Changes in Blood Circulation of the Tendons and Heart Rate Variability During and After Acupuncture.
Objective: The purpose of this study was to investigate the changes in blood circulation of tendons and heart rate variability (HRV) during and after acupuncture in order to elucidate the mechanisms of acupuncture-induced changes in tendon blood circulation. Materials and Methods: During 10 minutes of acupuncture treatment and a recovery period of 40 minutes, blood volume (THb) and oxygen saturation (StO2) of treated and nontreated tendons were measured using red laser lights. In addition, HRV was also measured during the experimental period. Results: THb and StO2 of the treated tendons significantly increased during acupuncture, and then remained high during the recovery period. THb and StO2 of the nontreated tendons did not change during acupuncture but gradually increased during the recovery period. In addition, the increase in THb of the nontreated tendons were significantly correlated with that of the treated tendons during the latter half of the recovery period. Heart rate (HR) continued to decrease during acupuncture and suddenly returned to the initial level after removal of the needle. The low-frequency (LF)/high-frequency (HF) ratio tended to increase during the recovery period. During the latter half of the recovery period, the changes in THb for both the treated and nontreated tendons were negatively correlated with the change in HR but not with changes in the LF/HF ratio. Conclusions: These results suggest that changes in blood circulation of tendons after acupuncture treatment were controlled by the autonomic nervous system, which could not be detected by HRV analysis.


A health fundraising experiment using the "foot-in-the-door" technique.
Foot-in-the-door (FITD) involves obtaining compliance with a small request to boost compliance with a larger request. Only a few studies to date have tested the technique in health and fundraising contexts, and even fewer have examined the psychological processes involved. To address these gaps, we conducted an experiment as an actual fundraiser for a cancer-awareness organization. The technique activated a self-concept as a supporter of cancer awareness among those in the FITD condition. Donation amount was also higher among those in FITD, but only among those with higher levels of worry and low to moderate levels of preference for consistency.


Collinear opto-optical loss modulation for carrier-envelope offset stabilization of a fiber frequency comb.
Opto-optical loss modulation (OOM) for stabilization of the carrier-envelope offset (CEO) frequency of a femtosecond all-fiber laser is performed using a collinear geometry. Amplitude-modulated 1064 nm light is fiber coupled into an end-pumped semiconductor saturable absorber mirror (SESAM)-mode-locked all-polarization-maintaining erbium fiber femtosecond laser, where it optically modulates the loss of the SESAM resulting in modulation of the CEO frequency. A noise rejection bandwidth of 150 kHz is achieved when OOM and optical gain modulation are combined in a hybrid analog/digital loop. Collinear OOM provides a simple, all-fiber, high-bandwidth method for improving the CEO frequency stability of SESAM mode-locked fiber lasers.


ARF induces autophagy by virtue of interaction with Bcl-xl.
The ARF tumor suppressor controls a well-described p53/Mdm2-dependent oncogenic stress checkpoint. In addition, ARF has recently been shown to localize to mitochondria, and to induce autophagy; however, this has never before been demonstrated for endogenous ARF, and the molecular basis for this activity of ARF has not been elucidated. Using an unbiased mass spectrometry-based approach, we show that mitochondrial ARF interacts with the Bcl2 family member Bcl-xl, which normally protects cells from autophagy by inhibiting the Beclin-1/Vps34 complex, which is essential for autophagy. We find that increased expression of ARF decreases Beclin-1/Bcl-xl complexes in cells, thereby providing a basis for ARF-induced autophagy. Our data also indicate that silencing p53 leads to high levels of ARF and increased autophagy, thereby providing a possible basis for the finding by others that p53 inhibits autophagy. The combined data support the premise that ARF induces autophagy in a p53-independent manner in part by virtue of its interaction with Bcl-xl.


Prostaglandin F2 alpha as the luteolysin in swine: VI. Hormonal regulation of the movement of exogenous PGF2 alpha from the uterine lumen into the vasculature.
To test the endocrine-exocrine theory of maternal recognition of pregnancy in the pig 16 gilts were assigned randomly to a 2 X 2 factorial involving pretreatment with sesame oil (SO) or estradiol valerate (5 mg; EV) injected on Days 11 through 14 of the estrous cycle and an intrauterine injection of saline (5 ml; SA) or prostaglandin F2 alpha (50 micrograms; PGF) on Day 14. Peripheral blood samples were collected for 120 min postinjection and analyzed for 15-keto-13,14-dihydro-PGF2 alpha (PGFM). PGFM concentrations were lower in EV than SO gilts (438 vs. 844 pg/ml; p less than 0.05). There was heterogeneity of regression between EV and SO gilts (p less than 0.01), with EV gilts having a slower release of PGF from the uterine lumen into the vasculature. Prostaglandin F2 alpha did not increase mean PGFM concentrations (p greater than 0.10), but resulted in an altered temporal pattern of PGFM (p less than 0.05) compared to SA gilts. There was an interaction between the two treatments over time, with EV-PGF gilts demonstrating a slower, more gradual release of PGFM than SO-PGF gilts. To test whether prostaglandins of the E series were involved in this mechanism, gilts were assigned to two 4 X 4 latin squares balanced for residual effects and treated with saline or flunixen meglumine (Banamine). Each gilt was treated with four PGE:PGF infusion sequences (SEQ) in each uterine horn: phosphate-buffered saline (PBS; PBS-SEQ), PGE1 (50 micrograms), PGE2 (50 micrograms), and PGE1 (25 micrograms) + PGE2 (25 micrograms) (PGE-SEQ), with each infusion followed 15 min later by PGF (25 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)


Collective dynamics in a monolayer of squirmers confined to a boundary by gravity.
We present a hydrodynamic study of a monolayer of squirmer model microswimmers confined to a boundary by strong gravity using the simulation method of multi-particle collision dynamics. The squirmers interact with each other via their self-generated hydrodynamic flow fields and thereby form a variety of fascinating dynamic states when density and squirmer type are varied. Weak pushers, neutral squirmers, and pullers have an upright orientation. With their flow fields they push neighbors away and thereby form a hydrodynamic Wigner fluid at lower densities. Furthermore, states of fluctuating chains and trimers, of kissing, and at large densities a global cluster exist. Finally, pushers at all densities can tilt against the wall normal and their in-plane velocities align to show swarming. It turns into chaotic swarming for strong pushers at high densities. We characterize all these states quantitatively.


Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.
Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.


Clinical phenotypic and genotypic characterization of NPRL3-related epilepsy.
As one of the assembly factors of the GATOR1 protein complex in the mechanism of rapamycin pathway, NPRL3 plays an important role in the pathogenesis of epilepsy. However, the correlation between genotype and clinical phenotype in patients with NPRL3-related epilepsy has not been clarified. A total of 11 Chinese children with NPRL3-related epilepsy were identified through whole-exome sequencing (WES). The data from the clinical presentation, laboratory data, brain imaging findings, genetic results, and treatment methods were collected. All previously reported cases with NPRL3-related epilepsy were collected and reviewed through PubMed search. Among the 11 children, eight have not been reported, and two of them presented infantile spasms (ISs) as a new phenotype of NPRL3-related epilepsy. In addition, WES identified five frameshift mutations, three nonsense mutations, two missense mutations, and one exon deletion. Based on bioinformatics analysis, it was found that two missense mutation sites were highly conserved, and the c.400G>A mutation site of the NPRL3 gene caused the alteration of the protein structure. To date, 88 patients have been reported with NPRL3-related defects, including our 11 cases. The most common presentations were sleep-related hypermotor epilepsy (SHE), frontal lobe epilepsy (FLE), and temporal lobe epilepsy. A majority of patients (70%) presented normal neuroimaging results, and focal cortical dysplasia was the most common neuroimaging abnormality (62.5%). Among the NPRL3 gene mutations, loss of function (nonsense mutations, frameshift mutations, and exons deletion) was the most common genetic variation (75%). For 73% of patients with NPRL3-related epilepsy, monotherapy of sodium channel blockers was effective. Surgery was effective for 75% of children with neuroimaging abnormalities. Two cases unresponsive to surgery or anti-seizure medications were treated with ketogenic diets (KD), which were effective. One case was treated with rapamycin at an early stage of epilepsy, which was effective as well. NPRL3-related epilepsy has high clinical and genetic heterogeneity. SHE and FLE are the most common clinical presentations. Furthermore, ISs are the new phenotypes of NPRL3-related epilepsy, while the variants c.275G>A, c.745G>A, and c.1270C>T may be the most common NPRL3 gene mutations. Sodium channel blockers, surgery, KD, and rapamycin may be the potential treatments for these patients. Our study expanded the clinical and genetic spectrum of NPRL3-related epilepsy and provided important information for the precise treatment of patients.


Optimising management of neutropenia and anaemia in cancer chemotherapy-advances in cytokine therapy.
Neutropenia and anaemia are serious complications of myelosuppressive chemotherapy. They have a negative impact on patient quality of life and may reduce response to treatment. Febrile neutropenia, a potentially life-threatening complication of neutropenia, frequently requires hospital admission, while fatigue and weakness from anaemia reduce patient's capacity for activity. Pegfilgrastim and darbepoetin alfa, were designed to simplify and optimise treatment for patients with cancer. Once-per-cycle pegfilgrastim is as effective as daily filgrastim with respect to duration of severe neutropenia (DSN) and may have a lower incidence of febrile neutropenia than filgrastim. Darbepoetin alfa has enhanced biological activity and a serum terminal half-life three-fold longer than that of erythropoietin (EPO), which translates into rapid and sustained correction of anaemia with less frequent dosing. These novel cytokines have the potential to simplify the management of neutropenia and anaemia with fewer injections and less disruption to patients daily lives.


