Modeling electrokinetics in ionic liquids.
Using direct numerical simulations, we provide a thorough study regarding the electrokinetics of ionic liquids. In particular, modified Poisson-Nernst-Planck equations are solved to capture the crowding and overscreening effects characteristic of an ionic liquid. For modeling electrokinetic flows in an ionic liquid, the modified Poisson-Nernst-Planck equations are coupled with Navier-Stokes equations to study the coupling of ion transport, hydrodynamics, and electrostatic forces. Specifically, we consider the ion transport between two parallel charged surfaces, charging dynamics in a nanopore, capacitance of electric double-layer capacitors, electroosmotic flow in a nanochannel, electroconvective instability on a plane ion-selective surface, and electroconvective flow on a curved ion-selective surface. We also discuss how crowding and overscreening and their interplay affect the electrokinetic behaviors of ionic liquids in these application problems.


Adenocarcinoma of rete testis.
Adenocarcinoma of the rete testis is a rare tumor of the genital tract. An advanced case of adenocarcinoma thought to arise from the rete testis is presented. We believe this is the eighteenth reported case.


Interactions among stream fishes: predator-induced habitat shifts and larval survival.
Adult largemouth bass alter habitat use by, and abundances of, other fishes in small streams. Experimental manipulations of bass in natural stream pools (Brier Creek, Oklahoma) showed that responses of other fishes to adult bass were highly dependent on prey size, and that both direct and indirect effects of adult bass influence the distribution and abundance of other stream fishes. Experiments measuring the distributional responses of members of natural pool assemblages to adult bass revealed differences among adult sunfishes, "small" fishes (16-80 mm SL), and larval sunfish and minnows. Adult sunfishes (Lepomis spp.) did not detectably alter their depth distribution in response to adult bass, but changes in abundance of adult Lepomis on the whole-pool scale appeared positively related to changes in the number of bass. Small fishes tended to occupy shallower water when adult bass were present; changes in abundance of small fishes were negatively related to the number of adult bass. Larval minnows and larval Lepomis occupied primarily deep, mid-regions of pools, and were found only in pools which contained, or had contained, adult bass. A second set of experiments was motivated by censuses of small prairie-margin streams which revealed co-occurrence of larval fishes (of both minnow and sunfish species) and adult largemouth bass. Experimental manipulation of bass and Lepomis larvae on the whole-pool scale showed that adult bass enhanced short-term survival of Lepomis larvae. This effect appears to be an indirect result of habitat shifts by small fishes in response to bass; additional experiments indicated that these small fishes are potentially important predators of larvae. The interactions suggested in this study are analogous to those hypothesized for bass and sunfish in lakes by Werner and Hall (1988).


Foetal remnants in the uterus and their relation to other uterine heterotopia.
Foetal remnants were found in uterine curettings obtained from three women complaining of irregular vaginal bleeding. These findings are discussed in relation to other cases in the literature in which heterotopic tissues have been found in curettings and also for the light they throw on the origin of the so-called uterine teratomas.


Molecular identification and typing of Mycobacterium massiliense isolated from postsurgical infections in Brazil.
One hundred thirty-one cases of postsurgical infections were reported in Southern Region of Brazil between August 2007 and January 2008. Thirty-nine (29.8%) cases were studied; this report describes epidemiological findings, species identification, antimicrobial susceptibility and clonal diversity of rapidly growing mycobacteria isolated in this outbreak. All 39 isolates were analyzed by Ziehl-Nielsen stained smear, bacterial culture and submitted to rpoB partial gene sequencing for identification. The isolates were also evaluated for their susceptibility to amikacin, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, tobramycin and sulfamethoxazole. Thirty-six isolates out of the confirmed cases were identified as Mycobacterium massiliense and the remaining three were identified as Mycobacterium abscessus, Mycobacterium chelonae and Mycobacterium fortuitum. All M. massiliense isolates were susceptible to amikacin (MIC90 = 8 µg/mL) and clarithromycin (MIC90 = 0.25 µg/mL) but resistant to cefoxitin, ciprofloxacin, doxycycline, tobramycin and sulfamethoxazole. Molecular analysis by pulsed-field gel electrophoresis clustered all 36 M. massiliense isolates and showed the same pattern (BRA 100) observed in three other outbreaks previously reported in Brazil. These findings suggest a common source of infection for all patients and reinforce the hypotheses of spread of M. massiliense BRA100 in Brazilian hospital surgical environment in recent years.


Chromosomal localization of ARSB, the gene for human N-acetylgalactosamine-4-sulphatase.
A deficiency of N-acetylgalactosamine-4-sulphatase (G4S, gene symbol ARSB), results in the accumulation of undegraded substrate and the lysosomal storage disorder, Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). In situ hybridization using an 3H-labelled human G4S genomic DNA fragment to human metaphase chromosomes localized ARSB to chromosome 5q13-5q14. This location is consistent with, an refines, previous chromosomal assignments based on the expression of human G4S in somatic cell hybrids.


TiO2 seeded on nitrogen-doped porous carbon nanofibers for superior electrochemical performance as freestanding anodes of lithium-ion batteries.
Fibrous mats piled by nitrogen-doped porous carbon nanofibers with seeded TiO2 are fabricated and punched directly into circles as lithium-ion battery anodes. The seeding structure is composed of semi-wrapped TiO2 nanoparticles on carbon nanofibers (CNFs) coated with a thin layer of carbon. Synchronously, pores with various widths are formed on CNFs. As a freestanding anode, an initial discharge capacity of 615 mAh g-1 with a coulombic efficiency of 56% is reached, and 322 mAh g-1 is obtained after 100 cycles at a current density of 100 mA g-1. This is assigned to the increasing number of active sites for the lithium ion from pores with various widths and improved conductivity originating from nitrogen doping. Superior rate performance (179 mAh g-1 at the current density of 2000 mA g-1) under various current densities compared with that of other counterparts is attributed to the structural stability originating from the seeding structure with the help of the C-O-Ti bond. An additional 800 cycles are displayed at the current density of 2000 mA g-1, and superior stability is also exhibited.


Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma.
Fibroblast growth factor receptor 2 (FGFR2) genetic alterations lead to tumor cell proliferation in various types of cancer. We hypothesized that FGFR2 amplification is associated with FGFR2 expression, resulting in tumor growth and poorer outcome in esophagogastric junction (EGJ) adenocarcinoma. A total of 176 consecutive chemo-naive patients with EGJ adenocarcinoma were enrolled from two academic institutions. FGFR2 amplification was examined by real-time PCR (N = 140) and FGFR2 expression with immunohistochemical staining (N = 176), and compared against clinicopathological factors and patient outcomes. The effects of FGFR2 inhibition or overexpression on cell proliferation, cell cycle, and apoptosis assays were investigated in EGJ adenocarcinoma cell lines. Downstream FGFR2, AKT and ERK were also examined. Based on the correlation between FGFR2 levels and FGFR2 overexpression in vitro, FGFR2 amplification was defined as copy number > 3.0. In clinical samples, FGFR2 amplification and FGFR2 IHC expression were 15% and 61%, respectively. Although these two statuses were significantly correlated (P < 0.05), only FGFR2 IHC expression was significantly associated with tumor depth (multivariate P < 0.001) and overall survival of patients (univariate P = 0.007). Supporting these findings, FGFR2 overexpression was associated with tumor cell proliferation, cell cycle progression, and anti-apoptosis. Selective inhibition of FGFR2 sufficiently suppressed tumor cell proliferation through de-phosphorylation of AKT and ERK. FGFR2 amplification was significantly associated with FGFR2 expression. FGFR2 expression (but not FGFR2 amplification) was associated with tumor growth and patient outcomes. Our findings support FGFR2 as a novel therapeutic target for EGJ adenocarcinoma.


[Cutis verticis gyrata, hypertrophic gastritis, motrice diarhea, and horse's tall syndrome, a new association an apudoma (carcinoid or chemodectoma) (author's transl)].
The authors report the observation of a 70 years male with Cutis Verticis Gyrata (without hypertrophying osteopathy), Menetrier's hypertrophic gastritis, motrice diarrhea of the endocrine type, flush syndrom, liver angiomatosis and a large sacral water clear cells tumor with horse's tail syndrom. The initial tumor was on the posterior wall of rectum, but was necrosed : bone metastasing chemodectoma, or locally invading carcinoid ? This new complex paraneoplastic disease seems to be associated with APUD tumor.


Structure and organization of a mammalian 5 S gene cluster.
We have cloned and characterized a G+C-rich 2.2-kilobase pair Bam HI fragment which contains a single Syrian hamster 5 S rRNA gene. The cloned fragment directs the synthesis in vitro of 5 S RNA catalyzed by RNA polymerase III. Southern hybridization analysis of genomic hamster DNA indicates that the sequences present in the clone are tandemly repeated with a redundancy of 2700 copies per diploid cell.


The interaction of N-oleylethanolamine with phospholipid bilayers.
Long chain acylamides of ethanolamine were previously found to increase in the infarcted canine myocardium. Subsequent in vitro experiments established a number of interesting biological and physiological properties of these compounds including alteration of rabbit skeletal sarcoplasmic reticulum function and inhibition of permeability dependent calcium release from heart mitochondria. These results suggested an interaction between the N-acylethanolamines and biological membranes. In the present work we show that the most potent species in previous studies, N-oleylethanolamine, forms stable complexes with phospholipid vesicles, lowers diphenylhexatriene polarization ratios in dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine uni- and multilamellar bilayer vesicles, and also produces a concentration dependent decrease in the phase transitions of these lipid structures. In addition studies with parinaric acids also suggested that N-oleylethanolamine partitions preferentially into more fluid areas of the bilayer. The results are discussed in terms of possible effects on biological membranes.


