Recent applications of capillary electrochromatography.
A review is presented of the most important recent applications of capillary electrochromatography (CEC) for the analysis of acidic, basic, and neutral compounds, of biomolecules, environmental substances, natural products, pharmaceuticals, and chiral compounds. Packed-column CEC (packed-CEC), open-tubular (OT-CEC), as well as pressure-assisted CEC (pseudo-CEC) are hereby considered. Papers published between July 1999 and April 2001 were taken into account. Applications before July 1999 have been reviewed in Electrophoresis 1999, 20, 3027-3065.


Does pre-operative chemoradiotherapy cause wound complications after abdominoperineal excision for rectal cancer? An observational study.
Neo-adjuvant chemoradiotherapy is commonly used before surgery for rectal cancer. Very low rectal cancers are still treated by abdominoperineal excision of the rectum (APER). Perineal wound complications are common after APER. There is evidence that radiotherapy increases wound complications. We wished to examine the effect of preoperative radiotherapy (SCPRT) and long course chemoradiotherapy (LCCRT) on perineal wound complications. We undertook a review of all patients undergoing APER at one institution between 2000 and 2010. Details of SCPRT, LCCRT and both minor and major wound complications were identified by retrospective notes review. Of 74 patients suitable for analysis, 38 (51%) had recorded wound complications, with 23 (31%) having major wound complications. 43 patients (58%) underwent LCCRT and 11 (15%) SCPRT. Overall wound complications were more common in the LCCRT group than those receiving no treatment (58% vs 30%, p = 0.03), and major wound complications more common after SCPRT than LCCRT (45% vs 35%, p = 0.04) or no treatment (45% vs 10%, p = 0.04). Use of mesh led to more wound complications (71% vs 41%), but almost all of these patients received LCCRT. Pre-operative LCCRT and SCPRT are both associated with increased perineal wound complications after APER.


On the role of aging in cancer incidence: an interpretation of the prostate cancer anomaly with implications for routine screening.
Cross-sectional age-incidence patterns for the common male and female cancers in Connecticut were normalized to describe the percentage of total incidence that occurred at each age. The pattern for prostate cancer was atypical--less than the 99% confidence limit from the mean at ages less than 60 and greater than the 99% confidence limit from the mean at ages greater than 75. The available international data on latent carcinoma of the prostate, when normalized as above, resembled the mean male and female cancer patterns in Connecticut and suggested that the atypical behavior of clinical prostate cancer was the result of a lag between the incidence of latent carcinoma and promotion to clinical disease. Confirmation of this suggestion, with the potential to distinguish epidemiologically those latent carcinomas that remain asymptomatic from those that progress to malignancy, awaits routine screening for the latent carcinoma.


NaKR1 regulates long-distance movement of FLOWERING LOCUS T in Arabidopsis.
Flowering plants perceive photoperiodic signals in leaves to generate mobile stimuli required for the induction of flower formation at shoot apices. Although FLOWERING LOCUS T (FT) has been identified as part of the mobile floral stimuli in Arabidopsis thaliana, the mechanisms underlying long-distance movement of FT from leaves to shoot apices remain largely unclear. Here we show that a heavy-metal-associated (HMA) domain-containing protein, SODIUM POTASSIUM ROOT DEFECTIVE 1 (NaKR1), is activated by CONSTANS (CO) under long-day conditions and regulates long-distance movement of FT in Arabidopsis. Loss of function of NaKR1 compromises FT transport to shoot apices through sieve elements, causing late flowering under long-day conditions. NaKR1 and FT share similar expression patterns and subcellular localization, and interact with each other in vivo. Grafting experiments demonstrate that NaKR1 promotes flowering through mediating FT translocation from leaves to shoot apices. Thus, photoperiodic control of floral induction requires NaKR1-mediated long-distance delivery of florigenic signals.


Elderly fall patients triaged to the trauma bay: age, injury patterns, and mortality risk.
Falls in the elderly are a significant cause of morbidity and mortality. We sought to better categorize this patient population and describe factors contributing to their falls. This is a retrospective review of geriatric patients presenting to a level 1 community trauma center. We queried our trauma database for all patients 65 years and older presenting with fall and triaged to the trauma bay from 2008 to 2013. Researchers reviewed the patients' trauma intake paperwork to assess mechanism, injury, and location of fall, whereas discharge summaries were reviewed to determine disposition, morbidity, and mortality. A total of 650 encounters were analyzed. Five hundred thirty-nine resided at home (82.9%), 110 presented from nursing homes or assisted living (16.9%), and 1 came from hospice (0.15%). Ninety-five patients died or were placed on hospice as a result of their falls (14.7%), of which 88 came from home. Controlling for Injury Severity Score, living at home was an independent risk factor for fall-related mortality (odds ratio, 3.0). Comparing the elderly (age 65-79 years; n = 274) and the very elderly (age ≥80 years; n = 376), there were no differences in Injury Severity Score (P = .33), likelihood of death (P = .49), likelihood of C-spine injury (P = 1.0), or likelihood of other axial or long bone skeletal injury (P = .23-1.0). There was a trend for increased likelihood of head injury in very elderly patients (P = 0.06). Prevention measures to limit morbidity and mortality in elderly fall patients should be aimed at the home setting, where most severe injuries occur. Very elderly patients may be at increased risk for intracranial fall-related injuries.


Temporal trends in 137Cs concentrations in the bark, sapwood, heartwood, and whole wood of four tree species in Japanese forests from 2011 to 2016.
To understand the changes in radiocesium (137Cs) concentrations in stem woods after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, we investigated 137Cs concentrations in the bark, sapwood, heartwood, and whole wood of four major tree species at multiple sites with different levels of radiocesium deposition from the FDNPP accident since 2011 (since 2012 at some sites): Japanese cedar at four sites, hinoki cypress and Japanese konara oak at two sites, and Japanese red pine at one site. Our previous report on 137Cs concentrations in bark and whole wood samples collected from 2011 to 2015 suggested that temporal variations were different among sites even within the same species. In the present study, we provided data on bark and whole wood samples in 2016 and separately measured 137Cs concentrations in sapwood and heartwood samples from 2011 to 2016; we further discussed temporal trends in 137Cs concentrations in each part of tree stems, particularly those in 137Cs distributions between sapwood and heartwood, in relation to their species and site dependencies. Temporal trends in bark and whole wood samples collected from 2011 to 2016 were consistent with those reported in samples collected from 2011 to 2015. Temporal variations in 137Cs concentrations in barks showed either a decreasing trend or no clear trend, implying that 137Cs deposition in barks is inhomogeneous and that decontamination is relatively slow in some cases. Temporal trends in 137Cs concentrations in sapwood, heartwood, and whole wood were different among species and also among sites within the same species. Relatively common trends within the same species, which were increasing, were observed in cedar heartwood, and in oak sapwood and whole wood. On the other hand, the ratio of 137Cs concentration in heartwood to that in sapwood (fresh weight basis) was commonly increased to more than 2 in cedar, although distinct temporal trends were not found in the other species, for which the ratio was around 1 in cypress and pine and below 0.5 in oak, suggesting that 137Cs transfer from sapwood to heartwood shows species dependency. Consequently, the species dependency of 137Cs transfer within the tree appears easily, while that from the environment to the trees can be masked by various factors. Thus, prediction of 137Cs concentrations in stem wood should be carried out carefully as it still requires investigations at multiple sites with a larger sample size and an understanding of the species-specific 137Cs transfer mechanism.


Monitoring the progression of renal failure in a horse with polycystic kidney disease: use of the reciprocal of serum creatinine concentration and sodium sulfanilate clearance half-time.
Sequential reciprocals of serum creatinine concentration and sodium sulfanilate clearance half-times were used to monitor a horse with chronic renal failure. The horse was diagnosed as having polycystic kidney disease; at least one cyst was of distal tubular origin. Using the plots of the sequential data, a reasonably accurate prediction was made for complete renal decompensation to develop.


Custody suicide with washrag: a case report with clinical and custodial consideration.
Custody or prison suicides with a washrag are rather unusual and few case reports present in the forensic literature. Completed suicide by using a washrag without the awareness of custody supervisors and medical staff ought to draw attention to related personnel. We report a case of suicide where the victim was a suspect with criminal cases, who had been put behind bars in local custody. However, the next day the man was found in an unconscious state and scant of breath. After admission and first-aid treatment, the victim was pronounced dead. Significantly, a half-piece of washrag was found blocked in his laryngeal cavity, inosculating with another piece concealed in his underpants. The psychological condition of criminal offenders is extremely complicated and varies with each individual. Effective administration and moderate counseling are not mutually exclusive with each other and both should afford the criminals a sense of calmness to face consequences.


Are there effective new strategies for the treatment of acute and chronic GvHD?
The molecular biology and pathophysiology underlying graft-versus-host disease (GvHD) remains an area of intensive research. Understanding normal and abnormal developments of both the innate and adaptive immune systems are beginning to provide understanding of the details of relevant pathways. Recent work in gene-expression profiling suggests a critical next step in identifying broader patterns that will stand up to examination in independent data sets and provide a sturdy basis for targeted therapy and preventive measures against GvHD.


Incidence of breast carcinoma-related lymphedema.
Of the 2 million breast carcinoma survivors, perhaps 15-20% are living currently with posttreatment lymphedema. Along with the physical discomfort and disfigurement, patients with lymphedema also must cope with the distress derived from these symptoms. To review the medical literature for the question of lymphedema incidence, a comprehensive, computerized search was performed. All publications with subject headings designating breast carcinoma-related lymphedema from 1970 to the present (116 reports) were found, and each summary or abstract was read. Of the 116 reports, 35 discussed the incidence of lymphedema. Of these, seven reports since 1990 from five countries with the most relevance to current patients were then chosen for greater analysis and comparison. The incidence of lymphedema ranged from 6% to 30%. The source of patients, length of follow-up, measurement techniques, and definition of lymphedema varied from report to report. In general, reports with shorter follow-up reported lower incidences of lymphedema. The definitive study to determine the incidence of lymphedema has not been performed to date. There has been no prospective study in which patients have been followed at intervals with accurate measurement techniques over the long term.


