Midwives' experiences of labour care in midwifery units. A qualitative interview study in a Norwegian setting.
In some economically developed countries, women's choice of birth care and birth place is encouraged. The aim of this study was to explore and describe the experiences of midwives who started working in alongside/free-standing midwifery units (AMU/FMU) and their experiences with labour care in this setting. A qualitative explorative design using a phenomenographic approach was used. Semi-structured interviews were conducted with ten strategically sampled midwives working in midwifery units. The analysis revealed the following five categories of experiences noted by the midwives: mixed emotions and de-learning obstetric unit habits, revitalising midwifery philosophy, alertness and preparedness, presence and patience, and coping with time. Starting to work in an AMU/FMU can be a distressing period for a midwife. First, it may require de-learning the medical approach to birth, and, second, it may entail a revitalisation (and re-learning) of birth care that promotes physiological birth. Midwifery, particularly in FMUs, requires an especially careful assessment of the labouring process, the ability to be foresighted, and capability in emergencies. The autonomy of midwives may be constrained also in AMUs/FMUs. However, working in these settings is also viewed as experiencing "the art of midwifery" and enables revitalisation of the midwifery philosophy.


The molecular biology and pathophysiology of hypertrophic cardiomyopathy due to mutations in the beta myosin heavy chains and the essential and regulatory light chains.
Hypertrophic cardiomyopathy (HCM) is perhaps the most common cause of inherited sudden death in otherwise healthy young individuals. There are presently seven known genes in which mutations have been shown to cause the disease. The first identified disease gene was beta myosin heavy chain (BMHC). Our laboratory has identified 32 distinct BMHC gene mutations in 62 kindreds after screening representatives of over 400 kindreds. Virtually all but one of approximately 50 known mutations are restricted to the head or head-rod junction region of the molecule. We have used the mutant alleles of the BMHC gene to demonstrate that both mutant message and protein is present in the skeletal muscle of patients with HCM. Muscle biopsies from patients with identified BMHC mutations show abnormal histology. Isolated myosin and skinned fibers from these patients have abnormal mechanical properties. The BMHC gene mutations are clustered in 4 regions of the myosin head. Because one of these regions is adjacent to the ELC, we scanned HCM patient DNA for mutations in either the ELC or RLC. Linkage analysis showed that a unique mutation in the ELC caused a rare phenotype of HCM in one family. Other mutations in either light chain were also associated with the same rare phenotype in other families. Through several lines of reasoning we hypothesized that the light chain mutations interfere with the stretch-activation response of papillary muscle and adjacent ventricular tissue. This property is critical to oscillatory power output of insect flight muscle. We conjectured that this property is also exploited by portions of the heart to increase power output. In order to test this hypothesis we constructed transgenic mouse lines expressing either the human normal or mutant ELC. The cardiac morphology and mechanical properties of the transgenic mouse papillary muscle is now being studied.


A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele amphibian). I. Lactate dehydrogenase-B and glucose-6-phosphate dehydrogenase.
On starch gel electrophoresis of erythrocyte hemolysates of Pleurodeles waltlii (Urodele Amphibian), both lactate dehydrogenase-B (LDH-B) and glucose-6-phosphate dehydrogenase (G6PDH) show polymorphism that depends on a pair of autosomal codominant alleles, confirmed by analysis of gynogenesis progeny. Diploid gynogenesis results from fusion of the female pronucleus with the second polar body. The heterozygous state of a female for a given character is maintained in certain progeny when crossing-over occurs between the locus in question and the centromere. So the high proportion of heterozygotes (45.7% for LDH-B and 76% for G6PDH) indicates the high frequency of crossing-over and hence the large distance between each of the loci and the centromere.


Micromethod for determination of middle ear gas composition.
This is a microchromatographic method for simultaneous determinations of O2, N2, CO2 and N2O in gas samples of 40-100 microliters. A Packard 836 U gas chromatograph with a thermal conductivity detector and helium gas as carrier was used. The combination of Porapak and 5A molecular sieve column system was found adequate and is described in detail. The fidelity of this method was proved by a high constancy of the retention time, the linearity of the response and the reproducibility of results. The present method proved to be reliable for determination of all middle ear gases in man and experimental animals during general anesthesia with N2O.


Heritability of cilioretinal arteries: a twin study.
To determine whether the presence of one or more cilioretinal arteries, a distinct element of the pattern of fundus vessels, is genetically programmed, influenced by environmental factors, or the result of random mechanisms of vascular development. The fundi of 112 pairs of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes. The majority of cilioretinal arteries, 88.2%, were located temporally, and 11.8% were located nasally. Monozygotic twins had higher concordance rates for cilioretinal arteries than dizygotic twins. Tetrachoric correlations and Mantel-Haenszel odds ratios demonstrated statistically significant evidence of a genetic effect underlying the presence of cilioretinal arteries (P < 0.01). Statistical analysis supported the hypothesis that additive genetic factors influenced the presence of cilioretinal arteries with a heritability of 71.4%, the remaining variance being attributable to nonshared or random environmental factors. The presence or absence of one or more cilioretinal arteries in healthy persons is markedly influenced by genetic factors.


Factors associated with abandoning exclusive breastfeeding in Mexican mothers at two private hospitals.
Exclusive breastfeeding (EBF) has multiple benefits for both the child and the mother; however, there is little data regarding the reason why Mexican mothers with a high socio-economic level abandon EBF before 6 months, and there is limited information about the practice of breastfeeding in private hospitals. The objective was to identify the factors associated with the cessation of exclusive breastfeeding in Mexican mothers at two private hospitals. A cross-sectional study was conducted with 218 upper-class mothers selected according to their place of residence by geographic location, socio-economic level, and pediatric consultations cost. They were over 18 years old and with children aged 6 to 24 months. Data were collected between July and November 2016 by face to face interview using a structured questionnaire while the mothers waited for the pediatric postnatal care consultation in two private hospitals in northeastern Mexico. Exclusive breastfeeding was measured according to World Health Organization (WHO) recommendations, which consist of providing only breast milk for the first 6 months of life. Chi-squared tests and multivariate logistic regression were performed. Mean maternal age was 31.4 years (SD of 4.4) and most of the participants had an undergraduate education, were married, and worked outside the home. The prevalence of exclusive breastfeeding at 6 months was 28%. Upper-class working mothers are less likely to continue breastfeeding. There was a negative association with employment (AOR 13.69; 95% CI 1.59, 111.11), bottle use in the first 6 months (AOR 7.93; 95% CI 3.07, 20.48), and a low level of knowledge (AOR 2.18; 95% CI 1.04, 4.56). After 6 months, only 61 mothers (28%) maintained exclusive breastfeeding. Knowledge level, bottle use, and employment are associated with premature cessation of EBF in Mexican upper-class mothers, attending two private hospitals. There was a high percentage of breastfeeding cessation in the sample. It is necessary to reinforce a strategy that coordinates the action of the different laws, regulations and programs affecting the exclusive breastfeeding practice, in order to adequately promote breastfeeding and support mothers in both public and private sectors.


Corrigendum to 'Efficacy of emicizumab is maintained throughout dosing intervals for bleed prophylaxis' [Research and Practice in Thrombosis and Haemostasis, Volume 7, Issue 2, February 2023, 100077].
[This corrects the article DOI: 10.1016/j.rpth.2023.100077.].


64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?
► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.


A transcriptome resource for pharaoh cuttlefish (Sepia pharaonis) after ink ejection by brief pressing.
Ink ejection is one of the most important defense mechanisms against external stimuli for pharaoh cuttlefish (Sepia pharaonis). The molecular changes during this process remain unknown. To understand the transcriptome changes after ink ejection by brief pressing, two cDNA libraries of pharaoh cuttlefish, from the inkjet group and control group were sequenced using Illumina HiSeq™ 2000. A total of 9,255,502,440nt bases were obtained and by de novo assembly, 73,298 unigenes were generated, which first provided numerous expressed sequence tags from pharaoh cuttlefish. By comparing the expression levels between the two groups, we identified 7064 up-regulated and 2024 down-regulated genes after ink ejection. These differentially-expressed genes included genes related to immunity, cancer, and blood coagulation, which indicated the various effects after ink ejection by brief pressing. These results provide new valuable resources for functional genomic and genetic studies on pharaoh cuttlefish.


Biological evaluation of N-2-hydroxypropyl trimethyl ammonium chloride chitosan as a carrier for the delivery of live Newcastle disease vaccine.
Mucosal immune system plays a very important role in antiviral immune response. We prepared Newcastle disease viruses (NDV) encapsulated in N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) nanoparticles (NDV/La Sota-N-2-HACC-NPs) by an ionic cross linking method, and assessed the potential of N-2-HACC-NPs as a mucosal immune delivery carrier. The properties of the nanoparticles were determined by transmission electron microscopy, Zeta potential and particle size analysis, encapsulation efficiency and loading capacity. NDV/La Sota-N-2-HACC-NPs have regular spherical morphologies and high stability; with 303.88±49.8nm mean diameter, 45.77±0.75mV Zeta potential, 94.26±0.42% encapsulation efficiency and 54.06±0.21% loading capacity. In vitro release assay indicated that the release of NDV from NDV/La Sota-N-2-HACC-NPs is slow. The NDV/La Sota-N-2-HACC-NPs have good biological characteristics, very low toxicity and high level of safety. Additionally, specific pathogen-free chickens immunized with NDV/La Sota-N-2-HACC-NPs showed much stronger cellular, humoral and mucosal immune responses than commercial attenuated live Newcastle disease vaccine, and NDV/La Sota-N-2-HACC-NPs reached the sustainable release effect. Our study here provides a foundation for the further development of mucosal vaccines and drugs, and the N-2-HACC-NPs should be a potential drug delivery carrier with immense potential in medical applications.