Patterns of activity correlate with symptom severity in major depressive disorder patients.
Objective measures, such as activity monitoring, can potentially complement clinical assessment for psychiatric patients. Alterations in rest-activity patterns are commonly encountered in patients with major depressive disorder. The aim of this study was to investigate whether features of activity patterns correlate with severity of depression symptoms (evaluated by Montgomery-Åsberg Rating Scale (MADRS) for depression). We used actigraphy recordings collected during ongoing major depressive episodes from patients not undergoing any antidepressant treatment. The recordings were acquired from two independent studies using different actigraphy systems. Data was quality-controlled and pre-processed for feature extraction following uniform procedures. We trained multiple regression models to predict MADRS score from features of activity patterns using brute-force and semi-supervised machine learning algorithms. The models were filtered based on the precision and the accuracy of fitting on training dataset before undergoing external validation on an independent dataset. The features enriched in the models surviving external validation point to high depressive symptom severity being associated with less complex activity patterns and stronger coupling to external circadian entrainers. Our results bring proof-of-concept evidence that activity patterns correlate with severity of depressive symptoms and suggest that actigraphy recordings may be a useful tool for individual evaluation of patients with major depressive disorder.


Myocardial damage after successful thrombolysis is associated with the duration of ST re-elevation at reperfusion.
The purpose of this study was to investigate the significance of ST re-elevation at reperfusion using strict criteria for patient inclusion and exclusion. Twenty-nine patients who had a first anterior infarction with single-vessel disease, successful recanalization by intracoronary thrombolysis (ICT) with urokinase, and an angiographically confirmed patent infarct-related artery after 4 weeks, were divided into three groups according to the deviation of the ST segment at reperfusion: Group A, 10 patients with sustained ST re-elevation; Group B, 10 patients with transient ST re-elevation; and Group C, 9 patients with ST reduction. Left ventricular (LV) function was evaluated from cineventriculograms performed in the 30 degrees right anterior projection 4 weeks after ICT. LV ejection fraction and regional wall motion of the infarct area, evaluated by the centerline method (SD/chords), were significantly lower in Group A (44 +/- 10%, -3.2 +/- 0.4) than in Group B (61 +/- 9%, -1.9 +/- 0.7) and Group C (60 +/- 5%, -2.0 +/- 0.4) (p < 0.01). Peak creatine kinase (CK) activity was significantly higher in Group A (5848 +/- 2112 IU) than in Group B (2485 +/- 1254 IU) and Group C (1889 +/- 1525 IU) (p < 0.05). These data suggest that a sustained ST re-elevation at reperfusion was strongly associated with marked LV dysfunction and higher peak CK activity. It was concluded that sustained, not transient, ST re-elevation associated with successful reperfusion indicates extensive myocardial damage.


A new technique applicable to pediatric laparoscopic surgery: abdominal wall 'area lifting' with subcutaneous wiring.
Recently, the authors developed a unique method of laparoscopic surgery without pneumoperitoneum: "area lifting of the abdominal wall with subcutaneous wiring." In this gasless procedure, the anterior abdominal wall is pulled upward by a pair of wires placed subcutaneously and held by thick sutures for "hanger lifting." Simultaneous lifting of a pair of subcutaneous wires across the abdomen, produces a wide, roof-shaped intraabdominal space sufficient for laparoscopic surgical procedures. The practical aspects of this gasless technique, as well as the authors' limited experience with this method in 24 children, ranging from 8 days to 15 years of age is presented. These children have had various pathologies including splenomegaly, rectal prolapse, ovarian cyst, gall stone, adrenal neuroblastoma, and abdominal wall abscess. Gasless laparoscopic surgery with double subcutaneous wiring is safe for children including neonates and those with respiratory compromise because all operative procedures are performed under normal abdominal pressure. Because of the highly elastic abdominal wall musculature inherent in children, this selective area lifting of abdominal wall creates a relatively larger peritoneal volume than in adults.


Synergistic interaction of gut microbiota enhances the growth of nematode through neuroendocrine signaling.
Animals are associated with a diverse bacterial community that impacts host physiology. It is well known that nutrients and enzymes synthesized by bacteria largely expand host metabolic capacity. Bacteria also impact a wide range of animal physiology that solely depends on host genetics through direct interaction. However, studying the synergistic effects of the bacterial community remains challenging due to its complexity. The omnivorous nematode Pristionchus pacificus has limited digestive efficiency on bacteria. Therefore, we established a bacterial collection that represents the natural gut microbiota that are resistant to digestion. Using this collection, we show that the bacterium Lysinibacillus xylanilyticus by itself provides limited nutritional value, but in combination with Escherichia coli, it significantly promotes life-history traits of P. pacificus by regulating the neuroendocrine peptide in sensory neurons. This gut-to-brain communication depends on undigested L. xylanilyticus providing Pristionchus nematodes a specific fitness advantage to compete with nematodes that rupture bacteria efficiently. Using RNA-seq and CRISPR-induced mutants, we show that 1-h exposure to L. xylanilyticus is sufficient to stimulate the expression of daf-7-type TGF-β signaling ligands, which induce a global transcriptome change. In addition, several effects of L. xylanilyticus depend on TGF-β signaling, including olfaction, body size regulation, and a switch of energy allocation from lipid storage to reproduction. Our results reveal the beneficial effects of a gut bacterium to modify life-history traits and maximize nematode survival in natural habitats.


Value elements and methods of value-based pricing for drugs in Japan: a systematic review.
Value-based pricing (VBP) can be a promising tool for optimizing drug prices. However, there is no consensus on the specific value elements and pricing method that should be used for VBP. We performed a systematic review and narrative synthesis to investigate the value elements and pricing method for VBP. The main inclusion criterion was that value elements, VBP method, and estimated prices for actual drugs were reported. We performed a search in MEDLINE and ICHUSHI Web. Eight articles met the selection criteria. Four studies adopted the cost-effectiveness analysis (CEA) approach and the others used different approaches. The CEA approach included the value elements of productivity, value of hope, real option value, disease severity, insurance value in addition to costs and quality-adjusted life years. The other approaches used efficacy, toxicity, novelty, rarity, research and development costs, prognosis, population health burden, unmet needs, and effectiveness. Each study used individual methods to quantify these broader value elements. Both conventional and broader value elements are used for VBP. To allow VBP to be widely applied to various diseases, a simple, versatile method is preferable. Further research is needed to establish VBP method which enables to incorporate broader values.


Groups of darkly stained chromosomes may be artifacts.
Groups or conglomerations of darkly stained chromosomes (GDSC) observed in this study appeared to be artifacts as they were strictly technique dependent. Two methods of cell fixation were compared. In method I, fixative was added drop by drop to cell pellets and agitated continuously over a rotamixer. In method II, a few drops of fixative were added to hypotonic solution suspended with cells and mixed using a Pasteur pipette. In 11 patients with acute myeloid leukemia (AML) and in one patient with preleukemia studied using method I, no GDSC were found in the total of 325 metaphases examined. In 36 patients with AML, one with Klinefelter's syndrome and one with neutropenia studied using method II, GDSC were found in 18 patients. A further comparative study using different methods for cell fixation was performed in three patients. The frequency of cells with GDSC varied sharply with different methods used in two patients. In one patient the cells with GDSC were analyzed in detail. The number of darkly stained chromosomes in each cell was found to vary from 4 to 14 with a mean of 8.26 and D- and G-group chromosomes were preferentially involved.


Percutaneous transluminal angioplasty in selected patients with severe carotid artery stenoses: the results of a consecutive series of 24 patients.
To assess clinically and with duplex scanning the results of percutaneous transluminal angioplasty in a subgroup of patients with carotid artery stenosis. A retrospective study. Twenty-four patients with focal hemispheric neurological symptoms from a concentric, smooth carotid stenosis more than 70% treated with balloon dilatation. Control investigations were performed with duplex scanning. Angiography after PTA revealed no residual stenosis in 15 patients (62%), a stenosis of less than 50 was seen in seven patients (30%) and PTA was ineffective in two patients (8%). Three patients (13%) had transient ischaemic attacks during the procedure but none had strokes. One patient experienced short lasting paraesthesia of the arm a few hours after the PTA procedure. After a follow-up of a mean of 11 months (1-38) no recurrent symptoms had occurred. Clinical success was thus achieved in 22 of 24 patients (92%). At duplex scanning, 16 (66%) patients had no stenosis, six patients (30%) had a stenosis of 70%, one patient (4%) a stenosis of 80%, and one patient had an occluded carotid artery. Our results indicate that PTA in a selected group of patients with carotid artery stenosis is safe and the interim, long-term results are promising. The procedure must be evaluated in a randomised prospective study against surgical treatment.


[Comparative experimental study of the effect of melatonin and 5-methoxytryptamine on the thyroid gland of rats].
The authors studied the reactivity of the pituitary-thyroid system as influenced by melatonin and mexamine at varying times of photoperiod. It is concluded that the drugs under study had uncertain effects on rat thyroid function. It is assumed that different components of the hypothalamus-pituitary-thyroid system experience seasonal alterations in the sensitivity to the action of pineal gland methoxyindoles.


Effect of thioridazine on phenytoin serum concentration: a retrospective study.
Serum phenytoin concentrations before and after the addition of thioridazine were retrospectively compared in 27 adults to determine if an interaction occurred between these two drugs. A change in the serum phenytoin concentration of +/- 4 micrograms/ml was considered clinically significant; by this definition four patients (14.8 percent) had an increase, two (7.4 percent) had a decrease, and most (77.8 percent) demonstrated no change. The mean difference was 0.8 microgram/ml +/- 3.7 micrograms/ml and was not found to be statistically significant (p less than 0.1). Clinically important alterations in phenytoin serum concentration as caused by thioridazine appear to be infrequent.