A raphe dendrite bundle in the rabbit medulla.
A Golgi-Cox, histofluorescence, and electron microscopic examination of the serotonergic raphe nuclei of the rabbit medulla has revealed a large, vertically-oriented midline dendrite bundle extending from the floor of the fourth ventricle to the ventral boundary of nucleus raphe pallidus. The bundle was confined to the medulla, and averaged 150-200 micrometer in width in the adult. This dendrite bundle received contributions from four major sources: (1) Dendrites of midline and paramedian neurons of nucleus raphe obscurus; (2) Dendrites of midline and paramedian neurons of nucleus raphe pallidus; (3) Shafts from tanycytes located on the midline floor of the fourth ventricle; and (4) Dendrites from neurons of the medullary reticular formation. Perikarya and dendrites of serotonergic raphe neurons frequently abutted tanycyte shafts, midline bhood vessels, and perikarya and dendrites of other raphe neurons. The tanycyte shafts extended from the floor of the fourth ventricle into the bundle, and often ran the entire length of the bundle, where they intertwined themselves among neurons and dendrites of the medullary raphe nuclei. This study suggests that neurons of the medullary raphe may be influenced by communication channels including dendro-dendritic contacts within the midline bundle, fourth ventricular cerebrospinal fluid-borne influences through tanycyte shafts, blood-borne influences through the direct neuronal-vascular relationship in the raphe, and traditionally described axonal contacts impinging upon raphe neurons. We suggest that the raphe neurons might act as both neurons and endocrine-neural transducer cells.


Safety and immunogenicity of a new heat-inactivated hepatitis B virus vaccine in adult recipients.
A new heat inactivated HBV vaccine has been evaluated for safety and immunogenicity in 203 adult recipients. The vaccine was found to be safe and highly immunogenic. Three doses of 3 micrograms given at 0, 1 and 6 months, resulted in 96% seroconversion. Three doses of 3 micrograms given at 0, 1 and 2 months produced, more rapidly, seroconversion in 92% of those immunized. Antibody to a pre-S determinant developed in four of six subjects tested.


Are there psychosocial differences in diagnostic subgroups of children with recurrent abdominal pain?
To examine psychosocial differences in diagnostic subgroups of children with recurrent abdominal pain (RAP). Children meeting Apley's 1975 definition of RAP were divided according to physician ratings into three subgroups, based on the Rome II diagnostic criteria of functional gastrointestinal disorders: functional dyspepsia (n=17), irritable bowel syndrome (n=18), and functional abdominal pain (n=27). Groups were compared using measures of (a) child psychopathology, (b) parent psychopathology, and (c) child pain, somatization, and functional disability. Multivariate results from a discriminant function analysis demonstrated that children classified according to these criteria could not be differentiated with respect to parent reported child psychopathology or child pain, somatization, and functional disability. There were significant univariate differences, however, between groups on parental psychopathology (F=4.39, P=0.02); parents of children with functional dyspepsia reported greater parental psychopathology symptoms than the other two groups. This study provides a preliminary comparison of pain, somatization, functional impact, and psychopathology ratings in the Rome II diagnostic subclassifications of children with RAP. Further investigation utilizing larger sample sizes, pain measures specifying pain location, and parental modeling of somatic behavior is indicated to better understand potential similarities and differences between these subgroups.


Development of the spinal nerves in the lamprey: I. Rohon-Beard cells and interneurons.
Two types of large neurons are described in the caudal one-third of the spinal cord of larval lampreys (26-day, 13-mm), Lampetra japonica. Rohon-Beard cells (RB cells) are large neurons (8-14 micron in diameter) consistently positioned superficially in the dorsolateral part of the medullary wall and separated from the extramedullary space only by a basal lamina and a thin glia limitans and from the central canal lumen by the ependyma. The RB cell contains an extensive Golgi apparatus and granular endoplasmic reticulum. Its two processes arise from the basal part of the perikaryon and join the dorsolateral tract (DLT) to extend rostrally and caudally within the DLT, which is formed exclusively by contribution of RB cell processes at least in the caudal one-third of the tail spinal cord. RB cells receive no synaptic nerve endings on their surfaces. The early developing RB cells exhibits an apical process that reaches the luminal surface of the central canal. Interneurons (15-19 microns in diameter) lie in the lateral region of the cord between the DLT and ependyma and receive from the DLT many synaptic nerve endings that contain aggregates of small, clear vesicles. They contribute axonal processes to the ventrolateral tract (VLT). Some developing interneurons have an apical process that contains abundant free ribosomes and granular ER. A presumptive model of how these cell classes are interconnected within the cord is presented.


Y-U pyloroplasty.
The Y-U pyloroplasty procedure was evaluated in forty-four patients. The technic described requires little dissection and little time, insures a wide pylorus, and has few complications.


Temperature-inducible surface fibrillae associated with the virulence plasmid of Yersinia enterocolitica and Yersinia pseudotuberculosis.
When cultivated at 37 degrees C in static broth, human clinical isolates of Yersinia enterocolitica (serogroups O:3, O:8, and O:9) and Yersinia pseudotuberculosis (serogroup O:III) produced numerous nonflagellar surface appendages, which appeared as a lawn of fine fibrillae, each having a diameter of 1.5 to 2.0 nm and a length of 50 to 70 nm. Cultivation at 22 degrees C resulted in complete disappearance of the fibrillae. The phenotypic expression of these appendages was correlated with the presence of the 40- to 48-megadalton virulence plasmid and was strongly affected by the growth medium. Evidence is presented which suggests that these plasmid-mediated, temperature-inducible surface fibrillae are responsible for autoagglutination and are related to production of one prominent, Sarkosyl-insoluble polypeptide of ca. 180 kilodaltons in the bacterial outer membrane.


Structure-based optimisation of orally active & reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'.
Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physicochemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model.


The impact of a pre-hospital critical care team on survival from out-of-hospital cardiac arrest.
To assess the impact of a pre-hospital critical care team (CCT) on survival from out-of-hospital cardiac arrest (OHCA). We undertook a retrospective observational study, comparing OHCA patients attended by advanced life support (ALS) paramedics with OHCA patients attended by ALS paramedics and a CCT between April 2011 and April 2013 in a single ambulance service in Southwest England. We used multiple logistic regression to control for an anticipated imbalance of prognostic factors between the groups. The primary outcome was survival to hospital discharge. All data were collected independently of the research. 1851 cases of OHCA were included in the analysis, of which 1686 received ALS paramedic treatment and 165 were attended by both ALS paramedics and a CCT. Unadjusted rates of survival to hospital discharge were significantly higher in the CCT group, compared to the ALS paramedic group (15.8% and 6.5%, respectively, p<0.001). After adjustment using multiple logistic regression, the effect of CCT treatment was no longer statistically significant (OR 1.54, 95% CI 0.89-2.67, p=0.13). Subgroup analysis of OHCA with first monitored rhythm of ventricular fibrillation or pulseless ventricular tachycardia showed similar results. Pre-hospital critical care for OHCA was not associated with significantly improved rates of survival to hospital discharge. These results are in keeping with previously published studies. Further research with a larger sample size is required to determine whether CCTs can improve outcome in OHCA.


Vascular endothelial growth factor is associated with histological instability of carotid plaques.
Vascular endothelial growth factor (VEGF) promotes events favouring carotid plaque instability: inflammatory chemoattraction, thrombogenesis, and upregulation of matrix metalloproteinases and cell adhesion molecules. The aim of this study was to assess neovascularization, VEGF and its receptors in high-grade stable and unstable carotid plaques. Immunohistochemical staining for CD34, VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 was performed in 34 intact carotid endarterectomy specimens, and compared in sections demonstrating maximal histological instability (cap rupture/thinning) or, if stable, maximal stenosis. VEGF staining was increased in 12 unstable compared with 22 stable plaques (median (interquartile range, i.q.r.) plaque score 4.0 (4.0-4.0) versus 3.0 (2.0-3.0); P = 0.002) with upregulation of VEGFR1 (plaque score 4.0 (2.0-4.0) versus 2.0 (1.0-3.0); P = 0.016). In unstable plaques this was associated with increased microvessel density in the cap (median (i.q.r.) 12.1 (4.0-30.0) versus 1.1 (0.0-7.3) microvessels/mm(2); P = 0.017) and shoulder regions (7.7 (3.4-21.4) versus 3.1 (0.4-10.8) microvessels/mm(2); P = 0.176). Increased VEGF and receptor staining were seen in histologically unstable carotid plaques. Although these differences could reflect cytokine-driven inflammatory events accompanying plaque instability, VEGF and VEGFR1 could be key mediators.


Microvascular decompression for spasmodic torticollis.
Twenty patients with spasmodic torticollis (ST) were treated by microvascular decompression (MVD) of the spinal accessory nerves, the upper cervical nerve roots and the brainstem. Thirteen were female and seven male. Median age was 47 years (range 39 to 70 years). Median duration of symptoms was 5 years (range 4 months to 17 years). Ten had right horizontal; nine, left horizontal; and one, retrocollis ST. Twenty-two operations were performed on twenty patients, suboccipital craniectomy and C1 laminectomy in 18 and retromastoid craniectomy in 4 operations. The most common compressing blood vessels were the vertebral artery and/or the posterior inferior cerebellar artery. No nerve section was performed. Three patients died of unrelated conditions, 3, 5 1/2, and 6 years postoperatively, respectively. Minimum follow-up period in the rest of the cases is 5 years (range 5 to 10 years). Thirteen (65%) were cured, four (20%) improved with minimal spasm, one (5%) improved with moderate spasm, and two (10%) improved minimally or unchanged. In most cases the cure or improvement was noticed gradually over 6 months to two years following the operation. There was no operative mortality. Postoperative morbidities included transient cerebrospinal fluid leakage through the surgical incision in one case and an apparent multiple small vessel stroke involving periventricular white matter in one reoperation case with full recovery. MVD for ST is a nondestructive benign procedure with high probability of cure or significant improvement.


Therapy of Aujeszky's disease (pseudorabies) in naturally infected and artificially inoculated piglets using BW B759U (9-[1,3-dihydroxy-2-propoxymethyl] guanine).
Two experimental porcine models of Aujeszky's disease (AD) were compared for assessing the efficacy of potential antiviral compounds. While signs were the same following intranasal inoculation and in-contact transmission of the causal herpesvirus, SHV-1 (Suid herpesvirus), the time-course of the disease was different. There was less variation in clinical signs between pigs following artificial infection, but the disease was more severe, making this a consistent but also more stringent test system. A nucleoside analogue, BW B759U (9-[1,3-dihydroxy-2-propoxy-methyl] guanine), was administered intramuscularly in divided twice daily doses at 50 mg kg-1 to three-week-old piglets in these two SHV-1 disease models. In artificially infected animals, in which treatment was begun 1.5 hours preinfection and continued for six days, there was a delay in the onset of clinical signs (4.8 compared with 3.2 days), a 1 log10 reduction in virus shedding, and a 1 to 2 log10 reduction in virus recovered from tissues, but all the treated piglets died from AD. In contrast, none of the BW B759U-treated piglets in the in-contact model system died during the eight-day medication period, although two piglets died subsequently. Mean serum concentrations of BW B759U two hours after intramuscular dosing were about 45 microM, at nine hours 15 to 20 microM and at 17 hours 3.5 microM. The in vitro IC50 of BW B759U against SHV-1 varies from 1.5 to 80 microM depending on the cell line in which the assay is carried out. There were no overt signs of BW B759U toxicity in the treated piglets.


