analysis. Microarray and polymerase chain reaction studies identified 252 and 61 genes, respectively, whose expression was altered in the lack of ovarian hormones. Pathway analysis revealed impact on neuroactive ligand-receptor interaction, endocannabinoid, and estrogen signaling, among others. Network and interaction analyses of proteins encoded by OVX-regulated genes revealed upregulation of growth/troph/transcription factor signaling assembly (Mdk, Fgf1, Igf2, Ngf, Ngfr, Ntf3, Ntrk1, Otx2, Hif1a, Esr1, Nr4a3), peptides/peptide receptors (Cartpt, Kl, Ttr, Gnrhr), neurotransmission (Grm1, Gria4, Gls, Slc18a2, Kcnj6), and genes serving immune functions (C3, Ccl2, Itgam, Il1b). Downregulated clusters included neuropeptides and their receptors (Adcyap1, Cbln2, Cck, Cckbr, Crhr1 and 2, Oprd1, Nts, Penk, Sstr1, Vip), neurotransmitter signaling (Htr2c, Chrna3, Chrm4, Grm8, Hrh3, Slc17a6), and potassium channels (Kcnk9, Kcnj9, Kcnma1, Kcnc2). Several transcription factors (Rxra, Thrb), solute carriers and defense molecules (Apitd1, Bcl2, C1ql3, Ilr3a, Sod1, Sncb) also underwent downregulation. The findings indicate that surgical gonadectomy carried out at middle-age robustly changes the hippocampal transcriptome that alters neurogenesis, synaptic plasticity, immune modulation, causing cognitive dysfunctions.


Difference in early development of presumed monozygotic twins with Rett syndrome.
Normal early development has generally been insisted on as an essential criterion for the diagnosis of Rett syndrome. A new set of monozygotic female twins is reported. Twin 1 was considered to be abnormal from birth while delay was not suspected in twin 2 until she was about one year old. Some regression occurred during the second year in both twins, who are now clinically indistinguishable from each other at age 4 years. Other than a slight difference in head circumference at birth, no environmental factor which could account for the clinical difference has been identified.


Attenuation of transforming growth factor beta-induced growth inhibition in human hepatocellular carcinoma cell lines by cyclin D1 overexpression.
Transforming growth factor-beta1 (TGF-beta1) causes growth inhibition in many cell types. Since its role in the outgrowth of human hepatocellular carcinoma (HCC) is not clearly understood, we investigated the growth inhibitory effects of TGF-beta1, the genetic and molecular integrity of TGF-beta receptors, and the expression levels of cell cycle regulating proteins in 11 human HCC cell lines. Of 11 cell lines, 3 (27%) showed growth inhibition to TGF-beta1, whereas the other 8 cell lines did not. We performed Southern and Northern analysis of TGF-beta type I and II receptors and examined poly-adenine track mutation of the TGF-beta type II receptor, but failed to find any genetic mutation. The transcriptional induction of plasminogen activator inhibitor-1 and p21(WAF1/CIP1) by TGF-beta were detected in all HCC cell lines, implying that the molecular integrity of the TGF-beta receptors might be intact. The amplification and overexpression of cyclin D1 gene was detected in 4 (50%) of 8 HCC cells that showed resistance to TGF-beta1. The suppression of cyclin D1 expression with antisense cyclin D1 facilitated the TGF-beta1-triggered growth inhibition in a TGF-beta1 resistant HCC cell line containing amplified cyclin D1 gene. In conclusion, the overexpression of cyclin D1 may be responsible for the attenuation of TGF-beta1 induced growth inhibition in some HCC cells.


Remodeling of vimentin cytoskeleton correlates with enhanced motility of promyelocytic leukemia cells during differentiation induced by retinoic acid.
The intermediate filament (IFs) cytoskeleton is one of the major determinants for the mechanical properties of cytoplasm. Vimentin is the major IFs protein in peripheral blood neutrophils. We investigated its expression and function during neutrophil differentiation using the promyelocytic leukemia cell line NB4. The differentiation of NB4 cells along the neutrophil lineage and the monocytic pathway was induced by all-trans retinoic acid (ATRA) and phorbol esters (PMA), respectively. We demonstrated a down-regulation of vimentin after ATRA treatment of NB4 cells by immunoblotting and immunofluorescence. The architecture of the vimentin cytoskeleton in differentiated NB4 cells resembled that observed in mature neutrophils. In contrast, we showed a slight increase of vimentin content in phorbol ester (PMA)-treated NB4 cells. The structural features of the vimentin cytoskeleton obtained by image analysis showed significant differences in network density and directionality between ATRA-treated NB4 cells and controls. The functional consequence of the cytoskeletal remodeling for the mechanical properties of NB4 cells was assessed in migration assays. After ATRA treatment, we found a 4-fold increased migration of NB4 cells across transwell membranes with a 8 microm pore size without any cell size modification. No significant differences between PMA-treated NB4 cells and control cells could be observed using similar tests. These results indicate that both vimentin expression and network architecture are tightly controlled during neutrophil differentiation to regulate the mechanical properties of these cells.


Expression of adiponectin and its receptors in the porcine hypothalamus during the oestrous cycle.
Adiponectin is a hormonal link between obesity and reproduction, and its actions are mediated by two types of receptors: adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). This study compares the expression levels of adiponectin and adiponectin receptor mRNAs and proteins in selected areas of the porcine hypothalamus responsible for GnRH production and secretion: the mediobasal hypothalamus (MBH), pre-optic area (POA) and stalk median eminence (SME). The tissue samples were harvested on days 2-3, 10-12, 14-16 and 17-19 of the oestrous cycle. Adiponectin mRNA expression in MBH was significantly lower on days 14-16, whereas in SME, the most pronounced gene expression was found on days 2-3 of the cycle (p < 0.05). Adiponectin protein in MBH was most abundant on days 17-19 and in POA on days 2-3 (p < 0.05). Adiponectin protein expression in SME was at similar level throughout the most of the cycle with a statistically significant drop (p < 0.05) on days 14-16. AdipoR1 gene expression in POA was potentiated on days 2-3 and 10-12 of the oestrous cycle (p < 0.05). In SME, the highest AdipoR1 mRNA expression was noted on days 2-3 (p < 0.05). The concentrations of the AdipoR1 protein in POA were similar throughout the luteal phase (days 2-14 of the cycle), and they decreased on days 17-19 (p < 0.05). In SME, AdipoR1 protein expression peak occurred on days 2-3 (p < 0.05). The expression patterns of the AdipoR2 gene in MBH, POA and SME revealed the highest mRNA levels on days 2-3 of the cycle (p < 0.05). The highest content of AdipoR2 protein in MBH was reported on days 2-3 (p < 0.05), while in POA on days 17-19 and in SME on days 10-12 and 14-16 (p < 0.05). This study demonstrated that adiponectin and adiponectin receptor mRNAs and proteins are present in the porcine hypothalamus and that their expression levels are determined by the pig's endocrine status related to the oestrous cycle.