Pulse wave analysis using the Mobil-O-Graph, Arteriograph and Complior device: a comparative study.
Pulse wave velocity (PWV) is a marker of arterial stiffness with major prognostic value. We compared Arteriograph and Complior devices with the Mobil-O-Graph for assessment of PWV and central systolic blood pressure (cSBP). We studied 316 consecutive subjects (age: 55 ± 14 years). For each individual, we measured PWV and cSBP with Arteriograph, Complior and Mobil-O-Graph and compared the readings. Differences in values among three devices were calculated for each measurement. We used Bland-Altman analysis, intraclass correlation coefficient (ICC) and coefficient of variation (CV). Bland-Altman analysis indicated a mean difference for PWV: i.0.5 m/s (limits of agreement -1.4-2.4) between Complior and Mobil-O-Graph, ii.0.6 m/s (limits of agreement -1.4-2.6) between Arteriograph and Mobil-O-Graph. cSBP mean difference was 3.8 mmHg between Complior and Mobil-O-Graph (limits of agreement -12.5-20.1) and 9.2 mmHg between Arteriograph and Mobil-O-Graph (limits of agreement -7.6-26). ICC for PWV was 0.86 between Arteriograph and Mobil-O-Graph, 0.87 between Complior and Mobil-O-Graph and for cSBP 0.92 and 0.91 respectively. CV for PWV was 9.5% between Arteriograph and Mobil-O-Graph, 8.8% between Complior and Mobil-O-Graph. Respective values for cSBP were 6.8% and 5.1%. Our study shows acceptable agreement among the three devices regarding pulse wave analysis markers though Mobil-O-Graph appears to underestimate the values of these markers. Further studies are needed to explore the agreement between the 3 devices in various clinical settings and patient populations.


Eprosartan mesylate, an angiotensin II receptor antagonist.
The title compound, eprosartan mesylate {systematic name: 2-butyl-1-(4-carb-oxy-benz-yl)-5-[(E)-2-carb-oxy-3-(thio-phen-2-yl)prop-1-en-yl]-1H-imidazol-3-ium methane-sulfonate}, C(23)H(25)N(2)O(4)S(+)·CH(3)O(3)S(-), one of the angiotensin II-receptor antagonists, is effective in regulating hypertension, induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure and glaucoma. In the eprosartan residue, which appears in this crystal in the cationic imidazolium form, the benzene ring plane is almost orthogonal to that of the imidazole ring, making a dihedral angle of 87.89 (2)°. The thio-phene ring forms dihedral angles of 66.54 (2) and 67.12 (2)° with the benzene and imidazole rings, respectively. The imidazolium NH group and the H atom of the aromatic carboxyl group participate in hydrogen bonds with the the O atoms of the anion, thus forming centrosymmetric aggregates made up of two cations and two anions each. The second carboxyl group further links the above-mentioned aggregates through a conventional centrosymmetric hydrogen-bonding motif into infinite chains along [011].


[Xanthogranulomatous pyelonephritis: clinical experience of 8 cases].
Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of granulomatous inflammation characterized by destruction of the renal parenchyma and replacement by solid sheets of lipid-laden macrophages. The first report was made by Schlagenhaufer in 1916. Due to diagnostic difficulties, relatively few cases have been reported. However, within the past 20 years, XGP has been recognized with increasing frequency. At present, over 400 cases have been reported. Recently, the computed tomographic (CT) findings of XGP have been described in a few sporadic case reports (1-4). Our clinical experience consists of 8 cases of XGP. The sonographic and computed tomographic findings in our cases are presented along with the correlation with the pathological specimens. We stress the importance of sonography and CT in preoperative planning. Moreover, in our cases we could obtain typical findings on sonography and CT, which enabled us to make a correct preoperative diagnosis. In this report we describe some specific features.


Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones.
Tobacco smoking is a well-known risk factor for subsequent alcohol abuse, but the neural events underlying this risk remain largely unknown. Alcohol and nicotine reinforcement involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to nicotine increases alcohol self-administration and decreases alcohol-induced dopamine responses. The blunted dopamine response was due to increased inhibitory synaptic transmission onto dopamine neurons. Blocking stress hormone receptors prior to nicotine exposure prevented all interactions with alcohol that we measured, including the increased inhibition onto dopamine neurons, the decreased dopamine responses, and the increased alcohol self-administration. These results indicate that nicotine recruits neuroendocrine systems to influence neurotransmission and behavior associated with alcohol reinforcement.


[Neurodegenerative disorders of the central nervous system in horses].
The most important neurodegenerative diseases of the horse are reviewed. In addition to the literature, neurodegenerative diseases occurring in patients (horses, Mongolian Przewalski-horses, and two zebras) referred to the Utrecht Veterinary Faculty are mentioned. Neurodegenerative diseases described are: I. ataxia associated with: A/ static stenosis, B/ dynamic stenosis, C/ lesions at various locations in the central nervous system, D/ equine herpesvirus infections, E/ equine degenerative myelo-encephalopathy, or F/ cerebellar abiotrophy; II. equine motor neuron disease; III. grass sickness or equine dysautonomia; IV. postanaesthetic myelomalacia; and V. equine leuko-encephalomalacia. The patient descriptions show, that mixed forms of some of the differentiated diseases can be diagnosed. Little is known with certainty about the aetiology of the neurodegenerative lesions found. In some patients vitamin E may play a role, possibly in combination with other factors. A mycotoxin known to interfere with myelin metabolism is involved in leuko-encephalomalacia.


A perfectly staged 'concerted action' against psychoanalysis: the 1913 congress of German psychiatrists.
An eyewitness account provides evidence of a significant clandestine effort to neutralize the legitimacy and authority of psychoanalysis. In a letter, the witness confirms the existence of a perfectly staged concerted action among German psychiatrists against Freud's influence in 1913. Their congress in Breslau was meant to present the united front of German psychiatrists, who were going on record as being against psychoanalysis and, in that context, to give Eugen Bleuler, a leading psychiatrist, whose (however half-hearted) support for psychoanalysis had alarmed his colleagues, a public opportunity for back-pedalling. The letter shows that Freud and his allies were not the only ones who tried to manage an intellectual movement by using informal networks and 'behind the scenes' manoeuvring.


Visible light crosslinkable human hair keratin hydrogels.
Keratins extracted from human hair have emerged as a promising biomaterial for various biomedical applications, partly due to their wide availability, low cost, minimal immune response, and the potential to engineer autologous tissue constructs. However, the fabrication of keratin-based scaffolds typically relies on limited crosslinking mechanisms, such as via physical interactions or disulfide bond formation, which are time-consuming and result in relatively poor mechanical strength and stability. Here, we report the preparation of photocrosslinkable keratin-polyethylene glycol (PEG) hydrogels via the thiol-norbornene "click" reaction, which can be formed within one minute upon irradiation of visible light. The resulting keratin-PEG hydrogels showed highly tunable mechanical properties of up to 45 kPa in compressive modulus, and long-term stability in buffer solutions and cell culture media. These keratin-based hydrogels were tested as cell culture substrates in both two-dimensional surface seeding and three-dimensional cell encapsulation, demonstrating excellent cytocompatibility to support the attachment, spreading, and proliferation of fibroblast cells. Moreover, the photocrosslinking mechanism makes keratin-based hydrogel suitable for various microfabrication techniques, such as micropatterning and wet spinning, to fabricate cell-laden tissue constructs with different architectures. We believe that the unique features of this photocrosslinkable human hair keratin hydrogel promise new opportunities for their future biomedical applications.


Muddy puddles - the microbiology of puddles located outside tertiary university teaching hospitals.
In the British Isles, the frequency of rain results in the formation of puddles on footpaths and roads in/around hospitals. No data are available demonstrating the microbiological composition of such puddles and therefore a study was undertaken to examine the microbiology of puddles in the grounds of two tertiary university-teaching hospitals (18 sites) and compared with control puddles from non-hospital rural environments (eight sites), estimating (i) total viable count; (ii) identification of organisms in puddles; (iii) enumeration of Escherichia coli: (iv) detection of Extended Spectrum β-Lactamase producing organisms and (v) direct antimicrobial susceptibility testing. A mean count of 2·3 × 103 CFU per ml and 1·0 × 109 CFU per ml was obtained for hospital and non-hospital puddles respectively. Isolates (n = 77; 54 hospital and 23 non-hospital) were isolated comprising of 23 species among 17 genera (hospital sites), where the majority (10/16; 62·5%) of genera identified were Gram-negative approximately, a fifth (20·6%) were shared by hospital and non-hospital rural samples. Escherichia coli was detected in half of the hospital puddles and under-half (37·5%) of the rural puddles extended spectrum β-lactamase organisms were not detected in any samples examined. Rainwater puddles from the hospital and non-hospital environments contain a diverse range of bacteria, which are capable of causing infections. This study demonstrated the presence of a wide diversity of bacterial taxa associated with rainwater puddles around hospitals, many of which are capable of causing human disease. Of clinical significance is the presence of Pseudomonas aeruginosa isolated from a hospital puddle, particularly for patients with cystic fibrosis. The presence of potentially disease-causing bacteria in puddles in and around hospitals identifies a new potential environmental reservoir of bacteria. Furthermore work is now needed to define their potential of entering or exiting hospital wards by contaminated footwear.