High-performance liquid chromatographic separation of peptide and amino acid stereoisomers.
Several high-performance liquid chromatographic (HPLC) methods are described for separation of peptide stereoisomers which are not well resolved by traditional reversed-phase chromatography. These chiral HPLC methods include investigations with a beta-cyclodextrin column, a Pirkle D-Phenyl Glycine column and a Chiral-Pak WH column. A method based on derivatization of dipeptides with a chiral reagent, N-acetyl-L-cysteine and o-phthalaldehyde, is also discussed. A series of linear and cyclic dipeptides and modified amino acids were chromatographed on the four systems. Resolution varied for the four different systems depending on the types of compounds that were chromatographed.


The inhibitory effects of danazol, danazol metabolites, gestrinone, and testosterone on the growth of human endometrial cells in vitro.
Danazol and gestrinone are effective drugs in the treatment of endometriosis. Their mechanism of action remains uncertain, but may be related to their androgenic activity. The authors examined the effect of danazol on human endometrial cells cultured in vitro, its two major metabolites, ethisterone and 2 hydroxymethyl ethisterone, gestrinone, and testosterone (T) at 1X and 10X expected plasma concentrations. Danazol and T suppressed growth by 20.8 and 25.0% (P less than 0.01), respectively, at the lower dose, and by 26.9 and 35.5% (P less than 0.01), respectively, at the 10-fold higher dose. No significant suppression of growth occurred with gestrinone, ethisterone, or 2 hydroxymethyl ethisterone. The results provide further evidence that danazol and T (but not gestrinone) may act by a direct effect on endometrial tissue.


Unveiling the mystery of ILC3s: Their functions and interactions in mucosal immunity.
Innate lymphoid cells (ILCs) are a recently discovered subset of immune cells that play a crucial role in preserving tissue health and combating infections. Among these, ILC3s are particularly vital in regulating mucosal immunity across multiple organs such as the gut, lungs, and skin. The purpose of this article is to present a comprehensive and detailed overview of current knowledge on ILC3s, with a specific emphasis on their intricate interactions with various components of the intestinal microenvironment. Recent research on the complex, bidirectional communication pathways between ILC3s and intestinal epithelial cells, stromal cells, immune cells, microbiota, their metabolites, and diet are highlighted. Furthermore, this review comprehensively examines the diverse functions of ILC3s, which include lymphoid tissue development, tissue repair, infection, inflammation, and metabolic diseases, as well as the effector molecules that facilitate these functions. Overall, this review provides valuable insights into the biological and functional aspects of ILC3s and underscores their potential for developing innovative therapies for immune-mediated disorders, while also acknowledging the remaining knowledge gaps and challenges that need to be addressed.


Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood.
Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 10(3)-10(6) cells (10(-3)-10(-6)) during follow-up of children with acute lymphoblastic leukaemia (ALL) can provide insight into the effectiveness of cytotoxic treatment. However, it is not yet clear how information on MRD can be applied to treatment protocols. We monitored 240 patients with childhood ALL who were treated according to national protocols of the International BFM Study Group. 60 patients relapsed and the patients in continuous complete remission (CCR) had a median event-free follow-up of 48 months. Bone-marrow samples were collected at up to nine time points during and after treatment. Standardised PCR analysis of patient-specific immunoglobulin and T-cell receptor gene rearrangements and TAL1 deletions were used as targets for semiquantitative estimation of MRD. Amount of MRD was classed as 10(-2) or more, 10(-3), and 10(-4) or less. MRD negativity at the various follow-up times was associated with low relapse rates (3-15% at 3 years), but five-fold to ten-fold higher relapse rates (39-86% at 3 years) were found in MRD-positive patients. The distinct degrees of MRD appeared to have independent prognostic value (p [trend]<0.001) at all separate time points, especially at the first two time points (at the end of induction treatment and before consolidation treatment). At these two time points a high degree of MRD (> or = 10(-2)) was associated with a three-fold higher relapse rate when compared with patients with a low degree of MRD (< or = 10(-4)). At later time points (including the end of treatment) even a low degree of MRD was associated with a poor outcome. Positivity in patients in CCR after treatment was rare (< 1%). With the combined MRD information from the first two follow-up time points, it was possible to recognise three different risk groups--55 (43%) were in a low-risk group and had a 3-year relapse rate of only 2% (95% CI 0.05-12%); 19 (15%) were in a high-risk group and had a relapse rate of 75% (55-95%); and 55 (43%) were in an intermediate-risk group and had a 3-year relapse rate of 23% (13-36%). Our collaborative MRD study shows that monitoring patients with childhood ALL at consecutive time points gives clinically relevant insight into the effectiveness of treatment. Combined information on MRD from the first 3 months of treatment distinguishes patients with good prognoses from those with poor prognoses, and this helps in decisions whether and how to modify treatment.


Device-measured sitting time and musculoskeletal pain in adults with normal glucose metabolism, prediabetes and type 2 diabetes-The Maastricht Study.
Detrimental associations of sedentary behaviour (time spent sitting) with musculoskeletal pain (MSP) conditions have been observed. However, findings on those with, or at risk of, type 2 diabetes (T2D) have not been reported. We examined the linear and non-linear associations of device-measured daily sitting time with MSP outcomes according to glucose metabolism status (GMS). Cross-sectional data from 2827 participants aged 40-75 years in the Maastricht Study (1728 with normal glucose metabolism (NGM); 441 with prediabetes; 658 with T2D), for whom valid data were available on activPAL-derived daily sitting time, MSP [neck, shoulder, low back, and knee pain], and GMS. Associations were examined by logistic regression analyses, adjusted serially for relevant confounders, including moderate-to-vigorous intensity physical activity (MVPA) and body mass index (BMI). Restricted cubic splines were used to further examine non-linear relationships. The fully adjusted model (including BMI, MVPA, and history of cardiovascular disease) showed daily sitting time to be significantly associated with knee pain in the overall sample (OR = 1.07, 95%CI: 1.01-1.12) and in those with T2D (OR = 1.11, 95%CI: 1.00-1.22); this was not statistically significant in those with prediabetes (OR = 1.04, 95%CI: 0.91-1.18) or NGM (OR = 1.05, 95%CI: 0.98-1.13). There were no statistically significant associations between daily sitting time and neck, shoulder, or low back pain in any of the models. Furthermore, the non-linear relationships were statistically non-significant. Among middle-aged and older adults with T2D, daily sitting time was significantly associated with higher odds of knee pain, but not with neck, shoulder, or low back pain. No significant association was observed in those without T2D for neck, shoulder, low back, or knee pain. Future studies, preferably those utilising prospective designs, could examine additional attributes of daily sitting (e.g., sitting bouts and domain-specific sitting time) and the potential relationships of knee pain with mobility limitations.


Health and access to care for undocumented migrants living in the European Union: a scoping review.
Literature on health and access to care of undocumented migrants in the European Union (EU) is limited and heterogeneous in focus and quality. Authors conducted a scoping review to identify the extent, nature and distribution of existing primary research (1990-2012), thus clarifying what is known, key gaps, and potential next steps. Authors used Arksey and O'Malley's six-stage scoping framework, with Levac, Colquhoun and O'Brien's revisions, to review identified sources. Findings were summarized thematically: (i) physical, mental and social health issues, (ii) access and barriers to care, (iii) vulnerable groups and (iv) policy and rights. Fifty-four sources were included of 598 identified, with 93% (50/54) published during 2005-2012. EU member states from Eastern Europe were under-represented, particularly in single-country studies. Most study designs (52%) were qualitative. Sampling descriptions were generally poor, and sampling purposeful, with only four studies using any randomization. Demographic descriptions were far from uniform and only two studies focused on undocumented children and youth. Most (80%) included findings on health-care access, with obstacles reported at primary, secondary and tertiary levels. Major access barriers included fear, lack of awareness of rights, socioeconomics. Mental disorders appeared widespread, while obstetric needs and injuries were key reasons for seeking care. Pregnant women, children and detainees appeared most vulnerable. While EU policy supports health-care access for undocumented migrants, practices remain haphazard, with studies reporting differing interpretation and implementation of rights at regional, institutional and individual levels. This scoping review is an initial attempt to describe available primary evidence on health and access to care for undocumented migrants in the European Union. It underlines the need for more and better-quality research, increased co-operation between gatekeepers, providers, researchers and policy makers, and reduced ambiguities in health-care rights and obligations for undocumented migrants.


Palladium-Catalyzed Coupling of Functionalized Primary and Secondary Amines with Aryl and Heteroaryl Halides: Two Ligands Suffice in Most Cases.
We report our studies on the use of two catalyst systems, based on the ligands BrettPhos (1) and RuPhos (2), which provide the widest scope for Pd-catalyzed C-N cross-coupling reactions to date. Often low catalyst loadings and short reaction times can be used with functionalized aryl and heteroaryl coupling partners. The reactions are highly robust and can be set up and performed without the use of a glovebox. These catalysts should find wide application in the synthesis of complex molecules including pharmaceuticals, natural products and functional materials.