Structural differences between blood-platelet tubulin and other mammalian tubulins.
Carboxymethylated pig blood-platelet tubulin subunits have been characterized by comparing their electrophoretic mobilities and two-dimensional tryptic peptide maps with those of tubulin subunits isolated from four other mammalian tissues. These were pig brain, pig lung, pig sperm and bovine kidney. In addition to the major blood-platelet alpha- and beta-tubulin subunits, minor alpha- and beta-components could be resolved on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The major blood-platelet beta-tubulin, as well as the minor brain beta 2-tubulin subunit, were clearly tissue specific. In both cases, their two-dimensional peptide maps contained unique heavily labelled peptides. Distinct peptide maps were also observed for the major blood-platelet alpha-tubulin subunit as well as for sperm tail alpha-tubulin, both of which were missing peptides (different in each case) that were present in all of the other alpha-tubulin maps. Under our conditions, a protein with a molecular weight of 70,000 and an isoelectric point of pH 6.4 co-purified with blood-platelet microtubules.


Erratum: Spontaneous transverse colon volvulus in a patient with Duchenne muscular dystrophy: An unreported complication.
[This corrects the article DOI: 10.1016/j.radcr.2022.12.062.][This corrects the article DOI: 10.1016/j.radcr.2023.03.026.].


Successful one-stage repair of unilateral agenesis of pulmonary artery.
Unilateral agenesis of the pulmonary artery is a rare congenital anomaly that is commonly associated with ventricular septal defect (VSD). Its clinical presentation is diverse, and if left untreated, it can lead to significant damage and even death. Several surgical techniques have been developed for its management, with variable results. We report the case of a 2-month-old infant with agenesis of the left pulmonary artery (PA) and VSD. One-stage primary surgical re-anastomosis was successful in establishing continuity to the main PA and preventing further damage to the heart.


18F-fluorodeoxyglucose positron emission tomography as a noninvasive method for the diagnosis of primary pulmonary artery sarcoma.
Pulmonary artery sarcomas are rare, difficult-to-diagnose tumors that frequently mimic chronic pulmonary thromboembolism. We report the cases of two female patients with clinical signs of dyspnea and lung masses associated with pulmonary artery filling defects on chest CT angiography. We performed 18F-fluorodeoxyglucose positron emission tomography, which revealed increased radiotracer uptake in those lesions. Pulmonary artery sarcoma was subsequently confirmed by anatomopathological examination. We emphasize the importance of this type of tomography as a noninvasive method for the diagnosis of these tumors.


Synergistic action of rapid chilling and nisin on the inactivation of Escherichia coli.
The effect of rapid and slow chilling on survival and nisin sensitivity was investigated in Escherichia coli. Membrane permeabilization induced by cold shock was assessed by uptake of the fluorescent dye 1-N-phenylnapthylamine. Slow chilling (2 degrees C min(-1)) did not induce transient susceptibility to nisin. Combining rapid chilling (2,000 degrees C min(-1)) and nisin causes a dose-dependent reduction in the population of cells in both exponential and stationary growth phases. A reduction of 6 log of exponentially growing cells was achieved with rapid chilling in the presence of 100 IU ml(-1) nisin. Cells were more sensitive if nisin was present during stress. Nevertheless, addition of nisin to cell suspension after the rapid chilling produced up to 5 log of cell inactivation for exponentially growing cells and 1 log for stationary growing cells. This suggests that the rapid chilling strongly damaged the cell membrane by disrupting the outer membrane barrier, allowing the sensitization of E. coli to nisin post-rapid chilling. Measurements of membrane permeabilization showed a good correlation between the membrane alteration and nisin sensitivity. Application involving the simultaneous treatment with nisin and rapid cold shock could thus be of value in controlling Gram negatives, enhancing microbiological safety and stability.


A family of new glutarate compounds: synthesis, crystal structures of: Co(H2O)5L(1), Na2[CoL2] (2), Na2[L(H2L)4/2] (3), {[Co3(H2O)6L2](HL)2}.4H2O (4), {[Co3(H2O)6L2](HL)2}.10H2O (5), {[Co3(H2O)6L2]L2/2}.4H2O (6), and Na2{[Co3(H2O)2]L8/2].6H2O (7), and magnetic properties of 1 and 2 with H2L = HOOC-(CH2)3-COOH.
Seven new glutaric acid complexes, Co(H 2O) 5L 1, Na 2[CoL 2] 2, Na 2[L(H 2L) 4/2] 3, {[Co 3(H 2O) 6L 2](HL) 2}.4H 2O 4, {[Co 3(H 2O) 6L 2](HL) 2}.10H 2O 5, {[Co 3(H 2O) 6L 2]L 2/2}.4H 2O 6, and Na 2{[Co 3(H 2O) 2]L 8/2].6H 2O 7 were obtained and characterized by single-crystal X-ray diffraction methods along with elemental analyses, IR spectroscopic and magnetic measurements (for 1 and 2). The [Co(H 2O) 5L] complex molecules in 1 are assembled into a three-dimensional supramolecular architecture based on intermolecular hydrogen bonds. Compound 2 consists of the Na (+) cations and the necklace-like glutarato doubly bridged [ C o L 4 / 2 ] 2 - infinity 1 anionic chains, and 3 is composed of the Na (+) cations and the anionic hydrogen bonded ladder-like [ L ( H 2 L ) 4 / 2 ] 2 - infinity 1 anionic chains. The trinuclear {[Co 3(H 2O) 6L 2](HL) 2} complex molecules with edge-shared linear trioctahedral [Co 3(H 2O) 6L 2] (2+) cluster cores in 4 and 5 are hydrogen bonded into two-dimensional (2D) networks. The edge-shared linear trioctahedral [Co 3(H 2O) 6L 2] (2+) cluster cores in 6 are bridged by glutarato ligands to generate one-dimensional (1D) chains, which are then assembled via interchain hydrogen bonds into 2D supramolecular networks. The corner-shared linear [Co 3O 16] trioctahedra in 7 are quaternate bridged by glutarato ligands to form 1D band-like anionic {[Co 3(H 2O) 2]L 8/2} (2+) chains, which are assembled via interchain hydrogen bonds into 2D layers, and between them are sandwiched the Na (+) cations. The magnetic behaviors of 1 and 2 obey the Curie-Weiss law with chi m = C/( T - Theta) with the Curie constant C = 3.012(8) cm (3) x mol (-1) x K and the Weiss constant Theta = -9.4(7) K for 1, as well as C = 2.40(1) cm (3) x mol (-1) x K and Theta = -2.10(5) K for 2, indicating weak antiferromagnetic interactions between the Co(II) ions.


Tear drainage in traumatic canalicular fistula.
To evaluate the function of the canaliculus with fistula after canalicular laceration repair. Patients with monocanalicular fistula following canalicular laceration repair were evaluated with dye disappearance test (DDT). Temporary collagen plugs were used to occlude the uninvolved canaliculus in the ipsilateral eye and the corresponding canaliculus in the contralateral eye. After 24 hours of placement of the temporary plugs, the same evaluation was repeated. Ten patients with unilateral monocanalicular fistulas were evaluated. None of the patients had epiphora before and after placement of temporary plugs and DDT, and tear meniscus continued to be normal both in the affected and the unaffected eyes after temporary plug placement. In this series, the presence of canalicular fistula at the site of repair did not affect tear drainage.


Fermentation optimization for the production of bioactive polysaccharides from Cordyceps sinensis fungus UM01.
The optimal fermentation conditions and medium for the production of bioactive polysaccharides from the mycelium of Cordyceps sinensis fungus UM01 were investigated by using orthogonal design and high performance size exclusion chromatography coupled with multi-angel laser light scattering and refractive index detector (HPSEC-MALLS-RID). Results showed that the optimal temperature, initial pH, rotation speed, medium capacity (ratio of medium volume to the volume of flask bottle) and inoculums volume for the mycelium growth were 15 °C, pH 6.0, 150 rpm, 2/5 (v/v), and 3% (v/v), respectively. Furthermore, bioactive polysaccharides from the mycelium of C. sinensis fungus UM01 were determined as polysaccharide fractions with the molecular weight above 10 kDa. The optimal fermentation medium was determined as a composition of glucose 30.0 g/L, sucrose 30.0 g/L, KH2PO4 1.0 g/L, CaCl2 0.5 g/L, yeast extract 3.0 g/L, and MgCl2 0.1g/L according to the maximum amount of the bioactive polysaccharides (486.16±19.60 mg/L) measured by HPSEC-MALLS/RID. Results are helpful to establish an efficient and controllable fermentation process for the industrial production of bioactive polysaccharides from C. sinensis UM01, and beneficial to develop a unique health and functional product in future.


Significance of myelodysplastic syndrome-associated somatic variants in the evaluation of patients with pancytopenia and idiopathic cytopenias of undetermined significance.
In this study, we set out to evaluate the frequency of mutations in 20 myelodysplastic syndrome-associated genes in 53 individuals with pancytopenia in which bone marrow evaluation failed to meet standard criteria for a diagnosis of myelodysplastic syndrome. These idiopathic pancytopenia cases were associated with no specific cause for their pancytopenia (n=28), aplastic anemia (n=13), pancytopenia attributable to liver disease (n=4), pancytopenia associated with autoimmune disease (n=4), and pancytopenia attributed to drug effect (n=4). We also selected 38 bone marrow aspirates from patients presenting with pancytopenia and meeting criteria for a diagnosis of myelodysplastic syndrome (n=21) or acute myeloid leukemia (n=17) as malignant comparison cases. Targeted sequencing of the 20 genes was performed on all cases. The idiopathic pancytopenia group had a lower average age (46 vs 66 years, P<0.0001) and a lower number of mutations per case that were statistically significant (0.81 vs 1.18, P=0.045). The frequency of cases with at least one mutation was higher for cases with a diagnosable myeloid neoplasm (68 vs 38%, P=0.012). Except for mutations in U2AF1, which was mutated in 5 of the 38 malignant cases (13.2%) and in none of the idiopathic pancytopenia cases (P=0.011), the frequency of mutations in the genes evaluated was not significantly different between idiopathic pancytopenia and malignant cases. Median and mean clinical follow-up for the idiopathic pancytopenia group was available for 444 and 739 days, respectively. Over this time frame, none of the idiopathic pancytopenia patients was diagnosed with a myelodysplastic syndrome or an acute myeloid leukemia. These findings provide further evidence that identification of mutations in several genes associated with myelodysplastic syndromes should not be used alone to support a diagnosis of a myelodysplastic syndrome.