Longitudinal data on speech outcomes in internationally adopted children compared with non-adopted children with cleft lip and palate.
At the beginning of the 21st century, international adoptions of children with cleft lip and/or palate increased dramatically in Sweden. Many children arrived partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. To date, the speech development of internationally adopted (IA) children has been described up to age 7-8 years, but later development remains unstudied. To investigate speech development between ages 5 and 10 years in children born with cleft lip and palate (CLP) adopted from China and to compare them with non-adopted (NA) children with CLP. A secondary aim was to compare the frequencies of secondary palatal surgery and number of visits to a speech and language pathologist (SLP) between the groups. In a longitudinal study, 23 IA children from China were included and matched with 23 NA children born in Sweden. Experienced SLPs blindly reassessed audio recordings from routine follow-ups at ages 5 and 10 years. Velopharyngeal function (VPF) was assessed with the composite score for velopharyngeal competence (VPC-Sum) for single words and rated on a three-point scale (VPC-Rate) in sentence repetition. Target sounds in words and sentences were phonetically transcribed. Per cent correct consonants (PCC) were calculated at word and sentence levels. For in-depth analyses, articulation errors were divided into cleft speech characteristics (CSCs), developmental speech characteristics (DSCs) and s-errors. Information on secondary palatal surgery and number of visits to an SLP was collected. VPF differed significantly between the groups at both ages when assessed with VPC-Sum, but not with VPC-Rate. Regardless of the method for assessing VPF, a similar proportion in both groups had incompetent VPF but fewer IA than NA children had competent VPF at both ages. IA children had lower PCC at both ages at both word and sentence levels. More IA children had CSCs, DSCs and s-errors at age 5 years, and CSCs and s-errors at age 10. The development of PCC was significant in both groups between ages 5 and 10 years. The proportion of children receiving secondary palatal surgery did not differ significantly between the groups, nor did number of SLP visits. CSCs were more persistent in IA children than in NA children at age 10 years. Interventions should target both cleft and DSCs, be comprehensive and continue past the pre-school years. What is already known on this subject At the beginning of the 21st century, IA children with cleft lip and/or palate arrived in Sweden partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. Studies up to age 7-8 years show that adopted children, compared with NA peers, have poorer articulation skills, demonstrate both cleft-related and developmental articulation errors, and are more likely to have velopharyngeal incompetence. Several studies also report that adopted children more often require secondary palatal surgery due to fistulas, dehiscence or velopharyngeal incompetence compared with NA peers. What this paper adds to existing knowledge This longitudinal study provides additional knowledge based on longer follow-ups than previous studies. It shows that the proportion of children assessed to have incompetent VPF was similar among IA and NA children. It was no significant difference between the groups regarding the proportion that received secondary palatal surgery. However, fewer IA children were assessed to have a competent VPF. Developmental articulation errors have ceased in most IA and all NA children at age 10 years, but significantly more adopted children than NA children still have cleft-related articulation errors. What are the potential or actual clinical implications of this work? Speech and language therapy should target both cleft-related and developmental articulation errors. When needed, treatment must be initiated early, comprehensive, and continued past the pre-school years, not least for adopted children.


Cough and the common cold.
To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.


The effects of naloxone on endotoxic and hemorrhagic shock in horses.
The effects of naloxone on the cardiovascular, hematologic and metabolic derangements associated with endotoxic and hemorrhagic shock were studied in unanesthetized horses. In the first of 3 experiments blood glucose and lactate levels, hematocrit, white, red and differential white cell counts, rectal temperature and clinical signs were obtained before and after endotoxin (10 micrograms/Kg) administration in 5 horses. In the second experiment, two groups of 3 horses received either intravenous naloxone (0.04 mg/Kg) or saline, 7 minutes prior to endotoxin. In a third experiment two groups of 4 horses received either saline or naloxone (0.20 mg/Kg) immediately following acute hemorrhage. In the second and third experiments, pulse, mean arterial and right ventricular pressures, and heart rate were also observed. Endotoxin and acute hemorrhage produced hypothermia, leukopenia, lymphopenia, neutropenia, elevations in hematocrit, blood glucose and blood lactate, and clinical signs of shock. Naloxone (0.040 mg/Kg IV) significantly lowered endotoxin-induced increases in right ventricular pressure and heart rate, and at a higher dose (0.20 mg/Kg) antagonized the decrease in pulse and heart rate, and tachycardia observed after acute hemorrhage. These results suggest endogenous opioids are involved in the pathogenesis of shock. Naloxone appeared to attenuate some of the cardiovascular responses associated with shock and thus may be of therapeutic value in shock management.


An unexpected diagnosis of human immunodeficiency virus-2 infection in an overseas visitor: a case report.
Human immunodeficiency virus 2 infection is endemic in West Africa but is also found in parts of Europe, North and South America, and India where it is thought to have been introduced secondary to migration and commercial trade ties. It is less common than Human immunodeficiency virus 1, with differences in pathogenicity, lower rates of transmission, longer asymptomatic period and slower progression to acquired immunodeficiency syndrome. Human immunodeficiency virus 2 is also associated with diagnostic challenges given the lack of commercially available diagnostic tests, and management challenges given intrinsic resistance to many anti-retroviral therapies. We describe a case of a 65 year old South Indian female, visiting her family in Australia, who presented with weight loss, pancytopaenia and generalised lymphadenopathy on a background of newly diagnosed congestive cardiac failure. Multiple investigations were performed to elucidate the cause of her presentation, with the eventual unexpected diagnosis of human immunodeficiency virus 2. She was commenced on anti-retroviral treatment and made a remarkable recovery. We describe the challenges associated with diagnosis of human immunodeficiency virus 2 due to lack of commercially available diagnostics, as well as the treatment and management challenges including the fact that human immunodeficiency virus 2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors. Human immunodeficiency virus 2 infection should be considered in patients who present with symptoms and signs that do not point towards a clear diagnosis, such as unexplained pancytopaenia or lymphadenopathy, and who have risk factors such as being from an endemic area or having had blood transfusions, especially prior to the commencement of blood-borne virus screening of blood donors.


[HSV-TK gene therapy of lung adenocarcinoma xenografts using a hypoxia/radiation dual-sensitive promoter].
Radio-genetic therapy is a novel strategy for cancer treatment; however, a limited success was shown due to lower sensitivity of tumor cells to radiation under hypoxia, which is a unique feature for solid tumors. In order to improve the efficacy of radiogenetic therapy for lung cancer, a hypoxia/radiation dual-sensitive promoter was constructed to enhance the expression of HSV-TK in transfected cells exposed to radiation under hypoxia. The chimeric promoter HRE-Egr was generated by insertion of hypoxia response elements (HREs) upstream of the Egr-1 (early growth response gene-1) promoter. HSV-TK expression vector was constructed by cloning HRE-Egr promoter upstream of HSV-TK gene, which was transfected into A549 cells via liposome. The expression of HSV-TK in transfected cells exposed to irradiation (6 Gy) and/or hypoxia (1% O2) were analyzed by Northern blot, and the relative survival rate of cells in presence of prodrug ganciclovir (GCV) was tested using MTT method. To examine the efficacy of this HRE-Egr-TK gene therapy in vivo, the A549 adenocarcinoma xenografts were planted in BALB/c nude mice. The tumor volumes and the suppression rates were assayed in nude mice bearing xenografts infected with plasmids and exposed to radiation. HSV-TK gene expression in transfected cells was markedly increased in both radiation (227 U) and hypoxia (94 U) groups compared with control group (21 U). The HSV-TK expression (769 U) in transfected cells exposed to radiation under hypoxia is much more higher than the former groups. The survival rate of transfected cells exposed to radiation under hypoxia in the presence of GCV was obviously decreased with comparison of cells under normoxia (7.2%+/-1.8 % vs 32.7%+/-4.6 %). HRE-Egr promoter transfected tumors regressed significantly after a combination therapy of irradiation and GCV in all mice (n=10), the tumor suppression rates was 91.2%. The hypoxia/radiation dual-sensitive promoter HRE-Egr can enhance the HSV-TK gene expression in solid tumors under hypoxia. Enhanced tumor suppression effect was observed in A549 xenografts infected with HRE-Egr promoter exposed to radiation.


Quantification of Thoracic Lymphatic Flow Patterns Using Dynamic Contrast-enhanced MR Lymphangiography.
Background Dynamic contrast material-enhanced MR lymphangiography has recently emerged as a technique to image the lymphatic anatomy and identify lymphatic flow abnormalities; however, a method to quantify lymphatic flow in health and disease is needed. Purpose To develop a method to quantify thoracic lymphatic flow patterns using dynamic contrast-enhanced MR lymphangiography. Materials and Methods The following patients with dynamic contrast-enhanced MR lymphangiography images collected in 2015 and 2016 were retrospectively identified: group A, neonates with chylothorax; group B, children with heart failure complicated by plastic bronchitis; and group C, adults with lymphatic plastic bronchitis and without heart failure. An automated image segmentation method was developed for segmenting the contrast-enhanced lymphatic flow in spatiotemporal domains from the dynamic contrast-enhanced MR lymphangiography images. The lymphatic flow rates were quantified for individual patients on the basis of their spatiotemporal dynamic contrast-enhanced MR lymphangiography segmentation results, and the flow rates were compared among the three patient groups by using Wilcoxon rank sum tests. Results Twenty-two patients were evaluated: seven neonates (mean age, 49 days ± 71 [standard deviation]; three boys, four girls), 10 children (mean age, 8 years ± 3; seven boys, three girls), and five adults (mean age, 46 years ± 10; three men, two women). The proposed method was used to obtain lymphatic flow segmentation results with Dice scores of 0.80, 0.82, and 0.83 for patients from groups A, B, and C, respectively. The mean flow rates for groups A, B, and C were 1.8 mL/min ± 1.4, 4.0 mL/min ± 1.8, and 12.5 mL/min ± 3.8, respectively. The flow rate differed significantly between groups A and B (P = .002), groups A and C (P = .01), and groups B and C (P = .01). Conclusion An automatic spatiotemporal segmentation method was used to determine thoracic lymphatic flow rates in individual patients based on their dynamic contrast-enhanced MR lymphangiographic images. © RSNA, 2020 Online supplemental material is available for this article.