Combined measurement of fetal lung volume and pulmonary artery resistance index is more accurate for prediction of neonatal respiratory distress syndrome in preterm fetuses: a pilot study.
The objective of this study is to estimate optimal cut-off values for mean fetal lung volume (FLV) and pulmonary artery resistance index (PA-RI) as non-invasive measures to predict neonatal respiratory distress syndrome (RDS) in preterm fetuses. A prospective study conducted at Ain Shams University Maternity Hospital, Egypt from May 2015 to July 2017: 80 eligible women diagnosed with preterm labor were recruited at 32-36 weeks' gestation. Before delivery, three-dimensional ultrasound was used to estimate FLV using virtual organ computer-aided analysis (VOCAL), while PA-RI was measured by Doppler ultrasonography. A total of 80 women were examined. Thirty-seven (46%) of the newborns developed neonatal RDS. FLV was significantly lower in neonates who developed RDS (p = .04), whereas PARI was significantly higher in those who did not (p = .02). Cut-off values of FLV ≤27.2 cm3 and PARI ≥0.77 predicted the subsequent development of RDS. Combining both cut-offs generated a more sensitive and specific methodical approach for the prediction of RDS (sensitivity 100%, specificity 88.5%). Measurement of FLV or PA-RI can predict RDS in preterm fetuses. Combined use of both measures bolstered their predictive significance.


The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D.
Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show that glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), and apolipoproteins are critical for glial LD formation. MCTs enable glia to secrete and neurons to absorb lactate, which is converted to pyruvate and acetyl-CoA in neurons. Lactate metabolites provide a substrate for synthesis of fatty acids, which are processed and transferred to glia by FATP and apolipoproteins. In the presence of high ROS, inhibiting lactate transfer or lowering FATP or apolipoprotein levels decreases glial LD accumulation in flies and in primary mouse glial-neuronal cultures. We show that human APOE can substitute for a fly glial apolipoprotein and that APOE4, an Alzheimer's disease susceptibility allele, is impaired in lipid transport and promotes neurodegeneration, providing insights into disease mechanisms.


The relationship between craving, anxiety, and other symptoms in opioid withdrawal.
Craving and anxiety share many similar attributes including comparable responses to pharmacological agents. To better characterize the relationship among craving, anxiety, and other opioid withdrawal signs and symptoms, we examined 32 opioid-dependent subjects undergoing clonidine-assisted opioid withdrawal. A 13-item analog scale measured subjective withdrawal symptoms. Statistical analyses of separate subscale items, using craving as the dependent variable, showed that the highest positive correlations occur for craving and anxiety. The high correlation between craving and anxiety suggests common mechanisms underlying both.


Robotic mesh explantation (RoME): a novel approach for patients with chronic pain following hernia repair.
Post-herniorrhaphy pain is common with an estimated 8-10% incidence of mesh-related complications, requiring mesh explantation in up to 6% of cases, most commonly after inguinal hernia repairs. Reoperation for mesh explantation poses a surgical challenge due to adhesions, scarring and mesh incorporation to the surrounding tissues. Robotic technology provides a versatile platform for enhanced exposure to tackle these complex cases. We aim to share our experience with a novel robotic approach to address these complex cases. A descriptive, retrospective analysis of patients undergoing a robotic mesh explantation (RoME) for mesh-related chronic pain, or recurrent ventral hernia by two surgeons between the period of March 2016 and January of 2020. The patients were evaluated for resolution of mesh related abdominal pain as well as early post-operative complications. RoME was performed with concomitant hernia repair in cases of recurrences. Twenty-nine patients underwent a robotic mesh explantation (RoME) for mesh-related chronic pain, or recurrent ventral hernia between March 2016 and January of 2020. Nineteen patients (65.5%) had a prior inguinal hernia repair and 10 patients (34.5%) had a prior ventral hernia repair. Indications for mesh removal included chronic pain with or without hernia recurrence. Seventeen patients (58.6%) reported improvement or resolution of pain postoperatively (63% with a prior inguinal hernia repair and 50% of patients with a prior ventral hernia repair). Five patients (17.2%) required mesh reinforcement after explantation. Nineteen patients (65.5%) underwent mesh explantation with primary fascial closure or no mesh reinforcement. The mean follow-up was 36.4 days. The most common postoperative complication was seroma formation (6.8%), with one reported recurrence (3.4%). Robotic mesh explantation in challenging cases due to the effect of chronic scarring, adhesions and mesh incorporation to the surrounding tissues is safe and provides an advantageous platform for concomitant hernia repair in these complex cases.


Heterophil/lymphocyte ratios predict the magnitude of humoral immune response to a novel antigen in great tits (Parus major).
Animals display remarkable individual variation in their capacity to mount immune responses against novel antigens. According to the life-history theory, this variation is caused by the costs of immune responses to the hosts. We studied one of such potential costs, depletion of somatic resources in wintering wild-caught captive passerines, the great tits (Parus major) by immune challenging the birds with a novel antigen, killed Brucella abortus (BA) suspension. We found that despite mild temperature conditions in captivity and ad libitum availability of food, immune challenge depleted somatic resources (as indicated by a body mass loss) and elevated relative proportion of heterophils to lymphocytes (H/L ratio) in the peripheral blood of birds. However, body mass loss did not covary with an increase in H/L ratios between two sampling events, which indicates that these two markers of health state describe different aspects of individual physiological condition. Antibody titres were not associated with the extent of body mass loss during the development of immune response, which shows that the somatic cost of immune response was not proportional to the amount of antibody produced. Birds with high pre-immunisation H/L ratios mounted weaker antibody response, which is indicative of stress-induced suppression of humoral immune response and is consistent with the concept of an antagonistic cross-regulation between different components of the immune system. The latter finding suggests a novel diagnostic value of H/L ratios, which reinforces the utility of this simple haematological index for prediction of the outcomes of complicated immune processes.


Skeletal photopenic appearance of Paget's disease with indium-111 white blood cell imaging.
A case of focal decreased skeletal uptake with In-111 labeled white blood cells representing Paget's disease is reported. Although uncommon, other causes for skeletal photon deficient areas using In-111 white blood cells have been described. To the authors' knowledge, this finding representing Paget's disease has not been previously described.


Aortic Aneurysm Natural Progression is Not Influenced by Concomitant Malignancy and Chemotherapy.
Aortic aneurysms occur concomitantly with malignancy in approximately 1.0-17.0% of patients. There is little published information regarding the effects of subsequent oncological therapies on aortic aneurysm growth. The aim of this study was to determine the effects of chemoradiation therapies on the natural progression of small abdominal aortic aneurysm (AAA), thoracic aortic aneurysm, and thoracoabdominal aortic aneurysm. Patients with aortic aneurysms with and without malignancy between 2005 and 2017 were identified within institutional databases using Current Procedural Terminology and International Classification of Disease codes. Inclusion criteria included complete chemotherapy documentation, a minimum of 3 multiplanar axial/coronal imaging or ultrasonography before, during, and after receiving therapy or 2 studies for patients without malignancy. Propensity matching, Cox and linear regression, and Kaplan-Meier survival analyses were performed. A total of 159 (172 aneurysms) patients with malignancy and 127 (149 aneurysms) patients without malignancy were included. Average patient demographics were 74.4 ± 9.8-years-old, Caucasian (66.8%), male (70.3%), with hypertension (71.1%), current smoking (24.5%), coronary atherosclerotic disease (26.2%), and AAA (71.0%). The most common malignancy was lung cancer (48.4%) with most chemotherapy regimens including a platinum-based alkylating agent and concurrent antimetabolite (56.0%). The overall median follow-up time was 28.2 (range 3.1-174.4) months. Aortic aneurysms in patients without malignancy grew to larger sizes (4.43 ± 0.96 vs. 4.14 ± 1.00, P = 0.008) with similar median growth rates (0.12 vs. 0.12 cm/year, P = 0.090), had more atypical morphologic features (14.1% vs. 0.6%, P < 0.001), more frequently underwent repair (22.1% vs. 8.7%, P = 0.001), and more frequently required emergency repair for rupture (5.4% vs. 0.0%, P = 0.087). Cox regression identified initial aortic size ≥4.0 cm (hazard ratio [HR] 3.028), AAA (HR 2.146), chronic aortic findings (3.589), and the use of topoisomerase inhibitors (HR 2.694). Linear regression demonstrated increased growth rates predicted by antimetabolite chemotherapy (β 0.170), initial aortic size (β 0.086), and abdominal aortic location (β 0.139, all P < 0.002). Small aortic aneurysms with concomitant malignancies are discovered at smaller initial sizes, grow at similar rates, require fewer interventions, and have fewer ruptures and acute dissections than patients without malignancy. Antimetabolite therapies modestly accelerate aneurysmal growth, and patients receiving topoisomerase inhibitors may require earlier repair. Patients with concomitant disease can be confidently treated according to standard institutional aneurysm surveillance protocols. Overall, we recommend treatment of the malignancy before small aortic aneurysm repair as these aneurysms behave similarly to those in patients without malignancy.


Radio-frequency ablation for symptom control in a patient with metastatic pancreatic insulinoma.
Malignant insulinomas are very rare endocrine tumours with a variable clinical course. We describe a 51-year-old man who had two large insulinomas resected from the body of the pancreas and 19 years later, having again become symptomatic, was found to have hepatic metastases. Medical treatment with diazoxide and octreotide failed to control his symptoms, but repeated hepatic embolization effected both symptomatic and biochemical improvements for a further 5 years. When symptoms recurred but further embolization failed to control his symptoms the hepatic metastases were treated by outpatient percutaneous radio-frequency ablation. He remains symptom-free 18 months later and levels of insulin and pro-insulin have nearly normalized. The survival, with liver metastases, for 27 years in a man with a malignant insulinoma has not been described previously. Malignant insulinoma may follow a rather indolent course and symptoms respond well to locally destructive therapies. Hepatic embolization is less traumatic than hepatic lobe resection and radio-frequency ablation offers an alternative if vascular access to the tumour is no longer possible.


