Breakpoints: current practice and future perspectives.
Much of the discussion over the past decades on the value and setting of breakpoints has been due to the fact that the breakpoint was used in two ways; as an indicator to predict the probability of clinical success and also to detect resistant (sub) populations. It is apparent that these two meanings have lead to a different approach to setting, interpretation and use of breakpoints based on clinical efficacy on the one hand and breakpoints based on detection of resistance on the other. Nevertheless, several of the current guidelines make no perceptible distinction between these two meanings. A case is therefore strongly made to recognize that there is a difference between clinical and microbiological breakpoints. The microbiological breakpoint may be used to detect organisms that do not belong to the natural bacterial population, but somehow have acquired resistance and might be useful in recognizing emergence of resistant subpopulations and may lead to subsequent measures to be taken. Alternatively, the clinical breakpoint is of principal value to the clinician in that it results in a classification of S (susceptible), I (intermediate susceptible) and R (resistant) and is used in clinical practice and correlate with a measure of clinical efficacy. Methods developed during the last few years to arrive at meaningful clinical breakpoints are discussed, such as CART analysis and Monte Carlo simulation. In discussing future developments, it is suggested that current reports containing S, I, and R be at least supplemented with the MICs measured and, using current techniques available such as Monte Carlo simulation, provide the probability of successful eradication of the micro-organism and successful treatment based on population pharmacokinetics and Minimal Inhibitory Concentration (MIC) distributions.


Low levels of high-density lipoprotein cholesterol in patients with atherosclerotic stroke: a prospective cohort study.
The purpose of this study was to evaluate the influence of baseline high-density lipoprotein cholesterol (HDL-C) on initial stroke severity and clinical outcomes in acute ischemic stroke. From August 2006 through December 2011, patients with acute atherosclerotic ischemic stroke were included. Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and HDL-C were checked and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at admission. The primary outcomes were a composite end point of all-cause mortality, recurrent stroke, or occurrence of ischemic heart disease during follow-up. Overall, 3093 subjects (mean age 66.8 years) were included and 675 patients (22%) had low HDL-C (≤35 mg/dL) at admission. These patients had higher NIHSS scores. After adjusting for all clinical factors in multivariate logistic analysis, low HDL-C at admission (OR, 1.79, 95% CI, 1.40-2.29) was significantly associated with higher stroke severity (NIHSS score > 6). During the follow-up period, 280 patients (9%) developed one of the components of the composite end point, including 76 (11.3%) in patients with low HDL-C and 204 (8.4%) in patients with normal HDL-C at admission (p < 0.001). In multivariate Cox regression analysis, after adjusting for all clinical factors, low HDL-C at admission (HR, 1.41, 95% CI, 1.02-1.95) was a significant independent predictor of the composite end point. Low baseline HDL-C (≤35 mg/dL) at admission was associated with higher stroke severity and poor clinical outcome during follow-up in patients with atherosclerotic ischemic stroke.


Effects of visnagin on cyclic nucleotide phosphodiesterases and their role in its inhibitory effects on vascular smooth muscle contraction.
1. Visnagin relaxed aortae previously contracted by noradrenaline. This effect was unalterated by endothelium removal and potentiated, at high concentrations, by the previous incubation with sodium nitroprusside. 2. Visnagin weakly inhibited the hydrolytic activity of the cyclic nucleotide phosphodiesterase (PDE) isozymes (PDE5, PDE4, PDE3, cyclic GMP activated PDE2 and PDE1). 3. The present results indicate an involvement of PDE inhibition in the relaxant effect of visnagin at high concentration (>5x10(-5) M).


SGLT-2 Inhibitors for Patients with Heart Failure: What Have We Learned Recently?
In this review, we discuss the mechanisms of action of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the purported protective effects for mitigating heart failure (HF)-related outcomes. Major randomized clinical trials have demonstrated the cardiovascular safety and efficacy of SGLT-2i among patients without known HF and those with established HF with reduced ejection fraction or preserved ejection fraction (HFrEF and HFpEF respectively). Recent HF guidelines have incorporated SGLT-2i in HF treatment algorithms. SGLT-2i have emerged as a novel treatment for both prevention of HF and reduction of cardiovascular morbidity and mortality among patients with existing HFrEF or HFpEF.