Overcoming the bottlenecks of anaerobic digestion of olive mill solid waste by two-stage fermentation.
Two-stage anaerobic digestion (AD) of two-phase olive mill solid waste (OMSW) was applied for reducing the inhibiting factors by optimizing the acidification stage. Single-stage AD and co-fermentation with chicken manure were conducted coinstantaneous for direct comparison. Degradation of the polyphenols up to 61% was observed during the methanogenic stage. Nevertheless the concentration of phenolic substances was still high; the two-stage fermentation remained stable at OLR 1.5 kgVS/m³day. The buffer capacity of the system was twice as high, compared to the one-stage fermentation, without additives. The two-stage AD was a combined process - thermophilic first stage and mesophilic second stage, which pointed out to be the most profitable for AD of OMSW for the reduced hydraulic retention time (HRT) from 230 to 150 days, and three times faster than the single-stage and the co-fermentation start-up of the fermentation. The optimal HRT and incubation temperature for the first stage were determined to four days and 55°C. The performance of the two-stage AD concerning the stability of the process was followed by the co-digestion of OMSW with chicken manure as a nitrogen-rich co-substrate, which makes them viable options for waste disposal with concomitant energy recovery.


The science of vaccination: establishing safety and efficacy.
Vaccination remains a critically important public health tool. It has been responsible for drastically reducing the occurrence of diseases that were once responsible for invoking extreme fear and anxiety. As a consequence, vaccines themselves, and not the diseases they help prevent, have now become the focus of fear and anxiety for many. This review describes the various activities and systems that are in place to ensure that modern vaccines continue to be safe and effective. A better understanding of existing safeguards may help bolster public confidence in immunization.


Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation.
Innate immune response to viral infection is often triggered by Toll-like receptor 3 (TLR3)-mediated signaling by double-stranded (ds) RNA, which culminates in the activation of the transcription factor NF-kappaB and induction of NF-kappaB-driven genes. We demonstrated that dsRNA-induced phosphorylation of two specific tyrosine residues, 759 and 858, of TLR3 was necessary and sufficient for complete activation of the NF-kappaB pathway. When Tyr-759 of TLR3 was mutated, gene induction was inhibited, although NF-kappaB was partially activated. It was released from IkappaB and translocated to the nucleus but failed to bind to the kappaB site of the target A20 gene promoter. This defect could be attributed to incomplete phosphorylation of the RelA (p65) subunit of NF-kappaB, as revealed by two-dimensional gel analyses of p65, isolated from dsRNA-treated cells expressing either wild type TLR3 or the Tyr-759 --> Phe mutant TLR3. Thus, two phosphotyrosine residues of TLR3 activate two distinct pathways, one leading to NF-kappaB release and the other leading to its phosphorylation.


Well-differentiated liposarcoma. The Mayo Clinic experience with 58 cases.
The clinicopathologic results from 58 patients with well-differentiated liposarcomas are reported. Thirty-two tumors involved the extremities, 20 the retroperitoneum, 4 the scrotum, 1 the abdominal wall, and 1 the cheek. Most tumors were large (mean, 22.6 cm). There were 31 (53%) lipoma-like, 23 (40%) sclerosing, and 4 (7%) primary dedifferentiated tumors. Six tumors underwent dedifferentiation after recurrence. The average follow-up period was 9.3 years. Thirty-seven patients (64%) were alive with no evidence of disease; 7 (12%) were alive with disease; 8 (14%) died of disease; and 6 (10%) died of other causes. Dedifferentiation did not indicate imminent death; 5 of the 10 patients were alive with no evidence of disease. Three dedifferentiated tumors subsequently recurred as pure well-differentiated liposarcomas. Patients with extremity tumors had a significantly better prognosis than those with retroperitoneal or scrotal tumors (P = .006). Extremity tumors treated by wide local excision recurred in only 11% of cases, whereas 60% of those treated by marginal or simple excision recurred.


Intraoperative cholangiography time in laparoscopic cholecystectomy: timing the radiographer.
The debate for and against the routine use of intraoperative cholangiography (IOC) continues. One of the main arguments against the routine use of the technique during laparoscopic cholecystectomy (LC) is the length of time it takes, which in turn increases the cost. In this study, we recorded the time spent by the radiographer providing IOC service in the context of optimizing the utilization of the radiographer and IOC time. A total of 91 consecutive LCS, including 19 laparoscopic bile duct explorations, from April 2003 to January 2004 were included in the study. We recorded the time the radiographer took from receiving a call to arriving in the theater, the time he or she spent performing the IOC, and the total time spent in theater. We also recorded the total operative time. The mean time from call to arrival was 9 min (SD = 3, n = 91). The mean total time spent by the radiographer in the theater involved in performing the IOC during LC was 15 min (SD = 8, n = 72), and that during laparoscopic exploration was 46 min (SD = 20, n = 19). The mean operative time was 67 min (SD = 24) and 135 min (SD = 59), respectively. Radiographer services as well as IOC time could be optimized to facilitate the routine use of this important technique in LC. Optimizing the logistics and time factor in IOC is an integral component of single-stage management of patients with suspected bile duct stones.


The Association Between Variability in Electrolytes and the In-Hospital Mortality in Critically Ill Children in Pediatric Intensive Care Units.
Objective: This study aimed to explore the association between the variability in electrolytes and the in-hospital mortality in critically ill children admitted into intensive care units (ICUs). Design: This is a retrospective case-control study. Setting and Participants: Total of 11,245 children have been admitted to ICUs of Children's Hospital of Zhejiang University from 2010 to 2018. Methods: The coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) were calculated as variability indices. High variability was defined as having values in the highest quartile for each parameter. Age, sex, diagnoses of disease, and surgical treatment were adjusted in the multivariable-adjusted logistic regression model. Results: A total of 11,245 children were included, and 660 patients died in the hospital. The median (P25, P75) potassium, sodium, and chloride of all patients were 3.8 (3.58, 4.09), 136.83 (135.11, 138.60), and 108.67 (105.71, 111.17), respectively. U-shaped relationships between the mean, lowest, and highest levels of potassium, sodium, and chloride and the in-hospital mortality were observed. The lowest mortality was noted when serum potassium, sodium, and chloride were between ~3.5 and 5.0, 135 and 145, and 105 and 115 mmol/l, respectively. The areas under the curve (AUCs) of three indices of variability in electrolytes were larger than those of the mean and lowest levels of electrolytes in predicting the in-hospital mortality. In the multivariable-adjusted model, the odds ratios and 95% confidence interval (CI) of the in-hospital mortality were 3.14 (2.44-4.04) for one parameter, 5.85 (4.54-7.53) for two parameters, and 10.32 (7.81-13.64) for three parameters compared with subjects having no parameters of high variability measured as the CV. The results were consistent when the variability was determined using the SD and VIM (all P for trend <0.001). Consistent results were noted in various subgroup analyses. Conclusions: This study showed that individuals with higher variability of each parameter were related with higher risk of in-hospital mortality. There was a linear association between the number of high variability parameters and the in-hospital mortality. The variability of electrolytes might be a good predictor for in-hospital mortality of children in ICUs.


UVAL-MED a universal visual associative language for medicine.
We describe UVAL-MED, a Universal visual associative language for medicine, and propose its use in combination with diagnostic reasoning and decision support systems. When fully developed, our system will automatically translate SNOMED terms to UVAL-MED terms. Grammar and syntax for UVAL-MED are defined and its features as a language-independent tool are discussed. The perceived advantages of our graphical language for rapid integration of knowledge and the assessment of developing situations could thus facilitate decision making.


DNA damage-associated dysregulation of the cell cycle and apoptosis control in cells with germ-line p53 mutation.
Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues 286A, 133R, 282W, 132E, and 213ter were established from five independent Li-Fraumeni syndrome families. When cell cycle regulation in response to gamma-irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all cases except for 282W LCL, which showed a normal G1 checkpoint. On the other hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase 2 activity was defective in all these LCLs. The mitotic checkpoint was also defective in the two LCLs analyzed as either competent or incompetent for G1 arrest. When radiation-induced apoptosis, which requires wild-type p53 function under optimal conditions, was studied, all of these LCLs showed significant failure compared to normal LCLs. These findings indicate that although p53-dependent transactivation and G1-S-phase cell cycle control are variably dysregulated, the induction of apoptosis and control of the cell cycle at S-phase-G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families to cancer. Furthermore, the approach presented is a potentially useful method for studying individual carriers of different germ-line p53 mutations and different biological features.


A new barbeled goby from south China (Teleostei: Gobiidae).
A new goby species Tridentiger radiatus sp. nov. is described from Zhuhai, Guangdong Province of China. The new species, found in sympatry with a widely distributed barbeled congener Tridentiger barbatus (Günther, 1861), is one of the only two Tridentiger species known to possess mandibular and cheek barbels. Tridentiger radiatus is diagnosed by having higher longitudinal and transverse scale counts, less developed barbels, unmottled colouration compared to T barbatus, and 3 dusky radiating infraorbital bands. Partial 12s rDNA sequence data obtained from 5 individuals of T radiatus and 2 individuals of T. barbatus, together with published sequence data of other congeners confirmed validity of the new species. The divergence between T. radiatus and T. barbatus well exceeds the divergence of other sister taxa in the same genus. Monophyly of the two barbeled species is supported.


Inclusion, Access, and Civility in Public Bioethics.
I could tell many war stories about my experience serving on the President's Council on Bioethics-one of the most controversial national bioethics commissions so far-but I want to focus instead on how the experience influenced my views on bioethics, politics, and the potential contributions of national commissions. The executive order that established the Council directed it to consider policy questions, but it spoke primarily of providing a forum for national discussion, inquiry, and education. In this sense, the Council's mission departed from that of other national bioethics commissions, which have had more direct policy functions. Most bioethics commissions consider a range of ethical positions in their reports, but their primary objective has been to develop consensus recommendations on whatever topic they are addressing. The Council's executive order moved away from the consensus-based policy model and called for deep attention to contested ideas. Although the search for consensus may be the most suitable approach for policy activities, it can lead to a bland and anemic version of bioethics. The Council sought to contribute thick bioethical analysis.