Mushroom tyrosinase inhibition activity of some chromones.
Currently, aloesin is used in the cosmetic industry as a whitening agent because it inhibits tyrosinase activity. Aloesin is a C-glycosylated chromone compound isolated from aloe, and it is difficult to synthesize because of C-glycosyl moiety in the molecule. The purpose of this study is to search for a new chromone compound which is easy to synthesize and which posesses stronger tyrosinase inhibitory activity than aloesin. Fourteen chromone derivatives were synthesized and screened for their mushroom-tyrosinase inhibitory activity. 5-Methyl-7-methoxy-2-(2'-benzyl-3'-oxobutyl)chromone (15) showed the strongest activity among tested compounds. Its activity was not only stronger than aloesin, but also stronger than arbutin and kojic acid. The kinetic analysis revealed a competitive inhibition of 15 with tyrosinase for the L-tyrosine binding site.


Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients.
The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.


The Bambuí Health and Aging Study (BHAS): private health plan and medical care utilization by older adults.
The aim of this cross sectional study was to investigate whether holding a private health plan affects the consumption of medical services (hospitalization and visits to a doctor) and use of medications by older adults. All residents in Bambuí town (Minas Gerais, Brazil) aged >/= 60 years (n = 1,742) were selected. From these, 92.2% were interviewed and 85.9% were examined (blood tests and physical measurements). After adjustments for worse health status, reported less visits to a doctor, and used a small number of prescribed medications. The main explanation for the aged holding a private health plan was economic, not health. Even though those who had only public health coverage complained more in relation to medical care (70.9%), an important proportion of the aged with a private health care plan presented some kind of complaint (45.2%). Another worrying factor was the difficulty to acquire medication because of financial problems (47.2 and 25.2% reported, respectively). Further investigations are needed to verify whether our results can be generalized to other communities of the country.


Liver Failure in Neonates With G6PD Deficiency.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly inherited enzyme defect that can present with hemolysis, hyperbilirubinemia, and jaundice and may cause kidney and liver dysfunction. G6PD deficiency may serve as a cofactor for chronic liver disease; however, an association with liver failure is not well described. We present the cases of 2 neonates with G6PD deficiency and progressive liver failure resistant to treatment with ursodiol that eventually required liver transplantation. Our cases underscore the importance of monitoring liver function in jaundiced neonates with underlying G6PD deficiency and demonstrate the potential precipitation of liver disease by G6PD deficiency.


[Palliative care: therapeutic possibilities for patients at the end of life].
Palliation seeks to provide alleviation of pain and all other physical complaints, together with psychologic and spiritual support. The commonly used symptomatic therapies are undoubtedly fit to significantly improve the patient's quality of life. Subjects of palliative medicine should be included in postgraduate nursing education, covering above all the basic notions listed by the WHO, such as the principles of efficient communication, the pathophysiology of symptoms in advanced cancer, the evaluation and importance of pain, the basic physiologic and spiritual needs of the seriously ill or the dying. It is also mandatory to care about the physiologic needs of the patient's family and to know the physiologic and psychologic reactions in coping with grief.


Content and chemical compositions of cerebrosides in lactose-assimilating yeasts.
Cerebrosides were found in ten lactose-assimilating yeasts. Representative component ceramide moieties of cerebrosides from nine of these yeasts contained 9-methyl-4-trans, 8-trans-sphingadienine, and 2-hydroxy fatty acid with carbon chain lengths of 16 or 18. The major ceramide moieties in Brettanomyces anomalus, however, differed from those in other yeasts, and were predominately moieties containing 2-hydroxymyristic acid. Thus we found that various cerebroside molecular species are present in yeasts.


Statistical moments of quantum-walk dynamics reveal topological quantum transitions.
Many phenomena in solid-state physics can be understood in terms of their topological properties. Recently, controlled protocols of quantum walk (QW) are proving to be effective simulators of such phenomena. Here we report the realization of a photonic QW showing both the trivial and the non-trivial topologies associated with chiral symmetry in one-dimensional (1D) periodic systems. We find that the probability distribution moments of the walker position after many steps can be used as direct indicators of the topological quantum transition: while varying a control parameter that defines the system phase, these moments exhibit a slope discontinuity at the transition point. Numerical simulations strongly support the conjecture that these features are general of 1D topological systems. Extending this approach to higher dimensions, different topological classes, and other typologies of quantum phases may offer general instruments for investigating and experimentally detecting quantum transitions in such complex systems.


[Self-microemulsifying drug delivery system increasing solubility and intestinal absorption in situ of tanshinones].
Study the effect of self-microemulsifying drug delivery system(SMEDDS) on the solubility and absorption of tanshinones to guide the selection of composition of tanshinone SMEDDS. The solubility of tanshinones in the solution of SMEDDS was determined by UV-spectrometer and the absorption of tanshinone SMEDDS was determined by HPLC as the detection method. The solubility of tanshinones in solution of SMEDDS was 10 times in water and 2.5 times in micelle solution. The solubility of tanshinones in solution of SMEDDS was increased with the increasing of oil (MCT) in composition of tanshinone SMEDDS. The absorption constants (Ka) in SMEDDS and micelle solution was 0.479 h(-1) and 0.326 h(-1) respectively, and the absorption half life (t1/2) was 1.44 h and 2.12 h respectively. The absorption was increased with the oil increasing in composition of tanshinone SMEDDS. SMEDDS can increase the solubility and absorption of tanshinones significantly and the increasing of oil content (MCT) in SMEDDS composition promote the dissolution and absorption of tanshinones.


