Antidepressant effects of acute sleep deprivation are reduced in highly controlled environments.
Numerous studies summarized in a recent meta-analysis have shown sleep deprivation rapidly improves depressive symptoms in approximately 50 % of individuals with major depressive disorder (MDD), however those studies were typically conducted in clinical settings. Here we investigated the effects of sleep deprivation utilizing a highly controlled experimental approach. 36 antidepressant-free individuals with MDD and 10 healthy controls (HC) completed a 5 day/4-night protocol consisting of adaptation, baseline, total sleep deprivation (TSD), and recovery phases. Light was kept consistently dim (≤50 lx), meals were regulated, and activity was restricted. In-the-moment mood was assessed using a modified Hamilton Rating Scale for Depression (HRSD) at screening and each morning following the experimental nights. Day of study had a significant effect on mood in both groups. Post-hoc analyses revealed that significant effects were attributed to mood improvement in the MDD group following study initiation prior to beginning TSD, and in the HC group following recovery sleep, but were not due to mood improvement in the MDD group during TSD. No further improvement in mood occurred during 36 h of TSD. Strict eligibility requirements may limit generalizability. The requirement to be medication free may have biased toward a less severely depressed sample. Results revealed that individuals with moderate MDD can experience a significant reduction in depressive symptoms upon entering a highly controlled laboratory environment. Environmental effects on mood can be substantial and need to be considered.


[Nerve cell clonal lines in culture--models for studying the molecular basis of neuropharmacological actions].
Nerve cell lines with stable properties are isolated from neuroblastomas, glioblastomas or pheochromocytomas by periodic cloning using defined culture media. After the action of different drugs, these cells show all morphological and biochemical signs of differentiation and maturation. Depending on the origin of the clone, the cell lines synthesise typical neurotransmitters, which are stored in vesicles. It is demonstrated on cell lines which synthesise catecholamines that noradrenergic and dopaminergic clones are particularly suitable test objects for basic research in neuropharmacology.


Insights into amphicarpy from the compact genome of the legume Amphicarpaea edgeworthii.
Amphicarpy (seed heteromorphy) is a unique and fascinating reproductive strategy wherein a single plant produces both aerial and subterranean fruits. This strategy is believed to be an adaptation to life under stressful or uncertain environments. Here, we sequenced and de novo assembled a chromosome-level genome assembly of the legume Amphicarpaea edgeworthii Benth. The 299-Mb A. edgeworthii genome encodes 27 899 protein-coding genes and is the most compact sequenced legume genome reported until date. Its reduced genome size may be attributed to the reduced long-terminal repeat retrotransposon content, which stems from the unequal homologous recombination. Gene families related to immunity and stress resistance have been contracted in A. edgeworthii, which is consistent with the notion that the amphicarpic reproductive strategy may be a complementary mechanism for its weak environmental-adaptation ability. We demonstrated the 'ABCE' model for the differentiation of chasmogamous and cleistogamous flowers. In addition, the characteristics of aerial and subterranean seeds in hard-seededness were explored. Thus, we suggest that the A. edgeworthii genome, which is the first of an amphicarpic plant, offers significant insights into its unusual reproductive strategy that is a key resource towards comprehending the evolution of angiosperms.


Evaluation of computerized provider order entry systems: assessing the usability of systems for electronic prescription.
The field of medicine has been influenced by the growth and development of information systems such as the Computerized Provider Order Entry (CPOE) System. This study aimed to evaluate the usability of CPOE systems for electronic prescription in Tehran, Iran. This was an evaluation study conducted in 2017. The research population consisted of the CPOE systems used in hospitals of Tehran (Iran) and nurses who had access to, and used, the CPOE systems. Five hospitals with CPOE systems were included in the research sample. The data were collected using a questionnaire, and included a total of 50 questions. The questionnaires were distributed among 254 nurses who were the users of the systems. Data analysis was performed by IBM-SPSS version 21, using independent-samples t-test. A p-value of ≤0.05 was considered statistically significant. Among the four aspects assessed, the "user-friendliness" (3.87±0.59) had the highest mean score. The lowest mean score (2.01±0.58) was related to the "decision support" feature of the systems. The highest and lowest mean scores for "prescription support" criterion belonged to system E (3.26±0.23) and system C (1.90±0.16), respectively. There was a statistically significant difference between the usability of the systems used in the private and the public hospitals (p<0.001). It was found that the CPOE systems in private hospitals had a higher level of usability (3.42+0.10) compared to those in public hospitals (2.91+0.25). Two main functions of the studied CPOE systems i.e., decision support and prescription support should be developed to make electronic prescription safer and more intuitive. Addressing usability aspects of CPOE systems in practice could improve the usability of these systems for prescription.


The genomic full-length sequence of the HLA-B*15:198 allele, identified by full-length group-specific sequencing.
The genomic full-length sequence of HLA-B*15:198 was identified by a group-specific sequencing approach from China.


Antibiotics for the common cold and acute purulent rhinitis.
It has long been believed that antibiotics have no role in treating common colds yet they are often prescribed in the belief that they may prevent secondary bacterial infections. Given the increasing concerns about antibiotic resistance it is important to examine the evidence for the benefit of antibiotics for the common cold. To determine:(1) the efficacy of antibiotics, in comparison with placebo, for reducing general symptoms and specific nasopharyngeal symptoms of acute upper respiratory tract infections; (2) if antibiotics have any influence on acute purulent rhinitis; (3) whether antibiotics cause significant adverse outcomes in patients with acute upper respiratory tract infections. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005); MEDLINE (January 1966 to March, Week 1, 2005); EMBASE (1980 to December 2004), the Family Medicine Database (1908, volume 1 to 1993, volume 13; this database was discontinued in 1993), and reference lists of articles, and we contacted principal investigators. Randomised trials comparing any antibiotic therapy against placebo in people with acute upper respiratory tract infections and with less than seven days of symptoms, or acute purulent rhinitis less than ten days in duration. Both authors independently assessed trial quality and extracted data. All analyses used the fixed-effect model unless otherwise stated. The overall quality of the included trials was variable. People receiving antibiotics did no better in terms of lack of cure or persistence of symptoms than those on placebo (relative risk (RR) 0.89, 95% confidence interval (CI) 0.77 to 1.04), based on a pooled analysis of six trials with a total of 1147 patients. Overall, the relative risk of adverse effects in the antibiotic group was RR 1.8 (95% CI 1.01 to 3.21), using a random-effects model. Adult patients had a significantly greater risk of adverse effects with antibiotics than with placebo (RR 2.62, 95% CI 1.32 to 5.18) (random-effects model) while there was no greater risk in children (RR 0.91, 95% CI 0.51 to 1.63). The pooled relative risk for persisting acute purulent rhinitis with antibiotics compared to placebo was 0.57 (95% CI 0.37 to 0.87) (random-effects model), based on 6 studies with 772 participants. There is insufficient evidence of benefit to warrant the use of antibiotics for upper respiratory tract infections in children or adults. Antibiotics cause significant adverse effects in adults. The evidence on acute purulent rhinitis and acute clear rhinitis suggests a benefit for antibiotics for these conditions but their routine use is not recommended.


Diltiazem does not increase the in vivo sensitivity of murine hemopoietic progenitor cells to doxorubicin.
The effect of doxorubicin and the calcium antagonist, diltiazem, on murine hemopoietic progenitor cells was studied in vivo. Dose-survival curves of murine bone marrow colony forming units (CFU)--spleen and granulocyte macrophage--were determined by in vivo and in vitro methods in DBA/2NCr/BR mice treated with doxorubicin alone or by simultaneous administration of doxorubicin (DX) and diltiazem (DTZ). Time response of bone marrow hematopoietic progenitor cells (HPC) was followed in mice similarly treated. Combination of DTZ with DX did not change the toxic effect of the latter on hemopoietic cells, either in the dose-survival model or in the time-related experiment.


Speciation of inorganic and organotin compounds in biological samples by liquid chromatography with inductively coupled plasma mass spectrometric detection.
This paper describes the effect of inorganic tin chloride on the separation of trimethyl-, tributyl- and triphenyltin-chlorides by reversed-phase ion-pair high-performance liquid chromatography with detection by inductively coupled plasma mass spectrometry. The detection limits are 1.6 pg, 1.5 pg and 2.3 pg as tin for trimethyltin, tributyltin and triphenyltin, respectively. The relative standard deviation for ten injections of 20 ng of the tin compounds was less than 5%. Inorganic tin was held strongly on the columns used, to a greater extent on the silica column compared to the polymer column. Extraction and determination of tributyltin and triphenyltin as chlorides in fish tissue (certified reference material) and tuna fish (grocery store) were performed. The recovery study from fish tissue showed an efficiency of over 90% for both tributyltin and triphenyltin and over 60% recovery for spiked tuna.


[Research Progress of Circular RNA in Lung Cancer].
Lung cancer is the most common malignant tumor with the highest morbidity and mortality worldwide, and its imposes an insupportable burden on patients due to its poor prognosis. The diagnosis and treatment of lung cancer is under great pressure. Therefore, it is urgent to explore effective therapeutic targets and molecular markers. Circular RNA (circRNA) is a kind of covalently closed non-coding RNAs, which has attracted much attention due to its conservation, stability and tissue specificity. Many studies have found that circRNA participates in the regulation of lung cancer through various mechanisms such as sponging miRNA and plays a part vital role in the early diagnosis, treatment and prognosis evaluation. In recent years, there have been numerous studies on circRNA in lung cancer. This paper summarizes the current progress of circRNA in the diagnosis, treatment and prognosis of lung cancer. .