A performance evaluation of the expert system ANEMIA.
This paper reports the results of an evaluation study of the current level of performance given by ANEMIA, a knowledge-based consultation system addressing the clinical problem of managing anemic patients. ANEMIA was developed on a mainframe using the AI programming scheme EXPERT and then translated into a version running on a personal computer. At present the system is able to provide assistance in the diagnosis and management of 65 disease entities. After extensive local testing of accuracy, completeness, and consistency of the knowledge base included into ANEMIA, we designed a study to evaluate whether the system is able to appropriately mirror also the reasoning of well-known hematologists other than those who provided the knowledge. We were also interested in testing whether there were conflicting opinions among hematologists. Thus, we designed a validation study in which ANEMIA's performance could be compared with that of six hematologists and the interexpert consensus evaluated. ANEMIA's overall performance was judged acceptable in 87% (26/30) of the cases, while expert evaluators agreed with their colleagues in 90% (27/30) of them. A low interexpert consensus was found: considering the ratings given by different hematologists to the same ANEMIA performance, complete agreement occurred only 47% of the time.


Adolescents' and Young Adults' Routine Care Use: The Role of Their Mothers' Care Use Behaviors.
Little is known whether mothers' own care use is differentially associated with their adolescents' routine care use by gender. The main purpose of this study is to examine whether mothers' healthcare use prospectively predicts their adolescents' routine care use stratified by gender, after controlling for predisposing (child's age, race/ethnicity, region of residence, urbanicity, and mother's age at child's birth), enabling (mother's education, adolescent and mother health insurance), and need (child health status) factors. In 2018, a prospective analysis was conducted using data from 5,040 adolescents aged 9-24 and their mothers who completed the two-generation National Longitudinal Survey of Youth in 2006 (first interview) and 2008 (second interview). Findings include percentages and adjusted odds ratios of the factors that predict adolescents' self-report of routine care use in the past year measured at the second interview. In 2008, over half of participants reported a routine doctor visit during the prior 12 months and this varied by gender; more females (68.7%) had a visit than males (53.5%). Factors that independently predicted a greater odds of adolescents' routine doctor visits included mothers with routine doctor visits at both interviews or the second interview only, and adolescents' health insurance and past routine visit, regardless of gender. Males aged 18-20 and 21-24 years had lower odds of having a routine doctor visit than males aged 9-11 years. This study provides evidence for the potential role that mothers' care use can play in their adolescents' routine care use, especially for their sons, independent of insurance status.


Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against Cisplatin-Induced Acute Kidney Injury.
Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.


Psychobiology of threat appraisal in the context of psychotic experiences: a selective review.
A key factor in the transition to psychosis is the appraisal of anomalous experiences as threatening. Cognitive models of psychosis have identified attentional and interpretative biases underlying threat-based appraisals. While much research has been conducted into these biases within the clinical and cognitive literature, little examination has occurred at the neural level. However, neurobiological research in social cognition employing threatening stimuli mirror cognitive accounts of maladaptive appraisal in psychosis. This review attempted to integrate neuroimaging data regarding social cognition in psychosis with the concepts of attentional and interpretative threat biases. Systematic review methodology was used to identify relevant articles from Medline, PsycINFO and EMBASE, and PubMed databases. The selective review showed that attentional and interpretative threat biases relate to abnormal activation of a range of subcortical and prefrontal structures, including the amygdala, insula, hippocampus, anterior cingulate, and prefrontal cortex, as well as disrupted connectivity between these regions, when processing threatening and neutral or ambiguous stimuli. Notably, neural findings regarding the misattribution of threat to neutral or ambiguous stimuli presented a more consistent picture. Overall, however, the findings for any specific emotion were mixed, both in terms of the specific brain areas involved and the direction of effects (increased/decreased activity), possibly owing to confounds including small sample sizes, varying experimental paradigms, medication, and heterogeneous, in some cases poorly characterised, patient groups. Further neuroimaging research examining these biases by employing experimentally induced anomalous perceptual experiences and well-characterised large samples is needed for greater aetiological specificity.


Congenital dyserythropoietic anaemia: report of three cases.
Between January 1985 and June 1992, the Paediatric Department of Hospital Universiti Sains Malaysia has diagnosed congenital dyserythropoietic anaemia in three children, two of whom were siblings. The age of onset ranged from 1 to 3 years. All of them became transfusion-dependent before the age of 4 months. One of them was successfully treated with bone marrow transplantation.


Induction of S. cerevisiae filamentous differentiation by slowed DNA synthesis involves Mec1, Rad53 and Swe1 checkpoint proteins.
A key question in eukaryotic differentiation is whether there are common regulators or biochemical events that are required for diverse types of differentiation or whether there is a core mechanism for differentiation. The unicellular model organism Saccharomyces cerevisiae undergoes filamentous differentiation in response to environmental cues. Because conserved cell cycle regulators, the mitotic cyclin-dependent kinase Clb2/Cdc28, and its inhibitor Swe1 were found to be involved in both nitrogen starvation- and short chain alcohol-induced filamentous differentiation, they were identified as components of the core mechanism for filamentous differentiation. We report here that slowed DNA synthesis also induces yeast filamentous differentiation through conserved checkpoint proteins Mec1 and Rad53. Swe1 and Clb2 are also involved in this form of differentiation, and the core status of Swe1/Clb2/Cdc28 in the mechanism of filamentous differentiation has therefore been confirmed. Because the cAMP and filamentous growth mitogen-activated protein kinase pathways that mediate nitrogen starvation-induced filamentous differentiation are not required for slowed DNA synthesis-induced filamentous growth, they can therefore be excluded from the core mechanism. More significantly, slowed DNA synthesis also induces differentiation in mammalian cancer cells, and such stimulus conservation may indicate that the core mechanism for yeast filamentous differentiation is conserved in mammalian differentiation.


Triplet Pregnancy in a Diabetic Mother With Kidney Transplant: Case Report and Review of the Literature.
Triplet and higher-order multiple pregnancies can carry increased fetal and maternal complications. Reports of triplet pregnancies after kidney transplant are scarce and have been associated with perinatal complications. Presence of diabetes in such cases worsens both fetal and maternal outcomes. Here, we present a triplet pregnancy in a kidney transplant recipient with diabetes. We also reviewed the literature for causes, prevalence, and outcomes in association with chronic kidney disease, kidney transplant, and diabetes mellitus. The patient, a 31-year-female who received a living-donor kidney transplant, had a first-time pregnancy 6 years after transplant. Pregnancy was complicated by gestational diabetes, preeclampsia, and miscarriage. She continued to have postpartum-impaired glucose tolerance. She became pregnant again after 6 months but required insulin therapy during her third trimester. Pregnancy was terminated by cesarean section for a viable small boy. Two years later, she had triplet pregnancy after ovulation induction with clomiphene. Glycemic control was maintained using intensive insulin therapy guided by frequent home blood glucose monitoring (HbA1c was 5.8% at 22 wk). Both gynecologic care and nephrologic care were carried out through outpatient follow-up. Pregnancy was complicated by hypertension and mild renal dysfunction without proteinuria and ended in elective premature cesarean section at 32 weeks of gestation. She had 3 male babies with low birth weights (1320, 1380, 1275 g), with the largest baby developing sepsis and requiring an intensive care unit stay and then incubator for 49 days. The other 2 required incubators for 36 days. Their weights after 22 months were 9, 16, and 11 kg. The mother is now normotensive with normal renal function and impaired glucose tolerance. Care of diabetic kidney recipients with triplet pregnancy constitutes a special challenge requiring a multispecialty skilled team to ensure the best outcome.


Sudden late onset of clozapine-induced agranulocytosis.
To report a patient who suddenly developed agranulocytosis after long-term clozapine therapy. A 41-year-old white man suddenly developed agranulocytosis after 89 months of nearly continuous clozapine therapy. During this time, which included the addition of risperidone to the treatment regimen, his white blood cell (WBC) and granulocyte counts remained stable. One week after having stable hematologic counts, the patient suddenly developed agranulocytosis. WBC and granulocyte counts returned to baseline shortly after discontinuation of all medications and administration of sargramostim. The main factor limiting the use of clozapine as a first-line agent in mentally ill patients is the risk of agranulocytosis. Although the greatest risk of developing this adverse reaction is during the initial 6-month exposure, clozapine-induced agranulocytosis continues to pose a risk after years of exposure. Current product labeling requires weekly WBC and granulocyte monitoring for the first 6 months of treatment with clozapine, which may be decreased to biweekly monitoring after 6 months. Based on the sudden and late onset of agranulocytosis in our patient, clinicians may consider opting for weekly monitoring of hematologic function for patients on long-term clozapine therapy. The likelihood that clozapine was the cause of the agranulocytosis was rated possible according to the Naranjo probability scale. Clinicians must remain vigilant to trends in WBC and granulocyte counts and may wish to consider weekly hematologic monitoring regardless of duration of clozapine therapy. Patient and treatment system compliance with the registries' protocol regarding WBC monitoring is instrumental in reducing morbidity and mortality rates associated with clozapine use.