State-dependent risky choices in primates: Variation in energy budget does not affect tufted capuchin monkeys' (Sapajus spp.) risky choices.
Economic models predict that rational decision makers' choices between a constant, "safe" option and a variable, "risky" option leading, on average, to the same payoff, should be random. However, a wealth of research has revealed that, when faced with risky decisions, both human and nonhuman animals deviate from economic rationality. According to the risk-sensitivity theory, individuals should prefer a safe option when they are in a positive energy state and a risky option when they are in a negative energy state. The abundance/risk hypothesis proposes that individuals should prefer risky options when diet quality exceeds their nutritional requirements. We tested how energy budget affects decision making under risk by presenting 22 capuchins belonging to two colonies (IT: N = 12, US: N = 10) with a risky choice task. Capuchins had to choose between a constant option (always four food items) and a variable option (one or seven food items with a 50% probability) in two conditions. In the Low-energy condition capuchins were tested before their main meal, whereas in the High-energy condition they were tested following a high-caloric meal. In neither colony did we find a significant difference between conditions, suggesting that the energy budget did not affect risk preferences. However, we found differences between colonies in their general response to risky choices: US capuchins were more risk-prone after selecting a safe option than a risky option and after selecting a bad (one food item) than a good (seven food items) risky option, whereas this did not hold true in IT capuchins. Furthermore, in the IT colony, males were more risk-prone under the High-energy condition compared to the Low-energy condition. Subtle differences in individual characteristics, management conditions, or stochastic founder effects may be implied, with relevant consequences for the outcomes of research on risky decision-making across laboratories.


A derived honey bee stock confers resistance to Varroa destructor and associated viral transmission.
The ectoparasite Varroa destructor is the greatest threat to managed honey bee (Apis mellifera) colonies globally. Despite significant efforts, novel treatments to control the mite and its vectored pathogens have shown limited efficacy, as the host remains naïve. A prospective solution lies in the development of Varroa-resistant honey bee stocks, but a paucity of rigorous selection data restricts widespread adoption. Here, we characterise the parasite and viral dynamics of a Varroa-resistant honey bee stock, designated 'Pol-line', using a large-scale longitudinal study. Results demonstrate markedly reduced Varroa levels in this stock, diminished titres of three major viruses (DWV-A, DWV-B, and CBPV), and a two-fold increase in survival. Levels of a fourth virus that is not associated with Varroa-BQCV-do not differ between stocks, supporting a disruption of the transmission pathway. Further, we show that when decoupled from the influence of Varroa levels, viral titres do not constitute strong independent predictors of colony mortality risk. These findings highlight the need for a reassessment of Varroa etiology, and suggest that derived stocks represent a tractable solution to the Varroa pandemic.


Photo-induced current amplification in L-histidine modified nanochannels based on a highly charged photoacid in solution.
By UV light irradiation, we can adjust the charge of bistable photoacid molecules reversibly, so that photo-induced current amplification can be obtained, which offers a way to control nanochannels by turning the UV light on and off, alternately.


Rupture of the pregnant uterus--a 21-year review.
To review the incidence of ruptured uteri at the Women's Hospital, Hamad Medical Corporation (HMC) and to analyze the causative factors of uterine rupture with a view to its prevention and to highlight the management approach taken to preserve the patient's reproductive potential. Case notes were reviewed for all patients (except for eight which were not available) with a ruptured uterus at the Women's Hospital in Doha for a period of 21 years from 1 July 1977 to 30 June 1997, relevant data relating to the clinical features characteristics of labor, operative procedures, and maternal perinatal outcome were assessed. There were 31 cases of ruptured uteri. The incidence of ruptured uteri was calculated to be 0.017%, 23 cases being available for the study. Ten cases (43.5%) occurred in patients with previous cesarean scars, while 13 cases (56.5%) were grand multiparous (para 5 or more). In 10 cases (43.5%) uterine rupture was associated with oxytocin use, and four cases (18.2%) were associated with PGE2 use. The ruptures occurred in the lower segment of 19 cases (90.9%). Fetal heart abnormalities were observed in all cases except one in which the uterus ruptured during labor. Abdominal hysterectomy was performed in 15 cases (65.2%). The remaining eight patients had suture repair, two of them had suture repair with sterilization and the other six cases (26.1%) had suture repair without sterilization. Five of them became pregnant and were delivered by cesarean section. Even though rupture of the uterus was rare in our study, its occurrence should be suspected when there are sudden fetal heart abnormalities during labor or unexpected postpartum shock. Suture repair should be considered whenever possible in order to maintain the patient's future fertility.


Cytophagic panniculitis and B cell lymphoma.
A 43-year-old woman had multiple, painful nodules of the legs and edema of both lower extremities for 3 years and leukopenia for 8 years. This histologic findings of lobular histiocytic panniculitis with "beanbag" cells were typical of cytophagic panniculitis. This case is unique in that B cell lymphoma developed in the spleen, as verified by immunoperoxidase staining, and demonstrates that the disease not only may be a progressive disease per se but also may be associated with nonhistiocytic malignancy.