BRAF(E600) in benign and malignant human tumours.
Of the RAF family of protein kinases, BRAF is the only member to be frequently activated by mutation in cancer. A single amino acid substitution (V600E) accounts for the vast majority and results in constitutive activation of BRAF kinase function. Its expression is required to maintain the proliferative and oncogenic characteristics of BRAF(E600)-expressing human tumour cells. Although BRAF(E600) acts as an oncogene in the context of additional genetic lesions, in primary cells it appears to be associated rather with transient stimulation of proliferation. Eventually, BRAF(E600) signalling triggers cell cycle arrest with the hallmarks of cellular senescence, as is illustrated by several recent studies in cultured cells, animal models and benign human lesions. In this review, we will discuss recent advances in our understanding of the role of BRAF(E600) in benign and malignant human tumours and the implications for therapeutic intervention.


Effect of plasma lipoproteins and lecithin-cholesterol dispersions on the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase of isolated rat hepatocytes.
Incubation of rat hepatocytes for 3 h in a medium containing amino acids, salts and albumin resulted in a 2-fold increase in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Inclusion of 10% human plasma, rat serum or dialysed rat serum in the medium resulted in an approximate 7-fold increase in reductase activity. These increases were specific since there was little change in the rate of fatty acid synthesis or in the activity of tyrosine aminotransferase. Reductase levels were increased above control values when high density lipoproteins or leithin dispersions were added to the cells. Lecithin dispersions were also shown to increase the rate of efflux of cell cholesterol to the medium. In contrast, reductase levels were reduced when cells were incubated with low density lipoproteins or cholesterol added as an equimolar cholesterol-lecithin dispersion. This inhibition of the reductase by cholesterol dispersions was dependent on the continued de novo protein synthesis. Our data indicate that in normal rat hepatocytes the relative rates of efflux and influx of cholesterol may be critical to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity and cholesterogenesis.


New insights on the role of the endocannabinoid system in the regulation of energy balance.
Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review.


Low-Frequency IL23R Coding Variant Associated with Crohn's Disease Susceptibility in Japanese Subjects Identified by Personal Genomics Analysis.
The common disease-common variant hypothesis is insufficient to explain the complexities of Crohn's disease (CD) genetics; therefore, rare variants are expected to be important in the disease. We explored rare variants associated with susceptibility to CD in Japanese individuals by personal genomic analysis. Two-step analyses were performed. The first step was a trio analysis with whole-exome sequence (WES) analysis and the second was a follow-up case-control association study. The WES analysis pipeline comprised Burrows-Wheeler Aligner, Picard, Genome Analysis Toolkit, and SAMTOOLS. Single nucleotide variants (SNVs)/indels were annotated and filtered by using programs implemented in ANNOVAR in combination with identity-by-descent (IBD), subsequently were subjected to the linkage based, and de novo based strategies. Finally, we conducted an association study that included 176 unrelated subjects with CD and 358 healthy control subjects. In family members, 234,067-297,523 SNVs/indels were detected and they were educed to 106-146 by annotation based filtering. Fifty-four CD variants common to both individuals of the affected sib pair were identified. The linkage based strategy detected five candidate variants whereas the de novo based strategy identified no variants. Consequently, five candidates were analyzed in the case-control association study. CD showed a significant association with one variant in exon 4 of IL23R, G149R [rs76418789, P = 3.9E-5, odds ratio (OR) 0.21, 95% confidence interval (CI) 0.09-0.47 for the dominant model (AA + AG versus GG), and P = 7.3E-5, OR 0.21, 95% CI 0.10-0.48 for AG versus GG, and P = 7.2E-5, OR 0.23, 95% CI 0.10-0.50 for the allele model]. The present study, using personal genomics analysis of a small CD pedigree, is the first to show that the low-frequency non-synonymous variant of IL23R, rs76418789, protects against CD development in Japanese subjects.


Lack of cross-reactive allergic response to brimonidine in patients with known apraclonidine allergy.
To assess the allergenic potential of topical brimonidine 0.2% in patients shown to be allergic to apraclonidine 0.5%. Eighteen glaucoma patients who developed allergy to apraclonidine were enrolled. Allergy was graded and documented photographically. Apraclonidine was then discontinued until the allergy resolved. Grading and photography were repeated, following which treatment with brimonidine was initiated. Patients were examined 1 h after the initial drop of brimonidine, twice weekly for 6 weeks, and at 3 monthly intervals thereafter. All other anti-glaucoma medications were continued. Mean patient age was 66.3 +/- 14.9 years (range 33.5-89.3 years). The mean time to apraclonidine allergy from initial exposure was 12.9 +/- 12.9 months (range 2.1-46.8 months). For the 10 patients rechallenged with apraclonidine, the mean time to allergy was 13.6 +/- 10.2 days (range 3-32 days). Mean duration of brimonidine therapy was 140.7 +/- 66.2 days (range 14-286 days), with 11 patients reaching at least 150 days of follow-up. Two patients developed symptomatic brimonidine allergy at 138 and 201 days respectively. For those patients who did not develop symptoms of allergy to brimonidine, there was no significant change in any of the parameters by which allergy was graded throughout the study. Patients with known apraclonidine allergy do not develop an early allergic response to brimonidine. These data rule against a cross-reactive allergic response between these two alpha 2-adrenoreceptor agonists.


Laser versus Anti-VEGF: A Paradigm Shift for Treatment-Warranted Retinopathy of Prematurity.
Retinopathy of prematurity (ROP), a leading cause of childhood blindness, has historically been associated with blindness from overgrowth of blood vessels from the retina into the vitreous that lead to complex retinal detachments. Our understanding of ROP has evolved with the survival of extremely low-birthweight infants and includes not only overgrowth of blood vessels, but also insufficient developmental retinal vascular growth in early phases of the disease. Our current treatments of ROP have focused on methods to improve perinatal and prenatal care, reduce premature birth, and prevent early phases of ROP. Nonetheless, addressing vasoproliferation in treatment-warranted eyes remains the mainstay of management. Two main treatment strategies co-exist today: laser treatment, which has been the standard of care since the 1990s, and anti-VEGF injections, which have been used since early reports in 2007 (Travassos et al. in Ophthalmic Surg Lasers Imaging, 38:233-237, https://doi.org/10.3928/15428877-20070501-09 , 2007, Shah et al. in Indian J Ophthalmol 55:75-76, https://doi.org/10.4103/0301-4738.29505 , 2007, Quiroz-Mercado et al. in Semin Ophthalmol 22:109-125, https://doi.org/10.1080/08820530701420082 , 2007).


Isolation of a human brain cDNA for glutamate dehydrogenase.
A cDNA has been isolated from a human brain expression library using anti-bovine glutamate dehydrogenase (GDH) antibodies. The cDNA has an open reading frame of 774 nucleotides, which codes for 258 amino acids. The 258-amino-acid sequence is 95% homologous to the carboxy terminus of human liver GDH. This high degree of homology indicates that the cDNA codes for brain GDH. Fourteen differences between the amino acid sequence deduced from this cDNA and the sequence reported for human liver GDH suggest that there may be two active human GDH genes. A cRNA probe synthesized from the cDNA detects a 3.7-kilobase (kb) mRNA from human brain. Rat liver and kidney each contain two GDH mRNAs, 3.5 and 2.8 kb, respectively. The 3.5-kb transcript is prominent in rat brain, whereas the 2.8-kb transcript is barely detectable, a result suggesting that GDH gene expression is differentially controlled in rat brain.


Effects of dexmedetomidine on cellular immunity of perioperative period in children with brain neoplasms.
To study the effects of dexmedetomidine (Dex) on cellular immunity during the perioperative period in children with brain neoplasms. Forty children with brain neoplasms scheduled for selective operation were recruited and divided randomly into two groups. The Dex group was given a loading dose of 1 μg*kg(-1) Dex 15 minutes before anesthesia induction followed by a continuous infusion of 0.5 μg × kg(-1) × h(-1) Dex. Patients in control group received a same volume of normal saline for a same time period. Venous blood was collected before anesthesia (T0), 1 h after operation started (T1), immediately after operation ended (T2), 1 day after operation (T3) and 3 days after operation (T4), respectively. CD3 (+), CD4 (+), CD4 (+)/CD8 (+), NK and B cells at T1-T3 decreased significantly (P < 0.05) in both groups compared with those at T0, while the decrease of CD3 (+), CD4 (+), CD4 (+)/CD8 (+) and NK cells at T1-T3 and B cells at T1-T2 in Dex group was significantly less than the control group (P < 0.05). All values at T4 recovered to the level before anesthesia in both groups. Dex given by a continuous intravenous infusion during general anesthesia may effectively inhibit the stress responses and reduce the inhibition of cellular immunity in children with brain neoplasms during the perioperative period.


Neuronal death induced by nanomolar amyloid β is mediated by primary phagocytosis of neurons by microglia.
Alzheimer disease is characterized by neuronal loss and brain plaques of extracellular amyloid β (Aβ), but the means by which Aβ may induce neuronal loss is not entirely clear. Although high concentrations of Aβ (μM) can induce direct toxicity to neurons, we find that low concentration (nM) induce neuronal loss through a microglia-mediated mechanism. In mixed neuronal-glial cultures from rat cerebellum, 250 nM Aβ1-42 (added as monomers, oligomers or fibers) induced about 30% loss of neurons between 2 and 3 days. This neuronal loss occurred without any increase in neuronal apoptosis or necrosis, and no neuronal loss occurred with Aβ42-1. Aβ greatly increased the phagocytic capacity of microglia and induced phosphatidylserine exposure (an "eat-me" signal) on neuronal processes. Blocking exposed phosphatidylserine by adding annexin V or an antibody to phosphatidylserine or inhibiting microglial phagocytosis by adding either cytochalasin D (to block actin polymerization) or cyclo(RGDfV) (to block vitronectin receptors) significantly prevented neuronal loss. Loss of neuronal synapses occurred in parallel with loss of cell bodies and was also prevented by blocking phagocytosis. Inhibition of phagocytosis prevented neuronal loss with no increase in neuronal death, even after 7 days, suggesting that microglial phagocytosis was the primary cause of neuronal death induced by nanomolar Aβ.