Effects of excitatory amino acids and their antagonists on the light response of luminosity and color-opponent horizontal cells in the turtle (Pseudemys scripta elegans) retina.
Both kainic acid (KA) and N-methyl-d-aspartatic acid (NMDA) depolarize luminosity-type horizontal cells (L-type H cells) in normal turtle retina. The presence of both NMDA and non-NMDA receptors for excitatory amino acids (EAAs) on these cells was highlighted by an unusual effect of the noncompetitive NMDA-antagonist, MK-801. In retinas that had been exposed to MK-801, the action of NMDA was irreversibly altered to one of hyperpolarization, while the depolarizing effect of KA was unaltered. The aim of the present study was to further characterize these receptors on L-type H cells and to extend the investigation to color-opponent H cells (C-type H cells). Intracellular recording was used to study the effects of KA, NMDA, MK-801, the competitive NMDA antagonists, 2-amino-5-phosphonopentanoic acid (AP5) and 2-amino-7-phosphonoheptanoic acid (AP7), and the nonspecific EAA antagonist, kynurenic acid (KYN) on the light responses of L-type and C-type H cells in turtle retina. The effects of combinations of these drugs were also studied. In L-type H cells the agonists caused depolarization and loss of light response, KYN caused hyperpolarization and loss of light response, and MK-801, AP5 or AP7 had no direct effect. However, application of NMDA following MK-801, AP5 or AP7, but not KYN, caused hyperpolarization and loss of light response. The depolarizing effect of KA was unaltered by these antagonists. These data confirm the presence of an unusual NMDA receptor on L-type H cells. In the case of red/green C-type H cells, application of KA caused loss of responses to both red and green light, with loss of green responses preceding loss of red responses. NMDA initially removed responses to both red and green light. The most striking effect of NMDA was seen during early washout where the responses to red were reversed (hyperpolarizing). These responses eventually recovered their normal polarity. These results suggest that the depolarizing response of C-type H cells to red light is mediated by L-type H cells, but not via inhibition of the excitatory input from green cones to C-type H cells.


[PROSPECTIVE INVESTIGATION OF POSTOPERATIVE NAUSEA AND VOMITING FOLLOWING DUAL PROPHYLAXIS AND LOW DOSE NEURAXIAL MORPHINE FOR CESAREAN DELIVERY].
Spinal morphine provides the optimal treatment for post-cesarean analgesia, despite frequent nausea and vomiting. We investigated the incidence of nausea and vomiting 24 hours after cesarean delivery in women receiving intrathecal morphine 100 µcg and intravenous prophylactic dexamethasone and ondansetron. In a prospective, observational, Institutional Review Board (IRB) approved study of women undergoing cesarean delivery according to a standardized anesthetic protocol, the subjects were approached preoperatively and underwent standardized interviews regarding prior anesthesia experience and history of postoperative nausea and vomiting. In the post anesthesia care unit and 24 hours postoperatively, the women were interviewed regarding the incidence of nausea and vomiting, Women with and without nausea at 24 hours were compared for potential associated risk factors. Among 201 women recruited, 29 (14.5%) had nausea and 7 (3.5%) vomited in the postoperative care unit. During the first 24 hours, 36 (17.9%) had experienced nausea and 19 (9.5%) had vomited when interviewed at the 24-hours postoperatively. Women who had nausea 24 hours postoperatively were more likely to have nausea in the post anesthesia care unit than women without nausea during 24 hours after cesarean delivery (41.7% versus 1.2%, p<0.001). We did not find preoperative risk factors for postoperative nausea and vomiting. We report that almost 20% of the women managed with prophylactic dual therapy of ondansetron and dexamethasone had nausea during the 24 hours after administration of low dose intrathecal morphine. Our findings suggested that women who experience nausea or vomiting in the immediate postoperative period are at increased risk of nausea and vomiting in the 24-hour postoperative period.


Slit2 Inhibits Breast Cancer Metastasis by Activating M1-Like Phagocytic and Antifibrotic Macrophages.
Tumor-associated macrophages (TAM) are heterogeneous in nature and comprise antitumor M1-like (M1-TAM) or pro-tumor M2-like (M2-TAM) TAMs. M2-TAMs are a major component of stroma in breast tumors and enhance metastasis by reducing their phagocytic ability and increasing tumor fibrosis. However, the molecular mechanisms that regulate phenotypic plasticity of TAMs are not well known. Here we report a novel tumor suppressor Slit2 in breast cancer by regulating TAMs in the tumor microenvironment. Slit2 reduced the in vivo growth and metastasis of spontaneous and syngeneic mammary tumor and xenograft breast tumor models. Slit2 increased recruitment of M1-TAMs to the tumor and enhanced the ability of M1-TAMs to phagocytose tumor cells in vitro and in vivo. This Slit2-mediated increase in M1-TAM phagocytosis occurred via suppression of IL6. Slit2 was also shown to diminish fibrosis in breast cancer mouse models by increasing the expression of matrix metalloproteinase 13 in M1-TAMs. Analysis of patient samples showed high Slit2 expression strongly associated with better patient survival and inversely correlated with the abundance of CD163+ TAMs. Overall, these studies define the role of Slit2 in inhibiting metastasis by activating M1-TAMs and depleting tumor fibrosis. Furthermore, these findings suggest that Slit2 can be a promising immunotherapeutic agent to redirect TAMs to serve as tumor killers for aggressive and metastatic breast cancers. In addition, Slit2 expression along with CD163+ TAMs could be used as an improved prognostic biomarker in patients with breast cancer. SIGNIFICANCE: This study provides evidence that the antitumor effect of Slit2 in breast cancer occurs by activating the phagocytic activity of M1-like tumor-associated macrophages against tumor cells and diminishing fibrosis.


Micro digital sun sensor with linear detector.
In this paper, the design of a novel micro digital sun sensor is described. It relies on V-shaped slit and linear array CCD to measure sun-ray angle against two axes. A highly integrated microprogram control unit) is used to make a very simple and compact system. V-shaped slit can simplify algorithm and achieve a wider field of view. Error compensation and accurate calibration are employed to improve accuracy. Adaptive threshold and adjustable expose time further improve reliability. Experiments and flight validation show that the FOV (Field of View) of the sun sensor is ±65° × ± 65° and the accuracy is 0.1° in the whole FOV. It can work reliably at an update rate of 25 Hz, while the consumption is only 200 mW. This sun sensor is proved to have a good prospect in micro/nanosatellites.


Nasal trigeminal inputs release the A5 inhibition received by the respiratory rhythm generator of the mouse neonate.
Experiments were performed on neonatal mice to analyze why, in vitro, the respiratory rhythm generator (RRG) was silent and how it could be activated. We demonstrated that in vitro the RRG in intact brain stems is silenced by a powerful inhibition arising from the pontine A5 neurons through medullary alpha(2) adrenoceptors and that in vivo nasal trigeminal inputs facilitate the RRG as nasal continuous positive airway pressure increases the breathing frequency, whereas nasal occlusion and nasal afferent anesthesia depress it. Because nasal trigeminal afferents project to the A5 nuclei, we applied single trains of negative electric shocks to the trigeminal nerve in inactive ponto-medullary preparations. They induced rhythmic phrenic bursts during the stimulation and for 2-3 min afterward, whereas repetitive trains produced on-going rhythmic activity up to the end of the experiments. Electrolytic lesion or pharmacological inactivation of the ipsilateral A5 neurons altered both the phrenic burst frequency and occurrence after the stimulation. Extracellular unitary recordings and trans-neuronal tracing experiments with the rabies virus show that the medullary lateral reticular area contains respiratory-modulated neurons, not necessary for respiratory rhythmogenesis, but that may provide an excitatory pathway from the trigeminal inputs to the RRG as their electrolytic lesion suppresses any phrenic activity induced by the trigeminal nerve stimulation. The results lead to the hypothesis that the trigeminal afferents in the mouse neonate involve at least two pathways to activate the RRG, one that may act through the medullary lateral reticular area and one that releases the A5 inhibition received by the RRG.


[Efficacy of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm post cardioverter-defibrillators implantation].
To evaluate the acute and long-term effects of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm (VAS) post implantable cardioverter-defibrillators (ICD) implantation. Acute and long-term effects of catheter radiofrequency ablation for the treatment of VAS post ICD implantation were retrospectively assessed in 11 patients from September 2008 to August 2011. A total of 15 ablation procedures were performed in 11 patients. Six ablation procedures were performed through epicardial approach. In 9 patients, 20 types of ventricular tachycardia (VT) (including 20% hemodynamically unstable VT) were induced during the procedures [mean cycle length (384 ± 141) ms] and polymorphic ventricular tachycardia were induced in 7 patients. The average X-ray fluoroscopy time and procedural time were (26 ± 17) min and (189 ± 60) min, respectively. Complete success, partial success, and failure rates immediately post catheter radiofrequency ablation were 46.7% (7/15), 26.7% (4/15) and 26.7% (4/15), respectively. All patients are alive at follow-up[(2.45 ± 9.6) months after the last catheter ablation] and the complete success, partial success, and failure rates during follow-up were 72.7% (8/11), 9.1% (1/11) and 18.2% (2/11), respectively. VAS can be effectively treated by catheter radiofrequency ablation in patients post ICD implantation.


Association between tea consumption and cognitive function in cognitively healthy older adults and older adults with mild cognitive impairment.
Prospective studies suggest that tea consumption may decrease the risk for cognitive impairment in late life. However, little research has examined the association between tea consumption and cognitive performance across multiple domains. In addition, no research has examined the benefit of tea consumption on cognitive performance among older adults with existing impairment. The current study examined the association between tea consumption and performance on tasks of global cognitive function, episodic memory and executive function in cognitively healthy (CH) older adults and older adults with mild cognitive impairment (MCI). The analytical sample included 1849 community-dwelling older adults from the Shanghai Brain Aging Study (65.6% female, mean age of 69.50 (8.02) years). Following ascertainment of cognitive function, 816 were categorised as MCI. In addition to completion of a demographics questionnaire, participants reported their tea consumption and completed a battery of tests to measure global cognitive function, episodic memory and working memory. Independent analyses of covariance revealed a significant association between tea consumption and measures of episodic memory; however, these associations were restricted to CH older adults but not older adults with MCI. Tea consumption was not associated with working memory performance. The current study suggests that the benefit of tea consumption is restricted to cognitively healthy older adults and does not extend to older adults with MCI.