GABA(B) receptors accentuate neural excitation contrast in rat insular cortex.
Synaptic transmission mediated by metabotropic GABA receptors, GABA(B) receptors, regulates physiological functions of cerebrocortical local circuits. It is, however, still unknown how GABA(B) receptors regulate excitatory propagation at more macroscopic level. We performed in vivo optical imaging to investigate the spatio-temporal profiles of GABA(B) receptor-mediated regulation of excitatory propagation in anesthetized rat insular cortex (IC). Repetitive electrical stimulation (a sequence of 10 pulses at 50 Hz) of the dysgranular IC (DI), a part of gustatory cortex (GC), elicited excitatory propagation along the rhinal fissure. Tonic activation of GABA(B) receptors by application of baclofen suppressed the optical signal amplitude to the early pulses in the sequence (first to third stimuli), typically in the rostral GC (rGC). In contrast, optical signal amplitude to later pulses was enhanced by baclofen in both the rGC and caudal GC (cGC). Baclofen reduced the area of excitation during the early pulses in the sequence but not during later pulses. Application of CGP 52432, which blocked GABA(B) receptor-mediated tonic and phasic inhibition, slightly suppressed optical responses to early pulses (though not to the first pulse), whereas it enhanced responses to later pulses, especially in the dorsolateral orbital cortex (DLO). Decay amplitude of the response to the first pulse was reversed to a large rise in amplitude by the GABA(A) receptor antagonist bicuculline. The decay amplitude was enhanced by CGP 52432 and reversed to a small rise by baclofen. This suggests that GABA(B) receptor activation reduced postsynaptic GABA(A) receptor activation indirectly via inhibition of presynaptic GABA release. Optical responses induced by DLO stimulation were reduced by pre-stimulation of the cGC 180 ms before DLO stimulation, which was blocked by CGP 52432. These results suggest that tonic and phasic activation of GABA(B) receptors cooperatively enhances the contrast of neural excitation at a level of millimeters.


Postprandial vitamin A and squalene clearances and cholesterol synthesis off and on lovastatin treatment in type III hyperlipoproteinemia.
Postprandial fat clearance and absorption, fecal elimination and synthesis of cholesterol, bile acid synthesis, and cholesterol precursors and plant sterols in serum were studied in five patients with type III dyslipoproteinemia off and on lovastatin. The basal values were related to those in nontreated normolipidemic control subjects with apolipoprotein E3/3 phenotype (apo E3 controls, n = 16). On regular home diets, cholesterol precursor concentrations and cholesterol precursor/cholesterol ratios were high in the type III group. However, cholesterol absorption efficiency, bile acid and cholesterol synthesis measured with sterol balance technique and the precursor sterol/plant sterol ratios in serum were similar to the control values, suggesting that cholesterol absorption and metabolism was normal in these subjects. Lovastatin normalized the increased lipoprotein concentrations and reduced biliary cholesterol secretion, absolute absorption of cholesterol, precursor sterol/cholesterol and precursor sterol/plant sterol ratios in serum, fecal neutral and total sterol outputs and cholesterol synthesis. Lovastatin had no effect on cholesterol absorption efficiency or bile acid synthesis. Despite normalization of the triglyceride-rich lipoprotein levels by lovastatin, the postprandial vitamin A and squalene peak concentrations and the areas under the curves remained above the control ranges. The findings show that in type III hyperlipidemia, the precursor sterol/cholesterol ratios do not predict cholesterol synthesis. The latter, bile acid synthesis, precursor sterol/plant sterol ratios in serum, and cholesterol absorption are normal under basal conditions. The normalization of increased lipids by lovastatin is mainly due to reduced synthesis and absolute absorption of cholesterol, while the retarded postprandial fat clearance was not normalized by the drug.


[RASBURICASE TREATMENT FOR NEONATAL ACUTE KIDNEY INJURY - A CASE REPORT].
Hyperuricemia can cause renal damage and acute kidney injury or be secondary to renal failure and reduced excretion. Rasburicase, a recombinant urate oxidase, is a common treatment for hyperuricemia from different etiologies. There are scarce reports on rasburicase treatment for neonatal Acute Kidney Injury (AKI) with hyperuricemia to prevent renal damage secondary to hyperuricemia. Herein we report a case of neonatal AKI with hyperuricemia that was treated with a single dose of rasburicase. Serum uric acid declined immediately after rasburicase infusion and remained in the normal range since then. In contrast to previous reports, the normalization of uric acid levels was not accompanied by recovery from AKI and serum creatinine levels remained elevated for a long period. The neonate recovered from AKI only 2 weeks post rasburicase treatment. This case report highlights the importance of uric acid levels in neonatal AKI and suggests treatment with rasburicase in cases of hyperuricemia and acute kidney injury in neonates.


Serum-free culture of Japanese quail kidney cells. Regulation of vitamin D metabolism.
Cells obtained from male quail kidneys by digestion with collagenase and hyaluronidase were plated and maintained in a chemically defined, serum-free medium. Culture dishes (35 mm) were inoculated with 1.5 . 10(6) cells which became confluent in 5 days. The cells maintained an epithelial-like morphology over the entire culture period. During a 2 h incubation the cells metabolized 25--30% of the 10 nM 25-hydroxyvitamin D-3 (25-OH-D-3) provided. Seven metabolites were chromatographically separated on Sephadex LH-20. Three have been identified as 1 alpha, 25-dihydroxyvitamin D-3 (1,25(OH)2D-3), 24,25-dihydroxyvitamin D-3 (24,25(OH)2D-3) and 1 alpha, 24,25-trihhydroxyvitamin D-3 (1,24,25(OH)3D-3). The activities of the 25-OH-D-3:1 alpha- and 24-hydroxylases increased eight times faster than the cell number in 5 days. Preincubation of the cells with 10 nM 25-OH-D-3 or 1,25(OH)2D-3 decreased 1,25(OH)2D-3 synthesis, and increased both 24,25(OH)2D-3 and metabolite IV synthesis. The decrease in 25-OH-D-3:1 alpha-hydroxylase activity required a 2 h preincubation with 25-OH-D-3, while stimulation of 25-OH-D-3:24-hydroxylase activity and metabolite IV production required a 6 h preincubation. Incubations of cells for 1 h with parathyroid hormone resulted in a 30-fold increase in cyclic AMP in the medium. A 6 h preincubation with parathyroid hormone decreased 24,25(OH)2D-3) synthesis 50% relative to control cells. These results demonstrate the amenability of this system for studying the regulation of 25-OH-D-3 metabolism, as well as its use for other in vitro studies on renal cell function in a chemically defined culture system.


Predation on artificial bird nests in chaparral fragments.
The predation rate of artificial bird nests was measured in disturbed chaparral habitat fragments and at an unfragmented site in coastal San Diego County, California USA. Local extinctions of chaparral birds has been previously shown to occur in these fragments. The predation rate was highest at the unfragmented site. Among fragments, predation was higher at moderately disturbed than at highly disturbed sites. These results suggest that nest predator species diversity or density is reduced in disturbed chaparral fragments. Nest predation is probably not the most important cause of the observed loss of chaparral breeding bird diversity in these fragments.


Anti-inflammatory and PPAR transactivational effects of secondary metabolites from the roots of Asarum sieboldii.
Phytochemical study on the roots of Asarum sieboldii resulted in the isolation of one new compound, (1R,2S,5R,6R)-5'-O-methylpluviatilol (1) and 12 known compounds (2-13). Their structures were determined by extensive spectroscopic methods, including 1D and 2D NMR, and MS spectra. The absolute configuration of compound 1 was established using CD spectrum. Compounds 4, 5, and 12/13 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values ranging from 6.4 to 9.4 μM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 1-3, 6,7, 10, and 11 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC(50) values ranging from 1.7 to 20.9 μM. Compounds 7, 10, and 11 exhibited significant dose-dependent PPARα transactivational activity, with EC(50) values of 19.5, 15.7, and 4.0 μM, respectively. Compounds 1, 6, 7, 10, and 11 activated PPARγ transcriptional activity, with EC(50) values ranging from 3.6 to 22.6 μM, whereas compounds 10 and 11 significantly increased PPARβ(δ) transactivational activity, with EC(50) values of 22.6 and 4.9 μM, respectively. These results provide a scientific support for the use of the roots of A. sieboldii and warrant further studies to develop new agents for the prevention and treatment of the inflammatory and metabolic diseases.


ZEB1 Transcriptionally Activates PHGDH to Facilitate Carcinogenesis and Progression of HCC.
Phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the de novo serine synthesis pathway (SSP), has been implicated in the carcinogenesis and metastasis of hepatocellular carcinoma (HCC) because of its excessive expression and promotion of SSP. In previous experiments we found that SSP flux was diminished by knockdown of zinc finger E-box binding homeobox 1 (ZEB1), a stimulator of HCC metastasis, but the underlying mechanism remains largely unknown. Here, we aimed to determine how SSP flux is regulated by ZEB1 and the contribution of such regulation to carcinogenesis and progression of HCC. We used genetic mice with Zeb1 knockout in liver specifically to determine whether Zeb1 deficiency impacts HCC induced by the carcinogen diethylnitrosamine plus CCl4. We explored the regulatory mechanism of ZEB1 in SSP flux using uniformly-labeled [13C]-glucose tracing analyses, liquid chromatography-mass spectrometry, real-time quantitative polymerase chain reaction, luciferase report assay, and chromatin immunoprecipitation assay. We determined the contribution of the ZEB1-PHGDH regulatory axis to carcinogenesis and metastasis of HCC by cell counting assay, methyl thiazolyl tetrazolium (MTT) assay, scratch wound assay, Transwell assay, and soft agar assay in vitro, orthotopic xenograft, bioluminescence, and H&E assays in vivo. We investigated the clinical relevance of ZEB1 and PHGDH by analyzing publicly available data sets and 48 pairs of HCC clinical specimens. We identified that ZEB1 activates PHGDH transcription by binding to a nonclassic binding site within its promoter region. Up-regulated PHGDH augments SSP flux to enable HCC cells to be more invasive, proliferative, and resistant to reactive oxygen species and sorafenib. Orthotopic xenograft and bioluminescence assays have shown that ZEB1 deficiency significantly impairs the tumorigenesis and metastasis of HCC, and such impairments can be rescued to a large extent by exogenous expression of PHGDH. These results were confirmed by the observation that conditional knockout of ZEB1 in mouse liver dramatically impedes carcinogenesis and progression of HCC induced by diethylnitrosamine/CCl4, as well as PHGDH expression. In addition, analysis of The Cancer Genome Atlas database and clinical HCC samples showed that the ZEB1-PHGDH regulatory axis predicts poor prognosis of HCC. ZEB1 plays a crucial role in stimulating carcinogenesis and progression of HCC by activating PHGDH transcription and subsequent SSP flux, deepening our knowledge of ZEB1 as a transcriptional factor in fostering the development of HCC via reprogramming the metabolic pathway.