Effects of a single exercise session on pain intensity in adults with chronic pain: a systematic review and meta-analysis.
Chronic pain is prevalent amongst society, making it necessary to find strategies to manage chronic pain. Regular exercise is efficacious; however, pain is a barrier to initiating exercise. A single exercise session is also believed to acutely reduce pain, however, the evidence for this is less robust. This systematic review and meta-analysis aimed to identify the effect of a single exercise session on pain intensity in adults with chronic pain. We searched eight databases and trial registries to identify randomised controlled trials evaluating the effect of a single exercise session on pain intensity in adults with chronic pain compared to a non-exercise control. Literature screening, data extraction, risk of bias (Cochrane 2.0) and quality assessment (GRADE) were conducted independently and in duplicate. Random-effects meta-analyses were performed using the metafor package in R. We included 17 trials (46 study arms with 664 adults [44% female]). There were no significant differences in pain intensity (mean difference on a 0-10 scale) immediately post-exercise -0.02 (95% CI = -0.06, 0.62; I2 = 77.1%) or up to 45-min post-exercise -0.17 (95% CI = -0.49, 0.16; I2 = 34.2%). All trials were at high risk of bias and the overall confidence in these findings was very low. A single exercise session did not reduce pain intensity up to 1-h post-exercise. Notably, increases in pain were not observed either, suggesting that while pain can be a barrier to initiating exercise, clinicians can educate patients on the unlikelihood of exercise acutely increasing pain intensity.


Novel pentahexosyl ganglioside of the globo series purified from chicken muscle.
A monosialosyl ganglioside, sialosylpentaglycosyl-ceramide, has been isolated from chicken pectoral muscle. This ganglioside is the first to be found which contains the glycosphingolipid structure of the globo series. It was extracted from tissue with a mixture of tetrahydrofuran and aqueous KCl and purified by anion exchange and silicic acid chromatography. Enzymic hydrolysis utilizing specific glycosidases and methylation technique were employed to establish the structure which is proposed to be: NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 3Gal alpha 1 leads to 4Gal beta 1 leads to 4GlcCer. The chain base was predominantly sphingosine and the fatty acids present were mainly stearate and oleate.


Immediate post-saccadic information mediates space constancy.
We recently demonstrated that the perceived stability of a visual target that is displaced during a saccade critically depends on whether the target is present immediately when the saccade ends; blanking a target during and just after a saccade makes its intra-saccadic displacement more visible (Deubel et al. Vis Res 1996;36:985-996). Here, we investigate the interaction of visual context and blanking. Subjects saw a saccade target and an equal-sized distractor. During a saccade one or the other was displaced left or right. At the same time, one of the objects could be blanked briefly. Subjects reported whether the target or the distractor had jumped. The object that was blanked was more often seen as jumping (Experiment 1), regardless of which object really jumped, implying that continuously visible objects are preferentially perceived as stable. When both objects were blanked, longer blanking led to better accuracy at identifying which had jumped during a saccade. When one object was jumped and the other, stationary object was blanked (Experiment 2), the blanked object was mistakenly seen as jumping until the jump covered 50% or more of the saccade amplitude. In Experiment 3 a large continuously present texture underwent an undetected jump during a saccade, biasing judgments of simultaneous jumps of a blanked target. The results demonstrate that space constancy in normal situations is dominated by the assumption that a continuously present pattern is stable--this pattern becomes the spatial reference for the post-saccadic recalibration of perceptual space.


Persistence of DNA on clothes after exposure to water for different time periods-a study on bathtub, pond, and river.
DNA traces on clothes of drowned bodies can provide important evidence for police investigations, especially in cases of suspected suicides or homicides. However, it is generally assumed that the water "erodes" a large part of the DNA depending especially on the exposure time. In forensic casework, DNA of suspects could be found frequently on clothes of drowned bodies after hours, sometimes days of exposure to water. This study was conducted to attempt a general statement about the conditions under which sufficient DNA remains can be expected for molecular genetic analysis. For this purpose, different scenarios were designed including DNA from three to five people, different types of waters (tap, pond, bathtub and river) for various time periods, with higher water pressure, different temperature, and soapy water (bathtub). Epithelial cells and blood cells were mounted on cotton cloths, and the DNA left after exposure was analyzed using the Powerplex® ESX17fast kit. In the indoor experiments, complete profiles could be seen even after 10 min rinsing of clothes under the tap and after 1 week in the bathtub. Outdoors, the results differed considerably between summer and winter as well as between pond and river. The longest exposure time still resulting in a complete profile was 2 weeks for a sample with skin cells in the pond during winter. In summer, the time period for erasing the bulk of DNA was 4 hours regarding epithelial samples and more than 1 day for blood samples in pond and river environments. All in all, the results demonstrate that DNA could still be recovered from clothes exposed to water for more than 1 week.


Spread of Sporothrix spp. through respiratory droplets from infected cats: A potential route of transmission.
Cases of cat-transmitted sporotrichosis in Brazil have increased in recent years. We collected respiratory secretions expelled while sneezing from 28 cats diagnosed with sporotrichosis. We identified the presence of Sporothrix spp. in respiratory droplets expelled in the sneeze of infected cats. The results raise concerns about a new transmission route for cat-transmitted sporotrichosis. Physicians who diagnose and treat human cases of sporotrichosis should be aware of this potential new transmission method to improve clinical suspicion. Approximately half of patients with granulomatous conjunctival sporotrichosis did not report experiencing traumatic injury from cats.


Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer.
Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, which influences patients' quality of life. Recently, circRNA regulated the mRNA levels by functioning as miRNA sponge in various disease, including diabetes mellitus. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved in DFU remains obscure. The aim of this study is to construct a competing endogenous RNA (ceRNA) network and screen biological indicators as diagnostic factors in DFU. All the differentially expressed circRNAs, miRNAs and mRNAs were derived from Gene Expression Omnibus database. Furthermore, circRNAs identified by cytoHubba analysis and miRNAs obtained by human miRNA-disease database were used to construct DFU-specific ceRNA network with intersection of mRNAs. Functional enrichment analysis displayed the function and pathway of dysregulated mRNAs. Hub genes with high diagnostic value were screened by ClusterONE, GO semantic similarity and receiver operating characteristic (ROC) curve. Here, the ceRNA network consisted of 8 circRNAs, 11 miRNAs and 91 mRNAs. Functional enrichment analysis demonstrated diabetic complications-related pathway including TGF-beta, FoxO and Wnt signaling pathway. GO semantic similarity and ROC curve analysis showed 6 hub genes with high diagnostic value (the area under the ROC curve ≥ 0.8) in patients with DFU, including BCL2, CCND1, IRAK4, SMAD4, SP1 and SUFU, which were identified as potential target genes for DFU diagnosis. In conclusion, the present study looked at a circRNA-miRNA-mRNA regulatory network with DFU and screened the potential function of mRNA, then identified novel diagnostic biomarkers and therapeutic targets for patients with DFU.


Role of protein phosphorylation in TNF-induced apoptosis: phosphatase inhibitors synergize with TNF to activate DNA fragmentation in normal as well as TNF-resistant U937 variants.
This study examined the role of protein phosphorylation in TNF induction of apoptosis in several tumor cell lines by testing the effects of agents that either stimulate or inhibit protein phosphorylation. The serine-threonine phosphatase inhibitors, okadaic acid (OKA) and calyculin A (CLA), synergistically augmented TNF-induced apoptosis in several TNF-sensitive tumor cell lines including the U937 histiocytic lymphoma, the BT-20 mammary carcinoma, and the LNCap prostatic tumor cell line. Furthermore, the phosphatase inhibitors completely reversed the TNF resistance of a variant (U9-TR) derived from U937. CLA also inhibited phosphatase activity in cell-free extracts from both U937 and U9-TR at the same concentrations (0.4-2.0 nM) that it synergized with TNF. In contrast, TNF treatment of U937 cells did not result in inhibition of phosphatase activity mediated by protein phosphatase 1 (PP1) and PP2A in cell extracts. Since the phosphatase inhibitors are known to increase the overall levels of protein phosphorylation in cells, this suggested that TNF may act by stimulating protein kinase (PK) activity. This hypothesis was supported by the results of testing a panel of relatively specific protein kinase inhibitors. TNF activation of DNA fragmentation was blocked by a potent inhibitor of myosin light chain kinase (MLCK) but was unaffected by inhibitors of cAMP or cGMP-dependent PKs. We postulate that a defect in the activation of MLCK or possibly some other as yet unknown PK may be responsible for the TNF resistance of U9-TR. Furthermore, this resistance may be circumvented by promoting protein phosphorylation with the serine-threonine-dependent phosphatase inhibitors.


Vestibular rehabilitation therapy on balance and gait in patients after stroke: a systematic review and meta-analysis.
There is limited evidence to support the use of vestibular rehabilitation therapy (VRT) on improving balance and gait in patients after stroke. This systematic review aimed to evaluate the effects of VRT in addition to usual rehabilitation compared with usual rehabilitation on improving balance and gait for patients after stroke. This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement guidelines. Ten electronic databases were searched up to 1 June 2023 without restrictions in language and publication status. The PEDro scale and the Grading of Recommendations Assessment Development, and Evaluation were used to evaluate the risk of bias and the certainty of evidence. The meta-analysis was conducted with Review Manager 5.3. Fifteen randomised controlled trials with 769 participants were included. PEDro scale was used to assess the risk of bias with a mean score of 5.9 (0.7). VRT was effective in improving balance for patients after stroke (SMD = 0.59, 95% CI (0.40, 0.78), p < 0.00001), particularly for patients after stroke that occurred within 6 months (SMD = 0.56, 95% CI (0.33, 0.79), p < 0.00001) with moderate certainty of evidence. Subgroup analysis showed that VRT provided as gaze stability exercises combined with swivel chair training (SMD = 0.85, 95% CI (0.48, 1.22), p < 0.00001) and head movements (SMD = 0.75, 95% CI (0.43, 1.07), p < 0.00001) could significantly improve balance. Four-week VRT had better effect on balance improvement (SMD = 0.64, 95% CI (0.40, 0.89), p < 0.00001) than the less than 4-week VRT. The pooled mean difference of values of Timed Up-and-Go test showed that VRT could significantly improve gait function for patients after stroke (MD = -4.32, 95% CI (-6.65, -1.99), p = 0.0003), particularly for patients after stroke that occurred within 6 months (MD = -3.92, 95% CI (-6.83, -1.00), p = 0.008) with moderate certainty of evidence. There is moderate certainty of evidence supporting the positive effect of VRT in improving balance and gait of patients after stroke. PROSPERO CRD42023434304.