Carbon dioxide laser for the treatment of microcystic lymphatic malformations (lymphangioma circumscriptum): a systematic review.
Lymphangioma circumscriptum (LC) is a rare, superficial, cutaneous lymphatic malformation. Management is difficult because of high recurrence rates, regardless of the treatment modality chosen. The carbon dioxide (CO2 ) laser may offer a less-invasive option than surgery that provides satisfactory functional and cosmetic results. To systematically review the efficacy and safety of the CO2 laser for the treatment of LC. The terms "lymphangioma circumscriptum" and "microcystic lymphatic malformation" were combined with "treatment," "laser," and "carbon dioxide" during separate searches in the PubMed database. The articles retrieved were then evaluated based on set criteria. We identified 16 studies (11 case reports, 5 case series) with a total of 28 separate patients who had been treated for LC using a CO2 laser. Eight patients remained disease free from 4 months to 3 years, 10 experienced partial recurrence, and two experienced complete recurrence. Various laser parameters were reported, and adverse effects were generally minor and infrequent, such as dyspigmentation and mild scarring. Available evidence indicates that the CO2 laser is a safe and efficacious option for the treatment of LC, particularly in large lesions that may not be amenable to surgical intervention.


Hollow ZSM-5 zeolite encapsulating Pt nanoparticles: Cage-confinement effects for the enhanced catalytic oxidation of benzene.
A zeolitic cage was introduced and rationally fabricated by encapsulating Pt nanoparticles (NPs) in hollow ZSM-5, a nanomaterial with a cavity and porous shell, for efficient catalytic oxidation of benzene. The structure and formation of the zeolitic cage were systematically investigated and characterized using transmission electron microscopy, nitrogen sorption investigations, X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, and X-ray diffraction. The obtained hollow 0.2 Pt@ZSM-5 exhibited a comparable low-temperature catalytic activity with 0.5Pt/ZSM-5 with T90 value of 178 °C. Various characterization techniques combined with adsorption experiments uncover the tremendous role of the zeolitic cage in the catalytic activity toward benzene oxidation. The porous shell prevented benzene dilution and the acidity originating from the hollow interior of ZSM-5 promoted the storage of benzene, thereby forming a high local concentration of benzene around Pt NPs, resulting in excellent catalytic performance. These findings provide valuable insights into the rational design of efficient catalysts for the catalytic oxidation of volatile organic compounds.


Toxicity of graphene oxide on growth and metabolism of Pseudomonas putida.
The increasing consumption of graphene derivatives leads to greater presence of these materials in wastewater treatment plants and ecological systems. The toxicity effect of graphene oxide (GO) on the microbial functions involved in the biological wastewater treatment process is studied, using Pseudomonas putida and salicylic acid (SA) as bacterial and pollutant models. A multiparametric flow cytometry (FC) method has been developed to measure the metabolic activity and viability of P. putida in contact with GO. A continuous reduction in the percentages of viable cells and a slight increase, lower than 5%, in the percentages of damaged and dead cells, suggest that P. putida in contact with GO loses the membrane integrity but preserves metabolic activity. The growth of P. putida was strongly inhibited by GO, since 0.05mgmL(-1) of GO reduced the maximum growth by a third, and the inhibition was considerably greater for GO concentrations higher than 0.1mgmL(-1). The specific SA removal rate decreased with GO concentration up to 0.1mgmL(-1) indicating that while GO always reduces the growth of P. putida, for concentrations higher than 0.1mgmL(-1), it also reduces its activity. Similar behaviour is observed using simulated urban and industrial wastewaters, the observed effects being more acute in the industrial wastewaters.


A simple method of delayed processing of tumor tissue in a soft agar clonogenic assay.
Sarcoma 180 tumor tissue from C57 mice was processed in a soft agar clonogenic assay immediately after removal from the animal and after various methods of storage. The sensitivity to the antineoplastic drug cis-platinum was not affected by different storage methods. The highest yield of colony forming cells per 100 mg tumor tissue was 2.3 X 10(4) cells following immediate processing of fresh tumor material. A 24-h storage of solid tumor tissue at 4 degrees C as well as cryopreservation of solid tumor tissue or cryopreservation of a single cell suspension prepared from fresh tumor specimens were found to reduce this value to 24%-37%. Storage of a tumor single cell suspension for 24 h at 4 degrees C however, proved to be a useful and simple method of delayed processing of tumor in a soft agar clonogenic assay. The observed cell yield was 1.91 X 10(4) colony forming cells, 83% of the immediately processed value. If this procedure is suitable for use with human tumor material obtained from biopsies and surgery, the 24 h time interval would be useful for transport from hospital to an appropriate special laboratory. This would result in the broader application of the human soft agar clonogenic assay in predictive testing and drug screening.


Increased circulating vasopressin may account for ethanol-induced hypertension in rats.
Long-term ethanol intake has been reported to evoke both hypertension and increase of systemic vasopressin levels in rats. In this work, we investigated the involvement of systemic vasopressin in the hypertension evoked in rats by long-term ethanol (20% vol/vol) intake for 2 weeks, by systemic treatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 microg/kg). Moreover, plasma arginine-vasopressin (AVP) content was quantified using an AVP radioimmunoassay and the expression of vasopressin mRNA in the supraoptic (SON) and paraventricular (PVN) nuclei was measured using real-time PCR. Mild hypertension was observed after 2 weeks of ethanol treatment when compared with control animals. Moreover, an increase in both the expression of vasopressin mRNA and the vasopressin blood content was observed in ethanol-treated rats in comparison to the control group. Basal blood pressure levels of ethanol-treated animals were significantly reduced by IV treatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP. However, dTyr(CH2)5(Me)AVP had no effect on the blood pressure of control animals. The results indicate that mild hypertension is already observed at an early phase of ethanol consumption in rats. Because the content of circulating vasopressin was increased in ethanol-treated rats and their basal blood pressure returned to control levels after IV treatment with a V1-vasopressin receptor antagonist, it is proposed that increased circulating vasopressin content may mediate the hypertension observed in ethanol-treated rats.


Alterations in the sleep-waking cycle induced by cooling of the locus coeruleus area.
Bilateral or unilateral, localized and reversible cooling (+10 degrees C) of the anterior part of the locus coeruleus area (LCp) in the cat induced, in rapid succession, slow wave sleep (SWS) and a transitory phase of SWS + PGO. These states of sleep were followed in 40-50% of the animals by paradoxical sleep (PS). These effects (on SWS, SWS + PGO and PS) occurred following repetitive periods of short duration cooling and were maintained during long duration cooling (70 min). Unilateral cooling of the ventral part of the locus coeruleus area (LC alpha) and peri-LC alpha induced wakefulness, regardless of the states of sleep in which the cooling was performed. After a cryolesion (-24 degrees C) of the nucleus raphe dorsalis, cooling of the LCp did not induce a hypnogenic effect. Electrical stimulation of the locus coeruleus area, however, always induced wakefulness.


Gene expression changes occurring at bolting time are associated with leaf senescence in Arabidopsis.
In plants, the vegetative to reproductive phase transition (termed bolting in Arabidopsis) generally precedes age-dependent leaf senescence (LS). Many studies describe a temporal link between bolting time and LS, as plants that bolt early, senesce early, and plants that bolt late, senesce late. The molecular mechanisms underlying this relationship are unknown and are potentially agriculturally important, as they may allow for the development of crops that can overcome early LS caused by stress-related early-phase transition. We hypothesized that leaf gene expression changes occurring in synchrony with bolting were regulating LS. ARABIDOPSIS TRITHORAX (ATX) enzymes are general methyltransferases that regulate the adult vegetative to reproductive phase transition. We generated an atx1, atx3, and atx4 (atx1,3,4) triple T-DNA insertion mutant that displays both early bolting and early LS. This mutant was used in an RNA-seq time-series experiment to identify gene expression changes in rosette leaves that are likely associated with bolting. By comparing the early bolting mutant to vegetative WT plants of the same age, we were able to generate a list of differentially expressed genes (DEGs) that change expression with bolting as the plants age. We trimmed the list by intersection with publicly available WT datasets, which removed genes from our DEG list that were atx1,3,4 specific. The resulting 398 bolting-associated genes (BAGs) are differentially expressed in a mature rosette leaf at bolting. The BAG list contains many well-characterized LS regulators (ORE1, WRKY45, NAP, WRKY28), and GO analysis revealed enrichment for LS and LS-related processes. These bolting-associated LS regulators may contribute to the temporal coupling of bolting time to LS.


Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function.
Somatotropin (GH) and insulin (INS) low dose, long-term brain rejuvenation effect was studied in the cerebral cortex using NE, EPI, DA and 5-HT receptor subtypes of young (group I-treatment started 4 weeks continued to 16 weeks) and old rats (group II-treatment started 60 weeks continued to 90 weeks). GH and INS treatment showed significant decrease in NE and EPI content in cerebral cortex of both young and old rats. alpha(2A)-adrenergic receptors showed decreased expression whereas beta(2)-adrenergic receptors showed enhanced expression with age. GH and INS treatment significantly increased alpha(2A)-adrenergic receptor protein in group I rats whereas INS treatment could increase beta(2)-adrenergic receptor protein expression in group II rats. DA and 5-HT content decrease with age. GH and INS administration showed increase in DA and 5-HT content in the brain regions-corpus striatum and brainstem of both young and old rats. Also, DA D(2) and 5-HT(2C) receptor gene expression were increased significantly by GH and INS treatment in both young and old rats. In conclusion, low dose, long-term treatment of INS and GH to ageing rats improved the adrenergic, dopaminergic and serotonergic receptor subtypes activity and rejuvenation of brain function.