The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNgamma-induced cell death in human ovarian carcinoma cells.
H-rev107-1 is a growth inhibitory RAS target gene capable of suppressing anchorage independent growth in vitro and in vivo. Using a tumour tissue array with 241 matched tumour and normal tissue cDNA pools, we found down-regulation of H-REV107-1 in 7 out of 14 ovary-derived cDNAs. RT-PCR analysis and immunohistochemical investigation confirmed expression of H-REV107-1 in normal ovarian epithelial cells but down-regulation in high grade ovarian carcinomas. H-REV107-1 is also strongly expressed in immortalized rat and human ovarian epithelial cells in vitro, but suppressed in transformed cells by two different mechanisms. KRAS-transformed rat ovarian cells and PA1 teratocarcinoma cells, reversibly repress H-REV107-1 via MAP/ERK signaling. In contrast, treatment of A27/80 and OVCAR-3 epithelial ovarian cancer cells with IFNgamma stimulated H-REV107-1 expression. In NIH3T3 cells harbouring an estrogen-inducible IRF-1, H-rev107-1 is directly induced after activation of IRF-1, indicating that H-rev107-1 is a target of IRF-1. Stimulation of H-REV107-1 expression was also observed in ovarian epithelial cells suggesting that IRF-1 is involved in H-REV107-1 regulation in human ovarian epithelium. In the IFNgamma-sensitive cell line A27/80, H-REV107-1 suppresses colony formation. A27/80 and OVCAR-3 cells overexpressing H-REV107-1 protein underwent apoptosis. These results demonstrate down-regulation of the class II tumour suppressor H-REV107-1 in human ovarian carcinomas and suggest an involvement of H-REV107-1 in interferon-dependent cell death.


Raw and salt-processed Achyranthes bidentata attenuate LPS-induced acute kidney injury by inhibiting ROS and apoptosis via an estrogen-like pathway.
Traditional Chinese medicine suggests that Radix Achyranthis Bidentatae nourishes and protects the kidneys, the effect of which is enhanced following a salt treatment. Raw and salt-processed Achyranthes bidentata are produced via different processing techniques from the same crude Achyranthes root. The anti-inflammatory and immunomodulatory properties of this plant have been verified earlier. However, there is a scarcity of experimental evidence for the renal-protective effects. The purpose of present study is to compare the protective effects of raw and salt-processed Achyranthes on lipopolysaccharide (LPS) - induced acute kidney injury in mice and chemically characterize their extracts. The monomer components of raw and salt-processed Achyranthes extracts were analyzed using high performance liquid chromatography (HPLC). The aggregation and distribution of 2-Deoxy-D-glucose (2-DG) near infrared fluorescence probe in mice was examined with a small animal imaging systems. The pathological and morphological changes of kidneys were observed by H&E staining, and the serum urea nitrogen (BUN) and serum creatinine (Scr) levels were used to evaluate the renal function. The levels of cytokines in serum were detected by cytometric bead array. Flow cytometry assay was performed to assess the apoptosis and reactive oxygen species (ROS) in the kidney cells, and cell surface marker expression including CD45+, F4/80+, and Ly-6G+. The estrogenic activities of the raw and salt-processed Achyranthes were observed by uterine weight gain test in sexually immature mice. Western blot was used to detect the protein expression levels in the kidney. Chemical analysis showed that the salt-processed Achyranthes contained more ginsenoside Ro and chikusetsusaponin Ⅳa than the raw Achyranthes, but there was no difference in the contents of β-ecdysterone, 25R-inokosterone, and 25S-inokosterone.in vivo near-infrared fluorescence imaging showed a significant reduced inflammation in the AKI mice. Histological studies showed that the raw and salt-processed Achyranthes markedly decreased the inflammatory infiltration, swelling and vacuolar degeneration in renal tissues and the Scr and BUN. Importantly, the raw and salt-processed Achyranthes extracts demonstrated different degrees of inhibition on the LPS-induced AKI, with salt-processed Achyranthes showing better inhibition. Results of flow cytometry showed a significant inhibition of IFN-γ, TNF-α, and IL-2, and promoted IL-10, along with reduced macrophages (CD45 + F4/80+), neutrophils (CD45+ Ly-6G+) and phagocytes. Furthermore, the extracts reduced the accumulation of ROS and apoptosis in the kidney, and also regulated the expression of apoptosis marker proteins TLR4, Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9 levels. Notably, they increased ERα, ERβ, and GPR30 in the renal tissues of AKI mice and LPS non-treated mice. In the subsequent experiments, it was found that the raw and salt-processed Achyranthes extracts increased the uterine coefficient in sexually immature mice, improved the LPS-induced decrease in NRK52e cell viability, and reduced the apoptosis, which could be antagonized by ICI182, 780 (estrogen receptor-unspecific antagonist, Faslodex). The renal-protective effect of raw and salt-processed Achyranthes was exhibited through antiapoptotic and antioxidant mechanisms via an estrogen-like pathway, along with a modulation of the inflammatory response by regulating immune cells. Ginsenoside Ro and Chikusetsu saponin IVa were found to be the key factors to enhance the protective effect of salt-processed Achyranthes.