Transformed bone marrow cells generate neoplasms of distinct histogenesis. a murine model of cancer transplantation.
The last several years have witnessed renewed interest regarding the contribution of cancer stem cells in tumorigenesis and neoplastic heterogeneity. It has been reported that patients who undergo bone marrow transplantation are more prone to develop a malignancy during their life time; usually hematological tumors, but solid neoplasms may also develop, which in certain instances are donor-derived. It has also been well documented that multipotent bone marrow derived cells can migrate to diverse organs, differentiating into various histological lineages. The present study reports an experimental syngeneic transplantation model, using fluorescently tagged bone marrow cells from p53 null male mice into female wild-type counterparts. We found that transplanted non-neoplastic mutant bone marrow cells can generate tumors of distinct histogenesis, including thymic lymphomas, sarcomas, and carcinomas after carcinogen induction, providing evidence that multipotent cancer-prone stem cells can reside in the bone marrow and are transplantable.


Chlamydial psittacosis during pregnancy: a case report.
Chlamydia psittaci infection typically causes a mild influenza-like illness in humans. However, during pregnancy, this disease may present with severe headache, hypoxemia, thrombocytopenia, anemia, hepatic dysfunction, and disseminated intravascular coagulation. Limited reports of ovine-acquired psittacosis indicate appreciable maternal-fetal morbidity and mortality. A 19-year-old woman, gravida 1, para 0, at 32 weeks and 3 days' gestation developed C psittaci pneumonia after exposure to a parakeet. Worsening maternal respiratory status, development of a coagulopathy, and fetal compromise prompted cesarean delivery. Avian strains of C psittaci can cause atypical pneumonia during pregnancy. Massive placental infection with impaired placental perfusion may ensue subsequently. Given the serious nature of the disease and the ineffectiveness of erythromycin treatment, administration of tetracyclines may be justified, despite the possible adverse fetal effects. With persistent disease, early delivery of the fetus may provide good maternal and fetal outcomes.


Generation of self-renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cells.
Dendritic cells (DC) play a key role in driving the adaptive immune response to Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB). However, studying these important yet very sparse immune cells in the context of MTB pathogenesis is severely restricted by the lack of suitable cell lines and the complexity of culturing of DC progenitors, usually obtained from the bone marrow. However, significant advances have been made towards generating long-term DC cultures from various lymphoid tissues. Here, we report the evidence for generating a long-term, self-renewing DC culture from the Balb/c mouse spleen. We demonstrate that these cells, termed IDC-3, have a myeloid DC origin, i.e. they are CD11c(+) CD11b(++) CD8-α(-) F4/80(+/-) and that they also display a phenotype MHC-II(+) CD16/32(++) CD80(+/-) CD86(+) , indicating that they are immature DC. Following incubation with Mycobacterium bovis BCG (Bacillus Calmette Guerin), the IDC-3 efficiently took up bacteria and acquired the morphology of mature DC. Importantly though, when IDC-3 were pre-stimulated with a mycobacterial antigen in vitro, they were able to induce proliferation of T lymphocytes from mice immunized with the same antigen. The T-cell stimulatory potential of IDC-3 was further enhanced when the cells were co-stimulated with an anti-CD40 mAb. We therefore suggest that the IDC-3 culture system could be a useful tool for studying the interaction of DC with mycobacteria.


Competence-based catalog of learning objectives for the subject area of quality management in medical studies - position paper of the working group Quality Management in Education, Training and Continuing Education of the Society for Quality Management in Health Care (GQMG).
Traditionally, direct medical competences are taught in medical studies, whereas leadership and quality management competences are hardly taught, although graduates are already confronted with management tasks at the beginning of their clinical work. With the upcoming amendment of the Medical Licensing Regulations, this topic area will probably be addressed and must be adequately taught by the faculties. The learning objectives in the area of quality management listed in the current working version of the German National Catalogue of Learning Objectives in Medicine (NKLM) 2.0 have so far been formulated in rather general terms and need to be concretized. To develop a competence-based learning objectives catalog for the topic area of quality management in medical studies as a structured framework recommendation for the design of faculty teaching-learning programs and as a suggestion for further development of the NKLM. The competence-based learning objectives catalog was developed by an eight-member working group "Quality Management in Education, Training and Continuing Education" of the Gesellschaft für Qualitätsmanagement in der Gesundheitsversorgung e.V. (GQMG) within the framework of a critical synthesis of central publications. The members of the project group have many years of project experience in quality management in health care as well as in university didactics. Six basic competence goals as well as 10 specific competence goals could be formulated and consented upon. These are each flanked by a list of essential basic concepts and examples. These focus on quality improvements, including patient safety and treatment success against the background of a physician leadership role in an interprofessional context. A competency-based set of learning objectives has been compiled that encompasses the necessary concepts and basic knowledge of quality management required for those entering the profession to understand and actively participate in quality management after completing medical school. To the authors' knowledge, no comparable learning objectives catalog is currently available for medical studies, even internationally.


IgE-mediated 14C-serotonin release from passively sensitized rat mast cells: comparative kinetic study with formaldehyde and ice-cold methods.
The kinetics of IgE-mediated release of serotonin from passively sensitized rat mast cells in vitro was studied by stopping 14C-serotonin release with the application of formaldehyde fixative or ice-cold mast cell medium (MCM). Antigen dose-release curves of 14C-serotonin and/or histamine were comparable when mediator release was terminated with either formaldehyde at a final concentration of 1% or ice-cold MCM 15 min after antigen challenge. However, the kinetic study of immunological mediator release stopped by formaldehyde showed that the addition of antigen resulted in a progressive increase of released 14C-serotonin for 7 min, the release curve being sigmoidal, whereas the application of ice-cold MCM artificially enhanced 14C-serotonin and histamine release in the first 2 min. The results suggest that stopping IgE-mediated release of 14C-serotonin with formaldehyde is a simple, rapid and accurate method of studying the kinetics of mediator release from mast cells.


Poly[di-ethyl-ammonium [tetra-μ2-cyanido-κ8 C:N-tricuprate(I)]], a two-dimensional network solid.
The title compound, (C4H12N)[Cu3(CN)4] n , crystallizes as a CuCN network solid, with di-ethyl-ammonium cations sandwiched between planar CuCN sheets comprised of trigonal planar and digonally coordinated CuI atoms bridged by linear CN groups to form 24-membered rings. The digonally coordinated CuI atoms and the di-ethyl-ammonium cations lie on separate crystallographic twofold rotation axes. One of the two independent CN groups has a 50:50 disordered orientation, while the other has one orientation favored due to a N-H⋯NC hydrogen bond between the di-ethyl-ammonium cation and the anionic CuCN framework. These hydrogen bonds link the sheets together into a three-dimensional network.


Cardio-renal syndrome type 1: epidemiology, pathophysiology, and treatment.
One third of heart failure admissions may be complicated by acute kidney injury, resulting in a three-fold increase in length of stay and a greater likelihood of rehospitalization. Cardio-Renal syndrome type 1 refers to acute decompensation of cardiac function leading to acute renal failure. It often complicates acute coronary syndrome and acute decompensated heart failure. Both components of the syndrome contribute to morbidity and mortality. The pathophysiology of renal dysfunction is complex. Reduced cardiac output, passive congestion of the kidneys, and increased intra-abdominal pressure may contribute to the disorder. The heart, kidneys, renin-angiotensin system, sympathetic nervous system, immune system, and vasculature interact through intricate feedback loops. An imbalance in this complex system often will cause deterioration in both cardiac and renal function. Appreciation of these interactions is crucial to understanding the overall burden of disease, as well as its natural history, risk factors, associated morbidity and mortality, and therapeutic implications.


MORPHOLOGIC CHARACTERISTICS AND PROGRESSION PATTERNS OF MACULAR NEOVASCULARIZATION-RELATED ATROPHY IN EYES WITH PATHOLOGIC MYOPIA.
To investigate the development and progression patterns of macular neovascularization (MNV)-related atrophies in eyes with pathologic myopia. Twenty-seven eyes of 26 patients with MNV followed from its onset to progression to macular atrophy were studied. A longitudinal series of autofluorescence and optical coherence tomography images were examined for the patterns of MNV-related atrophy. Changes in best-corrected visual acuity were determined for each pattern. The mean age was 67.2 ± 8.7 years. The mean axial length was 29.6 ± 1.5 mm. Three patterns of atrophy were identified: multiple-atrophic pattern, 63% of the eyes had small atrophies occurring at multiple sites around the MNV edge; single-atrophic pattern, 18.5% had atrophies occurring only on one side of the MNV edge; and exudation-related pattern, 18.5% had atrophy occurring within a previous serous exudation or hemorrhagic area and slightly away from the MNV edge. Eyes with atrophies in multiple-atrophic and exudation-related patterns progressed to large macular atrophies involving the central fovea and showed decrease in best-corrected visual acuity during the 3-year follow-up period. Eyes with single-atrophic pattern had a sparing of the fovea and had good recovery of the best-corrected visual acuity. There are three patterns of MNV-related atrophy in eyes with pathologic myopia with different courses of progression.


An in silico approach for understanding the molecular evolution of clinically important metallo-beta-lactamases.
Resistance to carbapenem, considered to be the drug of last resort for treating serious enterobacterial infections, is a growing problem. Metallo-beta-lactamase (MBL) mediated carbapenem resistance is considered to be clinically most important, since no traditional inhibitors work against them. Hence, we have investigated the changes in drug profile, affinity and binding stability of meropenem with clinically important MBLs viz., IMP, VIM and NDM during the course of molecular evolution. Phylogenetic trees were constructed and amino acids positions, presumed to be exposed to positive selection pressure were analyzed. Based on sequence diversity and selection pressure, IMP-1, IMP-8, IMP-9, IMP-21, IMP-27, IMP-20 and IMP-26 among IMP genes; VIM-1, VIM-2, VIM-13, VIM-29, VIM-18 and VIM-7 among VIM genes and NDM-1 had been selected for in silico analysis. Mode of interaction of selected MBL variants with meropenem were analyzed by Autodock4.0 and LIGPLOT analysis. In all the trajectories, we had found an increase in mouth opening/solvent accessible volume/area of the catalytic pocket and decrease in Gibbs' free energy (ΔG°) for binding with meropenem and Michealis-Menten constant (Km) - indicating an increase in choice of drugs, binding stability and meropenem affinity from primitive to advanced MBL variants, with exceptions of IMP-20, IMP-26, VIM-13 and VIM-18 which might be due to sign epistasis. Intergenic comparison revealed NDM-1 might have greater drug profile and catalytic efficiency than IMP-1 and VIM-2 due to largest pocket opening and least distance between the Zn-I ion and β-lactam oxygen of meropenem.