Relationship of eosinophils and plasma cells to biofilm in chronic rhinosinusitis.
This study investigates the relationship of eosinophils and plasma cells to biofilm in chronic rhinosinusitis (CRS). A prospective observational study was performed at the Keck Hospital, University of Southern California, Department of Otolaryngology, Los Angeles, CA. A total of 29 patients, 20 undergoing endoscopic sinus surgery for CRS and 9 control patients undergoing septoplasty for nasal obstruction without history or evidence of CRS, were included in this study. Contiguous sinonasal mucosa sample sections were examined by hematoxylin and eosin (H&E), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for biofilm, microbes, eosinophil major basic protein (EMBP), and cluster designation 27 (CD27). EMBP and CD27 were used as eosinophil and plasma cell markers, respectively. Biofilm was visualized in 15 of 20 patients with CRS on H&E sections, confirmed by microbial presence using FISH. Biofilm was not identified in tissue samples of the nine control patients. On IHC analysis, CD27 and EMBP expression were significantly higher in patients with CRS compared with control (p < 0.05) and had greater expression in biofilm-positive patients compared with biofilm-negative patients. Nasal polyps correlated with higher expression of CD27 and EMBP, but in CRS patients without polyps CD27 and EMBP was also significantly greater in biofilm-positive specimens compared with biofilm-negative specimens. Biofilm presence in CRS appears to correlate to host inflammatory response involving plasma cell and eosinophil recruitment.


Structural organization and chromosomal location of the chicken alpha-amylase gene family.
Characterization of the Gallus gallus alpha-amylase gene family revealed that the chicken genome contains two distinct amy loci. One of the two loci is expressed in the chicken pancreas while cDNA clones for the second locus were detected in a library constructed from liver mRNA. Fluorescent in situ hybridization to chromosome spreads showed that the two loci are both located on chromosome 8 within the chicken genome. Moreover, each locus contains both an intact, expressed gene copy as well as a pseudogene. The expressed gene and the pseudogene are arranged in a divergent configuration in the pancreatic amy locus, while in the hepatic locus the intact gene and the pseudogene are arranged in tandem. The data suggest a complex pattern of evolution for the chicken amylase gene family which includes multiple gene duplication events, insertion/deletion events, as well as changes in spatial expression patterns.


Parent satisfaction in pediatric intensive care: a critical appraisal of the literature.
To assess the content and characteristics of satisfaction surveys for the development of a parent satisfaction questionnaire to improve clinical practice in pediatric intensive care. A structured literature review process. The databases PubMed and CINAHL were searched, via identified search terms, for relevant articles published between May 1994 and May 2004. Assessment and analysis of the material was related to development, content, reliability and validity, scales for scoring, and distribution of the satisfaction questionnaires. Twelve original studies were identified using ten different satisfaction surveys in pediatric, neonatal, or adult intensive care units or in general pediatric wards. All surveys counted a total of 248 questions or statements. Six satisfaction questionnaires categorized the questions or statements in 21 different formulated domains. Most questionnaires showed sufficient results on reliability and validity. Except for one satisfaction instrument, Likert-type scales were used for rating. One study described the distribution of the questionnaire after discharge from the hospital, whereas other questionnaires were distributed during hospital admission. The use of parent satisfaction surveys in pediatric intensive care is not well documented. Family-centered care has become widely accepted as an important issue in quality of care, and satisfaction surveys are a valuable resource for measuring and improving clinical practice. Parent satisfaction surveys need to be developed based on the needs and experiences of parents, and emphasis should be put on methodologic issues to have the results accepted as valid and effective for possible changes in clinical practice.


Experimental assessment of ureteral free autograft.
To establish the sequence of ureteral events under ischemic and desvascularized conditions but without immunologic interference. Sixty-two rats were divided into four groups. NU group (n 20) control group, normal ureter; SC group (n 15) only surgical control ureterolysis; NIAFG group (n 13) ureter used as non integrated autologous free graft; IAFG group (n 14): ureter used as integrated autologous free graft. Urographic, histologic and histomorphometric studies were performed. We established ureteral changes in the NIAFG and IAFG groups, compared to the control groups (NU, SC). Surgical findings and urographic assessment revealed normal peristalsis with no ectasia in some cases, and no ureteral fistulas or extravasations were found in the IAFG group. Histologic findings showed preservation of the architecture of the three normal layers. Histomorphometric studies showed that ureterolysis caused edema in the lamina propria, while changes in ureter free graft depended on whether the ureter was integrated or not. In the NIAFG group only the urothelial layers showed differences and in the IAFG group the ureteral wall appeared thicker. Histomorphometric studies showed preservation of the normal histologic structures in all cases. The rat ureter can be used as a free autologous graft and represents an experimental model for immunologic events. We may assume that the necrosis and fibrosis observed in transplanted ureters are secondary to rejection in some cases.


Peripheral Insulin Edema and Pericardial Effusion in a 12-Year-Old Newly Diagnosed Girl with Type 1 Diabetes.
Introduction: Insulin induced edema (IIE) is a rare condition, usually found in newly diagnosed diabetes patients, either after insulin treatment initiation or after dose increment. It is a self-limited process, rarely associated with serosal effusions. Teenage girls with type 1 diabetes (T1DM) are most commonly affected. Patient and Methods: A 12-year-old girl was diagnosed with ketoacidosis (DKA). Seven days after initiation of the insulin treatment, at a stable total daily dose of insulin (TDDI) of 0.55 IU/kg, she came with two kilograms weight gain in only two days and edema of the feet and calves. Ultrasound of the heart found a 7 mm pericardial effusion. The diagnostic workout included clinical examination, biochemical, hormonal, allergen analyses and imaging which excluded other known causes of swelling. Conclusions: We describe an adolescent girl with newly diagnosed T1DM and a rare association of peripheral insulin-induced edema and pericardial effusion. Short-term diuretic treatment and salt restriction resolved this rare complication of insulin treatment.


[Different interbody fustion cages and combined fixation through intermuscular approach for lumbar diseases:a case control study].
To explore the clinical effect of combined fixation and interbody bone grafting through intermuscular approach with different fusion cages in the treatment of single segment lumbar diseases. From June 2014 to December 2016, the clinical data of 123 cases of single segment lumbar diseases were analyzed retrospectively, including 44 males and 79 females, aged 22 to 60 years old, with the diseases course of 6 to 84 months. The disease types involved lumbar disc degeneration in 65 cases, lumbar spinal stenosis in 30 cases, MeyerdingⅠslip in 21 cases, giant lumbar disc herniation in 7 cases. Lesions was L3, 4 in 5 cases, L4, 5 in 101 cases, L5S1 in 17 cases. According to the application of different interbody fusion cage, patients were divided into single common cage group, double common cage group and banana type cage group. The operation time, intraoperative hemorrhage, postoperative incision drainage fluid and incision length were observed in three groups; VAS score of lumbar incision and JOA score of preoperative and final follow up were recorded 72 hours after operation;the intervertebral space height, Cobb angle of lumbar coronal and sagittal plane before and after operation, and interbody fusion 12 months after operation were observed by imaging data. There was no significant difference in incision length, operation time, intraoperative bleeding volume, postoperative drainage volume and VAS score of lumbar incision 72 hours after operation among three groups (P>0.05). All cases were followed up for 12 to 36 (23.70±4.52) months. The height of intervertebral space in three groups recovered significantly (P<0.05), at the last follow-up, there were different degrees of loss, the loss degree of single common fusion cage group>banana type fusion cage group>double common fusion cage group. At the last follow-up, the Cobb angle in the coronaland sagittal planes of the three groups were significantly improved (P<0.05). During the follow-up, there were 42 cases of fusion cage subsidence, including 26 cases in the single common cage group, 5 cases in the double common cage group, 11 cases in the banana cage group, the difference was statistically significant (P<0.05). At 12 months after operation, the interbody fusion rate was 83% in the single common cage group, 95% in the double common cage group and 90% in the banana cage group, the interbody fusion rate in the two common cage group and the banana cage group was better than that in the single common cage group. No obvious degeneration was observed in the adjacent segments. At the last follow-up, the JOA scores of the three groups were statistically significant (P<0.05). The incidence of single common fusion cage group was 10%(4 / 42), that of double common fusion cage group was 9%(4 / 43), and that of banana fusion cage group was 10%(4 / 39). There was no significant difference among the three groups. Through the intermuscular approach, single pedicle screw and contralateral facet screw were used for fixation, and single common fusion cage, double common fusion cage or banana type fusion cage were used for interbody grafting to treat single segment lumbar disease. Although the application of different fusion cage could not increase the axial strength of fixed segment, the speed of fusion was accelerated by increasing the contact area, and the quality of the fusion cage reduces the settlement of the cage and the loss of the height of the intervertebral space. Therefore, two interbody fusion cages implanted in one side are of positive clinical significance for the fixation of unilateral pedicle screw combined with contralateral facet screw, without prolonging the operation time and increasing the complications.


Morphological and genetic abnormalities in a Jacobsen syndrome.
Jacobsen syndrome (JS) is a contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The syndrome is rare and there are very few observations regarding the pubertal period of the affected individuals. We report the case of a 22-year-old female, with JS, monitored since the age of three months. She presented intrauterine growth retardation, failure to thrive and feeding difficulties from the first year of the life, and she learned to walk at the age of four years. Phenotypically, the case is characterized by distinctive facial and limb abnormalities. She shows spasticity and profound delay in gross and fine motor skills. Additionally, she has severe learning difficulties, non-verbally communicates, and displays hetero-aggressive and auto-aggressive behavior. The evolution of puberty was characterized by hypogenitalism and primary amenorrhea. Thrombocytopenia and IgM deficiency became apparent also at puberty. Array comparative genomic hybridization (aCGH) analysis confirmed a deletion of 16.3 Mb on 11q23.3-q23.4. We report this case as the first documented case of JS in Romania, as well as for clinical particularities (long period of survival and late appearance of hematological and immunological disorders).