Expectancy in placebo-controlled trials of psychedelics: if so, so what?
Modern psychedelic research remains in an early phase, and the eventual introduction of psychedelics into clinical practice remains in doubt. In this piece, we discuss the role of blinding and expectancy in psychedelic trials, and place this in a broader historical and contemporary context of blinding in trials across the rest of healthcare. We suggest that premature and uncritical promotion ('hype') of psychedelics as medicines is not only misleading, but also directly influences participant expectancy in ongoing psychedelic trials. We argue that although psychedelic trials are likely to significantly overestimate treatment effects by design due to unblinding and expectancy effects, this is not a unique situation. Placebo-controlled RCTs are not a perfect fit for all therapeutics, and problems in blinding should not automatically disqualify medications from licencing decisions. We suggest that simple practical measures may be (and indeed already are) taken in psychedelic trials to partially mitigate the effects of expectancy and unblinding, such as independent raters and active placebos. We briefly suggest other alternative trial methodologies which could be used to bolster RCT results, such as naturalistic studies. We conclude that the results of contemporary placebo-controlled RCTs of psychedelics should neither be dismissed due to imperfections in design, nor should early data be taken as firm evidence of effectiveness.


Neuroblastoma in Adolescents and Children Older than 10 Years: Unusual Clinicopathologic and Biologic Features.
Neuroblastoma (NB) in children older than 10 years is rare. We reviewed our archives for patients with NB aged 10 to 18 years and summarized their clinicopathologic/genetic records. Of 96 patients, 4 patients were identified in this age group. Four tumors were abdominal; 1 patient had 2 tumors at diagnosis, one of which was presacral. Tumor sizes ranged from 3 to 20 cm. All tumors were high risk at clinical stages 3 and 4, with metastasis to bone marrow and other areas. Four tumors were poorly differentiated with unfavorable histology and one patient with bilateral adrenal disease had an intermixed ganglioneuroblastoma on one side. Another tumor exhibited pheochromocytoma-like morphology. MYCN amplification was present in bone marrow metastasis in one case. Complex chromosomal gains and 19p deletions were common. Exome sequencing revealed ALK variants in 2 cases and previously unreported MAGI2, RUNX1, and MLL mutations. All patients received standard chemotherapy and 2 patients received ALK-targeted trial therapy. Three patients died of disease, ranging 18 to 23 months after diagnosis. One patient has active disease and is receiving trial therapy. In conclusion, NB in children older than 10 years may exhibit unusual clinicopathologic and genetic features with large tumors, bilateral adrenal disease, rare morphologic features, complex DNA microarray findings and novel mutations. Patients often have grim prognoses despite genomic profiling-guided targeted therapy.


Incidence of nutritional risk and causes of inadequate nutritional care in hospitals.
Many patients in hospitals are undernourished and nutritional care is inadequate in most hospitals. The aim of this investigation was to gain insight into how this situation could be improved. Seven hundred and fifty randomly selected patients were screened at admission in three hospitals and surveyed during their entire hospitalization. Each time a patient was not treated according to a clearly defined nutritional standard, the nurse responsible for the patient was interviewed about possible reasons according to preformed questionnaires. The investigators found that 22% of the patients were nutritionally at-risk, and that only 25% of these patients received an adequate amount of energy and protein. The departments had only screened for nutritional problems in 60% of the cases. Only 47% of the patients, who the departments judged to be at-risk patients, had a nutrition plan worked out, and only about 30% of the at-risk patients were monitored by the departments by recording of dietary intake and/or body weight. The main causes for inadequate nutritional care were lack of instructions to deal with these problems, and lack of basic knowledge with respect to dietary requirements and practical aspects of the hospital's food provision. Patient-related aspects and the system of food provision also contributed, but only to a small degree. These findings form the basis of the strategy to improve nutritional care in these hospitals.


Wisconsin Cytology Proficiency Testing Program. Results of voluntary testing in 1994.
The Wisconsin Cytology Proficiency Testing Program (WCPTP) was developed cooperatively by the Wisconsin State Laboratory of Hygiene, the Wisconsin Society of Pathologists and the Wisconsin Society of Cytology to enable pathologists and cytotechnologists in Wisconsin to meet Clinical Laboratory Improvement Act of 1988 (CLIA '88) requirements for proficiency testing (PT). A joint steering committee designed the WCPTP to comply with all CLIA '88 regulations. The WCPTP application to the Health Care Financing Administration received tentative approval in May 1994. In 1994, mock PT was conducted at meetings of both state societies, and voluntary, on-site PT was conducted at 19 laboratories. Each of the 119 participants (49 pathologists, 70 cytotechnologists) was tested with sets of 10 glass slides, each representing one of four specified categories: A, unsatisfactory; B, normal/benign; C, low grade squamous intraepithelial lesion; and D, high grade squamous intraepithelial lesion and cancer. The failure rate for pathologists was 22.5% (11/49) and for cytotechnologists, 1.4% (1/70). The CLIA '88 scoring system for pathologists is more stringent. If cytotechnologists were scored as pathologists, 10% (7/70) would have failed. Using the cytotechnologist grid, 14.5% (7/49) of the pathologists would have failed. This voluntary program provided some preliminary insights into the issues related to PT evaluation of personnel competence and diagnostic criteria.


Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.
Clinical genetic evaluation has been demonstrated as an important tool to elucidate the causes of growth disorders. Genetic defects of collagen formation (the collagenopathies) have been reported to be associated with short stature and skeletal dysplasias. Etiological diagnosis of skeletal abnormality-related short stature is challenging, and less is known about recombinant human growth hormone (rhGH) therapy. This is a single-center cohort study which aims at exploring the genetic architecture of short-stature children with skeletal abnormalities and evaluating the frequency of collagenopathies to determine their phenotype, including the rhGH treatment response. One hundred and six children with short stature and skeletal abnormalities were enrolled who were evaluated by next-generation sequencing (NGS) to detect variants in the skeletal collagen genes including COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, and COL11A2. The results were evaluated using American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical characteristics and rhGH treatment response were summarized. Twenty-four pathogenic or likely pathogenic variants of collagen genes were found in 26 of 106 (24.5%) short-stature patients with skeletal abnormalities, of which COL2A1 mutations were the most common, accounting for about 57.7%. Other frequent mutations associated with skeletal development include FGFR3, ACAN, NPR2, COMP, and FBN1 in 12.2%, 0.9%, 0.8%, 0.4%, and 0.4%, respectively, resulting in significantly different degrees of short stature. An overview of clinical features of collagenopathies showed growth retardation, skeletal abnormalities, and heterogeneous syndromic abnormalities involving facial, eye, hearing, and cardiac abnormalities. The average height of 9 patients who received rhGH treatment improved from a median of -3.2 ± 0.9 SDS to -2.2 ± 1.3 SDS after 2.8 ± 2.1 years. The most significant height improvement of 2.3 SDS and 1.7 SDS was also seen in two patients who had been treated for more than 6 years. A proband-based NGS revealed that distinct genetic architecture underlies short stature in varying degrees and clinical features. Skeletal abnormality-related short stature involving multiple systems should be tested for skeletal collagen gene mutation. Limited rhGH treatment data indicate an improved growth rate and height, and close monitoring of adverse reactions such as scoliosis is required.