Long-term Stimulation of α7 Nicotinic Acetylcholine Receptor Rescues Hemorrhagic Neuron Loss via Apoptosis of M1 Microglia.
We previously revealed that long-term treatment with nicotine suppresses microglial activation, resulting in a protective effect against thrombin-induced shrinkage of the striatal tissue in organotypic slice cultures. Here, the effect of nicotine on impaired M1 and protective M2 microglial polarization was investigated using the BV-2 microglial cell line in the presence or absence of thrombin. Following nicotine treatment, α7 nicotinic acetylcholine receptor expression transiently increased and then gradually decreased until 14 days. Treatment with nicotine for 14 days slightly polarized M0 microglia to M2b and d subtypes. Co-exposure of thrombin and low concentration of interferon-γ recruited inducible NO synthase (iNOS)- and interleukin-1β-double-positive M1 microglia in a thrombin-concentration-dependent manner. Treatment with nicotine for 14 days significantly decreased the thrombin-induced increase of iNOS mRNA levels and conversely showed a tendency to increase arginase1 mRNA levels. Moreover, treatment with nicotine for 14 days suppressed thrombin-induced phosphorylation of p38 MAPK through the α7 receptor. Repeated intraperitoneal administration of α7 agonist PNU-282987 for 14 days selectively evoked the apoptosis of iNOS-positive M1 microglia at the perihematomal area and showed a neuroprotective effect in an in vivo intracerebral hemorrhage model. These findings revealed that long-term stimulation of α7 receptor causes suppression of thrombin-induced activation of p38 MAPK followed by apoptosis in neuropathic M1 microglia.


Cost estimates for hospital inpatient care in Australia: evaluation of alternative sources.
This paper presents a framework for evaluation of alternative sources of estimates of the costs of hospital inpatient care in Australia. It argues that the choice of costing methods depends on the decision-context and the sensitivity of the decision to estimation errors. Five criteria are proposed for evaluation of sources of hospital cost data, with detailed consideration of the way estimates are derived in two computerised approaches which use accounting data. Three broad approaches to cost estimation are evaluated against these criteria. Choosing an estimation method entails an optimisation analysis for each decision context. 'Microcosting' techniques remains the most valid approach to cost estimation, but are costly and this may, in turn, limit the sample of patients or institutions. Protocol-based cost estimates vary widely in their validity, depending on source data, but there is little justification for continued use of crude per diem cost estimates in such protocols. When precision and resolution are important objectives, clinical costing approaches provide the most valid inpatient cost estimates at a reasonable data cost. When external validity is important, or where standardisation of hospital costs is desired, use of published national cost weights may be preferred. Both primary and secondary sources of cost data must withstand challenges to internal and external validity. The 'resolution' (or precision) of cost estimates and the relative costs of collection must also be considered. Studies using estimates of the costs of hospital care should defend the appropriateness of the costing approach and data source for the decision context.


Determination of total arsenic using a novel Zn-ferrite binding gel for DGT techniques: Application to the redox speciation of arsenic in river sediments.
A new laboratory-made Zn-ferrite (ZnFe2O4) binding gel is fully tested using Diffusive Gradient in Thin films (DGT) probes to measure total As [including inorganic As(III) and As(V), as well as MonoMethyl Arsenic Acid (MMAA(V)) and DiMethyl Arsenic Acid (DMAA(V))] in river waters and sediment pore waters. The synthesis of the binding gel is easy, cheap and its insertion into the acrylamide gel is not problematic. An important series of triplicate tests have been carried out to validate the use of the Zn-ferrite binding gel in routine for several environmental matrixes studies, in order to test: (i) the effect of pH on the accumulation efficiency of inorganic As species; (ii) the reproducibility of the results; (iii) the accumulation efficiency of As species; (iv) the effects of the ionic strength and possible competitive anions; and (v) the uptake and the elution efficiency of As species after accumulation in the binding gel. All experimental conditions have been reproduced using two other existing binding gels for comparison: ferrihydrite and Metsorb® HMRP 50. We clearly demonstrate that the Zn-ferrite binding gel is at least as good as the two other binding gels, especially for pH values higher than 8. In addition, by taking into consideration the diffusion rates of As(III) and As(V) in the gel, combining the 3-mercaptopropyl [accumulating only As(III)] with the Zn-ferrite binding gels allows for performing speciation studies. An environmental study along the Marque River finally illustrates the ability of the new binding gel to be used for field studies.


Reproducibility of the low dose dexamethasone suppression test: comparison between direct plasma and salivary cortisol assays.
The low dose dexamethasone suppression test (DST) has been used to detect subtle variations in the feedback suppression of the hypothalamic-pituitary-adrenal axis, which may contribute to the pathogenesis of several diseases including depression, the metabolic syndrome and coronary artery disease. Little is known about the reproducibility of this test, or whether the test can be combined with analysis of salivary cortisol which would offer a significant advantage over plasma in population studies. A low dose DST was carried out in 29 healthy subjects (14 men, 15 women), aged 24-54 (mean 35.1) years, on two separate occasions 1-10 weeks apart. Following the administration of 0.25 mg dexamethasone (DXM) at 2200 h, plasma and saliva were sampled at 0830 h the next day. Cortisol was measured by radioimmunoassay in plasma and time-resolved immunofluorescent assay ('DELFIA') in saliva. Bland-Altman plots were produced for post-DXM plasma and salivary cortisol measures and used to derive a coefficient of repeatability for each measure, which describes the range of cortisol measurements within which 95% of repeated measurements will fall. The baseline, pre-DXM cortisol concentrations were far more variable for saliva (mean 16.5, range 4.4-34 nmol/l) than for plasma (mean 407.5; range 232-958 nmol/l). Following DXM both measurements showed an approximately 30% suppression from baseline but the variability of salivary cortisol was much greater. From the Bland-Altman plots the 95% range for the differences about their mean was calculated and used as an indication of repeatability. For plasma 95% of differences were within 0.78 log units, indicating that a repeated measurement was approximately half as small or twice as large as the first. For saliva 95% of differences were within 1.64, indicating that a repeated measurement was approximately five times as small or five times as large as the first. Assessment of dexamethasone suppression by salivary cortisol measurement is far less repeatable than the use of plasma cortisol. In the context of field studies of dexamethasone suppression, salivary cortisol measurements may only be appropriate for large numbers of subjects.


Sources of sulphur in rain collected below a wheat canopy.
Vegetation plays an important role in the cycle of sulphur between the atmosphere and the soil. We have measured the quantity of sulphur in rain collected below a maturing wheat canopy. This sulphur has three sources: first, the atmosphere, from which falling rain gains SO2 and sulphate; second, leaf surfaces, from which rain washes sulphur which was previously deposited by turbulent transfer ('dry deposition'), and third, leaf tissue, from which rain leaches sulphur. We have now deduced from field and laboratory measurements that leaching supplied nearly 90% of the sulphur gained by rain as it fell through the wheat canopy. Only a small fraction of sulphur which had been dry-deposited on the surface of leaves could be washed off.


The place of cadaveric dissection in post-COVID-19 anatomy education.
From time immemorial, cadaveric dissection has been commonly employed as a method of practical teaching and learning for anatomical education globally. Conventionally, cadaveric dissection has been embraced and widely accepted as the best fit for comprehensive and gross teaching in anatomy education, thus placing an undue rise in cadavers' demands. The emergence of the new coronavirus disease 2019 (COVID-19) has posed significant effects on medical education with substantial impacts on anatomy education, as seen in the shift from classroom to virtual learning. An essential area of anatomy education and training requiring immediate consideration is the position of cadaveric dissection in a post-COVID-19 era, which entails the safety of cadavers from possible SARS-CoV-2 infection before their use. This article explores the place of cadaveric dissection in post-COVID-19 anatomy education.


The ability of several high arctic plant species to utilize nitrate nitrogen under field conditions.
The ability to utilize NO inf3sup- in seven high arctic plant species from Truelove Lowland, Devon Island, Canada was investigated, using an in vivo assay of maximum potential nitrate reductase (NR) activity and applications of 15N. Plant species were selected on the basis of being characteristic of nutrient-poor and nutrient-rich habitats. In all species leaves were the dominant site of NR activity. Root NR activity was negligible in all species except Saxifraga cernua. NO inf3sup- availability per se did not appear to limit NR activity of the species typically found on nutrient-poor sites (Dryas integrifolia, Saxifraga oppositifolia, and Salix arctica), or in Cerastium alpinum, as leaf NR activities remained low, even after NO inf3sup- addition. 15NO inf3sup- uptake was limited in D. integrifolia and Salix arctica. However, the lack of field induction of NR activity in C. alpinum and Saxifraga oppositifolia was not due to restricted nitrate uptake, as 15NO inf3sup- labelled NO inf3sup- entered the roots and shoots of both species. Leaf NR activity rates were low in three of the species typical of nutrient-rich habitats (O. digyna, P. radicatum and Saxifraga cernua), sampled from a site containing low soil NO inf3sup- . Additions of NO inf3sup- significantly increased leaf NR activity in these latter species, suggesting that potential NR activity was limited by the availability of NO inf3sup- . 15N labelled NO inf3sup- was taken up by O. digyna. P. radicatum and Saxifraga cernua. Although two species (D. integrifolia and Salix arctica) showed little utilization of NO inf3sup- , we concluded that five of the seven selected high arctic plant species (C. alpinum, O. digyna, P. radicatum, Saxifraga cernua and Saxifraga oppositifolia) do have the potential to utilize NO inf3sup- as a nitrogen source under field conditions, with the highest potential to utilize NO inf3sup- occurring in three of the species typically found on fertile habitats.


Complete genome sequence of multidrug-resistant Staphylococcus sciuri strain SNUDS-18 isolated from a farmed duck in South Korea.
This study aimed to determine the complete genome sequence of multidrug-resistant Staphylococcus sciuri strain SNUDS-18 isolated from a farmed duck in South Korea. Genomic DNA was sequenced using a PacBio RS II system. The obtained genome was annotated and antimicrobial resistance and virulence genes were identified. The sequenced genome possessed a mecA homologue (mecA1) that was almost identical to that of other oxacillin-susceptible S. sciuri strains, whereas the staphylococcal cassette chromosome mec (SCCmec) was not detected. Moreover, various antimicrobial resistance genes conferring resistance to β-lactams, aminoglycosides, phenicols, tetracycline and macrolide-lincosamide-streptogramin B (MLSB) antimicrobials were identified. The SNUDS-18 genome and its associated genomic data will provide important insights into the biodiversity of the S. sciuri group as well as valuable information for the control of this potential pathogen.