Demystification of palliative care: what palliative care teams don't want you to think about them.
There is robust data that palliative care is prolonging life while there are still prejudices towards this discipline that have to be demystified. Patients, relatives and caregivers benefit from the concept of early integration of palliative care and therefore, palliative care should not be mainly regarded as end-of-life care.


Viewpoints: Dual-blocking antibody against VEGF-A and angiopoietin-2 for treating vascular diseases of the eye.
Faricimab, a bispecific antibody that targets the endothelial cell growth factors vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2 (Angpt2), was recently approved for treating neovascular age-related macular degeneration and diabetic macular edema. Here, Koh and Augustin review how mechanistic studies have translated into therapies, while Campochiaro evaluates their impact and value for clinical practice.


Associations of Pain Intensity and Frequency With Loneliness, Hostility, and Social Functioning: Cross-Sectional, Longitudinal, and Within-Person Relationships.
The current studies investigated associations between pain intensity and pain frequency with loneliness, hostility, and social functioning using cross-sectional, longitudinal, and within-person data from community-dwelling adults with varying levels of pain. Secondary analysis of preexisting data was conducted. Study 1 investigated cross-sectional (baseline data: n = 741) and longitudinal (follow-up data: n = 549, observed range between baseline and follow-up: 6-53 months) associations. Study 2 tested within-person associations using daily diaries across 30 days from a subset of the participants in Study 1 (n = 69). Cross-sectionally, pain intensity and frequency were associated with higher loneliness (βintensity = 0.16, βfrequency = 0.17) and worse social functioning (βintensity = - 0.40, βfrequency = - 0.34). Intensity was also associated with higher hostility (β = 0.11). Longitudinally, pain intensity at baseline predicted hostility (β = 0.19) and social functioning (β = - 0.20) at follow-up, whereas pain frequency only predicted social functioning (β = - 0.21). Within people, participants reported higher hostility (γ = 0.002) and worse social functioning (γ = - 0.013) on days with higher pain, and a significant average pain by daily pain interaction was found for loneliness. Pain intensity did not predict social well-being variables on the following day. Pain intensity and frequency were associated with social well-being, although the effects were dependent on the social well-being outcome and the time course being examined.


Pharmacy student decision making in over-the-counter medicine supply: A critical incident study.
Various factors influence decision making in over-the-counter (OTC) medicine consultations, yet limited studies have focused, in-depth, on the thought process of pharmacy staff. This includes pharmacy students as pharmacists-in-training. To explore the factors that influence pharmacy students' decisions in relation to OTC consultations and choice of OTC medicine/s. Semi-structured interviews using the critical incident technique were undertaken with ten pharmacy students in Australia, who also worked as part-time pharmacy staff. Nine key themes were identified to influence pharmacy student decision making in OTC consultations, including customer response, confidence and scope of practice. Product requests were reported as more challenging due to customer expectations and experiences in other pharmacies, states or countries. Although negative customer response influenced some students to supply medicines in contradiction of evidence, an overarching concern for safety meant that a medicine was only supplied if unlikely to cause harm. Students reported developing confidence in OTC decision making more from real-life practice than university training; greater confidence was identified for inquiries more frequently experienced in the pharmacy. Students perceived that customers had assumptions around support staff, and were happier to talk to students than assistants. This study further identified that OTC decision making is a complex process for pharmacy students. Additional opportunities for experiential learning within this area are suggested, such as work-based placements or in-class activities such as role-plays with simulated patients.


Numbers and Features of Patients With a Diagnosis of Celiac Disease Without Duodenal Biopsy, Based on a National Survey.
According to guidelines, individuals with symptoms of celiac disease should undergo duodenal biopsy analysis to establish a diagnosis, but little is known about physician adherence to these guidelines. We used a patient-powered research network (PPRN) to compare demographics, diagnoses, symptoms, and treatment between groups of patients with celiac disease diagnosed by biopsy analysis and patients with a diagnosis based on results of serology tests. We analyzed data from iCureCeliac-a voluntary, PPRN hosted and distributed by the Celiac Disease Foundation, from January 30, 2016, through August 25, 2016. We compared data from adults with a diagnosis of celiac disease (mean age, 43.4 years; 85.6% female) based on biopsy analysis (n = 780) vs patients with a diagnosis based on only serologic analysis (n = 202) using univariate and multivariable analyses. We collected demographic information, as well as data on type of health care practitioner, where patients obtain their primary information about celiac disease, and the Celiac Disease Quality of Life score, nutritionist referral rates, adherence to the gluten-free diet, ongoing symptoms and use of supplements. Among patients with a diagnosis based on serology results, 33.3% were diagnosed by non-gastroenterologists vs 20.7% in the biopsy diagnosed group (P < .001). Fewer patients with a diagnosis based on serology results sought nutritional counseling at the time of diagnosis (40.1%) than patients with a diagnosis based on biopsy (58.9%) (P < .001). A higher proportion of patients diagnosed by serology without biopsy took dietary supplements to aid in digestion of gluten (19.8%) than patients with a diagnosis based on biopsy (8.9%) (P < .001). After we adjusted for age and sex, patients with a diagnosis based on serology were less likely to seek nutritional counseling after diagnosis (odds ratio [OR], 0.45; 95% CI, 0.33-0.63), less likely to receive a diagnosis from a gastroenterologist (OR, 0.16; 95% CI, 0.07-0.37), and more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62-4.19). In an analysis of data from a PPRN, we found that 21% of adult participants with celiac disease did not have a diagnosis based on a duodenal biopsy. Patients with a diagnosis based on serology results were more likely to be diagnosed by non-gastroenterologists, less likely to seek nutritional counseling, and more likely to use dietary supplements. Patients require more education about management of celiac disease and referral to gastroenterologists for duodenal biopsy confirmation of their disease.


Effect of Inula viscosa extract on chitin synthesis in dermatophytes and Candida albicans.
An antimycotic effect of an extract from Inula viscosa leaves was demonstrated affecting chitin synthesis in dermatophytes and Candida albicans. The antimycotic effect was compared to the effect caused by miconazole nitrate--an antifungal drug. The inhibition effect on chitin synthesis was not correlated to the extent of growth inhibition caused by the antifungal agents: both miconazole nitrate and the I. viscosa extract inhibited the growth of dermatophytes and C. albicans. Miconazole nitrate did not affect chitin synthesis--except for M. canis--whereas I. viscosa extract caused a significant decline in chitin content.


Prescriptions for home hemodialysis.
Prescribing a regimen that provides "optimal dialysis" to patients who wish to dialyze at home is of major importance, yet there is substantial variation in how home hemodialysis (HD) is prescribed. Geographic location, patient health status and clinical goals, and patient lifestyle and preferences all influence the selection of a prescription for a particular patient-there is no single prescription that provides optimal therapy for all patients, and careful weighing of potential benefit and burden is required for long-term success. This article describes how home HD prescribing patterns have changed over time and provides examples of commonly used home HD prescriptions. In addition, associated clinical outcomes and adequacy parameters as well as criteria for identifying which patients may benefit most from these diverse prescriptions are also presented.


Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.
To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. Prospective case-control study. University-based practice. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). Cardiovascular risk markers and hormonal parameters were assessed. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. Weight and PCOS are two independent variables affecting the endothelial function.


Repetitive Peripheral Sensory Stimulation and Upper Limb Performance in Stroke: A Systematic Review and Meta-analysis.
Enhancement of sensory input in the form of repetitive peripheral sensory stimulation (RPSS) can enhance excitability of the motor cortex and upper limb performance. To perform a systematic review and meta-analysis of effects of RPSS compared with control stimulation on improvement of motor outcomes in the upper limb of subjects with stroke. We searched studies published between 1948 and December 2017 and selected 5 studies that provided individual data and applied a specific paradigm of stimulation (trains of 1-ms pulses at 10 Hz, delivered at 1 Hz). Continuous data were analyzed with means and standard deviations of differences in performance before and after active or control interventions. Adverse events were also assessed. There was a statistically significant beneficial effect of RPSS on motor performance (standard mean difference between active and control RPSS, 0.67; 95% CI, 0.09-1.24; I2 = 65%). Only 1 study included subjects in the subacute phase after stroke. Subgroup analysis of studies that only included subjects in the chronic phase showed a significant effect (1.04; 95% CI, 0.66-1.42) with no heterogeneity. Significant results were obtained for outcomes of body structure and function as well as for outcomes of activity limitation according to the International Classification of Function, Disability and Health, when only studies that included subjects in the chronic phase were analyzed. No serious adverse events were reported. RPSS is a safe intervention with potential to become an adjuvant tool for upper extremity paresis rehabilitation in subjects with stroke in the chronic phase.


Cardiovascular Disease in Women: An Update for Nurses.
Cardiovascular disease (CVD) is the leading cause of death in women but is often underrecognized and undertreated. Women are more likely to experience delay in treatment and worse outcomes, even though they experience similar symptoms as men. Women are more likely to experience ischemia related to microvascular dysfunction, which is not readily diagnosed by commonly used diagnostic tests. Nurses are ideally positioned to be patient advocates and use evidence-based guidelines to encourage primary prevention and ensure prompt treatment. This paper provides an update on CVD in women for clinical nurses based on the latest research evidence.


Disinfectants used for environmental disinfection and new room decontamination technology.
Environmental contamination plays an important role in the transmission of several key health care-associated pathogens. Effective and thorough cleaning/disinfecting of the patient environment is essential. Room decontamination units (such as ultraviolet-C and hydrogen peroxide systems) aid in reducing environmental contamination after terminal room cleaning and disinfection.