Formation of monometallic single-molecule magnets with an Stotal value of 3/2 in diluted frozen solution.
A combination of cobalt(II) complexes and pyridine ligands carrying organic spins, aminoxyl and carbene, provided single-molecule magnets with Stotal = 3/2 in diluted frozen solutions.


Surface topography of mitral valve endothelium from diet-induced, hypercholesterolemic rabbits.
Mammalian, cardiac endothelium has a surface topography that is characterized by plasmalemmal microappendages, nuclear bulges and ruffled cellular margins. SEM of the endothelial population over the two surfaces of the anterior cusp (leaflet) of the rabbit mitral valve revealed a very pleomorphic topography. The atrial and ventricular surfaces of the cusp displayed differences in microappendage population, cell density, nuclear contour and surface reactivity to Ruthenium Red and Concanavalin A. Comparative studies of similar populations from diet-induced hypercholesterolemic rabbits suggested an enhanced endothelial permeability as observed by an increase in cytoplasmic vesicles containing RR or Con A and by their intercellular passage into the subendothelium. Concomitant with these changes were disproportionate responses in the surface reaction of the carbohydrate cell coat (glycocalyx). The endothelial cells over the ventricular surface of the anterior cusp displayed the most dramatic changes with the appearance of numerous microappendages and intercellular fenestrations, the loss of RR and Con A surface reaction and the engorgement of the adjacent intima with foam-like cells containing the surface markers. Such surface responses appeared to precede or accompany alterations in endothelial integrity which suggests the importance of the blood-endothelial interface in the maintenance of the vascular wall.


In vitro evaluation of synthetic heparin-like conjugates comprising different thrombin binding domains.
The syntheses of several heparin-like glycoconjugates (i.e., 16a-f) containing identical AT III binding domains (ABD) and spacers but different thrombin binding domains (TBDs) are described. Biological activities of conjugates 16a-f indicate that the thrombin inhibitory activity is mainly determined by the charge density of the TBD moiety.


Frontal sinus repair with free autologous bone grafts and fibrin glue.
The authors describe a technique for repairing the frontal sinus with autologous bone grafts removed during craniotomy and fibrin glue. This technique was used in 12 patients who underwent craniotomy for aneurysms (n = 9), brain tumors (n = 2), and acute epidural hematoma (n = 1). The repair was successful in all cases. There were no instances of postoperative infection or leakage of cerebrospinal fluid. No complications from the repair have occurred over a mean follow-up of 51 months. This technique is simpler than others used to seal a frontal sinus.


Efficacy of a moxidectin/imidacloprid spot-on formulation (Advocate®) for the treatment of Troglostrongylus brevior in naturally infected cats in a field study in Greece.
Troglostrongylus brevior is a lungworm of wild felids that recently has been recognized as agent of severe respiratory disease in domestic cats in Mediterranean and Balkan countries. Nevertheless, the information on treatment options for feline troglostrongylosis is still poor. The aim of this pilot field trial was to evaluate the efficacy of the spot-on formulation containing 1% w/v moxidectin and 10% w/v imidacloprid (Advocate® spot-on solution for cats, Bayer Animal Health GmbH) in the treatment of T. brevior infection in naturally infected cats in Greece. The trial was a negative control, multicentre, clinical efficacy study conducted according to the standards of Good Scientific Practice (GSP). Sixteen cats in two study sites, naturally infected with T. brevior, were allocated to an untreated control group (G1, n = 8) or a treatment group (G2, n = 8), according to a randomization list. Animals assigned to G2 were treated with Advocate® for cats on days 0 and 28 at the recommended dose rate and animals assigned to G1 received a rescue treatment with the same product on days 56 and 84. Efficacy was assessed on days 28 and 56 in G2 and on days 84 and 112 in G1 by faecal larval counts. The primary efficacy criterion was the absence of T. brevior first-stage larvae (L1) following treatment. Other efficacy parameters were the quantitative comparison of L1 presence before (baseline) and after one or two treatments in both groups. All G2 cats were negative for T. brevior L1 at the first post-treatment evaluation (100% efficacy) while G1 cats were persistently shedding L1. The difference of the mean number of L1 per gram between G2 and G1 was statistically significant (P < 0.001). All G1 cats were negative (100% efficacy) for T. brevior L1 at the first post-rescue-treatment evaluation. Therefore, treatment efficacy at study completion was 100% in both groups in terms of stopping the L1 shedding in the faeces of the animals. No adverse effects were observed during the study. These results indicate that Advocate® spot-on solution for cats represents an option for treating cats naturally infected with T. brevior.


Is facial geometric morphometrics a useful method for age estimation in children and adolescents? Limited evidence and lack of studies leave us with an uncertain answer.
Facial geometric morphometrics is a non-invasive method that has recently shown potential applications, including age estimation, diagnosis of facial abnormalities, monitoring facial development, and evaluating treatment outcomes. A systematic review identified two studies that demonstrated the use of facial geometric morphometrics for age estimation in children and adolescents, showing promising results in terms of accuracy and error. This finding could be particularly relevant in forensic investigations. However, a research agenda should be established to prioritize the assessment of the diagnostic accuracy of facial morphometric geometrics in estimating age among children and adolescents.


[PRELIMINARY APPLICATION OF THREE-DIMENSIONAL PRINTING PERSONALIZED EXTERNAL FIXATOR IN SERIOUS TIBIOFIBULA FRACTURES].
To explore a new method of treating serious tibiofibula comminuted fracture by using three-dimensional (3-D) printing personalized external fixator. In April 2015, a male patient (aged 18 years with a height of 171 cm and a weight of 67 kg) with left tibiofibula comminuted fracture was included in the study. Computer-assisted reduction technique combined with 3-D printing was used to develop a customised personalized external fixator for fracture reduction. The effectiveness was observed. The operation time was about 10 minutes without fluoroscopy, and successful reduction was obtained. The patient had equal limb length after operation. X-ray films showed that the posterior angulation of distal fracture was corrected 37 degrees, and the eversion angle was corrected 4 degrees. The tibial fractures had good paraposition or alignment, and the lower limb force line was corrected completely. No new fracture displacement occurred. The clinical healing time of fracture was 3.5 months and the bone union was achieved after 8 months. The function of affected limb recovered well after operation. A personalized external fixator for serious tibiofibula comminuted fracture reduction made by 3-D printing technique has the merits of easy manipulation, high individuation, accurate reduction, stable fixation, and no need of fluoroscopy.


Professional tress code: I look like a pharmacist.
Hair color, style, and length are facets to a person's self-expression. There is evidence of bias against those who wear natural hair styles in job recruitment settings, which can affect how the candidate is perceived. In addition, there have been discriminatory hair policies that affect minoritized people. In the profession of pharmacy, most definitions of professionalism do not comment on physical appearance as a component but focus on characteristics such as knowledge, respect, communication, and empathy. It is critical to ensure that comments about someone's hair are not microaggressions. To embrace natural hair styles, pharmacists should combat any policies that are discriminatory and provide a safe space for others to feel comfortable wearing their hair in natural styles or with hair coverings. These actions will help create a space for authenticity, self-acceptance, and comfort.


Deep circumflex iliac perforator flap.
The increased freedom of the DCIP flap from the harvested iliac crest facilitates correct positioning. To ensure that the DCIP flap can be safely elevated, however, the presence of perforators (approximately 1 cm in diameter) must be confirmed preoperatively and intraoperatively.


The socialization of homosexuality and heterosexuality in a non-Western society.
Data on the Sambia--a tribe living in Papua New Guinea--are presented to demonstrate how Sambia males develop a homosexual orientation in boyhood and adolescence, then switch to become heterosexuals in adulthood. Social learning theory is used to explain how sexual orientation in the Sambia change from homo- to heterosexual during the transition to adulthood. Whereas most learning analyses of sexual orientation are based on data from Western cultures, this manuscript extends that literature to deal with a non-Western culture. While including Pavlovian and operant conditioning, which is stressed in many learning analyses of sexual learning, the present analysis also includes detail on the social and cognitive learning principles that are important in understanding the learning of sexual orientation and behavior.


Financial toxicity among cancer patients, survivors and their families in the United Kingdom: a scoping review.
The aim of this scoping review was to identify key research gaps and priorities in order to advance policy and practice for people living with cancer in the UK. The review adhered to PRISMA guidelines for scoping review. We searched MEDLINE, EMBASE, Scopus, Web of Science and Google Scholar on 16 July 2022. There were no restrictions in terms of study design and publication time; gray literature was included. The key words, 'financial' or 'economic', were combined with each of the following words 'hardship/stress/burden/distress/strain/toxicity/catastrophe/consequence/impact.' 29/629 studies/reports published during 1982-2022 were eligible to be included in the review. No study conducted a comprehensive inquiry and reported all aspects of financial toxicity (FT) or used a validated measure of FT. The most three commonly reported outcomes related to financial hardship were financial well-being (24/29), benefit/welfare (17/29) and mental health status (16/29). It is evident that FT is experienced by UK cancer patients/survivors and that the issue is under-researched. There is an urgent need for further research including rigorous studies which contribute to a comprehensive understanding about the nature and extent of FT, disparities in experience, the impacts of FT on outcomes and potential solutions to alleviate FT and related problems.