Sertindole antagonizes morphine-, cocaine-, and methamphetamine-induced place preference in the rat.
The motivational effect of sertindole, a limbic selective antipsychotic drug, was investigated in rats using a non-biased conditioned place preference method which could reliably detect the reinforcing effects of morphine, cocaine and methamphetamine. Sertindole (0.01-1.0 mg/kg, s.c.), like haloperidol and fluphenazine, produced neither place preference nor place aversion. However, sertindole, at a dose of 1.0 mg/kg, s.c., completely abolished the place preferences induced by morphine (8.0 mg/kg, i.p.), cocaine (4.0 mg/kg, i.p.) and methamphetamine (2.0 mg/kg i.p.). These results strongly suggest that sertindole itself does not induce a rewarding effect and may have therapeutic value in the treatment of drug abuse.


[Pendular test and ENG in rabbits (author's transl)].
25 rabbits are investigated by the pendular test. By an angular acceleration of 90 degrees/s2 the averaged values of the nystagmic parameters are: the amplitude 12 mm, the frequency 8 beats in a half periode, the angle velocity of the slow component 50--60 mm/s and the threshold for the pendular test 2--5 degrees/s2 and the rotationstest 1 degree/s2. There is no vestibular habituation and no fatigue. Always the nystagmic reaction is clear and reproducible.


Comparison of xpert MTB/RIF assay, line probe assay, and culture in diagnosis of pulmonary tuberculosis on bronchoscopic specimen.
In patients unable to expectorate good quality sputum or with minimal to none sputum production, bronchoscopic specimens may be collected. The objective of the study is to determine the use of Xpert MTB/RIF assay and line probe assay (LPA) in the diagnosis of pulmonary TB (PTB) using specimens collected by bronchoscopy in a tertiary care center. Bronchoscopy specimens received in the TB laboratory were processed by microscopy, Xpert MTB/RIF assay, LPA, and mycobacteria growth indicator tube (MGIT) culture. Results of MGIT culture are considered gold standard. Of the 173 specimens tested, MTB was detected in 48 (27.74%) samples by any of the above methods. Positivity in bronchoalveolar lavage was 31.4% (44/140) and in bronchial wash was 12.1% (4/33). Detection by microscopy, Xpert assay, and culture was 20 (11.56%), 45 (26.01%), and 38 (21.96%), respectively. Culture detected MTB in three additional specimens compared to Xpert assay. Xpert assay detected MTB in 45 (26%) specimens which include 10 specimens which were negative by culture. LPA detected MTB in 18 (90%) out of 20 smear-positive specimens. RIF resistance was detected in 20 (41.7%) specimens by Xpert and/or MGIT culture drug susceptibility testing (DST). Isoniazid (INH) resistance was detected in 19 specimens by LPA and MGIT culture DST. Bronchoscopy can provide alternative respiratory specimens for diagnosing PTB in patients with difficulty to expectorate sputum. The utility of Xpert MTB/RIF as a rapid, sensitive, and specific test should always be supplemented with culture in difficult-to-obtain and precious respiratory specimens. LPA plays an important role in rapid detection of INH monoresistance.


2-Aminofluorene modified DNA duplex exists in two interchangeable conformations.
One- and two-dimensional NMR shows that the carcinogen 2-aminofluorene exists in two unique, interchangeable conformations when covalently bound to a model human c-H-ras1 proto-oncogene codon 61 oligomer duplex. In one conformation the 2-aminofluorene moiety protrudes out of the major groove leaving the Watson-Crick base pairing of the cytosine and 2-aminofluorene-guanine bases intact, consistent with the ability of replicating enzymes to bypass the lesion and correctly incorporate cytosine. The second form of the modified oligomer duplex may be representative of a pre-mutagenic conformation in that the 2-aminofluorene moiety is stacked within the DNA helix, disrupting base pairing between the 2-aminofluorene-modified guanine and its complementary cytosine.


Patient reported activities after reverse shoulder arthroplasty: part II.
Reverse shoulder arthroplasty (RSA) is becoming a commonly performed procedure. Surgeons are advised to select older patients with lower demands. This study defines patient reported activities following RSA. Seventy-eight patients with 81 treated shoulders (average age 73 years; 49 women, 32 men) completed a survey asking about clinical parameters: pain, motion, strength, and 72 different activities. Diagnoses were rotator cuff tear arthropathy in 70 shoulders, massive rotator cuff tears with psuedoparalysis in 6, and failed treatment for proximal humeral fractures in 5. Average time from surgery to survey was 3.6 years (range, 3-5). All clinical parameters were favorable. The 3 most commonly reported activities were low demand (cooking, baking, and driving), medium demand (gardening, leaf raking, and lawn mowing), and high demand (snow shoveling, wheelbarrow use, and dirt shoveling). These were comparable to the activities reported for total shoulder arthroplasty and hemiarthroplasty. There was no clinical or activity difference between those components with a lateral or a medial center of rotation. A significant proportion of patients continue medium or high demand activities following RSA. These are similar to other types of shoulder arthroplasties. Future studies to determine the safety level of different activities would be helpful to counsel patients accordingly.


Call-handlers' working conditions and their subjective experience of work: a transversal study.
The present study sought to describe call-center working conditions and call-handlers' subjective experience of their work. A transversal study was performed in companies followed by the 47 occupational physicians taking part. A dedicated questionnaire included one part on working conditions (work-station organization, task types, work schedules, and controls) and another on the perception of working conditions. Psychosocial risk factors were explored by three dimensions of the Karasek questionnaire, decision latitude, psychological demands and social support. A descriptive stage characterized the population and quantified the frequency of the various types of work organization, working conditions and perception. Certain working conditions data were crossed with perception data. The total sample comprised 2,130 call-handlers from around 100 different companies. The population was 71.9% female, with a mean age of 32.4 years. The general educational level was high, with 1,443 (68.2%) of call-handlers having at least 2 years' higher education; 1,937 of the workers (91.2%) had permanent work contracts. Some working situations were found to be associated with low decision latitude and high psychological demands: i.e., where the schedule (full-time or part-time) was imposed, where the call-handlers had not chosen to work in a call-center, or where they received prior warning of controls. Moreover, the rate of low decision latitude and high psychological demands increased with seniority in the job. The rate of low decision latitude increased with the size of the company and was higher when call duration was imposed and when the call-handlers handled only incoming calls. The rate of high psychological demands was higher when call-handlers handled both incoming and outgoing calls. This study confirmed the high rate of psychosocial constraints for call-handlers and identified work situations at risk.


Pool Testing for COVID-19: Suitable Splitting Procedure and Pool Size for India.
Coronavirus disease (COVID-19) has emerged as a global pandemic for public health due to the large scale outbreak, therefore there is an urgent need to detect the infected cases quickly and isolate them in order to suppress the further spread of the disease. This study tries to identify a suitable pool testing method and algorithm for COVID-19. This study tries to derive a general equation for the number of tests required for a pooled sample to detect every infected individual in the specific pool. The gain in pool testing over the normal procedure is quantified by the percentage of tests required compared to individual testing. The percentage of tests required by the pool testing strategy varies according to the different splitting procedures, the size of the pooled sample, and the probability of an individual being infected in the population. If the probability of infection is 0.05, then for a pool size of 32, only 14 tests are sufficient to detect every infected individual. The number of tests required to detect infected individuals by using the pooling method is much lower than individual testing. This may help us with increasing our testing capacity for COVID-19 by testing a large number of individuals in less time with limited resources.


Isozyme variations in acetaldehyde dehydrogenase (e.c.22.214.171.124) in human tissues.
NAD-dependent acetaldehyde dehydrogenase (ALDH) of human tissues was investigated by electrophoresis and enzyme assay. ALDH is located mainly in the liver and kidney. The isozymes consist of at least six different components. Five different phenotypes were found in a total of 68 human liver and kidney specimens. It is likely that three isozyme sets are concerned in determining ALDH types. The distribution of various phenotypes of ALDH isozyme sets is presented.


Metastable tert-butylcalix[6]arene with unusually large tunable free volume for non-threshold enclathration of volatiles.
A metastable material with tunable free volume of molecular size, vapor sorption properties of a porous sorbent and variable thermal stability was prepared from tert-butylcalix[6]arene.


Cascade In Situ Phosphorylation and One-Pot Glycosylation for Rapid Synthesis of Heptose-Containing Oligosaccharides.
We report a one-pot glycosylation strategy for achieving rapid syntheses of heptose (Hep)-containing oligosaccharides. The reported procedure was designed to incorporate an in situ phosphorylation step into an orthogonal one-pot glycosylation. Hep-containing oligosaccharides were assembled directly from building blocks with minimal effort expended on manipulation of protecting and aglycone leaving groups. The utility of our one-pot procedure was illustrated by synthesizing partial core oligosaccharide structure present in the lipopolysaccharide of Ralstonia solanacearum.


Purification of human blood basophils by negative selection using immunomagnetic beads.
A simple and rapid method for isolating highly purified and functionally intact basophils from normal human blood is described. Blood from healthy volunteers was centrifuged through a two layer Percoll density gradient. The majority of the basophils were recovered between Percoll layers with densities of 1.070 and 1.080, constituting 45.6% of total leukocytes. Lymphocytes, monocytes and neutrophils were extracted from this fraction using a panel of mabs in a direct or indirect selection procedure using immunomagnetic beads (Dynabeads) coated with sheep anti-mouse IgG. These negative immunoselection procedures produced a high yield of basophils with a mean purity of 97.8% (range 93.0-99.5%) and 97.0% (range 96.2-99.0%) using the direct and indirect method, respectively. The cells isolated by this method are viable, release histamine to various stimuli in a normal manner, and appear morphologically normal in transmission electron microscopy.


Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department.
Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse events. With time to safe ED discharge as the outcome measure, the incremental cost-effectiveness ratios were 3.90 dollars and 387.27 dollars per hour of ED time saved for oral phenytoin versus intravenous phenytoin and for intravenous fosphenytoin versus intravenous phenytoin, respectively. Oral phenytoin is the most cost-effective loading method in most settings. Intravenous phenytoin is preferred if one is willing to pay an additional 20.65 dollars to 44.25 dollars per patient and willing to have more adverse events for a quicker average time to safe ED discharge. It is unlikely that intravenous fosphenytoin is justifiable in any setting.