Isolation, biological and whole genome characteristics of a Proteus mirabilis bacteriophage strain.
Proteus mirabilis, a naturally resistant zoonotic bacterium belonging to the Enterobacteriaceae family, has exhibited an alarming increase in drug resistance. Consequently, there is an urgent need to explore alternative antimicrobial agents. Bacteriophages, viruses that selectively target bacteria, are abundant in the natural environment and have demonstrated potential as a promising alternative to antibiotics. In this study, we successfully isolated four strains of Proteus mirabilis phages from sewage obtained from a chicken farm in Sichuan, China. Subsequently, we characterized one of the most potent lytic phages, Q29, by examining its biological and genomic features. Comparative genomic analysis revealed the functional genes and phylogenetic evolution of Q29 phages. Our findings revealed that Proteus mirabilis bacteriophage Q29 possesses an icosahedral symmetrical head with a diameter of 95 nm and a tail length of 240 nm. Moreover, phage Q29 exhibited stability within a temperature range of 37 ℃ to 55 ℃ and under pH conditions ranging from 4 to 9. The optimal multiplicity of infection (MOI) for this phage was determined to be 0.001. Furthermore, the one-step growth curve results indicated an incubation period of approximately 15 min, an outbreak period of approximately 35 min, and an average cleavage quantity of approximately 60 plaque-forming units (PFU) per cell. The genome of phage Q29 was found to have a total length of 58,664 base pairs and encoded 335 open reading frames (ORFs) without carrying any antibiotic resistance genes. Additionally, genetic evolutionary analysis classified phage Q29 within the family Caudalidae and the genus Myotail. This study provides valuable research material for further development of Proteus mirabilis bacteriophage biologics as promising alternatives to antibiotics, particularly in light of the growing challenge of antibiotic resistance posed by this bacterium.


Skin carotenoids status as a potential surrogate marker for cardiovascular disease risk determination in middle-aged and older adults.
Upon consumption, carotenoids, which may attenuate cardiovascular disease (CVD) risk, diffuse from the blood and accumulate in the skin. This study aimed to assess the associations between dietary, plasma, and skin carotenoids with CVD risk indicators and to examine the mediational role of plasma carotenoids in the relationship between skin carotenoids status (SCS) and CVD risk. Dietary, plasma, and skin carotenoids were assessed in a cross-sectional study from a community in Singapore (n = 103) aged 50 to 75 y. Multiple linear regression and binary logistics regression models were used to examine the associations between the carotenoids status with classical CVD risk factors and composite CVD risk indicators. After controlling for covariates, SCS and plasma carotenoids were inversely associated with systolic blood pressure (skin: P < 0.001; plasma: P < 0.05) and diastolic blood pressure (skin: P < 0.001; plasma: P < 0.005). Additionally, each increment of 1000 in SCS was associated with an odds ratio of 0.924 (P < 0.01) for metabolic syndrome diagnosis and 0.945 (P < 0.05) for moderate to high CVD risk classification. Associations between SCS and composite CVD risk indicators were null when adjusted for the corresponding plasma carotenoids, indicating complete mediation. Dietary carotenoids, however, showed no relationship with the CVD risk indicators. Carotenoids bioavailability may be important for cardiovascular protection. SCS, driven by the corresponding plasma carotenoids, could be a potential noninvasive surrogate marker for CVD risk determination in middle-aged and older adults. NCT03554954, https://clinicaltrials.gov/. 13 June 2018.


High dose rate brachytherapy in the management of anal cancer: A review.
To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included. Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively. Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.


Phosphatidylethanolamine is the donor of the ethanolamine residue linking a glycosylphosphatidylinositol anchor to protein.
Numerous cell surface glycoproteins from eukaryotic organisms including African trypanosomes and budding yeast (Saccharomyces cerevisiae), are anchored to the lipid bilayer by a glycophospholipid, glycosylphosphatidylinositol, covalently linked to the carboxyl terminus of the protein via a phosphoethanolamine bridge. In this paper we describe metabolic labeling experiments aimed at identifying the biosynthetic origin of the ethanolamine residue in the phosphoethanolamine bridge. Using yeast mutants generated by disruption of the ethanolaminephosphotransferase (EPT1) and cholinephosphotransferase (CPT1) genes, we report data consistent with the proposal that the ethanolamine residue is derived from phosphatidylethanolamine.