Immunological studies of patients with tumours of the prostate and bladder (a retrospective analysis).
A total of 25 patients with bladder tumour and 35 with prostatic tumour were tested for humoral and cellular immune responsiveness in 1977. Information on the subsequent course of disease was collected 5 years later and confronted with the results of these tests. The most marked deviations in the values of acute-phase proteins, complement and lymphocyte transformation tests were found in those patients who had died within the first year of the investigations. The results approached or attained the normal values parallel with the survival times. The parameters studied thus seem to lend themselves to diagnostic and monitoring purposes.


A case of robot-assisted adrenalectomy performed for an adrenal tumor (anastomosing hemangioma) exceeding 7 cm.
Anastomosing hemangioma in the adrenal area is extremely rare. We report a large anastomosing hemangioma in the adrenal area that underwent robot-assisted adrenalectomy. A 49-year-old man with left back pain underwent magnetic resonance imaging (MRI) that revealed a tumor in the left adrenal area; it was diagnosed as nonfunctional endocrinologically. However, the major axis of the tumor increased from 64 to 72 mm during the 4-month period. Robot-assisted left adrenalectomy was performed. Although the large tumor adhered to the surrounding tissues, it was safely resected by the effective use of an extra robotic arm. An anastomosing hemangioma was diagnosed since there were no malignant findings. Robotic surgical systems may serve as an effective treatment option for large adrenal tumors, and our report is the first robot-assisted adrenalectomy performed on an anastomosing hemangioma.


Clinical features of patients with Yin Yang 1 deficiency causing Gabriele-de Vries syndrome: A new case and review of the literature.
Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in YY1. In this study, we report a 10-year-old boy with a de novo novel pathogenic variant in YY1, the first Iranian patient with Gabriele-de Vries Syndrome. The novel de novo pathogenic variant detected in this study (NM_003403:c.690delA, p.Glu231Ilefs*25) was identified by whole-exome sequencing and confirmed by Sanger sequencing. The proband presented with delayed motor and speech development, ataxia, abnormal gait, autistic behavior, brain atrophy, and severe learning disability. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries Syndrome. Thus far, merely 13 Gabriele-de Vries Syndrome patients have been reported in the literature. The investigations for a suspected case of Gabriele-de Vries Syndrome must involve molecular diagnosis of the disease and its underlying genetic defect because the clinical investigations are generally variable and nonspecific.


Elimination of Theileria buffeli infections from cattle by concurrent treatment with primaquine phosphate and halofuginone lactate.
Fifty splenectomised calves naturally infected with Theileria buffeli were treated with primaquine phosphate (ICI, UK) and halofuginone lactate (Hoechst, Australia) either separately or in combination. Infections in treated calves were monitored for up to 26 weeks by examining Giemsa stained peripheral blood films for piroplasms and by an immunofluorescent antibody test. When used alone neither of the drugs eliminated infection. The most successful results were obtained when two treatments of halofuginone lactate, at a rate of 1 mg kg-1 body weight and six treatments of primaquine phosphate, at a rate of 2 mg kg-1 body weight, were administered concurrently. No theilerial relapses were observed in 14 of 16 calves so treated, and no antibody to T. buffeli was detected in these calves beyond the twelfth week after treatment. The results have application in the preparation of Theileria-free calves for use in the production of living vaccines against babesiosis and anaplasmosis.


Configurations of Adult Attachment, Indicators of Mental Health and Adverse Childhood Experiences in Women: A Cross-Sectional Study.
The relationship between adverse childhood experiences, attachment and adult mental health has been pointed out in a large amount of studies. In a sample of 339 women receiving support from mental health and social services, this research analyzed the association between three adult attachment variables (fear of rejection or abandonment-FRA; desire for closeness-DC; preference for independence-PI) and four mental health indicators. After dichotomizing these variables, we constructed eight configurations of attachment and examined their association with mental health indicators. BAB people (those below the median in FRA, above in DC and below in PI) obtained the most favorable scores in mental health, whereas the ABA configuration (above the median in FRA, below in DC and above in PI) was the least favorable. The association between attachment configurations and mental health indicators was different to what might be expected, aggregating the effects of individual attachment variables. When analyzing the relationship between configurations and adverse childhood experiences (ACEs), women with an ABA configuration reported the highest number of ACEs and eight ACE types had a higher-than-expected contingency coefficient. In conclusion, these findings suggest that certain adult attachment configurations are associated with a greater number of ACEs and poorer mental health indicators in adult women.


A simple defined medium for growth and maintenance of the mixotrophic protist Ochromonas danica.
A simple-defined medium was formulated that allows robust axenic-growth of the model mixotrophic protist Ochromonas danica at a neutral pH. This new defined medium, with a minimum number of constituents, facilitates more highly controlled studies of mixotrophic metabolism and nutrient regeneration than have previously been possible.


Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial.
The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety. In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews. At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001). VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children. Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.


Clinical Practice Pattern of Korean Medicine Doctors in Idiopathic Short Stature Treatment: A Survey Study.
Korean medicine (KM) interventions are attractive for children with idiopathic short stature (ISS). We investigated the real-world clinical practice patterns of KM doctors in ISS treatment. The survey targeted KM doctors who have treated patients with ISS in KM clinical settings for >3 years. We included questions on the diagnosis and treatment patterns, effects, cost, and opinions of doctors on KM treatment for ISS. A frequency analysis was performed. There were 58 respondents, and "heights of parents" (n = 57, 98.3%), "height, weight, and growth rate of child" (n = 55, 94.8%), and "amount of meals, digestive function" (n = 52, 89.7%) were frequently used as indicators for diagnosis and treatment. The most frequently used KM interventions were "herbal medicine" (n = 58, 100%), "acupuncture" (n = 49, 84.5%), "moxibustion" (n = 38, 65.5%), "dry cupping" (n = 26, 44.8%), and "physiotherapy" (n = 22, 37.9%). Herbal medicines were generally prescribed to tonify the spleen or kidney, and the most frequently used individual herbs were Acanthopanacis cortex, Astragali Radix, and Cervi parvum cornu. The most common acupuncture points were ST36, GB34, SP6, EX-LE5, and LI4. This study showed the use of KM for ISS in real-world clinical settings. In the future, well-designed clinical studies to verify the effect of KM treatment on ISS based on real-world clinical practice patterns should be actively performed.


Using binding competitors of albumin to promote the removal of protein-bound uremic toxins in hemodialysis: Hope or pipe dream?
Chronic kidney disease is associated with the accumulation of a large range of uremic retention solutes as referred to as uremic toxins. Some of these compounds belong to the group of Protein Bound Uremic Toxins (PBUT) due to their tight interactions with plasma proteins and especially serum albumin. These PBUT therefore exist in the bloodstream into two forms: a major bound (and non-diffusible) fraction and a minor free fraction. As a result, these compounds are poorly removed by most of the renal replacement therapies (such as hemodialysis) and their concentration can hardly be decreased in end-stage renal disease patients. An increase of the free fraction of PBUT could be achieved using chemical displacers that could compete with PBUT for binding to serum albumin. This review summarizes and discusses the interest of chemicals displacers as a valuable option to enhance PBUT removal in CKD patients.


Effect of Bridging Thrombolysis on the Efficacy of Stent Retriever Thrombectomy Techniques : Insights from the SWIFT-DIRECT trial.
There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques. We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c‑3 reperfusion (FPR). This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54). This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy.


Gallium-labelled peptides for imaging of inflammation.
Inflammation plays a major role in the development of many diseases. This review article summarizes recent research in the field of in vivo imaging of inflammation. Novel methodologies using PET with (68)Ga peptides targeting, for example, vascular adhesion protein 1 are discussed.


[Acceptance of dementia diagnostics by getriatric hospital patients : Comparison of various investigation methods with emphasis on FDG-PET imaging].
The number of people with dementia is continuously rising, in hospitals as well. For the diagnostics novel methods are available but the attitude of the patients to these methods is yet unknown. The aim of the study was to evaluatethe opinion of geriatric hospital patients with suspected dementia on the various possible methods of diagnosing dementia, especially fluorodeoxyglucose positron emission tomography (FDG-PET). Additionally, it was assessed if there are differences in toleration between imaging of the brain and conventional diagnostics by neuropsychological testing and if information on the diagnostic methods and the patient's physical or cognitive status influence their opinion. Within the framework of the iDSS001 clinical trial 90 geriatric hospital patients with suspected dementia were interviewed with respect to examinations performed for diagnosing dementia, e.g. anamnesis including physical and neurological examinations, neuropsychological testing, cerebrospinal fluid analysis, magnetic resonance imaging (MRI) and FDG-PET imaging. Imaging of the brain was tolerated less than anamnesis including physical and neurological examinations, neuropsychological testing and cerebrospinal fluid analysis and patients also felt they were less informed about these procedures. The generally well-accepted FDG-PET imaging procedure was received slightly better than MRI. Cognitively impaired and less depressed patients were less willing to allow repeat MRI examinations. The results suggest that imaging of the brain is perceived by cognitively impaired hospital patients as being more burdensome than conventional diagnostics, such as neuropsychological testing. Improved care during the investigations as well as physical and organizational adjustments could increase the acceptance.