Giant ossifying malignant thymoma in a child.
We present the first reported case of an ossifying pediatric thymoma. Our patient was diagnosed with a massive thymoma replacing the whole of the left thoracic cavity. Percutaneous biopsy was attempted 3 times followed by an open incisional biopsy and adjuvant chemotherapy. Complete resection required a median sternotomy and a "trap door" thoracotomy after the tumor failed to respond to chemotherapy. Histology confirmed World Health Organization type B1 lymphocyte-rich thymoma, Masaoka stage I, with extensive osseous metaplasia.


Permeability and functionality of pancreaticogastrostomy after pancreaticoduodenectomy with dynamic magnetic resonance pancreatography after secretin stimulation.
The aim of this study was to evaluate pancreatogastrostomy (PG) permeability after duodenopancreatectomy (PD) and to determine a correlation with pancreatic endocrine and exocrine functions. This prospective study included 19 patients who underwent PD with PG between 1992 and 1999. There were 12 men and 7 women, with a mean age of 58 years (range 35 to 76 years). The mean interval between operation and evaluation was 40.3 months (range 3 to 104 months). Indications for pancreatectomy were benign lesions (n = 13) or adenocarcinoma (n = 6). Histology of the pancreatic resection margin was normal in all patients with malignancy, and the pancreatic remnant was macroscopically normal without evidence of obstructive pancreatitis. Pancreatic exocrine and endocrine functions were respectively evaluated by fecal-1 elastase and fasting blood glucose concentrations. PG permeability was determined by secretin magnetic resonance cholangiopancreatography (Secretin-MRCP). Anastomotic permeability was considered good in seven patients (group 1, 36.8%), moderately stenosed in six patients (group 2, 31.6%), significantly stenosed in four patients (group 3, 21.1%), and obstructed in two patients (group 4, 10.5%). Fecal-1 elastase concentration was decreased in 18 patients, with a mean concentration of 80 microg/g in group 1, 98 microg/g in group 2, 67 microg/g in group 3, and 0 microg/g in group 4. There was a statistically significant correlation between Secretin-MRCP group and fecal-1 elastase concentration. Results of fasting glucose estimation were normal for 14 of 19 patients. There was no correlation between pancreatic endocrine function and Secretin-MRCP group. Exocrine pancreatic insufficiency was presented in 95% of the patients despite a PG permeability in 68.4%. These results may be explained in part by neutralization of pancreatic enzymatic secretions by gastric acid.


Lifetime direct medical costs of treating type 2 diabetes and diabetic complications.
Lifetime direct medical cost of treating type 2 diabetes and diabetic complications in the U.S. is unknown. This study provides nationally representative estimates of lifetime direct medical costs of treating type 2 diabetes and diabetic complications in people newly diagnosed with type 2 diabetes, by gender and by age at diagnosis. A type 2 diabetes simulation model was used to simulate the disease progression and direct medical costs among a cohort of newly diagnosed type 2 diabetes patients. The study sample used for the simulation was based on data from the 2009-2010 National Health and Nutritional Examination Survey. The costs of treating type 2 diabetes and diabetic complications were derived from published literature. Annual medical costs were accumulated over the life span of type 2 diabetes to determine the lifetime medical costs. All costs were calculated from a healthcare system perspective, and expressed in 2012 dollars. In men diagnosed with type 2 diabetes at ages 25-44 years, 45-54 years, 55-64 years, and ≥ 65 years, the lifetime direct medical costs of treating type 2 diabetes and diabetic complications were $124,700, $106,200, $84,000, and $54,700, respectively. In women, the costs were $130,800, $110,400, $85,500, and $56,600, respectively. The age-gender weighted average of the lifetime medical costs was $85,200, of which 53% was due to treating diabetic complications. The cost of managing macrovascular complications accounted for 57% of the total complication cost. Over the lifetime, type 2 diabetes imposes a substantial economic burden on healthcare systems. Effective interventions that prevent or delay type 2 diabetes and diabetic complications might result in substantial long-term savings in healthcare costs.


Price elasticity of demand for manufactured cigarettes and roll-your-own cigarettes across socioeconomic status groups in Thailand.
Pricing policies have been proven to be effective in reducing tobacco consumption. However, studies investigating the effectiveness of pricing policies across different types of tobacco products and socioeconomic status (SES) groups are limited, particularly in low-income and middle-income countries. This study aimed to quantify the price elasticity of demand for different types of cigarettes across different SES groups. This study used data from a nationally representative survey in Thailand conducted in 2017 and included current smokers aged at least 15 years. To quantify the price elasticity of demand for cigarette consumption, a two-part model was employed for five different types of cigarettes: domestic and imported manufactured cigarettes with a low and high price, and roll-your-own cigarettes. Personal income was used to determine SES. Price elasticity of demand for cigarettes exists for all types of cigarettes. The price elasticity of demand for manufactured and roll-your-own cigarettes was -0.49 (p<0.05) and -0.32 (p<0.05), respectively. People who smoked domestic manufactured cigarettes were more responsive to price change than those who smoked imported manufactured cigarettes. Low-income smokers of manufactured and roll-your-own cigarettes were more responsive to price change than those with high income. Smokers with a low income were more responsive to price change than those with higher income. The effectiveness of pricing policy in reducing demand for manufactured cigarettes was greater in domestic cigarettes than imported ones.


Environmental impact of accelerated clinical care in a high-volume center.
"Fast-track" surgery, involving multimodal care, improves efficiency and short-term outcomes in patients undergoing bowel resection. The sustainability of the benefits and the "drag" effect on non-participating surgeons through changed nursing and resident practice is undetermined. 297 consecutive elective colon resections (DRG149) within three study periods (pre-change, immediate post-change, long-term post-change) were retrospectively reviewed. Two surgeons began to "fast-track" their patients in 1999 independently from the other surgeons in the hospital. Surgeons were grouped into "fast-track surgeons," "high-volume surgeons," (>/=10 cases per year) and "low-volume surgeons," (<10 cases per year). Comparisons of duration of stay (DOS), readmission rates, and mortality were made for each of three time periods and surgeon groups. Trends were also compared with unrelated hospital non-colectomy control groups (uncomplicated craniotomy DRG 001 and pancreatic surgery DRG 192) and to a colectomy control group from a statewide database (DRG 149). Mean DOS for colon resection significantly decreased among the "fast-track" surgeons and among all the other surgeons in the hospital, from 6.3 +/- 0.3 days, down to 3.7 +/- 0.1 days. We found no significant difference in mortality or readmission rates between the study periods. 15% of the cases were performed laparoscopically, and the improvements in outcome were independent of surgical technique. Control group analyses demonstrated that the environmental impact on outcome was independent of hospital-wide or regional improvement efforts. Implementation of a new practice pattern in a shared environment leads to improved outcomes for patients of other surgeons within the same environment. Dissemination and cross-pollination of new methods through resident, nurse, and case manager practice pattern modification creates a favorable force for change and this impact is sustained over a 3-year period.


Wolbachia induce cytoplasmic incompatibility and affect mate preference in Habrobracon hebetor to increase the chance of its transmission to the next generation.
Wolbachia are common intracellular bacteria that are generally found in arthropods, including a high proportion of insects and also some nematodes. This intracellular symbiont can affect sex ratio with a variety of reproductive anomalies in the host, including cytoplasmic incompatibility (CI) in haplodiploids. In this study, we questioned if the parasitoid wasp, Habrobracon hebetor (Hym.: Braconidae), an important biological control agent of many lepidopteran larvae, is infected with Wolbachia. To test this, DNA was extracted from adult insects and subjected to PCR using specific primers to Wolbachia target genes. The results showed a high rate of Wolbachia infection in this parasitoid wasp. To determine the biological function of Wolbachia in H. hebetor, we removed this bacterium from the wasps using antibiotic treatment (cured wasps). Results of crossing experiments revealed that Wolbachia induced CI in H. hebetor in which cured females crossed with infected males produced only males, while both male and female progeny were observed for other crosses. Also, we showed that the presence of Wolbachia in females increased fecundity and female offspring of this parasitoid wasp. The presence of Wolbachia in the males had no significant effect on fecundity and female production, but might have incurred costs. We also investigated the effect of Wolbachia on mate choice and found that Wolbachia affects mating behavior of H. hebetor. Together, we showed that Wolbachia induces CI in H. hebetor and affects host mating behavior in favor of its transmission. Wolbachia utilize these strategies to increase the frequency of infected females in the host population.


Superior Visualization of Neovascularization with Silent Magnetic Resonance Angiography Compared to Time-of-Flight Magnetic Resonance Angiography After Bypass Surgery in Moyamoya Disease.
The evaluation of postsurgical neoangiogenesis in patients with moyamoya disease (MMD) is crucial for appropriate patient management. This study aimed to assess the visualization of neovascularization after bypass surgery using noncontrast-enhanced silent magnetic resonance angiography (MRA) with ultrashort echo time and arterial spin labeling. After bypass surgery, 13 patients with MMD were followed up for >6 months between September 2019 and November 2022. They underwent silent MRA in the same session as time-of-flight magnetic resonance angiography (TOF-MRA) and digital subtraction angiography (DSA). Two observers independently rated the visualization of neovascularization in both types of MRA from 1 (not visible) to 4 (nearly equal to DSA), with reference to DSA images as the standard. The mean scores were significantly higher for silent MRA compared with TOF-MRA (3.81 ± 0.48 and 1.92 ± 0.70, respectively) (P < 0.01). The intermodality agreements were 0.83 and 0.71 for silent MRA and TOF-MRA, respectively. TOF-MRA depicted the donor artery and recipient cortical artery after direct bypass surgery, although fine neovascularization developed after indirect bypass surgery was poorly visualized. Silent MRA could reveal the developed bypass flow signal and perfused middle cerebral artery territory, which was almost equal to the DSA images. Silent MRA achieves better visualization of postsurgical revascularization in patients with MMD than TOF-MRA. Moreover, it may have the potential to provide visualization of the developed bypass flow equivalent to DSA.