Biomechanical Effects of Facet Joint Violation After Single-Level Lumbar Fusion With Transpedicular Screw and Rod Instrumentation.
In vitro biomechanical study. This study aimed to investigate the biomechanical effects of facet joint violation (FV) on mobility and optically tracked intervertebral disc (IVD) surface strains at the upper level adjacent to L4-5 pedicle screw-rod fixation. FV is a complication that can occur when placing lumbar pedicle screws; the reported incidence is as high as 50%. However, little is known about how FV affects superior adjacent-level spinal stability, and especially IVD strain, after lumbar fusion. Fourteen cadaveric L3-S1 specimens underwent L4-5 pedicle-rod fixation, 7 in the facet joint preservation (FP) group and 7 in the FV group. Specimens were tested multidirectionally under pure moment loading (7.5 Nm). Colored maps of maximum (ε1) and minimum (ε2) principal surface strain changes on the lateral L3-4 disc were generated, with the surface divided into 4 quarters anterior to posterior (Q1, Q2, Q3, and Q4, respectively) for subregional analyses. Range of motion (ROM) and IVD strain were normalized to intact upper adjacent-level and compared between the groups using analysis of variance. Statistical significance was set at P <0.05. Normalized ROM was significantly greater with FV vs. FP in flexion (11% greater; P =0.04), right lateral bending (16% greater; P =0.03), and right axial rotation (23% greater; P =0.04). Normalized L3-4 IVD ε1 during right lateral bending was greater on average for the FV group than the FP group: Q1, 18% greater; Q2, 12% greater; Q3, 40% greater ( P <0.001); Q4, 9% greater. Normalized ε2 values during left axial rotation were greater in the FV group, the highest increase being 25% in Q3 ( P =0.02). Facet joint violation during single-level pedicle screw-rod fixation was associated with increased superior adjacent level mobility and alteration of disc surface strains, with significant increases in selected regions and directions of loading.


Crohn's disease of the appendix.
Although appendectomy is often the first surgical procedure in patients with Crohn's disease (CD), only few data exist on appendiceal CD. The aim of this study was to analyze appendices of CD patients undergoing surgery. We analyzed 149 specimens from consecutive patients with CD who underwent primary right ileocolonic or (sub)total colonic resection. The appendix was present in 90 resection specimens. Histologic findings were compared with those of 180 age and sex matched controls. Thirty-six appendices showed histologic signs of CD (40%): A transmural inflammation was found in 24 cases (67%), and a mucosal inflammation in 12 cases (33%). Histologic hallmarks of mucosal involvement were focal or discontinuous inflammation with crypt distortion and a histiocytic and lymphocytic predominant inflammation. Furthermore, epitheloid granulomas and erosions or ulcers with abundant histiocytes at the lesions base were observed. In comparison to controls luminal obliteration was significantly overrepresented in CD whereas acute phlegmonous appendicitis was underrepresented ( P<0.01). Patients with CD of the appendix showed a more widespread colonic involvement than those without ( P<0.01). This study shows that CD of the appendix exhibits specific histologic features that allow a differentiation from non-CD-associated appendicitis. CD-associated appendicitis is a frequent event, probably signifying a more widespread colonic involvement.


Modern Machine Learning Practices in Colorectal Surgery: A Scoping Review.
The use of machine learning (ML) has revolutionized every domain of medicine. Surgeons are now using ML models for disease detection and outcome prediction with high precision. ML-guided colorectal surgeries are more efficient than conventional surgical procedures. The primary aim of this paper is to provide an overview of the latest research on "ML in colorectal surgery", with its viable applications. PubMed, Google Scholar, Medline, and Cochrane library were searched. After screening, 27 articles out of 172 were eventually included. Among all of the reviewed articles, those found to fit the criteria for inclusion had exclusively focused on ML in colorectal surgery, with justified applications. We identified existing applications of ML in colorectal surgery. Additionally, we discuss the benefits, risks, and safety issues. A better, more sustainable, and more efficient method, with useful applications, for ML in surgery is possible if we and data scientists work together to address the drawbacks of the current approach. Potential problems related to patients' perspectives also need to be resolved. The development of accurate technologies alone will not solve the problem of perceived unreliability from the patients' end. Confidence can only be developed within society if more research with precise results is carried out.


The embryo as moral work object: PGD/IVF staff views and experiences.
We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of 'affected' or 'spare' embryos or using them for research. A variety of views were expressed on the 'embryo question' in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as 'moral work objects'. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of 'work objects' and focusing on negotiation of the social order in a morally contested field.


Superfine powdered activated carbon incorporated into electrospun polystyrene fibers preserve adsorption capacity.
A composite material consisted of superfine powdered activated carbon (SPAC) and fibrous polystyrene (PS) was fabricated for the first time by electrospinning. SPAC is produced by pulverizing powdered activated carbon. The diameter of SPAC (100-400nm) is more than one hundred times smaller than conventional powdered activated carbon, but it maintains the internal pore structure based on organic micropollutant adsorption isotherms and specific surface area measurements. Co-spinning SPAC into PS fibers increased specific surface area from 6m2/g to 43m2/g. Unlike metal oxide nanoparticles, which are non-accessible for sorption from solution, electrospinning with SPAC created porous fibers. Composite SPAC-PS electrospun fibers, containing only 10% SPAC, had 30% greater phenanthrene sorption compared against PS fibers alone. SPAC particles embedded within the polymer were either partially or fully incorporated, and the accessibility of terminal adsorption sites were conserved. Conserving the adsorptive functionality of SPAC particles in electrospun non-woven polymeric fiber scaffolding can enable their application in environmental applications such as drinking water treatment.