Investigation of genotoxicity, mutagenicity, and cytotoxicity in erythrocytes of Nile tilapia (Oreochromis niloticus) after fluoxetine exposure.
Fluoxetine (FLX) is an antidepressant that is increasingly being detected in aquatic environments. However, this contaminated FLX can affect aquatic organisms. Therefore, the aim of this study was to evaluate the genotoxic, mutagenic, and cytotoxic potential of FLX on erythrocytes in Nile tilapia (Oreochromis niloticus) after acute exposure. Fish were exposed to different concentrations of FLX (10, 100 and 1000 µg/L) for 96 h. Then, the condition factor (K value) was used to assess the general fish condition. The genotoxicity was investigated using a comet assay, and the mutagenicity was examined using micronucleus (MN) and erythrocytic nuclear abnormalities (ENAs) assays. In addition, the cytotoxicity was analyzed by erythrocyte morphometry and erythrocyte maturity index (EMI). The results showed that FLX did not affect the fish's health. Nevertheless, 100 and 1000 µg/L FLX significantly increased DNA damage. Furthermore, a higher concentration of FLX presented a significantly increased frequency of MNs and ENAs, also leading to changes in some erythrocyte morphometric indices and significantly decreased mature erythrocytes. In conclusion, our results indicate that FLX induces genotoxic, mutagenic, and cytotoxic effects in erythrocytes of O. niloticus.


'Diversity is my number one priority'.
RCVS president Amanda Boag talks to Josh Loeb about her career in emergency critical care and her aims to increase diversity in the profession.


Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases.
During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.


Construction of an MRI 3D high resolution sheep brain template.
Sheep is a developing animal model used in the field of neurosciences for the study of many behavioral, physiological or pathophysiological mechanisms, including for example, the central control of social behavior, brain injury or neurodegenerative diseases. However, sheep remains an orphan species in the field of magnetic resonance imaging (MRI). Therefore, a mean image (template), resulting of registrations of multiple subject images is needed and currently does not exist. In this study, we: i) computed multimodal high resolution 3D in-vivo sheep brain templates of T1 weighted (T1W) and T2W images, ii) computed gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) prior probability maps using linear and optimized non-linear registrations iii) used prior probability maps to perform the segmentation of a single brain tissues. Computed multimodal sheep brain templates showed to preserve and underline all brain patterns of a single T1W or T2W image, and prior probability maps allowed to improve the segmentation of brain tissues. Finally, we demonstrated that these templates and prior probability maps were able to be portable in other publicly available imaging software and could be used as standardized spaces for multi-institution neuroimaging studies or other neuroscience methods.


Gait speed, survival, and recommended treatment intensity in older adults with blood cancer requiring treatment.
Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' "gestalt" assessments. Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN-based categorizations of oncologists' treatment intensity recommendations, including gait speed. The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4-0.6 m/s), 34.0 months (0.6-0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6-0.8 m/s: HR, 1.76; 0.4-0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity. In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.


Alanine substitution for Thr268 and Asp269 of soluble ciliary neurotrophic factor (CNTF) receptor alpha component defines a specific antagonist for the CNTF response.
Ciliary neurotrophic factor (CNTF) associates with an alpha subunit (CNTFRalpha) of the receptor complex to initiate signal transduction by facilitating heterodimerization of the gp130 transducing protein and the leukemia inhibitory factor receptor (LIFR) beta. CNTFRalpha is anchored to the membrane by a glycosylphosphatidylinositol linkage; however, a soluble form of the alpha subunit can still bind CNTF to recruit the signal transducing components of the receptor complex. In the present study we show that alanine substitution for residues Thr268 and Asp269 of the CNTFRalpha subunit results in a mutated receptor subunit (R3), which can bind CNTF with an affinity similar to that of the wild type CNTFRalpha but, when expressed as a soluble receptor subunit, lowers the binding of CNTF to its tripartite receptor. In addition, CNTFR3alpha inhibits the proliferation of the TF1 hematopoietic cell line triggered by CNTF plus soluble wild type CNTFRalpha but not by IL-6 or oncostatin M. Similarly, CNTFR3alpha specifically antagonizes the induction of gp130 and LIFRbeta tyrosine phosphorylation observed in response to CNTF and wild type soluble CNTFRalpha in the HepG2 hepatoma cell line, as well as the subsequent events leading to haptoglobin synthesis. Positions 268 and 269 of CNTFRalpha appear to be critical for its interaction with gp130 and LIFRbeta, whereby alanine substitution of the residues at these positions results in antagonism of the CNTF-induced response.


Molecular basis for differences between human joints.
The molecular program of a cell determines responses including induction or inhibition of genes for function and activity, and this is true of the cells within articular cartilage, a major functional component of the joint. While our studies have previously focussed on differences in the molecular programs of the cells within the superficial and deep zones, we have recently begun to focus on relative differences between joints, such as the knee and ankle. In the human, these joints vary greatly in their susceptibility to joint diseases, such as osteoarthritis (OA). We have predicted that there would be a molecular basis for differences between joints that could lead to differences in susceptibility to OA, if inherent pathways locked into the resident cells induce differences in their response to their environment. We have been able to show that there are differences between the matrix components and water content; these properties correspond to a higher equilibrium modulus and dynamic stiffness but lower hydraulic permeability and serve to make the ankle cartilage stiffer, slowing movement of molecules through the cartilage. In addition to these biochemical differences in the cartilage matrix, we have also identified relative differences in the strength of the response to stimulation of chondrocytes from knee and ankle. The stronger response of the knee chondrocytes includes factors that increase damage to the cartilage matrix, such as a depression of matrix synthesis and increased enzyme activity. This response by the knee chondrocytes results in enzyme damage to the matrix that the cells may not be able to repair, while the weaker response of the ankle chondrocytes may allow the cells to repair their matrix damage.


An impressive case of isolated thoracic impalement.
A 61-year-old male construction worker was admitted to our Emergency Department due to being impaled in the chest after fall onto the long pole of his cement mixer. He was promptly scanned through the CT then transferred to theatre where unique technique for intubation was utilised prior to performing a Video Assisted Thoracoscopic Surgery exploration and extraction of the foreign object. Impalement injuries are classified into Types I or II depending on the direction of movement of the human body in relation to the foreign object. There currently is no consensus on the best management of chest wall injuries involving impalements. Our case utilised Video Assisted Thoracoscopic Surgery as the dominant method of intervention together with highly skilled anaesthetic preparation. The combined expert anaesthetic and surgical approach utilised collectively had a role in ensuring the best possible outcome for the patient.


Transnational public and global health education in China.
Transnational public and global health programs in China have rapidly expanded over the past 20 years, and have potential to make important contributions to China's global health workforce. However, there has been sparse if any literature specific to transnational public and global health higher education in China. In response, this perspective article aims to: (1) outline current transnational public and global health programs in China, and (2) delineate opportunities and challenges for transnational public and global health programs to enhance China's global health workforce. Based on internet searches, eight active transnational public and global health programs in China were identified in September 2022 (one Bachelors; four Masters; three doctorate). Degree awarding institutions are located in Australia, Portugal, the United Kingdom, and the United States. Courses for stand-alone transnational programs were co-delivered by faculty from the Chinese and foreign sponsoring institutions. The earliest and latest programs were respectively established in 2001 and 2022, and the average year of establishment was 2013. The endurance of some programs (three programs operating ≥ 10 years) indicates the potential sustainability of transnational public and global health programs in China. However, opportunities for cross-cultural engagement appear to be constrained by lack of English (or other language) requirements in some programs, limited recruitment of international students, pandemic travel restrictions, and a dearth of funding for global health research outside China. In addition, students enrolled at transnational universities in China are currently ineligible for China Scholarship Council funding. As China's need for global health capacity grows amid a rapidly shrinking population of younger citizens, strategic investments in transnational public and global health programs may be of increasing value.


The metabolism and detoxification effects of lead exposure on Aleurolyphus ovatus (Acari: Acaridae) via transcriptome analysis.
Aleurolyphus ovatus Troupeau is one of the most predominant species of the Acaridae family worldwide. Recent reports have demonstrated that the accumulation of lead in stored grains and dietary items exceeds the required standards. However, the molecular mechanism of heavy metal stress on mites has not been reported. To understand the mechanism underlying the heavy metal response of A. ovatus, comparative transcriptome analysis was performed in this study using an Illumina high throughput mRNA sequencing (RNA-seq) platform. A. ovatus was fed on artificial diets containing two different concentrations of lead, namely, a low concentration of 12.5 mg/kg (LAO) and a high concentration of 100 mg/kg (HAO), while the mites in the control (NAO) group were not exposed to lead. A total of 44,362 unigenes, with an average length of 1547 bp, were identified. Of these, 996 unigenes were successfully annotated in seven functional databases. The number of differentially expressed genes (DEGs) in A. ovatus under different lead concentrations was compared. In NAO versus LAO group, including 310 up-regulated and 1580 down-regulated DEGs. In NAO versus HAO group, including 3928 up-regulated and 1761 down-regulated DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that detoxification enzyme genes were significantly expressed in pathways, such as cytochrome P450 foreign body metabolism, glutathione metabolism and drug metabolism-cytochrome pathway. The results of gene annotation and quantitative real-time PCR showed that high concentration of lead significantly stimulated the expression of metabolic detoxification enzyme genes such as glutathione S transferase (GST) and superoxide dismutase (SOD), while low concentration inhibited their expression. This study will provide a basis for the molecular mechanism of A. ovatus in response to heavy metal lead stimulation in stored grain.