S-adenosyl-l-methionine antidepressant-like effects involve activation of 5-HT1A receptors.
S-adenosyl-l-methionine (SAMe), a methyl donor, induces antidepressant effects in preclinical and clinical studies of depression. However, the mechanisms behind these effects have been poorly investigated. Since SAMe is involved in monoamine metabolism, this work aimed at 1) testing the effects induced by systemic treatment with SAMe in mice submitted to the forced swimming test (FST) and tail suspension test (TST); 2) investigating the involvement of serotonergic neurotransmission in the behavioral effects induced by SAMe. To do that, male Swiss mice received systemic injections (1 injection/day, 1 or 7 days) of imipramine (30 mg/kg), L-methionine (400, 800, 1600, and 3200 mg/kg), SAMe (10, 25, 50, 100, and 200 mg/kg), or vehicle (10 ml/kg) and were submitted to the FST or TST, 30 min after the last injection. The effect of SAMe (50 mg/kg) was further investigated in independent groups of male Swiss mice pretreated with p-chlorophenylalanine (PCPA, serotonin synthesis inhibitor, 150 mg/kg daily, 4 days) or with WAY100635 (5-HT1A receptor antagonist, 0.1 mg/kg, 1 injection). One independent group was submitted to the FST and euthanized immediately after for collection of brain samples for neurochemical analyses. Serotonin (5-HT) and noradrenaline (NA) levels were measured in the hippocampus (HPC) and prefrontal cortex (PFC). Furthermore, to investigate if the treatments used could induce any significant exploratory/motor effect which would interfere with the FST results, the animals were also submitted to the open field test (OFT). The administration of imipramine (30 mg/kg), L-methionine (400, 800, 1600, and 3200 mg/kg), and SAMe (10 and 50 mg/kg) reduced the immobility time in the FST, an effect blocked by pretreatment with PCPA and WAY100635. None of the treatments increased the locomotion in the OFT. In conclusion, our results suggest that the antidepressant-like effects induced by SAMe treatment are dependent on serotonin synthesis and 5-HT1A receptor activation.


Control of eosinopilic meningitis caused by Angiostrongylus cantonensis in China.
Rat lungworm Angiostrongylus cantonensis is the major infective agent of human eosinophilic meningitis (EM) in the world. The parasite was first noted in China in 1933. However, the public health importance was not realized until several EM outbreaks occurred recent years. Such disease is considered as emerging infectious disease in the People's Republic of China (P.R. China) since the major source of infection is invasive snail species, particularly Pomacea spp. National Institute of Parasitic Diseases (NIPD) initiated a systematic implementation research on this disease since 2003. Our researchers in NIPD developed the lung-microscopy for detecting A. cantonensis larvae in Pomacea snails and further accomplished the atlas of larval morphology by this method. We studied the determinants in infection, which helped the field collection of snails and improved the infection procedure in laboratory. Our researches promoted the promulgation of diagnosis criteria of angiostrongyliasis cantonensis by the Ministry of Health. We explored the molecular diversity of rat lungworm and its major snail host for development of source-tracing technique. The transmission modelling could provide the vulnerable area for surveillance. All the studies supported the surveillance system of EM caused by A. cantonensis in P.R. China. Such implementation research will provide a case study for control of emerging infectious diseases.


[Seckel dwarfism based on a personal case].
Report on a girl with Seckel-syndrome (bird-headed dwarfism). In addition to the known symptomatology she had a congenital heart failure (ASD II, VSD, PDA). Endocrine evaluation revealed decreased growth hormone stimulation. In the CT-scan of the skull enlarged ventricles were demonstrated.


Cell death in the inner and outer nuclear layers of the developing cat retina.
The occurrence and distribution of pyknotic profiles (dying cells) in the inner (INL) and outer nuclear layers (ONL) were mapped from radial sections through 13 kitten retinae aged from the 30th postconceptional day (30PCD) to the 81PCD (17th postnatal day). Cell death in the INL occurs in two consecutive waves, each beginning at the area centralis and proceeding toward the retinal edge. The first wave involves cells located in the inner part of the INL, adjacent to the inner plexiform layer. It begins on the 50PCD and lasts until the 66PCD, with a peak of 72,000 profiles on the 58PCD. This wave of cell death seems to be associated with the formation of the inner plexiform layer and may be due to the elimination of amacrine cells which have failed to establish sustaining connections with their appropriate target cells. The second wave involves cells located in the outer part of the INL, adjacent to the outer plexiform layer. It begins on the 60PCD and lasts until after the 81PCD, with a peak of 65,000 on the 71PCD. This wave appears to be due to the elimination of ectopic photoreceptor cells displaced by the formation of the OPL and presumably prevented from establishing sustaining connections with their appropriate target cells. A phase of cell death in the ONL begins on about the 42PCD and lasts until after the 81PCD, with a peak of 10,300 pyknotic profiles on the 60PCD.(ABSTRACT TRUNCATED AT 250 WORDS)


Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes.
Insulin-degrading enzyme (IDE) hydrolyzes bioactive peptides, including insulin, amylin, and the amyloid β peptides. Polyanions activate IDE toward some substrates, yet an endogenous polyanion activator has not yet been identified. Here we report that inositol phosphates (InsPs) and phosphatdidylinositol phosphates (PtdInsPs) serve as activators of IDE. InsPs and PtdInsPs interact with the polyanion-binding site located on an inner chamber wall of the enzyme. InsPs activate IDE by up to ∼95-fold, affecting primarily Vmax The extent of activation and binding affinity correlate with the number of phosphate groups on the inositol ring, with phosphate positional effects observed. IDE binds PtdInsPs from solution, immobilized on membranes, or presented in liposomes. Interaction with PtdInsPs, likely PtdIns(3)P, plays a role in localizing IDE to endosomes, where the enzyme reportedly encounters physiological substrates. Thus, InsPs and PtdInsPs can serve as endogenous modulators of IDE activity, as well as regulators of its intracellular spatial distribution.


Frequency doubling perimetry in glaucoma.
To evaluate the validity of frequency doubling perimetry (FDP) in the detection of glaucomatous field defects. Group I consisted of 85 eyes of 85 patients with established field defects in automated perimetry, classified by severity of defect. Group II consisted of 48 eyes of 48 control subjects. Both groups underwent Swedish Interactive Testing Algorithm (SITA) standard tests as well as FDP screening strategies (C20-1 and C20-5 and full threshold test). Sensitivity and specificity measures for the FDP tests were calculated using one new and two previously published algorithms. A described scoring system provided the best sensitivity (85.9%) and specificity (95.1%). For moderate and severe cases, the sensitivity improved to 91%. Quantification of the defect did not improve detection. FDP is a valid screening test for glaucoma. The scoring system described by Patel et al. provided the best results.


Factors influencing forces during laparoscopic pinching: Towards the design of virtual simulator.
The design of good virtual simulators for laparoscopic training requires realistic visual and tactile perception. This is a study to characterize the factors that contribute to forces during laparoscopic pinching. Surgeons were divided into four groups according to years of experience in laparoscopic surgery. They were asked to grasp six different types of porcine abdominal tissue in a randomly sequenced manner, using two different types of sensorized graspers, under two regimes of perceptual feedback (with and without visual feedback). The forces (grasper handle force and grasper tip force) and grasper handle angle were recorded and analyzed. The factors that determine forces during laparoscopic pinching can be ranked as follows: surgical experience (p < .001), tissue type (p = .007) and visual feedback (p = .033), but not grasper type (p = .071). Handle force depends significantly on surgical experience (p < .001), tissue type (p = .001) and visual feedback (p = .019), but not on grasper type (p = .203). Tip force depends significantly on surgical experience (p < .001) and marginally on tissue type (p = .082) and visual feedback (p = .053) but not on the grasper type (p = .180). Forces during laparoscopic pinching depend on surgical experience, tissue type and presence of visual feedback but not on grasper type. Our data can be an input in the design of virtual simulators with force feedback, for training laparoscopic pinching.


Recombinant human interferon gamma therapy for osteopetrosis.
A defect in leukocytic superoxide formation has been demonstrated in patients with congenital osteopetrosis. This leukocyte defect appears to be related to defective bone resorption. Because recombinant human interferon gamma therapy enhances superoxide production in patients with chronic granulomatous disease, we sought to determine whether a similar strategy could reverse the osteopetrotic condition. Interferon gamma, 1.5 micrograms/kg three times a week, was administered by subcutaneous injection for 6 months to eight patients with osteopetrosis. Urinary hydroxyproline and urinary calcium excretion increased markedly during therapy in parallel with a significant decrease in trabecular bone volume. Bone marrow scans demonstrated increased bone marrow production. The hemoglobin concentration, platelet count, and leukocyte production of superoxide increased significantly. No serious infections were encountered during the therapy. These data suggest that interferon gamma administration enhances bone resorption and leukocyte function in patients with osteopetrosis.


FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism.
Human genome-wide association studies have identified FAN1 and several DNA mismatch repair (MMR) genes as modifiers of Huntington's disease age of onset. In animal models, FAN1 prevents somatic expansion of CAG triplet repeats, whereas MMR proteins promote this process. To understand the molecular basis of these opposing effects, we evaluated FAN1 nuclease function on DNA extrahelical extrusions that represent key intermediates in triplet repeat expansion. Here, we describe a strand-directed, extrusion-provoked nuclease function of FAN1 that is activated by RFC, PCNA, and ATP at physiological ionic strength. Activation of FAN1 in this manner results in DNA cleavage in the vicinity of triplet repeat extrahelical extrusions thereby leading to their removal in human cell extracts. The role of PCNA and RFC is to confer strand directionality to the FAN1 nuclease, and this reaction requires a physical interaction between PCNA and FAN1. Using cell extracts, we show that FAN1-dependent CAG extrusion removal relies on a very short patch excision-repair mechanism that competes with MutSβ-dependent MMR which is characterized by longer excision tracts. These results provide a mechanistic basis for the role of FAN1 in preventing repeat expansion and could explain the antagonistic effects of MMR and FAN1 in disease onset/progression.