Factors predicting labor induction success: a critical analysis.
Because of the risk of failed induction of labor, a variety of maternal and fetal factors as well as screening tests have been suggested to predict labor induction success. Certain characteristics of the woman (including parity, age, weight, height and body mass index), and of the fetus (including birth weight and gestational age) are associated with the success of labor induction; with parous, young women who are taller and lower weight having a higher rate of induction success. Fetuses with a lower birth weight or increased gestational age are also associated with increased induction success. The condition of the cervix at the start of induction is an important predictor, with the modified Bishop score being a widely used scoring system. The most important element of the Bishop score is dilatation. Other predictors, including transvaginal ultrasound (TVUS) and biochemical markers [including fetal fibronectin (fFN)] have been suggested. Meta-analyses of studies identified from MEDLINE, PubMed, and EMBASE and published from 1990 to October 2005 were performed evaluating the use of TVUS and fFN in predicting labor induction success in women at term with singleton gestations. Both TVUS and Bishop score predicted successful induction [likelihood ratio (LR)=1.82, 95% confidence interval (CI)=1.51-2.20 and LR=2.10, 95%CI=1.67-2.64, respectively]. As well, fFN and Bishop score predicted successful induction (LR=1.49, 95%CI=1.20-1.85, and LR=2.62, 95%CI=1.88-3.64, respectively). Although TVUS and fFN predicted successful labor induction, neither has been shown to be superior to Bishop score. Further research is needed to evaluate these potential predictors and insulin-like growth factor binding protein-1 (IGFBP-1), another potential biochemical marker.


The In Vitro Enzymatic Degradation of Cross-Linked Poly(trimethylene carbonate) Networks.
The in vitro enzymatic degradation of cross-linked poly(trimethylene carbonate) networks (PTMC-Ns) was performed in lipase solutions at 37 °C, and the effect of the initial molecular weight and cross-linker amount as well as the cross-linker type on the degradation rate of PTMC-Ns was investigated. Due to their denser structure and more hydrophobic surface as well as the higher glass transition temperature, a slower degradation rate was seen for PTMC-Ns with high initial molecular weight at a given cross-linker amount. Similar results could be observed as the cross-linker amount increased, and cross-linker type also influenced the degradation rate of PTMC-Ns. Furthermore, the enzymatic degradation of PTMC-Ns was accelerated by the surfactants role of lipase via surface erosion mechanism, the enzymatic degradation rate was higher than that of hydrolysis case. The results indicated that PTMC-Ns were promising candidates for clinical subcutaneous implants, especially due to their tunable degradation rate and enhanced form-stability as well as no acidic degradation products.


Disentangling Risk and Uncertainty: When Risk-Taking Measures Are Not About Risk.
Many studies claim to measure decision-making under risk by employing the Domain-Specific Risk-Taking (DOSPERT) scale, a self-report measure, or the Balloon Analogue Risk Task (BART), a behavioural task. However, these tasks do not measure decision-making under risk but decision-making under uncertainty, a related but distinct concept. The present commentary discusses both the theoretical and empirical basis of the distinction between uncertainty and risk from the viewpoint of several scientific disciplines and reports how many studies wrongfully employ the DOSPERT scale and BART as risk-taking measures. Importantly, we call for proper distinguishing between (tasks measuring) decision-making under uncertainty and decision-making under risk in psychology, and related fields. We believe this is vital as research has shown that people's attitudes, behaviour, and brain activity differ between both concepts, indicating that confusing the concepts may lead researchers to erroneous conclusions.


CD9 antigen interacts with heparin-binding EGF-like growth factor through its heparin-binding domain.
Heparin/heparan-sulfate proteoglycan (HSPG) binds to heparin-binding epidermal growth factor-like growth factor (HB-EGF) through its heparin-binding domain (HBD), which consists of 21 amino acid residues (P21). The CD9 antigen also interacts with a membrane-anchored form of HB-EGF (proHB-EGF) and enhances its juxtacrine activity. The CD9 antigen potentiates the juxtacrine activity of both proHB-EGF and proamphiregulin, but has no effect on proTGF-alpha. While both HB-EGF and amphiregulin contain an HBD, TGF-alpha does not. This suggests that the HBD of HB-EGF is also involved in CD9 antigen binding. Mutant CHO cells which lack HSPG recovered their capacity to bind to immobilized P21 when transfected with CD9 antigen cDNA. This binding was competitively inhibited by heparin in a dose-dependent manner. The interactions between synthetic peptides corresponding to the extracellular domain of CD9 antigen and the immobilized P21 were analyzed with surface plasmon resonance. The 119VIKEVQEFYKDTYNKLKTKD138 sequence of the CD9 antigen is thought to represent the binding site for HB-EGF. The k(D) values for heparin/P21 and 119V-D138/P21 were (2.82+/-0.10) x 10(-8) M and (3.71+/-0.71) x 10(-5) M, respectively. These results suggest that the 119V-D138 sequence of the CD9 antigen is the site which interacts with the HBD and may play an essential role in the upregulation of the juxtacrine activity of proHB-EGF.


Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease.
In the present study, the changes in circulating IGF-1 and its binding protein IGFBP-3 were determined in adult patients with active inflammatory bowel disease (IBD) in order to assess the effect of this inflammatory condition on the IGF system. IGF-1 and IGFBP-3, as well as interleukin-6 (IL-6) were measured in serum obtained from 22 consecutive newly diagnosed patients (mean age 41.3 years) with active IBD, including 10 patients with Crohn's disease (CD), and 12 with ulcerative colitis (UC). For comparison the same parameters were determined in 30 healthy volunteers matched for age, sex and Body Mass Index (BMI). Serum IGF-1 and IGFBP-3 levels were similar in the two subgroups of patients and the values from all patients were combined for comparison with those from the control group. The mean (+/- SD) serum IGF-1 concentration (178 +/- 91 ng/ml) in the patients with IBD was lower compared with that in the controls (227 +/- 79 ng/ml, P<0.035). Similarly, the mean IGFBP-3 concentration in the patients was lower than in the controls (1.6 +/- 0.6 ng/ml vs 3.2 +/- 0.7 ng/ml respectively, P<0.001), Serum IL-6 levels were higher in the patients compared with the controls (5.5 +/- 4.2 vs 0.65 +/- 0.11 pg/ml, P<0.0001). The reduced IGF-1 and IGFBP-3 levels in patients with active IBD suggest that this systemic inflammatory condition is associated with a degree of acquired GH resistance, possibly induced by inflammatory cytokines.