Intraoperative use of the pelvic c-clamp as an aid in reduction for posterior sacroiliac fixation.
Posterior pelvic ring injuries with dissociation of the sacroiliac joint can be a therapeutic challenge. Open procedures for reduction have a significant risk for wound complications although inadequate reductions using percutaneous methods can have poor long-term outcomes. Several indirect reduction methods have been previously described for closed reduction of the sacroiliac joint. We present our technique for the intraoperative use of the pelvic c-clamp as a reduction aid for the posterior pelvis in conjunction with percutaneous iliosacral screw fixation. This technique has been used routinely in our patients who sustain injuries to the sacroiliac joint and are candidates for closed reduction and percutaneous fixation. Our objective is to provide orthopedic surgeons an additional means by which to reduce sacroiliac disruptions by percutaneous means.


The functional SYNTAX score - a huge step forward or research in motion?
In a recent manuscript in the Journal of the American College of Cardiology, the newly introduced "functional SYNTAX score" (FSS) was found to be a better tool to assess the extent and severity of coronary artery disease than the SYNTAX score (SS) and has reclassified 1/3 of the studied cohort into lower-risk categories. Besides being more invasive, costly, and time consuming, FSS still suffers from inherent deficiencies of its own. Like SS, FSS does not incorporate clinical risk predictors and consequently is a suboptimal tool for predicting PCI risk. FSS is not supported by a wealth of contemporary outcome data in a wide range of patient and lesions subsets. Key unanswered questions are whether PCI of hemodynamically significant lesions (FFR <0.80) is superior to optimal medical therapy (OMT) and whether complete revascularization yields considerably better outcomes than partial revascularization. Since partial revascularization is still an option, operational FSS (taking into account only the FSS of lesions subject to PCI) combined with a clinical risk score will probably better predict the procedural risk of the planned PCI.


[Strengthening Families Program: key points for the French adaptation].
The Strengthening Families Program (SFP) is an American evidence-based family skills training intervention, developed in 35 countries around the world.The aim of this study was to identify potential key-points to ensure successful implantation of SFP in France. SFP was implemented in three cities of Alpes Maritimes to test acceptability and feasibility, and to identify an efficient implementation protocol. Each step was accompanied by necessary adaptations. The trial was completed by assessment of immediate efficacy. SFP was tested with four groups of families, providing positive results in terms of family retention rate and immediate efficacy.Cultural adaptation of the programme identified the need for a local partnership, information and training in order to support implementation of SFP. This very positive experience shows that it is possible to use successfully standardized programmes in France. This adaptation must now be validated by a larger scale study.


Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation.
Eliminating alloreactive cells from T-cell populations would enable the transfer of immune function to patients who receive stem cell transplants. However, high-efficiency depletion has proved difficult to achieve. We sought to develop ex vivo approaches for the maximal depletion of alloreactive CD4(+) T cells. Using a flow cytometric cell sorting approach after mixed lymphocyte reaction (MLR) culture, we have found that sorted CFSE(bright) (5-(and-6)-carboxyfluorescein diacetate succinmidyl ester) (nondivided) and activation antigen-negative cells are markedly depleted of alloreactivity. With HLA-mismatched peripheral blood mononuclear cell (PBMC) stimulators we have consistently attained (90%-95%) depletion of alloreactivity. Importantly, when purified matured monocyte-derived dendritic cells (DCs) are used as stimulators, a 100-fold (99%) reduction in alloreactivity was attained, resulting in abrogation of the secondary MLR. Significantly, the CFSE(bright) CD25(-) cells recovered from these cultures retained general immunoreactivity, including responses to Candida and cytomegalovirus (CMV) antigens. In addition, a CFSE-based approach was tested and found to be sufficient for graft-versus-host disease (GVHD) prevention in vivo, in a major histocompatibility complex (MHC) class II disparate murine model. This efficient approach to selectively deplete mature alloantigen-specific T cells may permit enhanced immune reconstitution without GVHD.


The colocalizations of pulp neural stem cells markers with dentin matrix protein-1, dentin sialoprotein and dentin phosphoprotein in human denticle (pulp stone) lining cells.
The primary dentin, secondary dentin, and reactive tertiary dentin are formed by terminal differentiated odontoblasts, whereas atubular reparative tertiary dentin is formed by odontoblast-like cells. Odontoblast-like cells differentiate from pulpal stem cells, which express the neural stem cell markers nestin, S100β, Sox10, and P0. The denticle (pulp stone) is an unique mineralized extracellular matrix that frequently occurs in association with the neurovascular structures in the dental pulp. However, to date, the cellular origin of denticles in human dental pulp is unclear. In addition, the non-collagenous extracellular dentin matrix proteins dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), and dentin phosphoprotein (DPP) have been well characterized in the dentin matrix, whereas their role in the formation and mineralization of the denticle matrix remains to be clarified. To characterize the formation of denticle, healthy human third molars (n = 59) were completely sectioned and evaluated by HE staining in different layers at 720 µm intervals. From these samples, molars with (n = 5) and without denticles (n = 8) were selected. Using consecutive cryo-sections from a layer containing denticles of different sizes, we examined DMP1, DSP, and DPP in denticle lining cells and tested their co-localizations with the glial stem cell markers nestin, S100β, Sox10, and P0 by quantitative and double staining methods. DMP1, DSP and DPP were found in odontoblasts, whereas denticle lining cells were positive only for DMP1 and DSP but not for DPP. Nestin was detected in both odontoblasts and denticle lining cells. S100β, Sox10, and P0 were co-localized with DMP1 and DSP in different subpopulations of denticle lining cells. The co-localization of S100β, Sox10, and P0 with DMP1 and DSP in denticle lining cells suggest that denticle lining cells are originated from glial and/or endoneurial mesenchymal stem cells which are involved in biomineralization of denticle matrix by secretion of DMP1 and DSP. Since denticles are atubular compared to primary, secondary, reactionary tertiary dentin and denticle formed by odontoblasts, our results suggest that DPP could be one of the proteins involved in the complex regulation of dentinal tubule formation.


A measurement of the maximal forces in plasmonic tweezers.
Plasmonic tweezers that are designed to trap nanoscale objects create many new possibilities for single-molecule targeted studies. Numerous novel designs of plasmonic nanostructures are proposed in order to attain stronger forces and weaker laser intensity. Most experiments have consisted only of immobilization observations--that is, particles stick when the laser is turned on and fall away when the laser is turned off. Studies of the exertable forces were only theoretical. A few studies have experimentally measured trap stiffness. However, as far as we know, no studies have addressed maximal forces. In this paper, we present a new experimental design in which the motion of the trapped particle can be monitored in either parallel or orthogonal directions to the plasmonic structure's symmetric axis. We measured maximal trapping force through such monitoring. Although stiffness would be useful for force-calibration or immobilization purposes, for which most plasmonic tweezers are used, we believe that the maximal endurable force is significant and thus, this paper presents this aspect.


Purification and enzymological characterization of murine neurotrypsin.
An increasing number of studies indicate that serine proteases play an important role in structural plasticity associated with learning and memory formation. Neurotrypsin is a multidomain serine protease located at the presynaptic terminal of neurons. It is thought to be crucial for cognitive brain functions. A deletion in the neurotrypsin gene causes severe mental retardation in humans. For a biochemical characterization, we produced murine neurotrypsin recombinantly in a eukaryotic expression system using myeloma cells. From the culture medium we purified neurotrypsin using heparin-, hydrophobic interaction- and immobilized metal affinity chromatography. For an enzymological characterization two fragments of agrin containing the natural cleavages sites of neurotrypsin were used as substrates. The highest catalytic activity of neurotrypsin was observed in the pH range between 7.0 and 8.5. Calcium ions were required for neurotrypsin activity and an ionic strength exceeding 500 mM decreased substrate cleavage. Site-specific mutations of the amino acids flanking the scissile bonds showed that cleavage is highly specific and requires a basic amino acid preceded by a glutamate residue on the N-terminal side of the scissile bond. This sequence requirement argues for a unique substrate binding pocket of neurotrypsin. This observation was further substantiated by the fact that almost all tested serine protease inhibitors except dichloroisocoumarin and PMSF did not affect neurotrypsin activity.


Anterior and posterior ruptures of the urethra: simplified methods of immediate surgical management.
The aetiology and relative incidence of anterior and posterior ruptures of the urethra are briefly discussed. Methods of surgical management of both types of injury are described, which obviate any necessity to expose the site of rupture. A series of five such cases is reported, the outcome in each being satisfactory.


The ultrastructure of C1t, a subcomponent of the first component of complement: an E.M. and ultracentrifuge study.
C1t is a 9.5 S alpha1 glycoprotein that has been shown to be a fourth subcomponent of the first component of complement. The m.w. of C1t was found to be 233,000 by sedimentation equilibrium in the ultracentrifuge. A subunit m.w. of 23,000 was obtained by sedimentation equilibrium in 5.95 M guanidinium chloride. No change in either m.w. was produced by prior reduction and alkylation. In the electron microscope characteristic pentagonal figures of 85 A diameter were observed together with rod-like figures which appear to be stacked assemblies of the pentagonal figures. These observations lead us to propose that C1t is a noncovalent, decameric protein with the subunits disposed at the vertices of two regular pentagons joined at one of their faces. A possible relationship between C1t and the P-component of amyloid is discussed.