Selective use of ultrasonographic vascular mapping in the assessment of patients before haemodialysis access surgery.
Use of routine preoperative ultrasonography to determine the optimum site for haemodialysis access surgery increases the number of distal arteriovenous fistulas formed and improves overall patency rates. Nevertheless its use in all patients is time consuming and costly. This study examined whether clinical parameters could be used to determine the requirement for preoperative ultrasonography. Between March 2002 and October 2003, 145 consecutive patients were reviewed in the vascular access clinic. Patients were first assessed clinically, a site for vascular access surgery was proposed, and the need for radiological mapping studies recorded. A second, blinded, clinician determined the site for vascular access surgery using ultrasonography. The correlation between clinical and ultrasonographic findings was then examined. Ultrasonography was considered unnecessary using clinical criteria in 106 patients. Subsequent ultrasonographic mapping altered the management of only one patient. In contrast, the management of 18 of the 39 patients in whom ultrasonography was thought necessary was influenced by radiological imaging. A 1-year primary patency rate of 77.0 per cent was achieved following vascular access surgery on the study population. Clinical parameters could be used to determine the need for preoperative vascular ultrasonographic mapping; imaging was not required in the majority of patients.


Isolation and hydroxylysine glycoside content of some cyanogen bromide-cleaved fragments of collagen from bovine corneal stroma.
Six CNBr-cleaved fragments of insoluble collagen from bovine cornea were isolated, characterized and examined for hydroxylysine glycosides. Thus the general distribution of most of the glycoside along the collagen molecule was determined. Collagen from bovine stroma is almost entirely type I. This work forms a basis for the pinpointing of glycoside-attachment sites along the collagen molecules of bovine cornea.


Physical conditioning in children and adolescents with cerebral palsy: Systematic review and meta-analysis.
Cerebral palsy (CP) can be described as a group of permanent non-progressive disorders that occur in the developing fetal or infant brain. Studies have shown that children and adolescents with CP have low cardiorespiratory fitness and higher energy expenditure during daily activities when compared to typical children. Therefore, interventions focused on the physical conditioning of this population could be critical. To evaluate the effect of physical conditioning training on distance walked and maximum oxygen consumption (VO₂ max) in individuals with CP, through a systematic review. Two independent researchers performed systematic searches in the PUBMED, SciELO, PEDro, ERIC, and Cochrane databases using the search terms "physical fitness", "aerobic training" or "endurance" combined with "cerebral palsy". (1) population (children and adolescents with CP between 5 and 18 years old); (2) type of study (experimental studies); (3) type of intervention (physical conditioning protocols); (4) outcome (distance walked in the 6 min walking test - 6MWT, and VO₂ max). 386 studies were identified and 5 articles were considered eligible. After physical conditioning training, there was an increase of 46.34 m (p = 0.07) and 5.93. ml. kg-1. min -1 (p < 0.001) in the 6MWT and VO₂ max, respectively. Physical conditioning training appears to be clinically beneficial to the cardiorespiratory fitness of children and adolescents with CP.


Long-standing prion dementia manifesting as posterior cortical atrophy.
Prion diseases commonly manifest with the phenotype of subacute myoclonic encephalopathy. However, genetic forms of prion disease may have prolonged evolution mimicking neurodegenerative disease. We present the clinical and neuropathological features of a family with an early and long-standing dementia manifesting with posterior cortical atrophy and related to a 120 bp insertional mutation of the prion protein gene. Two cases exhibited mixed prion and Aβ pathology. The differential diagnosis with Alzheimer disease is discussed.


Change in incidence rates for psychosis in different ethnic groups in south London: findings from the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) study.
A higher incidence of psychotic disorders has been consistently reported among black and other minority ethnic groups, particularly in northern Europe. It is unclear whether these rates have changed over time. We identified all individuals with a first episode psychosis who presented to adult mental health services between 1 May 2010 and 30 April 2012 and who were resident in London boroughs of Lambeth and Southwark. We estimated age-and-gender standardised incidence rates overall and by ethnic group, then compared our findings to those reported in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses (ÆSOP) study that we carried out in the same catchment area around 10 years earlier. From 9109 clinical records we identified 558 patients with first episode psychosis. Compared with ÆSOP, the overall incidence rates of psychotic disorder in southeast London have increased from 49.4 (95% confidence interval (CI) 43.6-55.3) to 63.1 (95% CI 57.3-69.0) per 100 000 person-years at risk. However, the overall incidence rate ratios (IRR) were reduced in some ethnic groups: for example, IRR (95% CI) for the black Caribbean group reduced from 6.7 (5.4-8.3) to 2.8 (2.1-3.6) and the 'mixed' group from 2.7 (1.8-4.2) to 1.4 (0.9-2.1). In the black African group, there was a negligible difference from 4.1 (3.2-5.3) to 3.5 (2.8-4.5). We found that incidence rates of psychosis have increased over time, and the IRR varied by the ethnic group. Future studies are needed to investigate more changes over time and determinants of change.


Anorexia of aging.
Anorexia of aging is a physiologic decrease in food intake, which gradually leads to weight loss accompanied by age-related changes in body composition. Animal experiments have revealed that advanced age is associated with altered regulation of food intake and energy homeostasis: suppression of orexigenic mechanisms mediated by neuropeptide Y, orexins, and ghrelin, and by increased activity of the major anorexigenic neuropeptide, α-MSH. In the elderly, a reduced sense of smell and taste may contribute to the loss of appetite, and in old humans, increased serum cholecystokinin concentration may delay gastric emptying resulting in a prolonged feeling of satiety. Although leptin and insulin play a major role in the control of energy homeostasis, their role in the loss of body weight in healthy elderly persons remains to be established. In some of the elderly, loss of body mass may result in malnutrition or even cachexia. Anorexia of aging plays some role in sarcopenia, involuntary loss of muscle mass and strength; however, there are intrinsic age-related changes in skeletal muscle, which underlie this health-endangering condition. Currently, there is no efficient pharmacological treatment for the anorexia of aging; however, it may be partially prevented by improved processing and presenting of food, physical training, and an appropriate social environment.


UV-induced second readout of LiF thermoluminescent dosimeters in the therapeutic dose range.
A previously developed technique for reading out LiF thermoluminescent dosimeters (TLD) a second and subsequent time by means of ultraviolet (UV)-induced repopulation of dosimetry traps was studied to determine the feasibility of maintaining a second readout capability in a radiotherapy clinical setting. It was found that with grouping of the TLDs according to second readout sensitivity, the UV-induced readout attained a precision comparable to that of the initial readout. However, the UV-induced TL response retained a strong previous dose memory following a standard high-temperature anneal, and routine calibration before each reuse is recommended.


Portal-hepatic venous malformation: ultrasound, computed tomographic, and angiographic findings.
A 59-year-old woman was evaluated for a mass in the right lobe of the liver. Ultrasonography (US) demonstrated multiple anechoic areas with enlargement of portal and hepatic veins. These areas were enhanced uniformly after bolus injection of contrast material during computed tomography (CT). The diagnosis of portal-hepatic venous fistula was confirmed by the portal venous phase of a superior mesenteric angiogram.


Identification of a region of the tobacco mosaic virus 126- and 183-kilodalton replication proteins which binds specifically to the viral 3'-terminal tRNA-like structure.
UV irradiation of a mixture of an isolated tobacco mosaic virus (TMV; tomato strain L [TMV-L]) RNA-dependent RNA polymerase complex and the TMV-L RNA 3'-terminal region (3'-TR) resulted in cross-linking of the TMV-L 126-kDa replication protein to the TMV-L 3'-TR. Using both Escherichia coli-expressed proteins corresponding to parts of the 126-kDa protein and mutants of the 3'-TR, the interacting sites were located to a 110-amino-acid region just downstream of the core methyltransferase domain in the protein and a region comprising the central core C and domain D2 in the 3'-TR. Mutation to alanine of a tyrosine residue at position 409 or a tyrosine residue at position 416 in the protein binding region abolished cross-linking to the 3'-TR, and corresponding mutations introduced into TMV-L RNA abolished its ability to replicate in tomato protoplasts, with no detectable production of either plus- or minus-strand RNA. The results are compatible with a model for initiation of TMV-L minus-strand RNA synthesis in which an internal region of the TMV-L 126-kDa protein first binds to the central core C and domain D2 region of the TMV-L 3'-TR and is then followed by binding of the 183-kDa protein to this complex and positioning of the catalytically active site of the polymerase domain close to the 3'-terminal CCCA initiation site.


Potential roles of insulin and IGF-1 in Alzheimer's disease.
Aging is characterized by a significant decline of metabolic and hormonal functions, which often facilitates the onset of severe age-associated pathologies. One outstanding example of this is the reported association of deranged signaling by insulin and insulin-like-growth-factor 1 (IGF-1) with Alzheimer's disease (AD). Recent compelling biological data reveal effects of insulin and IGF-1 on molecular and cellular mechanisms underlying the pathology of AD. This review discusses available biological data that highlight the therapeutic potential of the insulin-IGF-1 signaling pathway in AD.