Dabigatran reduces thrombin-induced neuroinflammation and AD markers in vitro: Therapeutic relevance for Alzheimer's disease.
Vascular risk factors such as atherosclerosis, diabetes, and elevated homocysteine levels are strongly correlated with onset of Alzheimer's disease (AD). Emerging evidence indicates that blood coagulation protein thrombin is associated with vascular and non-vascular risk factors of AD. Here, we examined the effect of thrombin and its direct inhibitor dabigatran on key mediators of neuro-inflammation and AD pathology in the retinoic acid (RA)-differentiated human neuroblastoma cell line SH-SY5Y. SH-SY5Y cells exposed to thrombin concentrations (10-100 nM) +/- 250 nM dabigatran for 24 h were analyzed for protein and gene expression. Electrophoretic mobility shift assay (EMSA) was used to determine DNA binding of NFkB. Western blotting, qRT-PCR and ELISA were used to measure the protein, mRNA, and activity levels of known AD hallmarks and signaling molecules. Dabigatran treatment attenuated thrombin-induced increase in DNA binding of NFκB by 175% at 50 nM and by 77% at 100 nM thrombin concentration. Thrombin also augmented accumulation of Aβ protein expression and phosphorylation of p38 MAPK, a downstream molecule in the signaling cascade, expression of pro-apoptotic mediator caspase 3, APP, tTau and pTau. Additionally, thrombin increased BACE1 activity, GSK3β expression, and APP, BACE1, Tau and GSK3β mRNA levels. Co-incubation with dabigatran attenuated thrombin-induced increases in the protein, mRNA, and activities of the aforesaid molecules to various extents (between -31% and -283%). Our data demonstrates that thrombin promotes AD-related pathological changes in neuronal cultures and suggests that use of direct oral anticoagulants may provide a therapeutic benefit against thrombin-driven neuroinflammation and downstream pathology in AD.


Ultra-low Esfenvalerate concentrations increase biomass and may reduce competitiveness of Daphnia magna populations.
Aquatic communities are frequently exposed to pesticides at sublethal concentrations, known to affect fitness parameters such as feeding, reproduction and population growth. Beside adverse effects, beneficial responses to toxicants at low concentrations may also occur. Positive effects, however, are thought to involve trade-offs. To identify such trade-offs, we quantified the population level effects on Daphnia magna during population carrying capacity in laboratory nanocosms after exposure to a single pulse of the pyrethroid insecticide esfenvalerate, including ultra-low concentrations ≤1/30 EC50. Population abundance and biomass were monitored 3 times per week for 3 months using a non-invasive imaging technique. High concentrations ≥1/10 EC50 resulted in reduced fitness endpoints. In contrast, ultra-low concentrations in the range of 0.01 μg/L significantly increased the population abundance of small (+160 %), medium (+130 %) and large organisms (+340 %) and their combined biomass (+200 %) during the 2 months after exposure. During the first five days after exposure to 0.01 μg/L and 0.03 μg/L esfenvalerate, population biomass increased by 0.1 mg/day while staying constant in the controls. While high control mortality makes firm conclusions about population responses of D. magna to esfenvalerate difficult, we hypothesize that population increases at ultra-low concentrations may be due to a hormetic response, where reduced intraspecific competitiveness is the trade-off that enables this response.


[The use of composite materials for the orthodontic treatment of patients with the vertical form of pathological tooth abrasiveness].
The author summarizes his experience with 34 patients with localized vertical pathological teeth abrasion. The coronal defects of 189 anterior teeth were corrected using individually fitted polymeric caps and composition materials: carbodent and epacryl (USSR), evicrol (CSSR), microrest (Japan). The technique is described in detail with its advantages, indications and contraindications.


Neuronal degeneration in the brain of the brindled mouse. I. Chromological studies on the long-surviving group.
Brindled mutant mouse (MObr) is clinically closely similar to kinky hair syndrome (KHS) in humans. Hemizygous males (MObr/Y) of this mutant usually cannot survive beyond the 15th -- 16th postnatal day. However, some were found to survive into the adult life. Extensive neuronal degeneration in the cerebral cortex was a prominent neuropathological feature of MObr/Y (Yajima and Suzuki, 1979a). In the long surviving one, however, such neuronal degeneration gradually disappeared and cortical neuronal loss and axonal degeneration of the underlying white matter were the predominant neuropathological features. which are closely similar to those of KHS, in particular in those patients who survive for more than 1 year. On the basis of our observations on the brain of MObr/Y mice, we hypothesized the possible chronological events on the development of neuropathological lesions in KHS in humans.


[A experimental study on arthroscopic auricular cartilage transplantation for repair of osteochondral defect of temporomandibular joint(TMJ)].
To study the feasibility and resurfacing ability of auricular cartilage transplantation for osteochondral defect of TMJ. Arthroscopic auricular cartilage transplantations were undertaken in 12 rhesus monkeys(24 joints) to repair the osteochondral defects in TMJs. The repaired tissues were examined by gross examination, light microscope and immunohistochemistry(IHC) 4 weeks,8 weeks,12 weeks and 24 weeks postoperatively. The defects were repaired 8 weeks after operation. As time goes on, the chondrocytes in defects declined and fibroblast increased at the same time. The IHC showed slight positive stain of type II collagen. The osteochondral defects of TMJ can be restored by autologous auricular cartilage. The nature of repaired tissue was fibrocartilage like tissue at first and then fibrotic tissue.


Gender equity in health care in Sweden--minor improvements since the 1990s.
A report by the Swedish National Committee on Gender Disparities in Patient Care (1996) identified many shortcomings in the ability of the health sector to gear patient management and treatment to the specific needs of men and women. To promote gender equity in health care, the Committee presented several proposals relating to research, education, monitoring, and evaluation of health services and the responsibilities of health authorities. In 2002, the Swedish Government authorised the National Board of Health and Welfare to review and analyse gender equity trends in health care. Data from, e.g. the national quality registers, epidemiological health data registers, population surveys, and Patient Trust Boards were compiled to identify gender disparities in the quality and accessibility of health services. The curricula of medical universities and the policies of major research funds were reviewed, as were developments in major fields of health research. The National Board found that many of the gender disparities identified in the 1990s still exist, e.g. access to advanced evidence-based technologies such as coronary interventions. As previously, women account for around 60%, and men for 40%, of complaints, e.g. to the Patients' Advisory Committees. Many of the proposals of the National Committee have not been fully implemented by the national authorities or the county councils. We conclude that promoting gender equity in health care is an important but difficult task for health authorities. To make health services more gender sensitive a combination of strategies, including enforcement by guidelines and regulations, may be needed.


Surface plasmon resonance sensor for heparin measurements in blood plasma.
Surface plasmon resonance (SPR) was used as an affinity biosensor to determine absolute heparin concentrations in human blood plasma samples. Protamine and polyethylene imine (PEI) were evaluated as heparin affinity surfaces. Heparin adsorption onto protamine in blood plasma was specific with a lowest detection limit of 0.2 U/ml and a linear window of 0.2-2 U/ml. Although heparin adsorption onto PEI in buffer solution had indicated superior sensitivity to that on protamine, in blood plasma it was not specific for heparin and adsorbed plasma species to a steady-state equilibrium. By reducing the incubation time and diluting the plasma samples with buffer to 50%, the non-specific adsorption of plasma could be controlled and a PEI pre-treated with blood plasma could be used successfully for heparin determination. Heparin adsorption in 50% plasma was linear between 0.05 and 1 U/ml so that heparin plasma levels of 0.1-2 U/ml could be determined within a relative error of 11% and an accuracy of 0.05 U/ml.


Investigation on Protic Ionic Liquids as Physical Solvents for Absorption of NO at Low Pressures.
Nitric oxide (NO) absorption in ionic liquids (ILs) is an interesting issue, but little attention has been focused on the removal of NO at low partial pressures. Herein, a series of protic ionic liquids (PILs) based on polyamines as the cation and hydroxybenzenes as the anion were prepared for capturing low-concentration NO (0-0.6 bar). Triethylenetetramine phenolate ([TETAH][PhO]) showed an excellent absorption performance, with low viscosity, fast absorption rate, and high absorption capacity. The experimental solubility data were fitted by the Krichevsky-Kasarnovsky (K-K) equation, and the absorption enthalpy (ΔH) of NO in [TETAH][PhO] was thus calculated to be -43.60 kJ/mol. Density functional theory calculations were further performed to better understand the interaction of [TETAH][PhO] with NO on the molecular level, and the results suggest that the weak interaction of NO with the PIL was induced by the presence of H protons. It is believed that this work may provide a new method for the efficient and reversible absorption of low-concentration NO.


Pervasive RNA folding is crucial for narnavirus genome maintenance.
A synthetic biology approach toward constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. For the precise design of an artificial RNA replicon either from scratch or based on a natural RNA replicon, understanding structure-function relationships of RNA sequences is critical. However, our knowledge remains limited to a few particular structural elements intensively studied so far. Here, we conducted a series of site-directed mutagenesis studies of yeast narnaviruses ScNV20S and ScNV23S, perhaps the simplest natural autonomous RNA replicons, to identify RNA elements required for maintenance and replication. RNA structure disruption corresponding to various portions of the entire narnavirus genome suggests that pervasive RNA folding, in addition to the precise secondary structure of genome termini, is essential for maintenance of the RNA replicon in vivo. Computational RNA structure analyses suggest that this scenario likely applies to other "narna-like" viruses. This finding implies selective pressure on these simplest autonomous natural RNA replicons to fold into a unique structure that acquires both thermodynamic and biological stability. We propose the importance of pervasive RNA folding for the design of RNA replicons that could serve as a platform for in vivo continuous evolution as well as an interesting model to study the origin of life.


The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium.
To compare the tocolytic potency of ritodrine, nicardipine and atosiban, used alone and in dual combinations, to see whether combinations of these drugs, which act via different pathways, could improve inhibition of uterine contractility. Study on myometrial contractility in vitro. Laboratory of physiology, Lyon, France. Longitudinal myometrial strips from non-labouring timed pregnant Wistar rats (18 gestational days). Strips were simultaneously exposed to EC(25), EC(50) or EC(75) of dual combinations of either ritodrine and nicardipine, ritodrine and atosiban or nicardipine and atosiban (n = 10/group). Basal contractile activity and contractile activity after addition of each combination was measured using the 10 min integral of activity. Changes were expressed as percentage from the basal 10 min integral activity. The observed percentage inhibition of activity was compared with the expected percentage inhibition in an additive pharmacological model. When no significant difference occurred, the combination was deemed simply to have an additive tocolytic effect. When inhibition of activity was significantly greater compared with the expected percentage inhibition, the combination was deemed to have a synergistic effect. Changes in integral contractile activity in response to tocolytic combinations. Ritodrine and atosiban inhibited integral activity to a greater extent than expected [e.g. using EC(50): observed inhibition 88.9% (13.8%) vs expected inhibition 75%; P < 0.015]. Actual inhibition by nicardipine/ritodrine [78.55% (20.4%) vs 75%; P = n.s.] and nicardipine/atosiban [78.94% (17.8%) vs 75%; P = n.s.] was not significantly different from expected. A combination of ritodrine plus atosiban exhibits a synergistic inhibition for myometrial activity, thus allowing the use of lower concentrations of each drug to achieve the same effect compared with each drug used alone. Combination of nicardipine plus ritodrine and nicardipine plus atosiban achieves only an additive effect. The potential for decreasing side effects (beta-mimetics) and costs (atosiban) when using a combination in clinical practice needs to be evaluated.