Identification of rectal ganglion cells using monoclonal antibodies.
A monoclonal antibody has been developed that reacts specifically with ganglion cells of the myenteric and submucous plexuses of the gastrointestinal tract. This antibody also recognizes an axonal antigen that is distributed throughout the circular muscle of normal colon and rectum. Aganglionic segments of colon and rectum from patients with Hirschsprung's disease showed no specific antibody binding using a fluorescent labelled assay. The use of monoclonal antibodies should provide further insights into the pathophysiology of Hirschsprung's disease and allied disorders.


Crataegus sinaica defatted methanolic extract ameliorated monosodium iodoacetate-induced oxidative stress andinhibited inflammation in a rat model of osteoarthritis.
Osteoarthritis is a degenerative joint disease without definite treatment. It is characterized by intra-articular inflammation, cartilage degeneration, subchondral bone remodeling, and joint pain. The objective of the current study was to assess the anti-osteoarthritic effect and the possible underlying mechanism of action of Crataegus sinaica extract (CSE). Intra-articular injection of monosodium iodoacetate in the right knee joint of all rats was done except for the sham group. One week later, the anti-inflammatory efficacy of CSE (100, 200, 300 mg/kg, daily p.o) for 4 successive weeks versus ibuprofen (40 mg/kg, p.o) was assessed. Serum inflammatory cytokines; as well as weekly assessment of knee joint swelling, joint mobility, and motor coordination were done. At the end of the experiment, a histopathological investigation of the affected knee joints and an x-ray investigation were also executed. CSE significantly decreased joint swelling, pain behaviors, and serum levels of TNF-α, IL6, hyaluronic acid, and CTX-II. The radiographic findings revealed almost normal joint space with normal radiodensity and diameter in CSE-treated rats. As well, the histopathological and immunohistochemical investigations of the knee joints in CSE-treated groups retained the cartilage structure of knee joints. A significant reduction in the percentage of caspase-3-stained chondrocytes and a decrease in TGF-β1 immuno-positive areas in the synovial lining and sub lining were recorded in CSE-treated rats, compared to the osteoarthritis control group. This study approved the chondroprotective effects of CSE, and its ability to inhibit the pain associated with osteoarthritis.


Clinical diagnosis of ruptures of the anterior cruciate ligament: a comparison between the Lachman test and the anterior drawer sign.
A comparative study of the diagnostic accuracy between the Lachman test and the anterior drawer test was performed by examining 144 knees with ruptured anterior cruciate ligaments. The diagnosis of anterior cruciate ligament rupture is often difficult to establish, especially in recent injuries with acute haemarthrosis. The diagnostic accuracy of the Lachman test in recent ruptures when the patient is examined without general anaesthetic is superior to that of the anterior drawer test, while in chronic cases with third-degree instability the two tests are equally reliable.


Autoradiographic evidence of opioid binding sites in rat growth plate chondrocytes.
After 125I-beta-endorphin was intravenously injected in rats, an autoradiographic study of distal femur growth plates was performed. Results show a specific binding of the radiolabelled peptide to chondrocytes suggesting the possible existence of an opiate modulation of growth plate physiology.


Effects of Compound Zhebei Granule () Combined with Doxorubicin on Expression of Specific Surface Antigens in Mice with Transplanted KG-1a Cells.
To investigate the effects of Compound Zhebei Granule (, CZG) combined with doxorubicin hydrochloride (adriamycin, ADM) on specific surface antigens in mice with KG-1a transplanted cells. A subcutaneous tumor xenograft model was established by injection of the acute myeloid leukemia cell line KG-1a into the axillary flfl anks of BALB/c-nude mice. Twenty-four tumor bearing mice were divided into 4 groups according to a random number table, including normal saline control group, ADM group, high-dose CZG group, and mid-dose CZG group, with 6 mice in each group. Drug administration occurred on the 14th day after cell inoculation, and normal saline control group mice were gavaged with normal saline at 0.2 mL/10 g every other day. ADM group mice were intraperitoneally injected with ADM 1 mg/kg [conversion of adults, 40 mg/(m2•d)] every other day. High- and mid-dose CZG groups mice were gavaged with CZG at the dose of 8 and 4 g/kg respectively every other day and intraperitoneally injected with ADM (1 mg/kg) every other day. The administration period lasted for 10 days. The tumor xenografts were made into mononuclear cell suspensions after dissection, and the expressions of specific surface antigens, including CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+, in KG-1a cell line tumor xenografts were detected by flfl ow cytometry. Compared with the control and ADM groups, expression of CD34+CD38- in the two CZG groups was significantly lower (P<0.05). Compared with the control group, expression of CD34+CD38-CD123+ in the two CZG groups decreased (P<0.05). The high-dose CZG group showed more obvious outcomes compared with the ADM group (P<0.05). Compared with the control and ADM groups, the expression of CD34+CD38-CD96+ and CD34+CD38-CD33+ in the two CZG groups decreased (P<0.05). CZG combined with doxorubicin could reduce the expression of CD34+CD38-, CD34+CD38-CD123+, CD34+CD38-CD96+ and CD34+CD38-CD33+ in KG-1a cell line tumor xenografts, which shows that CZG could target leukemia stem cells and play a role in chemosensitization.