Synthesis, Characterization, and Biological Activity of N (')-[(Z)-(3-Methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide and Its Co(II), Ni(II), and Cu(II) Complexes.
Reaction of 1-phenyl-3-methyl-4-benzoyl-pyrazol-5-one and benzoyl hydrazide in refluxing ethanol gave N (')-[(Z)-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide (HL(1)), which was characterized by NMR spectroscopy and single-crystal X-ray structure study. X-ray diffraction analyses of the crystals revealed a nonplanar molecule, existing in the keto-amine form, with intermolecular hydrogen bonding forming a seven-membered ring system. The reaction of HL(1) with Co(II), Ni(II), and Cu(II) halides gave the corresponding complexes, which were characterized by elemental analysis, molar conductance, magnetic measurements, and infrared and electronic spectral studies. The compounds were screened for their in vitro cytotoxic activity against HL-60 human promyelocytic leukemia cells and antimicrobial activity against some bacteria and yeasts. Results showed that the compounds are potent against HL-60 cells with the IC50 value ≤5 μM, while some of the compounds were active against few studied Gram-positive bacteria.


Effects of ozone on normal and potentially sensitive human subjects. Part I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects.
We report here the results of a multiphase project to assess the significance of airway responsiveness and airway injury in ozone (O3)* sensitivity. In Phase I, we measured the preexposure methacholine responsiveness of 66 normal subjects and then exposed these subjects to 0.2 ppm O3 for 4 hours with moderate exercise. Preexposure methacholine responsiveness was weakly correlated with O3-induced increases in specific airway resistance (sRaw) but not O3-induced declines in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). In addition, O3-induced lower respiratory symptoms were not well correlated with O3-induced changes in lung function. In Phase II, we exposed 23 normal subjects to O3, following an identical protocol to that of Phase I, and then performed bronchoscopy with proximal airway lavage (PAL), bronchoalveolar lavage (BAL), and bronchial biopsy at 18 hours after exposure. Ozone-induced increases in percentage of neutrophils and total protein concentration were observed in both bronchial fraction and BAL fluids; increased percentage of neutrophils also was observed in PAL fluid. These increases were correlated with O3-induced increases in sRaw, but not with O3-induced declines in FEV1 or FVC. Ozone also appeared to increase expression of intercellular adhesion molecule-1, an important mediator of neutrophil recruitment, in bronchial mucosa. In Phase III, we exposed a group of 19 asthmatic subjects to O3, following a protocol identical to that of Phase II. We then compared the lower respiratory symptom and lung function responses of the asthmatic subjects to those of the 81 normal subjects who participated in Phase I, Phase II, or both. The changes in the PAL and BAL fluids of the asthmatic subjects were compared with those of the normal subjects who participated in Phase II. Although both the asthmatic and nonasthmatic subjects showed significant O3-induced changes in lower respiratory symptoms, FEV1, FVC, and sRaw, no significant differences were found between the groups. For sRaw, however, a nonsignificant trend toward a greater O3-induced increase was noted for the asthmatic subjects. In contrast, the O3-induced increases in percentage of neutrophils and total protein concentration in BAL fluid were significantly greater for the asthmatic subjects than for the nonasthmatic subjects. These data suggest that although the lower respiratory symptom and lung function responses to O3 are not markedly greater in asthmatic subjects than in healthy subjects, the inflammatory response of the asthmatic lung may be more intense.


Pitfalls in epidemiological analysis.
Epidemiologists rely heavily on the relative risk in their analyses and presentations. As an index it is intelligible and intuitively appealing but can give an exaggerated impression of the strength of the association and is unreliable for comparisons. This can be shown by deriving relative risks from a normal correlation surface with an unimpressive level of correlation. Relative risks ought to be handled with caution; the underlying population risk and the relative size of exposed and reference categories should be reported. Efforts to control for additional variables, confounders, by some kind of multi-variate technique, another standard procedure, could easily give a false sense of security. From time to time it has been made clear in the literature that errors of measurement in the third variable or in the additional variables could lead to the appearance of false independent effects, but these warnings do not seem to have been heeded nearly as much as they deserve. A simulation experiment is used to bring the lesson home, with realistic numerical assumptions. A moderate degree of error contamination will produce spurious effects. This has nothing to do with sampling errors, large samples rather aggravate this danger. In meta-studies this is a source of error and conflicting results to take account of.


Nociceptin/orphanin FQ receptors modulate glutamate extracellular levels in the substantia nigra pars reticulata. A microdialysis study in the awake freely moving rat.
Intracerebral microdialysis was employed in awake freely moving rats to investigate the effects of nociceptin/orphanin FQ receptor ligands on glutamate extracellular levels in the substantia nigra pars reticulata. Nociceptin/orphanin FQ, ineffective at 0.1 microM, induced a prolonged stimulation of nigral glutamate levels at 1 and 10 microM (mean effect of 137+/-9 and 167+/-13%, respectively, of basal values). These effects were prevented by the novel nociceptin/orphanin FQ receptor antagonist [Nphe(1)]nociceptin/orphanin FQ(1-13)NH(2) (100 and 300 microM, respectively) but not by the non-selective opioid receptor antagonist naloxone (10 microM). [Nphe(1)]nociceptin/orphanin FQ(1-13)NH(2) (100 microM) inhibited by itself glutamate outflow (maximal reduction to 71+/-4%) while naloxone was ineffective. The nociceptin/orphanin FQ receptor ligand [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin/orphanin FQ(1-13)NH(2) also facilitated glutamate outflow at 10 microM (mean effect of 145+/-10%). Intranigral perfusion with tetrodotoxin (1 microM) or with the dopamine D(2) receptor antagonist raclopride (1 microM), failed to affect basal glutamate output and prevented the facilitatory effect of nociceptin/orphanin FQ (10 microM). However, perfusion with the GABA(A) receptor antagonist bicuculline (10 microM) increased local glutamate extracellular levels by itself and attenuated the effect of the peptide. Our data suggest that nociceptin/orphanin FQ increases glutamate extracellular levels in the substantia nigra pars reticulata via activation of nociceptin/orphanin FQ receptors located on non-glutamatergic, possibly dopaminergic and GABAergic, neuronal elements.