Intracellular IL-1Ra type 1 inhibits IL-1-induced IL-6 and IL-8 production in Caco-2 intestinal epithelial cells through inhibition of p38 mitogen-activated protein kinase and NF-kappaB pathways.
Interleukin-1 (IL-1) plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). IL-1 action is regulated in part by its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1Ra). Four splice variants of IL-1Ra gene product have been described, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3). Although sIL-1Ra and icIL-1Ra1 bind to type I IL-1 receptor with equal affinity, icIL-1Ra1 may carry out unique functions inside cells. The goal of this study was to determine the role of icIL-1Ra1 in regulation of cytokine-induced IL-6 and IL-8 production in Caco-2 intestinal epithelial cells. icIL-1Ra1 inhibited IL-1-induced IL-6 and IL-8 production. IL-1 activated all three mitogen-activated protein (MAP) kinase family members: p38 MAP kinase, extracellular-regulated kinases (ERK), and c-Jun amino-terminal kinases (JNK). Specific inhibitors of each MAP kinase pathway decreased IL-1-induced IL-6 and IL-8 production. Overexpression of icIL-1Ra1 inhibited p38 MAP kinase phosphorylation, but had no effect on ERK and JNK phosphorylation. In addition, icIL-1Ra1 inhibited nuclear translocation of NF-kappaB after IL-1 stimulation. In conclusion, these data indicate that icIL-1Ra1, acting in the cytoplasm of Caco-2 cells, decreased IL-1-induced IL-6 and IL-8 production. This intracellular anti-inflammatory activity of icIL-1Ra1 was mediated through inhibition of p38 MAP kinase and NF-kappaB signal transduction pathways.


[First experiences with temporary vena cava filters].
For prophylactic measures we used 3 different temporarily insertable vena cava filters. In 49 patients we inserted 12 Cook-filters (6 transjugular, 6 transfemoral), 11 Angio-cor-filters (1 transjugular, 10 transbrachial), 26 Antheor-filters (1 transjugular, 1 transfemoral, 24 transbrachial). 35 patients underwent a lysis therapy, 11 a major operation of the pelvis, and 3 patients a Caesarean section. No patient suffered from a clinically significant pulmonary embolism after filter insertion, but complications occurred caused by the basic therapy (1 lethal abdominal aortic aneurysm operation, 1 cerebral bleeding, 2 retroperitoneal haematomas, 2 streptokinase fever reactions, 1 compartment syndrome, 1 macro-haematuria) or by therapy joined with the filters insertion (2 groin haematomas, 2 haematomas of the bend of the elbow, 2 subclavian vein thrombosis, 1 catheter dislocation, 1 infection, 1 air embolism, 1 break of a leg of the filter basket). Temporary vena cava filters are highly efficient in preventing pulmonary embolism, but the side-effects show that they should only be inserted in patients with known deep vein thrombosis and a high risk treatment of the underlying disease.


Assessment of atmospheric heavy metal pollution in Qinghai-Tibet Plateau: Using mosses as biomonitor.
Atmospheric heavy metal (HM) pollution may pose a significant threat to the fragile ecosystem of Qinghai-Tibet Plateau (QTP). To investigate potential atmospheric HM pollution within the QTP region of China, mosses, along with other higher plants and soil, were collected from 33 sites for heavy metal measurement. The concentration ranges of Zn, Pb, Cd, and Cu in mosses were 6.07-69.9, 5.36-23.9, 0.60-1.05, and 14.4-50.5 mg·kg-1 (dry weight), respectively, significantly higher than those in other higher plants, except for Zn. The spatial distribution of relative concentrations (RCs; moss to top soil) of HMs varied considerably, indicating distinct differences in atmospheric Zn and Cu pollution levels between the northern and southern QTP. This study first reported that moderate regional atmospheric Cu pollution, primarily due to large-scale mining in recent years, had occurred, particularly in southern QTP. Pb also presented slight pollution due to anthropogenic activities. However, Cd showed almost no atmospheric pollution, while Zn concentrations were relatively high in southern QTP. Although less severe than atmospheric pollution levels in Chinese inland or coastal cities, the atmospheric pollution of Pb and Cu in QTP indicated by mosses were far more severe than global background areas, or even worse than most European cities.


Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility.
The incidence of multiple sclerosis (MS) is rising in women. To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. We identified 400 women with incident MS/CIS and 3904 matched controls. Forty- percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.


Attributes of Psychosocial Distress from the Perspectives of Head-and-Neck Cancer Patients - A Thematic Analysis.
Patients diagnosed with head-and-neck cancer (HNC) face unique challenges in comparison to other types of cancers. Sources of psychosocial distress (PSD) are multifactorial and recognising the key attributes would facilitate better understanding of the experienced distress, potentially enabling directed intervention strategies. The present research was conducted to explore the key attributes of PSD from HNC patients' perspective to develop a tool. The study adopted a qualitative approach. The data were collected from nine HNC patients receiving radiotherapy through focus group discussion. Data were transcribed, read and reread through for searching the meanings and patterns, to familiarise with the data and obtain ideas on experiences related to PSD. Similar experiences identified across the dataset were sorted and then collated into themes. Detailed analysis of themes and related quotes of the participants are reported with each theme. The codes generated from the study are grouped under four major themes; 'Irksome symptoms are distressing,' 'Distressing physical disability inflicted by the situation,' 'Social Curiosity - a distressing element' and 'Distressing uncertainty of future'. The attributes of PSD and the magnitude of psychosocial problems were reflected in the findings. Psychosocial health of HNC patients is greatly impacted due to disease and/or treatment. Dynamic patterns of attributes identified from the study contributed to developing a tool on PSD. The findings of this study also necessitate the need for constructing an intervention for reducing PSD based on the attributes from the HNC patient's perspective.


Alterations in the conjunctival surface bacterial microbiome in bacterial keratitis patients.
Microbial keratitis is an infectious disease of the eye, in which the cornea is inflamed. Under severe conditions, keratitis can lead to significant loss of vision and enucleation of the eye. Ocular trauma is the major risk factor causing keratitis and microorganisms viz., bacteria, fungi, viruses are the causative agents. The current study characterized the conjunctival bacterial microbiomes of healthy individuals and individuals with bacterial keratitis (BK) and assessed whether ocular microbiome dysbiosis is prevalent in BK patients. Ocular bacterial microbiomes were generated from the conjunctival swabs of healthy controls (HC-SW) and conjunctival swabs (BK-SW) and corneal scrapings (BK-CR) of BK patients using V3-V4 amplicon sequencing and data analysed using QIIME and R software. The Alpha diversity indices, diversity and abundance of different phyla and genera, heat map analysis, NMDS plots and inferred functional pathway analysis clearly discriminated the bacterial microbiomes of conjunctival swabs of healthy controls from that of BK patients. Preponderance of negative interactions in the hub genera were observed in BK-CR and BK-SW compared to HC-SW. In addition, a consistent increase in the abundance of pathogenic bacteria, as inferred from published literature, was observed in the conjunctiva of BK patients compared to HC and this may be related to causing or exacerbating ocular surface inflammation. This is the first study demonstrating dysbiosis in the ocular bacterial microbiome of conjunctiva of bacterial keratitis patients compared to the eye of healthy controls. The bacterial microbiome associated with the corneal scrapings of keratitis individuals is also described for the first time.


Light-Fueled Polymer Film Capable of Directional Crawling, Friction-Controlled Climbing, and Self-Sustained Motion on a Human Hair.
Recent efforts in stimuli-responsive soft materials have enabled wirelessly controlled actuation with increasing degrees of freedom, yielding miniature robots capable of various locomotion in open environments such as on a plane or inside fluids. However, grand challenges remain in harnessing photomechanical deformation to induce locomotion and control of friction during the movement, especially for robotic actuations within constrained spaces. Here, the authors report a centimeter-long polymer strip made of a liquid crystal network that is capable of versatile light-fueled motions along a human hair. The soft polymer robot can translocate directionally upon temporally modulated excitation and climb vertically through friction control with light. A self-oscillating strip is demonstrated to continuously translocate along the hair upon a constant light stimulus, and its gaiting is associated to the smoothness of the hair surface. The results offer new insights to small-scale photo-actuator, mechanical control, and automation in soft micro robotics.


Patient satisfaction with intravenous regional anaesthesia or an axillary block for minor ambulatory hand surgery: A randomised controlled study.
Intravenous regional anesthesia (IVRA) and the axillary brachial plexus block are popular alternatives to general anaesthesia in ambulatory hand surgery. Although both have proven their effectiveness, patients' preferences have never been evaluated. We investigated patient satisfaction with both techniques and hypothesised that satisfaction after IVRA is noninferior compared with axillary brachial plexus block. A prospective, randomised controlled trial. Ambulatory surgical day care centre, University Hospitals of Leuven, Belgium, from September 2016 to November 2017. One hundred and twenty adults undergoing minor ambulatory hand surgery were included in this study. Patients received either IVRA with 300 mg lidocaine or an axillary block with 280 mg mepivacaine. The primary endpoint was the evaluation of patient satisfaction using the 'Evaluation du Vécu de l'Anésthesie Locoregional' (EVAN-LR) questionnaire. Secondary outcomes included different procedural times, block quality, tourniquet discomfort, the incidence of block failure and postoperative nausea and vomiting (PONV), the severity of postoperative pain and the need for postoperative analgesics during the first 24 h. Noninferiority of IVRA was shown for the median [IQR] total score on the EVAN-LR questionnaire, IVRA-group: 92 [87 to 96] vs. axillary brachial plexus block-group: 91[87 to 97]; Hodges--Lehmann estimator (95% confidence interval (CI)] for the shift: -0.25 (-2.60 to 2.20). Induction of anaesthesia and time to discharge, requiring partial recovery of the motor block, were significantly longer in the axillary brachial plexus block group. The IVRA-group had a lower block quality, a higher incidence of tourniquet-discomfort and higher median intra-operative and postoperative pain scores on day 0; 0 [0 to 2] vs. 0 [0 to 0] and 0.8 [0 to 1.8] vs. 0 [0 to 0.25], respectively, but no increase in the need for supplementary analgesics or conversion rate to general anaesthesia. IVRA and axillary brachial plexus block result in comparably high patient satisfaction in ambulatory hand surgery. EudraCT 2016-002325-11.