Photochemistry and stereoselectivity of cellular retinaldehyde-binding protein from bovine retina.
11-cis-Retinaldehyde bound to cellular retinaldehyde-binding protein (CRALBP) is unaffected in bovine eyecup preparations by illumination that bleaches approximately 70% of the rhodopsin. Illumination of retinal homogenates to which CRALBP X [3H]11-cis-retinaldehyde had been added did not result in a reduction of the specific activity of recovered 11-cis-retinaldehyde, ruling out a bleaching regeneration cycle. The quantum efficiency of photoisomerization for CRALBP X 11-cis-retinaldehyde was determined by comparing the rate of photoisomerization of 11-cis-retinaldehyde bound to purified CRALBP and opsin. The low value obtained (0.07), coupled with a low molar extinction coefficient (15,400 M-1 cm-1), results in a photosensitivity only about 4% that of rhodopsin. CRALBP binds 9-cis- and 11-cis-retinaldehyde, producing complexes with absorption maxima at 405 and 425 nm, respectively. No complexes were detected with 13-cis- and all-trans-retinaldehyde. Following incubation of CRALBP X 11-cis-retinol with an equimolar mixture of 9-, 11-, 13-cis-, and all-trans-retinaldehydes, only 11-cis-retinaldehyde and residual 11-cis-retinol are present on the protein following separation from excess retinoids. A similar result is obtained following incubation of CRALBP X 11-cis-retinol with mixtures of 9- and 11-cis-retinaldehyde ranging in composition from 9:1 to 1:9 (9-cis-:11-cis-,mol/mol). The results indicate that CRALBP X 11-cis-retinol is sufficiently stereoselective in its binding properties to warrant consideration as a component of the mechanism for the generation of 11-cis-retinaldehyde in the dark.


[Is the implantation of a second intraocular lens prior to the removal of the first implants remaining in the vitreous cavity incorrect medical treatment?].
The implantation of an intraocular lens into the capsular bag is a common procedure in modern cataract surgery. In case of a break of the posterior capsule it is possible to implant the intraocular lens by rhexis-, ciliary sulcus- or pars-plana-fixation. The following case is in so far remarkable, as a second intraocular lens has been implanted while a dislocated intraocular lens was still in the vitreous cavity. We report on a 70-year-old patient who underwent cataract surgery. After a break in the posterior capsule the intraocular lens dislocated into the vitreous cavity. A second intraocular lens has been implanted in the ciliary sulcus. 41 days after cataract surgery the dislocated intraocular lens has been removed by pars-plana-vitrectomy without any problems. Intraocular lens implantation in the ciliary sulcus is not proved to be a hindrance with regard to the transcleral removal of a posteriorly dislocated intraocular lens, following the principles of intraocular foreign body surgery.


[Medical examinations of workers in the artificial leather plant in 1975-1980].
The studies of general morbidity rate and that related to circulatory, respiratory and alimentary systems covered altogether 232 subjects, in this: 151 men and 81 women. The population was evaluated taking into account: exposure factors, age, employment duration, magnitude of exposure to chemical hazards, expressed by MAC excess. The percentage indices of analysed parameters registered in the first and fourth examinations, carried out at an interval of five years, were compared. Increased general morbidity rate in men occupationally exposed to chemical hazards was found, which was particularly due to increased cardiovascular diseases rate. Women exposed to chemical hazards revealed increased morbidity rate due to alimentary tract diseases.


Combined spinal-epidural versus epidural analgesia for labor and delivery.
The rapid onset of analgesia and improved mobility with combined spinal-epidural (CSE) techniques has been associated with a higher degree of maternal satisfaction compared with conventional epidural analgesia. However, controversy exists in that initiation of labor analgesia with a CSE may be associated with an increased risk for nonreassuring fetal status (ie, fetal bradycardia) and a subsequent need for emergent cesarean delivery. Overall, both epidural and CSE techniques possess unique risk/benefit profiles, and the decision to use one technique rather than the other should be determined based on individual patient and clinical circumstances.