Bipolar tetraether lipids derived from thermoacidophilic archaeon Sulfolobus acidocaldarius for membrane stabilization of chlorin e6 based liposomes for photodynamic therapy.
The initial burst release of water-soluble photosensitizers is one of the major problems encountered the development of controlled release formulations. In this study, the freely water soluble chlorin e6 (Ce6) was assembled with cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to improve its loading efficiency in the liposomal bilayer. Tetraether lipids (TELs) derived from Sulfolobus acidocaldarius were added to DOTAP:Ce6 assembly in a concentration range of 2.5×10(-4)-1.6×10(-3)M to stabilize the membrane rigidity of the liposomes and to provide controlled release system. From the comparative spectroscopic experiments, it has been shown that the assembled DOTAP:Ce6 along with addition of TELs have improved the loading efficiency of Ce6 in TELs-liposomes and obviously modified the release profile of Ce6. The in vitro cell viability of Ce6 in mouse neuro-blastoma (Neuro-2a) and ovarian cell carcinoma (SK-OV-3) confirmed neglected dark cytotoxicity and presented potential photo-induced cytotoxicity with the effect was being more pronounced in Neuro 2a than in SK-OV-3. In-situ IV-injection of chick chorioallantoic membrane (CAM) showed hemorrhage and necrosis 30 min post irradiation at 1.8 mol% TELs (19.9J/cm(2)). Higher TELs of 2.2 and 3.7 mol% in particular demonstrated localized vascular destruction within the irradiated area. Our results suggest that TELs favored slower release rates of Ce6. This, in turn, tetraether lipids can be considered as a versatile class of lipids for photodynamic modality for destruction of cancer cells and tumor vasculature while sparing the quiescent ones.


Risperidone: a review of its use in the management of the behavioural and psychological symptoms of dementia.
Risperidone is a benzisoxazole derivative which has proven efficacy against the positive and negative symptoms of schizophrenia. It has more recently been investigated and shown efficacy as a treatment for the behavioural and psychological symptoms associated with dementia in the elderly. Risperidone has pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the conventional antipsychotic haloperidol. Risperidone has antagonistic activity primarily at serotonin 5-HT2A and dopamine D2 receptors. In the first 2 large, well controlled trials of an antipsychotic agent used in the treatment of elderly patients with Alzheimer's dementia, vascular dementia or mixed dementia, risperidone 1 mg/day was at least as effective as haloperidol and superior to placebo, as assessed by the rating scales for global behaviour, aggression and psychosis. In extension phases of the 2 trials, clinical benefits were maintained for treatment periods of up to 1 year, with an incidence rate of tardive dyskinesia (2.6%) one-tenth of that seen with conventional antipsychotics. Risperidone, administered at a low dosage of 1 mg/day was associated with fewer extrapyramidal symptoms compared with haloperidol in elderly patients. Risperidone was well tolerated with no clinically relevant abnormalities in laboratory tests, vital signs or electrocardiogram results. The efficacy of risperidone has been demonstrated in the treatment of the behavioural and psychological symptoms associated with dementia in the elderly. Preliminary results from 1-year extension studies confirm the favourable efficacy and tolerability profile of risperidone 1 mg/day. Although head to head studies with other atypical antipsychotic agents are required and the long term use of the drug requires clarification, risperidone represents a generally well tolerated and effective treatment in the management of dementia-associated behavioural and psychological symptoms in the elderly.


Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine.
A number of quinolone antibacterial agents, particularly enoxacin, pefloxacin, pipemidic acid and ciprofloxacin, are known to decrease the clearance of methylxanthines. The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers. Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo, temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence. A doubling of the area under the plasma concentration-time curve (77.8 vs 31.8 mg/L.h) and terminal-phase half-life (9.7 vs 4.5h) of caffeine were observed in the presence of ciprofloxacin. The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline. This may partly be explained by intertrial differences in dosage and study design. Coadministration of temafloxacin did not have any effect on the pharmacokinetics of caffeine, confirming results of other studies suggesting that this agent does not affect methylxanthine clearance. Accordingly, it appears that restriction of caffeine intake during temafloxacin therapy is not necessary.


Head Start as a social support for mothers: the psychological benefits of involvement.
Parents' participation in Head Start activities was investigated for its possible effect on their psychological well-being. A pretest and posttest design was used. Results indicated a positive relationship: mothers who participated more reported fewer psychological symptoms, greater feelings of mastery, and greater current life satisfaction at the end of the program year. Implications for policy and research are discussed.


Physiological changes during temporary occlusion of the superior vena cava in cynomolgus monkeys.
To evaluate the physiological changes that occur after temporary occlusion of the superior vena cava, we clamped the vena cava for one hour in 6 cynomolgus monkeys, monkeys with a venous system most resembling that of humans. The data from arterial blood gas analysis, ie, pH, arterial oxygen tension, arterial carbon dioxide tension, and HCO3-, were within normal limits during and after occlusion of the superior vena cava. Intracranial pressure was 8.6 +/- 0.8 mm Hg (mean +/- standard error) before occlusion and rose to 22.1 +/- 2.2 mm Hg during clamping. It decreased significantly to 17.7 +/- 1.9 mm Hg just before removal of the clamp and recovered to 8.6 +/- 0.9 mm Hg after the clamp was removed. Regional cerebral blood flow was 45 +/- 9 mL/min/100 g before clamping and decreased to 37 +/- 3 mL/min/100 g during clamping. It recovered to 47 +/- 5 mL/min/100 g after removal of the clamp. Cerebral perfusion pressure was within the margin of safety during clamping. Histological findings in the brain showed the effect of congestion in 1 monkey, but the change was slight. The electroencephalogram and electrocardiogram showed no abnormalities in this experiment. In conclusion, one-hour clamping of the superior vena cava with the azygos vein ligated was safe in 6 cynomolgus monkeys. We believe that in the clinical setting, one-hour occlusion of the superior vena cava would result in findings similar to those in this study, unless particular complications, such as arteriosclerosis or a cerebrovascular disorder, exist.


Salzmann's nodular degeneration.
Salzmann nodular corneal degeneration is a non-inflammatory, progressive corneal degeneration characterized by bluish-white nodules of varying shapes classically located in the mid-peripheral cornea. It was first described by Maximilian Salzmann in 1925 and was noted at that time to be associated with "eczematous keratoconjunctivitis". Since then, significant progress has been made to understand environmental and genetic risk factors associated with SND. However, etiopathogenesis remains poorly understood. A review of the literature was performed to highlight our recent understanding of SND and its management.


Staying connected in old age: associations between bonding social capital, loneliness and well-being and the value of digital media.
We examined associations between age, bonding social capital (BSC), loneliness and psychological, social and emotional well-being in old age. As in theory digital media can support both preservation of and access to someone's social capital, we also explored associations between the use of WhatsApp, social network sites (SNS) and Internet applications and respectively BSC and loneliness. In this cross-sectional study a sample of 349 older adults (range = 70y-93y; Mean(SD)=74.8y(4.9y); 59.6% male) filled out a questionnaire including the bonding social capital subscale of the personal social capital scale for elderly (PSCSE), validated scales measuring social, emotional, and psychological well-being and loneliness, the SNS intensity scale and items measuring frequencies of Whatsapp use and use of various Internet functions. Also relevant demographic and other covariates were included. Regression analyses including relevant covariates confirmed our hypotheses, finding negative associations between BSC and both age and loneliness, and positive associations between BSC and psychological, social and emotional well-being. WhatsApp and Internet use were both found positively associated with BSC, whilst a negative association between WhatsApp use and loneliness was found. SNS use was not associated with BSC nor with loneliness. Our findings indicate BSC as an important factor in positive aging and illustrate a widening gap between the need for socio-emotional resources versus their availability. With regard to digital media, we conclude that its value in old age should be sought in providing access to one's bonding social capital rather than adding to it by expanding the number of social relations.


Ageing, musculoskeletal health and work.
Changing demographics mean that many patients with soft tissue rheumatism, osteoarthritis, inflammatory arthritis, large joint prostheses and age-related co-morbidities are seeking to work beyond the traditional retirement age. In this chapter, we review the evidence on musculoskeletal health and work at older ages. We conclude that musculoskeletal problems are common in older workers and have a substantial impact on their work capacity. Factors that influence their job retention are described, together with approaches that may extend working life. Many gaps in evidence were found, notably on the health risks and benefits of continued work in affected patients and on which interventions work best. The roles of physicians and managers are also considered.


Subthalamic 85 Hz deep brain stimulation improves walking pace and stride length in Parkinson's disease patients.
Mobile gait sensors represent a compelling tool to objectify the severity of symptoms in patients with idiopathic Parkinson's disease (iPD), but also to determine the therapeutic benefit of interventions. In particular, parameters of Deep Brain stimulation (DBS) with its short latency could be accurately assessed using sensor data. This study aimed at gaining insight into gait changes due to different DBS parameters in patients with subthalamic nucleus (STN) DBS. An analysis of various gait examinations was performed on 23 of the initially enrolled 27 iPD patients with chronic STN DBS. Stimulation settings were previously adjusted for either amplitude, frequency, or pulse width in a randomised order. A linear mixed effects model was used to analyse changes in gait speed, stride length, and maximum sensor lift. The findings of our study indicate significant improvements in gait speed, stride length, and leg lift measurable with mobile gait sensors under different DBS parameter variations. Notably, we observed positive results at 85 Hz, which proved to be more effective than often applied higher frequencies and that these improvements were traceable across almost all conditions. While pulse widths did produce some improvements in leg lift, they were less well tolerated and had inconsistent effects on some of the gait parameters. Our research suggests that using lower frequencies of DBS may offer a more tolerable and effective approach to enhancing gait in individuals with iPD. Our results advocate for lower stimulation frequencies for patients who report gait difficulties, especially those who can adapt their DBS settings remotely. They also show that mobile gait sensors could be incorporated into clinical practice in the near future.