Researchers in cardiology - Why and how to get on Twitter?
Social media (SoMe) for professional use has gained importance for scientific impact. In cardiology, Twitter is among the preferred SoMe platforms for scientific dissemination. We are in the middle of a paradigm shift within scientific dissemination as more scientific content is presented on Twitter, and it is crucial to embrace it. Therefore, this paper includes a description and discussion of the existing literature reporting the impact of Twitter on research dissemination, as well as a guide on how to get started. In addition, we describe a case of the Danish Cardiovascular Academy Summer Meeting 2021 as an example of a scientific event that was promoted on Twitter before, during and after the event and present a survey showing that participants were inspired to increase the use of SoMe professionally. Finally, the paper addresses limitations of Twitter and SoMe for scientific use and discuss a need for an increased evidence base.


A genetic explanation for ten-year cycles of grouse.
Chitty's Polymorphic Behavioural Hypothesis (Chitty 1967) was logically reduced to three main assumptions that were mathematically modelled: 1) Level of aggression is genetically determined by simple Mendelian selection. 2) Recruitment is inversely related to female parental level of aggression. 3) Aggressives are completely successful in breeding competition. The model utilized data from willow ptarmigan populations, but was generalized to other grouse species. Simulation results were indistinguishable from the behaviour of real world grouse populations lending support to Chitty's hypothesis as the explanation of cyclicity. The model also seems applicable to ther species. Eight tests that would falsify the model were identified.


Flavor preferences conditioned by intragastric polycose infusions: a detailed analysis using an electronic esophagus preparation.
The present series of experiments examined the rat's conditioned preference for flavors associated with intragastric (IG) Polycose infusions. Adult female rats were fitted with two chronic intragastric catheters and were trained to drink flavored water (CS+; e.g., cherry-water) paired with IG infusions of 32% Polycose. On alternate days a different flavor (CS-; grape-water) was paired with IG water infusions. The flavored water and chow were available 23 hr/day. In subsequent two-choice tests the rats displayed strong preferences for the CS+ flavor (up to 98%). The CS+ preference persisted for several weeks during extinction tests when both the CS+ and CS- were paired with IG water or with no infusions. The rats also preferred the CS+ to plain water which contrasts with the mild aversion naive rats display to the flavored water. The acquired preference for the CS+ flavor was not as strong, however, as the rats' innate preferences for the taste of saccharin or Polycose. Also, unlike their response to saccharin and Polycose, the rats' acceptance (absolute intake) of the CS+ flavor was not elevated. CS+ intake was increased, though, when saccharin was added to the flavored water. The rats reversed their flavor preference when the reinforcement contingencies were reversed. Also, in the absence of unique flavor cues, the rats learned to prefer, apparently based on somatosensory cues, the sipper tube that was paired with IG Polycose infusions. The effects of flavor and IG Polycose infusions on drinking patterns and caloric intake are also described.


The effect of propylthiouracil on glutathione S-transferase activity of rat spleen in vitro and in vivo.
Propylthiouracil (PTU) inhibited glutathione (GSH) S-transferase (EC 18.104.22.168) activity of rat spleens in a concentration dependent manner in vitro. PTU (1.5 mmoles/kg) treatment of rats for 1 or 2 weeks caused a decrease in leukocyte number and spleen weight. Nevertheless, GSH S-transferase activity was not affected by the same treatment.


Crystallographic changes in calcium phosphates during plasma-spraying.
Coating hydroxyapatite (HA) onto metal implant surfaces using the plasma-spraying technique has been investigated in several laboratories as a means of improving the mechanical properties of the bulk ceramic. This study describes crystallographic changes which can occur during the plasma-spraying of calcium phosphate powders. A precipitated calcium-deficient apatite and a high temperature near-stoichiometric HA were each sprayed onto metal substrate in an argon plasma using several hydrogen gas flow conditions at various temperatures. The surfaces were examined by X-ray diffraction and scanning electron microscopy. The plasma-sprayed products were identified as a mixture of calcium phosphates including HA, beta-tricalcium phosphate (beta-TCP) and calcium oxide. Stoichiometric HA when plasma-sprayed showed the least (5%) degradation. Since beta-TCP is more resorbable than HA in vivo, varying the HA/beta-TCP ratio on the plasma-sprayed surface may provide a method to control surface dissolution of the coating.


Barbara Webb.
Interview with Barbara Webb, who uses robots to model the behavioural capabilities of insects at the University of Edinburgh.


An integrated strategy for rapid discovery and identification of the potential effective fragments of polysaccharides from Saposhnikoviae Radix.
Saposhnikoviae Radix (SR) is a traditional Chinese medicine, known as "Fangfeng". As one of the main active components, Saposhnikoviae Radix polysaccharides (SP) demonstrated a range of biological activities, especially immunity regulation activity. This study aimed at exploring whether polysaccharides have activity after degradation, then discovering the potential effective fragments of SP. Here we establish the chromatographic fingerprints method for 32 batches of 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of oligosaccharides by HPLC, meanwhile evaluating its immunomodulatory activity in vivo. Then, the potential effective fragments of SP were screened out based on the spectrum-effect relationship analysis between fingerprints and the pharmacological results. Besides, liquid chromatography ion trap-time of flight mass spectrometry (LC-IT-TOF MS) coupled with multiple data-mining techniques was used to identify the potential effective oligosaccharides. These findings showed that the hydrolysate of SP have significant immunomodulatory, and the immunity regulation activity varies under different hydrolysis conditions. The 4 potential effective peaks of the hydrolysate of SP were mined by spectrum-effect relationship. Finally, the chemical structure of 4 potential effective oligosaccharide fragments of SP was elucidated based on LC-IT-TOF MS. F10 was inferred tentatively to be Hex1→6Hex1→6Hex1→6Hex1→6Hex1→6Gal; F18 was confirmed to be Rhamnose; F14 was inferred tentatively to be Hex1→4Hex1→ 4Hex1→4Gal and F25 was tentatively inferred to be Ara1→6Gal. This study may provide a sound experimental foundation in the exploration of the active fragments from macromolecular components with relatively complex structures such as polysaccharides.


Bio-refinery approach for spent coffee grounds valorization.
Although normally seen as a problem, current policies and strategic plans concur that if adequately managed, waste can be a source of the most interesting and valuable products, among which metals, oils and fats, lignin, cellulose and hemicelluloses, tannins, antioxidants, caffeine, polyphenols, pigments, flavonoids, through recycling, compound recovery or energy valorization, following the waste hierarchy. Besides contributing to more sustainable and circular economies, those products also have high commercial value when compared to the ones obtained by currently used waste treatment methods. In this paper, it is shown how the bio-refinery framework can be used to obtain high value products from organic waste. With spent coffee grounds as a case study, a sequential process is used to obtain first the most valuable, and then other products, allowing proper valorization of residues and increased sustainability of the whole process. Challenges facing full development and implementation of waste based bio-refineries are highlighted.


Outbreak of New Delhi metallo-β-lactamase-1-producing Enterobacter cloacae in an acute care hospital general ward in Singapore.
Autochthonous infections with New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have been reported in Singapore since 2011, but occurrences of nosocomial transmission have not. We report an outbreak of NDM-1-producing Enterobacter cloacae among adults admitted to an acute hospital's general ward. On detecting the index case with a culture specimen positive for NDM-1-producing E cloacae, active case finding was conducted by screening all possible patient contacts. On-site ward assessment was performed, and electronic patient medical records were reviewed to conduct a case-control study to identify factors associated with colonization. Of 55 screened patient contacts, 3 further cases were detected, with isolates genetically related to the index case. None of these 4 cases was housed within the same cubicle. However, 3 were managed by the same medical team. Being managed by this team was positively associated with being a case (adjusted odds ratio = 15.64; 95% confidence interval, 0.91-270.27; P = .06) after adjusting for age, sex, Charlson comorbidity index score, and recent antibiotic use. Our report suggests nosocomial transmission of NDM-1-producing E cloacae occurred via health care staff. Improvements in infection control measures, especially pertaining to staff hand hygiene practices and ward staffing, are needed to reduce the spread of highly resistant pathogens, such as NDM-1-producing Enterobacteriaceae.


Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels.
Bulk matrix stiffness has emerged as a key mechanical cue in stem cell differentiation. Here, we show that the commitment and differentiation of human mesenchymal stem cells encapsulated in physiologically soft (∼0.2-0.4 kPa), fully synthetic polyisocyanopeptide-based three-dimensional (3D) matrices that mimic the stiffness of adult stem cell niches and show biopolymer-like stress stiffening, can be readily switched from adipogenesis to osteogenesis by changing only the onset of stress stiffening. This mechanical behaviour can be tuned by simply altering the material's polymer length whilst maintaining stiffness and ligand density. Our findings introduce stress stiffening as an important parameter that governs stem cell fate in a 3D microenvironment, and reveal a correlation between the onset of stiffening and the expression of the microtubule-associated protein DCAMKL1, thus implicating DCAMKL1 in a stress-stiffening-mediated, mechanotransduction pathway that involves microtubule dynamics in stem cell osteogenesis.


Conductance changes during bath application of beta-alanine and taurine in giant interneurons of the isolated lamprey spinal cord.
(1) Input conductances of giant interneurons in the isolated spinal cord of lampreys were measured with two separate intracellular electrodes. Bath applications of 0.4--3 mM beta-alanine and taurine produced large, reversible conductance increases which were Cl-dependent. (2) Strychnine at 1--2.5 microM might be a competitive antagonist of both amino acids, but had a stronger effect on taurine. Bicuculline and picrotoxin were weak antagonists of beta-alanine and taurine in some cells. (3) A few giant interneurons desensitized after repeated application of the amino acids, but most became more sensitive. Responses to the amino acids also increase at low temperatures in in Na-free fluid, suggesting effect of uptake mechanisms.


Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model.
The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver. Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.