MicroRNA -383-5p restrains the proliferation and migration of breast cancer cells and promotes apoptosis via inhibition of PD-L1.
MicroRNAs (miRs) play pivotal roles in breast cancer development. The dysregulation of miRs has been associated with PD-L1-mediated immune suppression. This study aimed to examine the effect of transfected miR-383-5p on breast cancer cells and T-cells and its association with clinicopathological features in affected patients. Initially, miR-383-5p and PD-L1 expression levels were investigated in breast cancer tissues. Then, MDA-MB-231 cells were transfected with miR-383-5p mimics to perform analyses. Cell viability was investigated using the MTT assay, and the annexin V/PI staining assay was performed to examine apoptosis induction. Furthermore, the effect of miR-383-5p on cell migration and cell cycle progression was analyzed using the wound-healing assay and flow cytometry, respectively. Gene and protein expressions were studied using qRT-PCR and western blotting. Finally, the effect of miR-383-5p on T-cells, which were co-cultured with cancer cells, was investigated. Compared to non-malignant tissues, PD-L1 was up-regulated, and miR-383-5p expression was downregulated in breast cancer tissues. Moreover, miR-383-5p reduced breast cancer cell viability via inducing apoptosis and modulating the expression of apoptosis-related genes. Besides, miR-383-5p could inhibit the migration of breast cancer cells via down-regulating metastasis-related genes. Besides, transfected miR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells. Furthermore, the results showed that miR-383-5p might exert its tumor-suppressive effect via inhibiting the PI3K/AKT/mTOR pathway. The inhibitory effect of transfected miR-383-5p on the PI3K/AKT/mTOR pathway might be the underlying mechanism for inhibiting tumoral PD-L1 expression. Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.


Is the transition from primary to secondary school a risk factor for energy balance-related behaviours? A systematic review.
The substantial changes in the physical and social environment during the transition from primary to secondary school may significantly impact adolescents' energy balance-related behaviours (i.e. dietary behaviour, sedentary behaviour, sleep behaviour and physical activity (PA)). This is the first review systematically summarising evidence on changes in four energy balance-related behaviours of adolescents across the school transition from primary to secondary school. For this systematic review, the electronic databases Embase, PsycINFO and SPORTDiscus were searched for relevant studies from inception to August 2021. PubMed was searched for relevant studies from inception to September 2022. Inclusion criteria were: (i) longitudinal studies reporting; (ii) one or more energy balance-related behaviours; and (iii) across the school transition, that is, with measurement(s) during both primary and secondary school. Transition from primary to secondary school. Adolescents across the transition from primary to secondary school. Thirty-four studies were eligible. We found strong evidence for an increase in sedentary time, moderate evidence for a decrease in fruit and vegetable consumption, and inconclusive evidence for a change in total, light, and moderate-to-vigorous PA, active transport, screen time, unhealthy snack consumption, and sugar-sweetened beverages consumption among adolescents across the school transition. During the transition from primary to secondary school, sedentary time and fruit and vegetable consumption tend to change unfavourably. More high-quality, longitudinal research is needed specifically on changes in energy balance-related behaviour across the school transition, especially regarding sleep behaviour. (Prospero registration: CRD42018084799).


Delayed infectious reactions of dermal filler injections in the face: Causes and management.
Nowadays, dermal filler injections in the face, are widespread. However, late complications are rarely reported and misunderstood. Moreover, they could be potentially severe, particularly cellulitis which is life-threatening. Reactivation of the biofilm and the hypersensitivity reaction are the main etiopathogenic factors of such unpredictable infections and granuloma reactions. Through four cases of foreign-body cellulitis, this article aims to explain the causality of filler material, and trigger conditions while emphasizes the prompt and adequate solution. This work is a retrospective study and chart review which was granted an exemption by the author's institutional review board (IRB). Four women ranging from 27 to 55 years old, presented with onset symptoms of cellulitis of the face and inflammatory swelling of the lip. The hyaluronic acid filler was injected a long date prior. Trigger conditions caused the hatching of such complications which were solved with medical treatment without any filler dissolution or removal. Improvement of the symptoms was remarkable within the three and fifth days of antibiotic therapy. There was no abscess formation or, recurrence for more than one-year follow-up. The screening for dermal filler deposits must be considered for any inflammatory reaction of the face. Their causality should be discussed as well as the infectious and/or immunologic etiology, ensuring prompt and adequate medical treatment. Thus abscess formation could then not happen, and the resolution of the inflammatory reaction will be obtained. The extraction of filler material or the use of hyaluronidase should not be mandatory and will be done on a case-by-case basis.


Dietary lipid and iron modify normal colonic mucosa without affecting phospholipase A2 activity.
Phospholipase A2 (PLA2) functions as the rate-limiting step in arachidonic acid metabolism and in the removal of damaged or peroxidized membrane lipids. It is elevated in some human tumors and may be involved with mechanisms of tumor promotion. In vitro systems have shown PLA2 activity to be altered by variations in fatty acid and antioxidant components. This study encompassed two objectives. First, PLA2, activity in colon tumors produced using azoxymethane (AOM) in Fischer-344 rats was examined. Secondly, this study tested the effect of iron supplementation as a potential pro-oxidant in diets of varied fatty acid composition on PLA2 activity. Diets included 35 or 140 mg/kg or iron in AIN-76A based diets high in corn oil, menhaden oil, or beef tallow. Results for the first objective showed PLA2 activity to be significantly higher in colon tumors than in normal mucosa with the increase due primarily to an increase in activity within a particulate subcellular fraction. In the second objective, fatty acid composition of colon mucosa was altered by both dietary fat and iron. Animals fed beef tallow had the highest level of oleic acid and corn oil-fed animals had the highest level of linoleic acid. Animals fed menhaden oil had the lowest level of arachidonic acid and highest level of alpha-linolenic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. Iron supplementation in diets high in corn oil resulted in decreased membrane composition of palmitoleic and delta-linolenic acid. In spite of these changes in membrane composition, there were no changes in PLA2 activity. These results show that PLA2 activity is increased in AOM-induced tumors but that diet alone does not influence PLA2 activity in this model.


High Expression of Circular RNA-Mitochondrial tRNA Translation Optimization 1 Assists the Diagnosis of High-Risk Human Papillomavirus Infection in Cervical Cancer.
Persistence of high-risk human papillomavirus (HR-HPV) infection is a paramount determinant in cervical cancer (CC) development. Circular RNAs have the potential to be promising biomarkers for various cancers. This study explored circular RNA-mitochondrial tRNA translation optimization 1 (circMTO1) expression in the serum of CC patients and its clinical value in diagnosing CC and predicting HR-HPV infection. In total, 125 CC patients (including 78 cases with HR-HPV) were enrolled, with another 76 healthy people as controls. Serum circMTO1 and miR-199a expressions were detected by reverse transcription-quantitative polymerase chain reaction, and the diagnostic efficacy of circMTO1 for CC and HR-HPV infection was analyzed by the receiver operating characteristic curve. According to the median of serum circMTO1 expression, CC patients were assigned into circMTO1 low/high expression groups to analyze the correlation between circMTO1 and clinical parameters using the Fisher and χ 2 tests. Independent association of circMTO1 with HR-HPV infection in CC was evaluated via logistics multivariate regression analysis. Targeted relationship between miR-199a and circMTO1 was predicted by Starbase Web site and validated via dual-luciferase assay, with their correlation further assessed by Pearson analysis. Serum circMTO1 was increased in CC patients and prominently elevated in HR-HPV-positive CC patients, with a level greater than 1.485 assisting CC diagnosis and a level greater than 2.480 assisting HR-HPV-positive diagnosis. The circMTO1 was interrelated to clinical stage, tumor differentiation, lymph node metastasis, invasion depth, and independently linked with HR-HPV infection in CC. Serum miR-199a was downregulated in HR-HPV-positive CC patients and inversely correlated with circMTO1. Serum circMTO1 is upregulated in HR-HPV-positive CC patients and has a diagnostic value for HR-HPV infection in CC.


Quantitative phase imaging of living cells: application of the phase volume and area functions to the analysis of "nucleolar stress".
We applied coherent phase microscopy to develop a method of quantitative evaluation of functional state of eukaryotic cells using the coordinates of characteristic points (CP) in the functions of the phase volume W and area S. In a fragment of a single cell image (HCT116 human colon carcinoma cell line) with detectable nucleolus, the values of the phase thickness, area, and volume were calculated. These values dramatically changed within the initial minutes of cell exposure to the transcriptional inhibitor actinomycin D. The positions of CP in the graphs of S and W functions allowed for monitoring the time-dependent decrease of nucleolar contrast, a major optical hallmark of "nucleolar stress." Given that the area and volume functions reflect optical heterogeneity of the cell and are independent of its optical model, these functions can be applicable as general mathematical tools for the analysis of cell morphology and physiology.


Gelatinous drop-like corneal dystrophy is not one of the beta ig-h3-mutated corneal amyloidoses.
To discover if beta ig-h3 is mutated in gelatinous drop-like corneal dystrophy, as has been suggested. Genomic DNA was isolated from unrelated individuals with lattice corneal dystrophy type I (n = 3), Avellino corneal dystrophy (n = 3), and gelatinous drop-like corneal dystrophy (n = 3) and used as a template for polymerase chain reaction to amplify all exons in beta ig-h3. The polymerase chain reaction product was then sequenced. Beta ig-h3 is mutated in lattice corneal dystrophy type I (Arg124Cys) and Avellino corneal dystrophy (Arg124His). In gelatinous drop-like corneal dystrophy, on the other hand, no mutation was detected in the entire coding region of beta ig-h3 (all 17 exons). Unlike the amyloidotic corneal dystrophies lattice type I and Avellino, gelatinous drop-like corneal dystrophy is not likely to be caused by a mutation in beta ig-h3.