Acyclic distonic acylium ions: dual free radical and acylium ion reactivity in a single molecule
Three gaseous acyclic distonic acylium ions: *CH2-CH2-C+=O, *CH2-CH2-CH2-C+=O, and *CH2=C(CH2)-C+=O, are found to display dual free radical and acylium ion reactivity; with appropriate neutrals, they react selectively either as free radicals with inert charge sites, or (and more pronouncedly) as acylium ions with inert radical sites. The free radical reactivity of the ions is demonstrated via the Kenttamaa reaction: CH3S* abstraction with the spin trap dimethyl disulfide; their ion reactivity by two reactions most characteristic of acylium ions: transacetalization with 2-methyl-1,3-dioxolane and the gas-phase Meerwein reaction, that is, expansion of the three-membered epoxide ring of epichlorohydrin to the five-membered 1,3-dioxolanylium ion ring. In "one-pot" reactions with gaseous mixtures of epichlorohydrin and dimethyl disulfide, the ions react selectively at either site, but more readily at the acylium charge site, to form the two mono-derivatized ions. Further reaction at either the remaining free radical or acylium charge site forms a single bi-derivatized ion as the final product. Becke3LYP/6-31G(d) calculations predict the reactions at the acylium charge sites of the three distonic ions to be highly exothermic, and both the "hot" transacetalization and epoxide ring expansion products of *CH2-CH2-CH2-C+=O to dissociate rapidly by H2C=CH2 loss in overall exothermic processes. The calculations also predict highly spatially separate odd spin and charge sites for the novel cyclic distonic ketal ions formed by the reactions at the acylium charge sites.


The functional impact of 1,570 individual amino acid substitutions in human OTC.
Deleterious mutations in the X-linked gene encoding ornithine transcarbamylase (OTC) cause the most common urea cycle disorder, OTC deficiency. This rare but highly actionable disease can present with severe neonatal onset in males or with later onset in either sex. Individuals with neonatal onset appear normal at birth but rapidly develop hyperammonemia, which can progress to cerebral edema, coma, and death, outcomes ameliorated by rapid diagnosis and treatment. Here, we develop a high-throughput functional assay for human OTC and individually measure the impact of 1,570 variants, 84% of all SNV-accessible missense mutations. Comparison to existing clinical significance calls, demonstrated that our assay distinguishes known benign from pathogenic variants and variants with neonatal onset from late-onset disease presentation. This functional stratification allowed us to identify score ranges corresponding to clinically relevant levels of impairment of OTC activity. Examining the results of our assay in the context of protein structure further allowed us to identify a 13 amino acid domain, the SMG loop, whose function appears to be required in human cells but not in yeast. Finally, inclusion of our data as PS3 evidence under the current ACMG guidelines, in a pilot reclassification of 34 variants with complete loss of activity, would change the classification of 22 from variants of unknown significance to clinically actionable likely pathogenic variants. These results illustrate how large-scale functional assays are especially powerful when applied to rare genetic diseases.


Correction to: Two novel methylesterases from Olea europaea contribute to the catabolism of oleoside-type secoiridoid esters.
Page 5, paragraph 3, line 14, GenBank Accession Number which should read MK234850 instead of MK23485.


The combined inactivation of tumor necrosis factor and interleukin-6 prevents induction of the major acute phase proteins by endotoxin.
The constellation of changes known as the acute phase response (APR) is a cytokine-driven process initiated by tissue inflammation. The proinflammatory cytokines, TNF, IL-1 and IL-6, are considered to be the primary mediators of the APR. IL-6 and IL-1beta gene-deleted mice (Fattori et al., J. Exp. Med. 1994. 180: 1243-1250; Kopf et al., Nature 1994. 368: 339-342; Fantuzzi et al., J. Immunol. 1996. 157: 291-296, respectively), exhibit impaired APR to turpentine injection but only a slight reduction in plasma acute phase protein levels in response to lipopolysaccharide (LPS). This infers an important role for TNF in the LPS-induced APR, however, in the present study, normal APR to both turpentine and LPS were observed in TNF/LTalpha-deficient mice. A striking absence of elevated major acute phase proteins, SAP and SAA, was observed in mice deficient in TNF/LTalpha and IL-6, suggesting that TNF-alpha or LTalpha do indeed exert important nonredundant synergism in the IL-1/IL-6 primary response. The regulation of other parameters typically altered in an APR, body weight, blood glucose and haptoglobin, was normal in LPS-dosed TNF/LTalpha-deficient and wild-type mice. The observed transcriptional response for SAA and SAP in these TNF/LTalpha/IL-6-deficient mice, in lieu of elevated plasma levels, suggests that SAA and SAP expression is possibly posttranscriptionally regulated.


Long-term RNase P-mediated inhibition of HIV-1 replication and pathogenesis.
Advances in genetic analysis and a greater understanding of human immunodeficiency virus (HIV) molecular pathogenesis have identified critical viral targets for gene interference strategies. RNase P molecules have been proposed as a novel approach for gene targeting based upon their potent catalytic activity, as well as versatile external guide sequence (EGS) which can be modified to specifically recognize almost any target mRNA. We designed a truncated EGS to specifically recognize the highly conserved U5 region of HIV-1 mRNA and mediate subsequent cleavage of hybridized mRNA by the RNase P enzyme component. The active U5-EGS (560), as well as a disabled U5 EGS (560D) control, were cloned into plasmids containing proviral constructs and transfected into a CD4(+) T cell line that was thereafter infected with HIV-1 MN. CD4(+) T cells treated with the active U5 EGS (560) were observed to maintain CD4(+) expression and did not produce HIV p24 gag antigen, form syncytia or undergo apoptosis up to 30 days after infection. Identical cells expressing the inactivated form of the U5 RNase P EGS completely down-regulated CD4 expression, produced elevated levels of HIV-1, formed large syncytia and underwent apoptosis similar to untreated cells. HIV-1 replication and related cytopathology can be effectively inhibited in CD4(+) T cells expressing a protective U5 EGS (560).


Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation.
It has been hypothesized that transthyretin (TTR) amyloidosis may progress after orthotopic liver transplantation (OLT) as a result of continued amyloid fibril synthesis and deposition from normal TTR. To test this hypothesis amyloid fibrils were isolated from cardiac tissues of three patients who died 1(1/2) to 5(1/2) years after OLT: two with Val30Met and one with Thr60Ala TTR. The ratio of variant to normal TTR in each case was determined and compared with the ratio of variant to normal in cardiac tissues from seven patients who died with TTR amyloidosis but who had not had liver transplantation. Tissues from patients with TTR amyloidosis without OLT included three with Val30Met, two with Thr60Ala, one with deltaVal122, and one with Val122Ile. All tissues from patients without OLT had greater amounts of variant TTR than normal TTR except for the Val122Ile in which the ratio was 50:50. The overall median variant to normal ratio was 60:40 with a range of 50-70% variant. In contrast, the mean percentage of variant TTR in the three tissues from patients after OLT was 25% (range 20-35). These data are consistent with the continued deposition of normal TTR in cardiac tissue after liver transplantation.


Quantitative analysis of the current status and research trends of biochar research - A scientific bibliometric analysis based on global research achievements from 2003 to 2023.
Biochar has excellent physical and chemical properties such as porosity, high carbon content, high cation exchange capacity, and rich surface functional groups and has been widely used in environmental remediation. Over the past 20 years, although various reviews have described the application of biochar as an environmentally friendly multifunctional material in environmental remediation, no comprehensive summary and analysis of the research trends in this field exists. To promote the rapid and stable development of the field of biochar, the current state of research on biochar is clarified using the bibliometric method in this report, and potential development directions and challenges for the future are identified. All relevant biochar literature from 2003-2023 was collected from the Chinese National Knowledge Infrastructure and Web of Science Core Collection. A total of 6,119 published Chinese papers and 25,174 English papers were selected for the quantitative analysis. CiteSpace, VOSviewer, and Scimago graphics software was used to summarize the numbers of papers published over the years, as well as the countries, institutions, and authors that published the most articles. Secondly, using keyword co-occurrence and emergence analysis, the recognized research hotspots in different areas such as adsorbents, soil remediation, catalytic oxidation, supercapacitors, and "biochar-microbial" synergy were analyzed. Finally, the prospects and challenges of biochar were assessed to provide new perspectives for further promoting its development in technological, economic, environmental, and other aspects.


Magnetic resonance imaging of propagating waves of spreading depression in the anaesthetised rat.
Gradient echo magnetic resonance (MR) imaging was used to demonstrate propagating waves of cortical spreading depression (SD) in the anaesthetised rat. SD was initiated by remote perfusion with 150 mM KCl applied for 0.5-2 min to the left parietal cortex. Gradient echo MR images were obtained every 12-30 s in either a vertical coronal section or a horizontal section including the superficial cortex in plan view. Within 2 min of application of KCl, we observed a zone of increased signal intensity (3-15%) on the MR image, up to 2 mm across, lasting approximately 1 min and propagating away from the site of initiation. The mean velocity for 27 of such waves seen in seven animals was calculated to be 2.79 mm/min, with means (+/- SD) in individual animals averaging 2.90 +/- 0.46 mm/min (n = 7). Increased signal intensity in gradient echo images has been attributed to an increased level of oxygenation within the venous blood. Our results are consistent with this interpretation although other physiological changes during SD may also contribute to the signal changes.


Taxonomic review of Kuzicus Gorochov, 1993 (Tettigoniidae: Meconematinae), with two new species from Thailand and key to species.
The taxonomy of genus Kuzicus Gorochov, 1993 (Tettigoniidae: Meconematinae) is reviewed. Two new species are described from Thailand: Kuzicus pakthongchai sp. n. Tan et al. and Kuzicus multidenticulatus sp. n. Tan et al. Kuzicus denticuloides (Kevan, 1993) comb. nov. is transferred from genus Xiphidiopsis. Parakuzicus is removed as a subgenus and considered a distinct genus. A key to species of Kuzicus is provided.