Microbial Efflux Pump Inhibitors: A Journey around Quinoline and Indole Derivatives.
Antimicrobial resistance (AMR) is a complex threat to human health and, to date, it represents a hot topic in drug discovery. The use of non-antibiotic molecules to block resistance mechanisms is a powerful alternative to the identification of new antibiotics. Bacterial efflux pumps exert the early step of AMR development, allowing the bacteria to grow in presence of sub-inhibitory drug concentration and develop more specific resistance mechanisms. Thus, efflux pump inhibitors (EPIs) offer a great opportunity to fight AMR, potentially restoring antibiotic activity. Based on our experience in designing and synthesizing novel EPIs, herein, we retrieved information around quinoline and indole derivatives reported in literature on this topic. Thus, our aim was to collect all data around these promising classes of EPIs in order to delineate a comprehensive structure-activity relationship (SAR) around each core for different microbes. With this review article, we aim to help future research in the field in the discovery of new microbial EPIs with improved activity and a better safety profile.


Action of myeloperoxidase-hydrogen peroxide-chloride system on the egg white lysozyme.
The enzyme system composed of human neutrophilic myeloperoxidase (H2O2-oxidoreductase, EC 22.214.171.124), H2O2 and Cl-, at pH 4.5 interacts with egg white lysozyme (EC 126.96.36.199) in several stages. In the first stage, occurring at lysozyme to H2O2 molar ratio of 1:1.4-1.8, the lysozyme loses its enzyme activity but does not yield any derivative distinguishable from the native protein on polyacrylamide gel electrophoresis (PAGE). The second stage of oxidation begins at lysozyme to H2O2 molar ratio above 1:5, producing a change in the lysozyme spectrum at 260-290 nm, and yielding protein derivatives with molecular masses equal to multiples of 14.3 kDa, i.e. the lysozyme molecular mass. This implies that an excessive oxidation of lysozyme by the myeloperoxidase-H2O2-Cl- system produces cross-linking of lysozyme molecules to di-, tri-, tetra-, and pentameric structures. At lysozyme to H2O2 molar ratio exceeding 1:12 a water insoluble white product, which consists of a set of lysozyme cross-linked derivatives, is obtained.


Evidence of intramolecular cross-linked A alpha.gamma chain heterodimers in plasma fibrinogen.
A peptide band of approximately 105 kDa migrating near the gamma dimer position of disulfide bond reduced human plasma fibrinogen prepared from fresh single donor or outdated plasma was identified by SDS-PAGE. The band, amounting to approximately 2% of the total A alpha/gamma chain population, was thrombin and plasmin sensitive and reacted with antibodies to A alpha or gamma chains but not with antibodies to B beta chains, plasminogen, or factor XIII. Amino acid sequencing revealed a double sequence corresponding to that of A alpha and gamma chains, indicating that the band consists of covalently cross-linked A alpha.gamma chain heterodimers. A alpha.gamma heterodimers were identified as a component of monomeric fibrinogen by two-dimensional SDS-PAGE and by SDS-PAGE analysis of the monomer fraction isolated by gel sieving chromatography, thus indicating that A alpha.gamma heterodimers arise by intramolecular A alpha/gamma chain cross-linking.


Variation in Nutrient Composition of Seafood from North West Africa: Implications for Food and Nutrition Security.
Fish and seafood may play an important role for nutrition and food security as they contain essential vitamins, minerals, and essential fatty acids. The aim of this study was to describe the nutrient composition, including fatty acids, amino acids, vitamins, and minerals, in commonly consumed fish species (fillet- and whole fish samples) sampled off the Northwest African coast. Furthermore, we assessed the species' contributions to the recommended nutrient intake (RNI) values from the World Health Organization (WHO). Samples of commercially important fish species (Sardina pilchardus, Engraulis encrasicolus, Trachurus trachurus, Pagellus acarne) were collected using trawling on the R/V Dr. Fridtjof Nansen in May 2017 and analyzed for nutrients at the Institute of Marine Research as individual and composite samples. All the analyzed fish species were good dietary sources of several vitamins and minerals and whole fish were substantially more nutrient dense than fillet samples, especially with regard to vitamin A, iodine, zinc, calcium, and iron. Including 100 g of sardine or anchovy (whole fish) in the diet, would contribute substantially to the RNI for vitamin B12, vitamin D and vitamin A, EPA and DHA as well as the minerals iodine, zinc, and calcium. This study shows that fish consumed with skin, bone, and viscera may be very nutrient dense and important for local food and nutrition security.


[Experimental investigation of neovascularisation in large prefabricated flaps after arteriovenous pedicle implantation].
The principle of prefabricated flaps is based on the transformation of a formerly random-pattern vascularized flap, through implantation of a vascular pedicle, into a newly neovascularized axial flap, which can be transferred after a period of neovascularisation from the prepared donor site to the recipient site by using microvascular techniques. In 30 Chinchilla Bastard rabbits weighing from 3700 to 4200 g, a skeletonized arteriovenous pedicle with distal ligation harvested from the femoral and saphena magna artery and vein was implanted beneath an 8 x 15 cm abdominal skin flap to investigate the neovascularisation process in the flap over the course of time. In order to prevent neovascularisation occurring from the underlying vascular bed into the flap, a silicon sheet measuring 8 x 15 cm x 0.25 mm was placed and fixed on the abdominal wall. Flap vitality and neovascularisation process in prefabricated flaps were evaluated by macroscopic observation, blood analysis, selective microangiography, histology and scintigraphy at the various time intervals of 4, 8, 12, 16 and 20 days. The study results showed that newly formed vessels sprouting from the implanted pedicle were seen four days after pedicle implantation. With the retention time of pedicle in the flaps, they continued to grow, became meander and more dense. Respective connections between newly formed vessels and the originally available vasculature of the abdominal flap were markedly observed in the 12- and 16-day groups. Twenty days after prefabrication, the abdominal flap was completely perfused by the blood flow supplied from the newly implanted arteriovenous pedicle through newly formed vessels arising from the implanted pedicle and their rich vascular communications. The neovascularisation in the prefabricated flap consisted of the implanted pedicle, newly formed vessels, the originally available vasculature and their vascular connections. In comparison to the control group (the quantification was determined of 100 %), the vessel quantity in the prefabricated flap of the 20-day group had increased to 98.7 %. As a pre-clinical test, prefabricated flaps through arteriovenous pedicle implantation with special advantages can be a new useful method in plastic and reconstructive surgery.


Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface.
Chitosan (CS) was covalently immobilized onto polylactic acid (PLA) film surface using the photosensitive hetero-bifunctional crosslinking reagent, 4-azidobenzoic acid, which was previously bonded to chitosan by reaction between an acid group of the crosslinking reagent and a free amino group of chitosan. The immobilization was accomplished by irradiating with ultraviolet light, the modified chitosan being coated on the film surface to photolyze azide groups, thus crosslinking chitosan and PLA together. The hydroxyl and amino groups of chitosan may provide the opportunity for them being further derived by chemically immobilizing a variety of functional groups. These modifications could be carried out to tailor PLA biomaterial to meet the specific needs of different biomedical applications. For example, chitosan molecules immobilized on the PLA could be modified by heparin (Hp) solution to form a polyelectrolyte complex on the PLA surface. Platelet adhesion assay showed that PLA surface modified by chitosan/heparin complex could inhibit platelet adhesion and activation. Cell culture assay indicated that PLA surface with CS/Hp complex showed enhanced cell adhesion.


The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb.
The protooncogene for Spi-1/PU.1 is an Ets-related transcription factor overexpressed during Friend erythroleukemia. The molecular basis by which Spi-1/PU.1 is involved in the erythroleukemic process remains to be elucidated. By using an immobilized protein binding assay, we have identified a 55-kDa protein as a putative partner of Spi-1/PU.1 protein. Microsequence analysis revealed that this 55-kDa protein was p54nrb (nuclear RNA-binding protein, 54 kDa) a RNA-binding protein highly similar to the splicing factor PSF (polypyrimidine tract-binding protein-associated splicing factor). In this paper, we show that Spi-1/PU.1 impedes the binding of p54nrb to RNA and alters the splicing process in vitro. Moreover, we present evidence that the transcriptional factor Spi-1/PU.1, unlike other Ets proteins, is able to bind RNA. Altogether, these results raise the intriguing possibility that the functional interference observed between Spi-1/PU.1 and RNA-binding proteins might represent a novel mechanism in malignant erythropoiesis.


Cheilitis glandularis: two case reports of asian-Japanese men and literature review of Japanese cases.
Cheilitis glandularis (CG) is a rare disorder characterized by swelling of the lip with hyperplasia of the labial salivary glands. CG is most frequently encountered in the lower lip, in middle-aged to older Caucasian men; however Asian cases were rarely reported. In this paper we present two cases of CG in Asian-Japanese men. One was a 23-year-old male with CG of the superficial suppurative type. The other was a 54-year-old male with deep suppurative type. We also reviewed the Japanese cases of CG in the literature and discussed about clinical feature of Japanese CG.


Adenosine triphosphate content and seed vigor.
ATP content in imbibed seeds is significantly correlated with seedling size in fatty, starchy and proteinaceous seeds, and it indicates viability in seed lots. ATP content thus appears to be a useful biochemical index of seed vigor.


Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles.
The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754-0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716-0.995, P = 0.033). In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence.


Achilles Tendon Xanthoma Thickness and Carotid Intima-Media Thickness in a Patient With Heterozygous Familial Hypercholesterolemia on PCSK9 Inhibition: A Case Report and Literature Review.
Ultrasound-guided measurement of carotid intima-media thickness can be used as a surrogate marker to predict future risk of atherosclerotic cardiovascular disease, and to understand the efficacy of lipid-lowering drugs. Aggressive lipid-lowering drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce carotid artery plaque burden, total cholesterol, and low-density lipoprotein-c in patients with heterozygous familial hypercholesterolemia (FH). We describe a patient with heterozygous FH treated with PCSK9 inhibitor over the course of two years, and the drug's impact on carotid intima-media thickness, Achilles tendon thickness, and cardiovascular disease risk reduction.


Interaction between F1-ATPase and its naturally occurring inhibitor protein. Studies using a specific anti-inhibitor antibody.
An antibody was raised to cross-linked ox-heart mitochondrial inhibitor protein, which cross-reacts with the free inhibitor but with no other mitochondrial membrane protein. This antibody yields an immunoprecipitate with the cross-linked inhibitor protein, but a soluble antibody-antigen complex with free inhibitor. The antibody binds well to inhibitor protein whether the latter is complexed with F1-ATPase or not. Antibody binding has no effect on the ability of the inhibitor protein to inhibit the ATPase activity of F1. These findings suggest that the antibody does not block the site of interaction between the inhibitor and F1. The inhibitor protein content of submitochondrial membrane preparations was determined by radioimmunoassay, activity measurements and an immunochemical 'back titration' technique. The inhibitor content of the membranes is shown to decrease after energisation, suggesting a loss of inhibitor from the membranes into solution. Binding antibody to the inhibitor protein on submitochondrial particles has no effect on the steady-state rate of phosphorylation, but it increases the lag phase preceding phosphorylation from 30 to 54 s. The rate constant for the approach to the steady state drops from 0.078 to 0.052 s-1. This effect confirms that the lag phase is due to inhibition of phosphorylation by the inhibitor protein. The increase in ATPase activity following energisation takes place by a fast phase (80% maximal activity reached within 90 s) and a slower phase (lasting about 10 min.). The rate constant of the rapid phase (0.017 s-1) is of the same order as that for the activation of phosphorylation. It is concluded that the rapid phase of ATPase induction is fast enough for this process to occur simultaneously with the activation of phosphorylation.


Glomerular filtration rate in dogs as estimated via plasma clearance of inulin and iohexol and use of limited-sample methods.
To compare plasma clearance of inulin and iohexol determined by use of 9 plasma samples for evaluation of glomerular filtration rate in dogs and to evaluate limited-sample approaches for evaluation of plasma clearance of these markers. 43 dogs of various breeds that weighed between 5.5 and 63 kg and that had various degrees of renal function. 9 plasma samples were obtained from each dog at 5 minutes to 6 hours after IV bolus injection of iohexol and inulin. Clearance was calculated by use of results for all 9 samples (ie, reference method). Results for 3 limited-sample strategies for determination of plasma clearance of iohexol and inulin were compared with results for the reference method. Mean clearance of inulin and iohexol for the reference method was 2.72 and 2.48 mL/min/kg, respectively. The mean difference between clearance of these 2 markers for the reference method was 0.24 mL/min/kg. In general, use of the limited-sample strategies yielded clearance values similar to those for the reference method. More accurate estimates of clearance were obtained for iohexol than for inulin by use of the limited-sample methods. Use of iohexol and inulin yielded similar but not identical results for plasma clearance. Accuracy for limited-sample methods would be acceptable for many clinical and research situations.