The clinical value of ERCP-guided cholangiopancreatoscopy using a single-operator system.
Single-operator, per-oral cholangiopancreatoscopy (SOPCP) enables direct biliopancreatic ductal visualization, targeted tissue sampling, and therapeutic intervention. At Karolinska University Hospital, SOPCP was introduced early and has since been extensively utilized according to a standardized protocol. We analysed the clinical value of SOPCP in the diagnosis and treatment of biliopancreatic diseases in a single high volume center. All SOPCP procedures performed between March 2007 and December 2014 were retrospectively reviewed. Each procedure's diagnostic yield and therapeutic value was evaluated using a predefined 4 grade scale; 1 - no diagnostic or therapeutic value, 2 - information gained did not impact clinical decision-making and in case of a therapeutic intervention, did not alter the clinical course of the patient, 3 - information gained had an impact on clinical decision-making and in the case of a therapeutic intervention, assisted subsequent disease management, and finally, 4 - information gained was essential and critical for clinical decision-making and in case of a therapeutic intervention, solved the clinical problem requiring no further therapeutic actions. Descriptive statistics were used to analyse results, with uni- and multivariate analyses completed to assess risk of adverse events. During the study period, 365 SOPCP procedures were performed. We found SOPCP of pivotal importance (grade 4) in 19% of cases, and of great clinical significance (grade 3) in 44% of cases. SOPCP did not affect clinical decision-making or alter clinical course (grade 1 and 2) in 37% of cases. SOPCP offers direct access to the biliopancreatic ducts for both diagnostic and therapeutic purposes, adding significant clinical value in 64% of cases. As this is a purely observational and retrospectively registered study in which the assignment of the medical intervention was not at the discretion of the investigator, it has not been registered in a registry.


Long-term systemic glucocorticoid therapy: patients' representations, prescribers' perceptions, and treatment adherence.
Glucocorticoids have been used since 1948 for their anti-inflammatory and structural effects in various inflammatory diseases. The optimal use of glucocorticoids remains controversial. Patients may have a number of concerns about the effects of glucocorticoids. Many factors can adversely affect treatment adherence. To evaluate the main adverse effects reported by patients and physicians, and to assess representations associated with glucocorticoid therapy and the underlying disease, via measurements of treatment adherence, with the goal of optimizing treatment strategies and improving patient information. From December 2011 to May 2012, we conducted two surveys in 125 patients receiving long-term glucocorticoid therapy and followed-up at the rheumatology department of the teaching hospital in Casablanca, Morocco, and in 85 hospital physicians in various specialties, respectively. Mean glucocorticoid therapy duration was 6 years, mean maximal prescribed dosage was 44.87 mg/d, and 50.4% of the patients had inflammatory joint disease. Adverse neuropsychiatric effects were reported by 70 out of 125 (56%) patients. Weight gain was the adverse effect deemed most bothersome by the physicians, who significantly underestimated the occurrence of neuropsychiatric adverse effects (27% vs 56%, P=0.034). Adherence was poor in 80 out of 125 (64%) patients, and 22 out of 125 (18%) patients reported episodes of treatment discontinuation. Prescribers underestimate the frequency of neuropsychiatric adverse effects of long-term systemic glucocorticoid therapy. Regular follow-up visits during treatment, with collection of systemic adverse effects might improve treatment adherence.


Expect the unexpected: patients' and families' expectations and experiences of new clinical procedures.
Early stage clinical innovation often occurs 'under the radar' of governance systems for established procedures. Previously impossible or unavailable techniques still being developed involve additional uncertainty and unknown risks and benefits compared with standard procedures. Patient and family expectations, perceptions and experiences of these new procedures and their possible impacts on aspects of patient safety are under-researched. To explore patient and family expectations and experiences of undergoing new clinical procedures. A large UK Hospital NHS Foundation Trust with a range of clinically innovative specialties. We interviewed 15 patients who received new clinical procedures in a variety of medical and surgical specialties. Qualitative interviews were used to facilitate in-depth exploration of patient and family views and experiences. Topics included patient and family access to and expectations of the procedure, informed decision making regarding acceptance of new procedures and post-procedure experiences. Some patients sought out specific interventions, while others accepted new treatment options that clinicians proposed. Most participants reported that explanations about the procedure and risks were clear, and there were opportunities to ask questions prior to the procedure. Most participants also regarded their procedures as successful. However, post-procedure information follow-up was often reported as lacking and some outcomes were considerably problematic and raised patient safety issues. The importance of patients' and family views in evaluating health care are increasingly recognized. We discuss the implications of our findings for informed decision making and post-intervention follow-up.


Cystathionine-beta-synthase inhibition for colon cancer: Enhancement of the efficacy of aminooxyacetic acid via the prodrug approach.
Colon cancer cells contain high levels of cystathionine-beta-synthase (CBS). Its product, hydrogen sulfide (H2S) promotes the growth and proliferation of colorectal tumor cells. In order to improve the antitumor efficacy of the prototypical CBS inhibitor aminooxyacetic acid (AOAA), we have designed and synthesized YD0171, a methyl ester derivative of AOAA. The antiproliferative effect of YD0171 exceeded the antiproliferative potency of AOAA in HCT116 human colon cancer cells. The esterase inhibitor paraoxon prevented the cellular inhibition of CBS activity by YD0171. YD0171 suppressed mitochondrial respiration and glycolytic function and induced G0/G1 arrest, but did not induce tumor cell apoptosis or necrosis. Metabolomic analysis in HCT116 cells showed that YD0171 affects multiple pathways of cell metabolism. The efficacy of YD0171 as an inhibitor of tumor growth was also tested in nude mice bearing subcutaneous HCT116 cancer cell xenografts. Animals were treated via subcutaneous injection of vehicle, AOAA (1, 3 or 9 mg/kg/day) or YD0171 (0.1, 0.5 or 1 mg/kg/day) for 3 weeks. Tumor growth was significantly reduced by 9 mg/kg/day AOAA, but not at the lower doses. YD0171 was more potent: tumor volume was significantly inhibited at 0.5 and 1 mg/kg/day. Thus, the in vivo efficacy of YD0171 is 9-times higher than that of AOAA. YD0171 (1 mg/kg/day) attenuated tumor growth and metastasis formation in the intracecal HCT116 tumor model. YD0171 (3 mg/kg/day) also reduced tumor growth in patient-derived tumor xenograft (PDTX) bearing athymic mice. YD0171 (3 mg/kg/day) induced the regression of established HCT116 tumors in vivo. A 5-day safety study in mice demonstrated that YD0171 at 20 mg/kg/day (given in two divided doses) does not increase plasma markers of organ injury, nor does it induce histological alterations in the liver or kidney. YD0171 caused a slight elevation in plasma homocysteine levels. In conclusion, the prodrug approach improves the pharmacological profile of AOAA; YD0171 represents a prototype for CBS inhibitory anticancer prodrugs. By targeting colorectal cancer bioenergetics, an emerging important hallmark of cancer, the approach exemplified herein may offer direct translational opportunities.


Urochordate whole body regeneration inaugurates a diverse innate immune signaling profile.
The phenomenon of whole body regeneration (WBR) from minute soma fragments is a rare event in chordates, confined to the subfamily of botryllid ascidians and is poorly understood on the cellular and molecular levels. We assembled a list of 1326 ESTs from subtracted mRNA, at early stages of Botrylloides leachi WBR, and classified them into functional categories. Sixty-seven (15%) ESTs with roles in innate immunity signaling were classified into a broad functional group, a result supported by domain search and RT-PCR reactions. Gene ontology analysis for human homologous to the immune gene category, identified 22 significant entries, of which "peptidase activity" and "protease inhibitor activity", stood out as functioning during WBR. Analyzing expressions of serine protease Bl-TrSP, a representative candidate gene from the "peptidase activity" subgroup, revealed low transcript levels in naïve vasculature with upregulated expression during WBR. This was confirmed by in situ hybridization that further elucidated staining restricted to a circulating population of macrophage cells. Furthermore, Bl-TrSP was localized in regeneration niches within vasculature, in regenerating buds, and in buds, during blastogenesis. Functional inhibition of serine protease activity disrupts early remodeling processes of the vasculature microenvironment and hinders WBR. Comparison of genome-wide transcription of WBR with five other developmental processes in ascidians (including metamorphosis, budding and blastogenesis), revealed a broad conservation of immune signaling expressions, suggesting a ubiquitous route of harnessing immune-related genes within a broader range of tunicate developmental context. This, in turn, may have enabled the high diversity of life history traits represented by urochordate ascidians.


Iron potentiates microglial interleukin-1β secretion induced by amyloid-β.
Alzheimer's disease (AD) is characterized by accumulation of amyloid-beta (Aβ) senile plaques in patients' brain tissues. Elevated levels of interleukin-1beta (IL-1β) have been identified in cerebrospinal fluid of living AD patients and in animal models of AD. Increased expression of IL-1β and iron accumulation have been identified in microglial cells that cluster around amyloid plaques in AD mouse models and post-mortem brain tissues of AD patients. The goals of this study were to determine the effects of Aβ on the secretion of IL-1β by microglial cells and whether iron status influences this pro-inflammatory signaling cue. Immortalized microglial (IMG) cells were incubated with Aβ with or without iron. qRT-PCR and western blot analyses showed that Aβ induces biosynthesis of IL-1β by IMG cells. IMG cells secrete the mature form of IL-1β in a caspase 1-dependent manner. Incubation with iron provoked a greater pro-inflammatory response. Inhibition of the iron transporter divalent metal transporter 1 protected IMG cells against Aβ-induced inflammation. Potentiation of Aβ-elicited IL-1β induction by iron was also antagonized by ROS inhibitors, supporting the model that divalent metal transporter 1-mediated iron loading and subsequent increase in ROS contribute to the inflammatory effects of Aβ in microglia. Immunoblotting and immunofluorescence microscopy indicate that iron enhances Aβ activation of NF-κB signaling to promote IL-1β synthesis. These results support the hypothesis that Aβ stimulates IL-1β expression by activating NF-κB signaling in microglia cells. Most importantly, iron appears to exacerbate the pro-inflammatory effects of Aβ to increase IL-1β levels.