A comparison of gene transfer and antigen-loaded dendritic cells for the generation of CD4+ and CD8+ cytomegalovirus-specific T cells in HLA-A2+ and HLA-A2- donors.
Dendritic cells have been used effectively to select for human cytomegalovirus (CMV)-specific T cells for immunotherapy applications. The ability to process and present relevant major histocompatibility complex class I and II peptides to T cells makes them ideal for selecting CD4+ and CD8+ T cells regardless of HLA tissue type. This study compared the generation of CMV-specific T cells by using dendritic cells loaded with either CMV pp65495-503 peptide or CMV lysate or transduced with adenovirus encoding the pp65 gene (Ad5pp65GFP) for the generation of CD4+ and CD8+ CMV-specific T cells in HLA-A2+ and HLA-A2 - donors. In HLA-A2+ donors, CD8+ tetramer+ T cells increased with all antigens but were greatest in peptide- and Ad5pp65GFP-stimulated T cells. The CD4+ /CD8+ ratio in the stimulated T-cell cultures proved to be dependent on the antigen used. CMV lysate-stimulated cells were primarily CD4+, whereas peptide- and Ad5pp65GFP-stimulated cultures were mostly CD8+. Analysis of cells from lysate-stimulated or gene-transduced-stimulated cultures showed expansion of CMV-specific CD4+ T cells, indicating that major histocompatibility complex class II peptides were present in both antigens. Furthermore, CMV-specific T cells were generated from HLA-A2 - donors by using Ad5pp65GFP transduction or CMV lysate stimulation and were able to recognize a pp65 peptide restricted to the HLA-B35 allele. These data indicate that either CMV lysate or adenovirus encoding CMV antigenic genes may be useful for the generation of both CD4+ and CD8+ CMV-specific T cells in donors irrespective of HLA tissue type and may be applicable to clinical immunotherapy.


Characterization, Antioxidant and Antitumor Activities of Oligosaccharides Isolated from Evodia lepta (Spreng) Merr. by Different Extraction Methods.
Evodia lepta (E. lepta) is a traditional Chinese herbal medicine with various biological activities. One of the active components of this widely used medicinal plant is believed to be an oligosaccharide. The extraction yields, structural characteristics, antioxidant, and antitumor activities of four oligosaccharide extracts obtained by hot water extraction (HEO), ultrasound-assisted extraction (UEO), enzyme-assisted (EEO), and microwave-assisted extraction (MEO) were investigated. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) results indicated that the extraction methods had a difference on the molecular mass distribution, structure, and morphology of the EOs. In addition, HEO and MEO showed strong antioxidant activities, which might be related to their uronic acid and protein contents. More interestingly, MEO was more active toward MDA-MB-231 cells compared to other cells, and cell growth inhibition was proposed to occur through apoptosis. Overall, microwave-assisted extraction is a promising technique for the extraction of high quality EO.


[Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia].
To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot. Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured. The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05). Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.


Biliary Stricture After Necrotizing Pancreatitis: An Underappreciated Challenge.
Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound locoregional inflammatory response of NP creates challenging biliary strictures. NP patients treated between 2005 and 2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to <75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. Among 743 NP patients, 64 died, 13 were lost to follow-up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ± 3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (interquartile range, 1.8 to 10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8 to 9.8). A mean of 3.3 ± 2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. Biliary stricture occurs frequently after NP and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.


Prolonged diplopia following a mandibular block injection.
A case is presented in which a 14-yr-old girl developed diplopia after injection of the local anesthetic Xylotox E 80 A (2% lidocaine with 1:80,000 epinephrine). Since the complication had a relatively slow onset and lasted for 24 hr, the commonly suggested explanations based on vascular, lymphatic, and neural route theories do not adequately fit the observations. No treatment, other than reassurance, was necessary, and the patient recovered fully.


Shiny-SoSV: A web-based performance calculator for somatic structural variant detection.
Somatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools for guiding study design nor are there applications that could predict the performance of somatic structural variant detection. To address this gap, we developed Shiny-SoSV, a user-friendly web-based calculator for determining the impact of common variables on the sensitivity, precision and F1 score of somatic structural variant detection, including choice of variant detection tool, sequencing depth of coverage, variant allele fraction, and variant breakpoint resolution. Using simulation studies, we determined singular and combinatoric effects of these variables, modelled the results using a generalised additive model, allowing structural variant detection performance to be predicted for any combination of predictors. Shiny-SoSV provides an interactive and visual platform for users to easily compare individual and combined impact of different parameters. It predicts the performance of a proposed study design, on somatic structural variant detection, prior to the commencement of benchwork. Shiny-SoSV is freely available at https://hcpcg.shinyapps.io/Shiny-SoSV with accompanying user's guide and example use-cases.


Biological and Phytochemical Investigations on Caesalpinia benthamiana, a Plant Traditionally Used as Antimalarial in Guinea.
Caesalpinia benthamiana is widely used as antimalarial in Guinean traditional medicine. Leaf extracts of the plant were tested for their in vitro antiprotozoal activity against Trypanosoma brucei brucei and T. cruzi and the chloroquine-sensitive Ghana strain of Plasmodium falciparum along with their cytotoxicity on MRC-5 cells. The methanolic extract showed the strongest antiprotozoal activity against P. falciparum (IC50 4 μg/ml), a good activity against T. brucei (IC50 13 μg/ml), and a moderate activity against T. cruzi (IC50 31 μg/ml) along with an IC50 on human MRC-5 cells of 32 μg/ml. Bioassay-guided fractionation from the methanolic extract led to antiplasmodially active subfractions. A prospective, placebo-controlled ethnotherapeutic trial assessed the antimalarial effectiveness and tolerability of C. benthamiana syrup administered orally to children with uncomplicated malaria as compared with chloroquine syrup. Phytochemical screening of the leaf extracts indicated the presence of flavonoids, terpenoids, tannins, saponins, and iridoids.