DNA replication in human diploid cells of different origin.
DNA-fiber autoradiography has been used to study the replication of chromosomal DNA from cultured human cells of different origin. In normal embryonic fibroblasts, brain cells, heart cells, hepatocytes, and post-natal fibroblasts and lymphocytes the rate of DNA replication in a single fork varies from 0.2 to 1.0 micrometer/min with a mean of about 0.6 micrometer/min; and the size of replication units varies from 80 to 400 micrometer with a mean of about 200 micrometer. The data obtained indicate that in cultured somatic cells of various tissues of the same organism, the rate of DNA replication and the number of functioning replication units are practically the same.


European Union-28: An annualised cost-of-illness model for venous thromboembolism.
Annual costs for venous thromboembolism (VTE) have been defined within the United States (US) demonstrating a large opportunity for cost savings. Costs for the European Union-28 (EU-28) have never been defined. A literature search was conducted to evaluate EU-28 cost sources. Median costs were defined for each cost input and costs were inflated to 2014 Euros (€) in the study country and adjusted for Purchasing Power Parity between EU countries. Adjusted costs were used to populate previously published cost-models based on adult incidence-based events. In the base model, annual expenditures for total, hospital-associated, preventable, and indirect costs were €1.5-2.2 billion, €1.0-1.5 billion, €0.5-1.1 billion and €0.2-0.3 billion, respectively (indirect costs: 12 % of expenditures). In the long-term attack rate model, total, hospital-associated, preventable, and indirect costs were €1.8-3.3 billion, €1.2-2.4 billion, €0.6-1.8 billion and €0.2-0.7 billion (indirect costs: 13 % of expenditures). In the multiway sensitivity analysis, annual expenditures for total, hospital-associated, preventable, and indirect costs were €3.0-8.5 billion, €2.2-6.2 billion, €1.1-4.6 billion and €0.5-1.4 billion (indirect costs: 22 % of expenditures). When the value of a premature life-lost increased slightly, aggregate costs rose considerably since these costs are higher than the direct medical costs. When evaluating the models aggregately for costs, the results suggests total, hospital-associated, preventable, and indirect costs ranging from €1.5-13.2 billion, €1.0-9.7 billion, €0.5-7.3 billion and €0.2-6.1 billion, respectively. Our study demonstrates that VTE costs have a large financial impact upon the EU-28's healthcare systems and that significant savings could be realised if better preventive measures are applied.


Scientometric analysis of highly cited papers on avascular necrosis of the femoral head from 1991 to 2022.
A highly cited paper (HCP) is considered a landmark that can influence both research and clinical practice. The characteristics of HCPs in avascular necrosis of the femoral head (AVNFH) were identified and the research status was explored in a scientometric analysis. The present bibliometric analysis were based on the Scopus database from 1991 to 2021. Microsoft Excel and VOSviewer were used for co-authorship, co-citation, and co-occurrence analysis. From 8496 papers, only 2.9% (244) were HCPs, with 200.8 citations registered per article. Of the HCPs, 11.9% and 12.3% were externally funded and had international collaboration, respectively. These were published in 84 journals by 1625 authors from 425 organizations of 33 countries. The USA, Japan, Switzerland, and Israel were the leading countries.The lead research organizations were Sinai Hospital and John Hopkins University (USA). The most impactful organizations were University of Arkansas for Medical Science, and Good Samaritan Hospital (USA). R.A. Mont (USA) and K.H. Koo (South Korea) were the most prolific contributing authors, while R. Ganz (Switzerland) and R.S. Weinstein (USA) registered the most impactful contributions. The most prolific publishing journal was the Journal of Bone and Joint Surgery. The HCPs contributed to the knowledge of AVNFH by examining research perspectives and identifying important subareas through keyword analysis. Not applicable. Not applicable.


The sociodemographic characteristics and clinical features of the late-life depression patients: results from the Beijing Anding Hospital mental health big data platform.
The sociodemographic characteristics and clinical features of the Late-life depression (LLD) patients in psychiatric hospitals have not been thoroughly studied in China. This study aimed to explore the psychiatric outpatient attendance of LLD patients at a psychiatric hospital in China, with a subgroup analysis, such as with or without anxiety, gender differences. This retrospective study examined outpatients with LLD from January 2013 to August 2019 using data in the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) in Beijing Anding Hospital. Age, sex, number of visits, use of drugs and comorbid conditions were extracted from medical records. In a sample of 47,334 unipolar depression patients, 31,854 (67.30%) were women, and 15,480 (32.70%) were men. The main comorbidities of LDD are generalized anxiety disorder (GAD) (83.62%) and insomnia (74.52%).Among patients with unipolar depression, of which benzodiazepines accounted for the largest proportion (77.77%), Selective serotonin reuptake inhibitors (SSRIs) accounted for 59.00%, a noradrenergic and specific serotonergic antidepressant (NaSSAs) accounted for 36.20%. The average cost of each visit was approximately 646.27 yuan, and the cost of each visit was primarily attributed to Western medicine (22.97%) and Chinese herbal medicine (19.38%). For the cost of outpatient visits, depression comorbid anxiety group had a higher average cost than the non-anxiety group (p < 0.05). There are gender differences in outpatient costs, men spend more than women, for western medicine, men spend more than women, for Chinese herbal medicine, women spend more than men (all p < 0.05). The utilization rate of SSRIs and benzodiazepines in female patients is significantly higher than that in male patients (p < 0.05). LLD patients are more commonly women than men and more commonly used SSRIs and NaSSAs. Elderly patients with depression often have comorbid generalized anxiety. LLD patients spend most of their visits on medicines, and while the examination costs are lower.


[Development of malignant tumors in rats under the influence of nickel-containing aerosols].
The authors conducted observations of 70 nonpedigree white rats, subjected to inhalation, intraperitoneal or intratracheal effect of nickel-containing dusts (feinstein, nickel monoxide) typical for nickel black production. It was found that intraperitoneal injection of feinstein dusts after 6-15 months was followed by the development of sarcomas at the site of injection (in 6 of 39 rats). Following inhalation dusting with feinstein dust in one of 5 cases squamous cell lung carcinoma without keratinization has arisen. Intracheal injection of nickel monoxide dust resulted in the development of squamous cell lung carcinoma without keratinization in one of 26 rats. In control series no tumors were found. The data obtained indicate the blastomogenic effect of dusts of nickel black production and are in keeping with the results of epidemiological studies and dictate the necessity of radical measures of the combat against dust at nickel-production plants.


Measuring the deformation of a ferrogel sphere in a homogeneous magnetic field.
A sphere of a ferrogel is exposed to a homogeneous magnetic field. In accordance to theoretical predictions, it gets elongated along the field lines. The time dependence of the elastic shear modulus causes the elongation to increase with time, similar to mechanic creep experiments, and the rapid excitation causes the sphere to vibrate. Both phenomena can be well described by a damped harmonic oscillator model. By comparing the elongation along the field to the contraction perpendicular to it, we can calculate Poisson's ratio of the gel. The magnitude of the elongation is compared to the theoretical predictions for elastic spheres in homogeneous fields.


Involvement of kappa opioid receptors in formalin-induced inhibition of analgesic tolerance to morphine in mice.
This study examined the role of kappa opioid receptors (KOR) in the mechanism underlying tolerance to the analgesic effects of morphine induced by chronic pain. The analgesic effect of morphine (10 mg kg(-1)), estimated by the tail-flick test in mice, gradually decreased during repeated daily morphine treatment. A significant decrease in the analgesic effect of morphine was seen on the fifth day of repeated morphine treatment compared with the first day. Chronic pain was induced by subcutaneous administration of 2% formalin into the dorsal part of the left hind paw, which significantly inhibited development of tolerance to morphine analgesia. The effect of formalin-induced pain on inhibition of morphine tolerance was reversed by the KOR antagonist nor-binaltorphimine. Furthermore, an antisense oligodeoxynucleotide, but not a missense oligodeoxynucleotide, against KOR completely suppressed the inhibitory effect of formalin-induced pain on morphine tolerance. Naltrindole, an antagonist of delta opioid receptor, did not affect chronic-pain-induced tolerance to morphine. Our findings show that the inhibitory effect of chronic pain on analgesic tolerance to morphine is mediated by KOR rather than delta opioid receptors.


Validation of a type 1 diabetes algorithm using electronic medical records and administrative healthcare data to study the population incidence and prevalence of type 1 diabetes in Ontario, Canada.
We aimed to develop algorithms distinguishing type 1 diabetes (T1D) from type 2 diabetes in adults ≥18 years old using primary care electronic medical record (EMRPC) and administrative healthcare data from Ontario, Canada, and to estimate T1D prevalence and incidence. The reference population was a random sample of patients with diabetes in EMRPC whose charts were manually abstracted (n=5402). Algorithms were developed using classification trees, random forests, and rule-based methods, using electronic medical record (EMR) data, administrative data, or both. Algorithm performance was assessed in EMRPC. Administrative data algorithms were additionally evaluated using a diabetes clinic registry with endocrinologist-assigned diabetes type (n=29 371). Three algorithms were applied to the Ontario population to evaluate the minimum, moderate and maximum estimates of T1D prevalence and incidence rates between 2010 and 2017, and trends were analyzed using negative binomial regressions. Of 5402 individuals with diabetes in EMRPC, 195 had T1D. Sensitivity, specificity, positive predictive value and negative predictive value for the best performing algorithms were 80.6% (75.9-87.2), 99.8% (99.7-100), 94.9% (92.3-98.7), and 99.3% (99.1-99.5) for EMR, 51.3% (44.0-58.5), 99.5% (99.3-99.7), 79.4% (71.2-86.1), and 98.2% (97.8-98.5) for administrative data, and 87.2% (81.7-91.5), 99.9% (99.7-100), 96.6% (92.7-98.7) and 99.5% (99.3-99.7) for combined EMR and administrative data. Administrative data algorithms had similar sensitivity and specificity in the diabetes clinic registry. Of 11 499 711 adults in Ontario in 2017, there were 24 789 (0.22%, minimum estimate) to 102 140 (0.89%, maximum estimate) with T1D. Between 2010 and 2017, the age-standardized and sex-standardized prevalence rates per 1000 person-years increased (minimum estimate 1.7 to 2.56, maximum estimate 7.48 to 9.86, p<0.0001). In contrast, incidence rates decreased (minimum estimate 0.1 to 0.04, maximum estimate 0.47 to 0.09, p<0.0001). Primary care EMR and administrative data algorithms performed well in identifying T1D and demonstrated increasing T1D prevalence in Ontario. These algorithms may permit the development of large, population-based cohort studies of T1D.


Functional and physiopathological implications of TRP channels.
Transient Receptor Potential (TRP) channel proteins are a diverse family of proteins that are expressed in many organisms, tissues and cell types. TRP channels respond to a variety of stimuli, including light, mechanical or chemical stimuli, temperature, pH or osmolarity. In addition, several TRP family members have been identified as downstream molecules in the G protein-coupled receptor signaling pathway. TRP proteins are involved in a variety of cell functions both in non-excitable and excitable cells due to their diverse permeability to cations and their ability to modulate intracellular Ca2+ signaling. Emerging evidence suggests that TRP channel dysfunction significantly contributes to the physiopathology of a number of diseases, including cardiovascular, neurological, metabolic or neoplastic disorders. This review focuses on the implication of TRP proteins in the pathogenesis of some of the most prevalent disorders in human. We summarize the current findings regarding the role of TRP proteins in the development of cardiovascular disease, diabetes mellitus as well as diabetic complications, and tumorigenesis and present TRP proteins as targets of potential diagnostic and therapeutic strategies.


Allergen Immunotherapy: History and Future Developments.
Allergen immunotherapy (AIT) was introduced in clinical practice more than 100 years ago. The clinical effectiveness in allergic rhinitis (and asthma) and in hymenoptera allergy was apparent early on but it was not until the mid-1900s that randomized placebo-controlled trials proved its efficacy. In the 1980s, sublingual immunotherapy (SLIT) was accepted in official guidelines. The availability of safer routes, such as SLIT, prompted increasing investigation of AIT for food allergy. The introduction of molecular-based diagnosis introduced the possibility of better targeted prescription of AIT. Other approaches are being explored, such as immunogenic peptides, recombinant allergens, and adjuvants.


An International Collaborative Study of the assay of human placental lactogen: Establishment of WHO International Reference Preparation of human placental lactogen.
A reference preparation of human placental lactogen (HPL) for use in immunoassays is described. In an international collaborative study is was found to be stable and suitable for use as a standard for HPL in plasma. Estimates of HPL in plasma made in different laboratories agreed more closely when expressed in terms of this reference preparation than in terms of individual laboratory standards. The reference preparation is available in ampoules (coded 73/545) which each contain an identical amount of HPL, found in the study to be approximately 850 microgram. The preparation has been established as the International Reference Preparation for HPL for immunoassay and, based on the results of the study, the content of each ampoule is defined as 850 micro International Units.


Advances in urological laparoscopy.
Since its introduction 5 years ago, almost all open urological procedures have been performed laparoscopically. We provide an in-depth critical review. More than 200 articles on laparoscopic urology were reviewed. All laparoscopic procedures were divided into clinically established, clinically anecdotal and laboratory procedures. Comparisons between the laparoscopic and open method were carefully analyzed. There were 5 clinically established procedures identified. In general, the laparoscopic procedures were as efficacious but less morbid and required less convalescence than their open counterparts; however, none was less costly. Despite the time-consuming and costly nature of laparoscopy, the decreased morbidity and brief convalescence that are the hallmarks of minimally invasive surgery are evident and well documented. Further dissemination of laparoscopic skills through postgraduate urology training programs and during urology residency is of the utmost importance.


Blunt rectal trauma causing intramural rectal hematoma: report of a case.
An unusual case is reported in which intramural rectal hematoma resulted from rectal insertion of a foreign body. The patient was admitted to the hospital for observation and was catheterized because of urinary retention. The patient was discharged from the hospital after four days; for the last two days of this hospital stay, the patient received a liquid diet. We conclude that for some cases of uncomplicated intramural rectal hematoma, conservative management is safe and preferable to surgically draining the hematoma, which would increase the risk of infection.


Distribution and molecular composition of heterochromatin in the holocentric chromosomes of the aphid Rhopalosiphum padi (Hemiptera: Aphididae).
In order to study the structure of holocentric chromosomes in aphids, the localization and the composition of Rhopalosiphum padi heterochromatin and rDNA genes have been evaluated at cytogenetic and molecular level. In particular, heterochromatin resulted located on all the chromosomes both in intercalary and telomeric positions. Moreover, enzymatic digestion of R. padi genome put in evidence a DraI satellite DNA which has been isolated, cloned and sequenced. FISH experiments showed that this satellite DNA clusters in an intercalary C-positive band on the two X chromosomes.


[The need of regulation of production of components for forensic-medical molecular-genetic technologies and improvement of legal basis of forensic-medical molecular-genetic expert examinations in the Russian Federation].
Of late, Ministry of Health of Russian Federation has developed instructions concerning forensic-medical molecular genetic methods of analysis promoting creation of standardized forensic-medical genetic service. However, some legal uncertainty exists in respect to design and production of the materials for forensic-medical molecular-genetic technologies, unification and standardization of molecular-genetic kits and methods. It is thought necessary to regulate legally forensic medical molecular-genetic technologies from foreign countries and production and use of domestic components for forensic medical molecular-genetic expert examinations.


[Hopkins' syndrome in the differential diagnosis of flaccid paralysis in children: clinical and neurophysiological features. Case report].
Hopkins syndrome is a motor neuron disease which leads to a flaccid paralysis affecting one or more limbs resembling poliomyelites. It follows an asthmatic attack and the prognosis is poor. All the 34 related cases occured after 13 months of age and there is no report in South America. Our objective is to describe a case of Hopkins Syndrome in Brazil affecting a patient younger than 1 year. Male 4 months-old infant, started presenting wheezing that turned into respiratory failure which required mecanical ventilation. Three days later he initiated with loss of strength in the lower limbs (LL). The patient was dismissed from hospital better of his respiratory complains but still paraparetic. Five months later, the patient returned with another episode of severe bronchospasm. At that time, he presented with flaccid paralysis, arreflexia and atrophy of the LL. There were no upper limbs and sensory abnormalities. The patient undergone to lumbar puncture, spinal MRI and SEPs which were all normal. MUSCLE BIOPSY: type grouping. EMG and NCS were in keeping with motor neuron disease affecting just the lumbosacral region. Hopkins syndrome should be included in the differential diagnosis of any flaccid paralysis when it is associated with an asthma attack.


Provora.
Tikhonenkov et al. introduce the Provora-a newly described, yet ancient, supergroup of unicellular protists encompassing as much genetic diversity as animals and fungi combined.


Understanding NF-kappaB signaling via mathematical modeling.
Mammalian inflammatory signaling, for which NF-kappaB is a principal transcription factor, is an exquisite example of how cellular signaling pathways can be regulated to produce different yet specific responses to different inflammatory insults. Mathematical models, tightly linked to experiment, have been instrumental in unraveling the forms of regulation in NF-kappaB signaling and their underlying molecular mechanisms. Our initial model of the IkappaB-NF-kappaB signaling module highlighted the role of negative feedback in the control of NF-kappaB temporal dynamics and gene expression. Subsequent studies sparked by this work have helped to characterize additional feedback loops, the input-output behavior of the module, crosstalk between multiple NF-kappaB-activating pathways, and NF-kappaB oscillations. We anticipate that computational techniques will enable further progress in the NF-kappaB field, and the signal transduction field in general, and we discuss potential upcoming developments.


Meta-Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.
Concurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC. Two reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC. Eight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083; p = .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905; p = .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760; p < .001). Although ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted. Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC.


Food composition activities in South Africa.
Researchers at the South African Medical Research Council used the Bangkok Declaration, Thailand, 2009, as a guideline for their food composition activities. The vision is to build a comprehensive food composition database for the country. Activities are directed at increasing the number of food items with country-specific nutrient information; encouraging research organisations, universities and the food industry to become involved in nutrient data generation and the generation of yield factors for South African dishes. The introduction of the South African Food Data System (SAFOODS) website and a symposium were major food composition activities. Educating users on the correct application of food composition data is an important endeavour. The national South African Food Data Advisory Group (SAFDAG) formed in 2008, advises and supports food composition activities at SAFOODS. In conclusion, with the support of SAFDAG, SAFOODS activities are aimed at compiling a country-specific food composition database and promoting its scientific use.


Relativism in Feyerabend's later writings.
This paper reconstructs, and distinguishes between, Feyerabend's different forms of relativism in his later writings. Science in a Free Society remains close to familiar forms of relativism, while, at the same time, developing an original but under-argued form of political relativism, and rejecting "conversion" models of cultural exchange. Farewell to Reason moves away from common renderings of relativism, and develops a range of different new forms. Central here are links between relativism, skepticism and infallibilism. In the last six years of his life, Feyerabend often criticizes a peculiar radical form of relativism that arguably no-one has ever proposed or defended. In the same context, Feyerabend sketches an "ontological" form of relativism. It combines "Kantian humility", metaphysical pluralism and constructivism.


Radical cystectomy with or without planned preoperative irradiation in the treatment of bladder cancer.
A retrospective analysis of 342 patients with carcinoma of the bladder treated by radical cystectomy at Memorial Sloan Kettering Cancer Center with or without planned preoperative irradiation revealed that preoperative irradiation significantly improved survival of patients with deeply infiltrating tumours (pathological Stage B2 and C), and reduced the prognostic importance of distinctions between pathological B1 and B2 neoplasms. Preoperative irradiation had no discernible effect on the survival of patients with superficially infiltrating neoplasms.