QRS morphology-dependent pharmacodynamics in multiform ventricular ectopic activity.
The effect of an infusion of intravenous procainamide on the frequency of ventricular premature complexes (VCPs) of differing QRS morphologies was studied in 20 patients with multiform ectopic activity. In 17 of 20 patients, there was differential suppression of single VPCs with different QRS morphologies. VPCs of the most frequent QRS morphology and the second most frequent QRS morphology were compared with respect to the procainamide level at the escape of VPCs from 85% suppression and the duration of suppression measured from the onset of the procainamide infusion. In 8 patients, VPCs of the most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the second most frequent QRS morphology (escape procainamide concentration = 2.8 +/- 1.7 versus 5.4 +/- 2.3 micrograms/ml, p less than 0.025; time to escape 244 +/- 138 versus 98 +/- 114 min; p less than 0.05). In 9 other patients, VPCs of the second most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the most frequent QRS morphology (escape procainamide concentration 2.9 +/- 1.4 versus 8.3 +/- 6.3 micrograms/ml, p less than 0.025; time to escape 317 +/- 114 versus 63 +/- 80 min; p less than 0.001). Thus, in individual patients there are specific patterns of suppression of VPCs of different QRS morphologies which are independent of the frequency of each morphology. There is apparently a differential pharmacologic effect of procainamide on the foci or pathways responsible for the different QRS morphologies of multiform VPCs.


A Meta-analysis on the Effectiveness of Offsetting Strategies to Address Harm to Freshwater Fishes.
Offsetting aims to compensate for negative impacts due to authorized anthropogenic impacts associated with development. While anchored into legislation, residual or chronic impacts can occur after offset establishment. Advice and best practice on how to approach these impacts is rare. To address this, we reviewed 30 projects based on a systematic review and meta-analysis in freshwater ecosystems dealing with residual or long-term negative impacts to provide application advice for: habitat creation, habitat restoration, and biological and chemical manipulation. Project information was obtained through Boolean search terms and web-scraping. Habitat creation projects had a pooled effect size of 0.8 and offsetting ratios of 1:5 with high biomass increases of >140% compared to pre-establishment, associated with them. Habitat restoration projects targeted a wide range of species and communities with a pooled effect size of 0.66, offset ratios ranging from 1:1.2 to 1:4.6, and biomass increases generally > 100% compared to pre-restoration. Biological manipulation had the lowest effect size (0.51) with stocking being highly variable both in terms of biomass benefits and project outcomes pointing towards being mostly applicable in cases of direct fish harm not related to habitat aspects. We conclude that (1) all three assessed approaches have a potential application use for offsetting residual or chronic harm with approach-specific caveats. (2) Implementation costs differ across offset methods, with connectivity and side-channel projects having the lowest biomass gain per area costs (3) Time to first benefits required one to two years with time lags needing to be accounted for in the implementation and monitoring process.


Critical care stress and burnout.
Burnout may be one of the most common problems affecting critical care physicians. Burnout can best be defined as disillusionment and a flattening of the effervescence of life. Recognizing the symptoms of burnout and the sources of stress enables one to incorporate preventive strategies and self-rescue techniques.


Infant health and family functioning in a poor socio-economic status multi-ethnic municipality.
In a longitudinal epidemiological study of 272 infants in a poor socio-economic, multi-ethnic municipality, the physical growth of infants was found to be within a normal range. Two percent of infants had major, and 2% minor developmental delays due mainly to congenital defects or psychosocial disturbance or neglect in the home. Although there was a high prevalence of episodic, continuing and recurrent illness, this caused little serious morbidity. The most significant finding was that approximately one third of mothers perceived their infants to have moderate or severe behavioural disturbances which were significantly associated with their own psychological ill-health. The findings from this urban population contrasted with previous studies. Serious infective illnesses, associated with poor physical and psychosocial environments, were no longer major health problems. These organic diseases in infants were largely replaced by behavioural and developmental disturbances, also associated with psychosocial problems in families.


Oncologic Applications of Long Axial Field-of-View PET/Computed Tomography.
New protocols for imaging cancer have been developed to take advantage of the improved imaging capabilities of long axial field-of-view PET scanners. Both research and clinical applications have been pursued with encouraging early results. Clinical studies have demonstrated improved image quality and the ability to image with less injected activity or for shorter duration. With the increased sensitivity inherent in total-body PET scanners and new imaging paradigms, new challenges in image interpretation have emerged. New research applications have also emerged, including dosimetry, cell tracking, and dual-tracer applications.


Global transcriptomic profiling of microcystin-LR or -RR treated hepatocytes (HepaRG).
The canonical mode of action (MOA) of microcystins (MC) is the inhibition of protein phosphatases, but complete characterization of toxicity pathways is lacking. The existence of over 200 MC congeners complicates risk estimates worldwide. This work employed RNA-seq to provide an unbiased and comprehensive characterization of cellular targets and impacted cellular processes of hepatocytes exposed to either MC-LR or MC-RR congeners. The human hepatocyte cell line, HepaRG, was treated with three concentrations of MC-LR or -RR for 2 h. Significant reduction in cell survival was observed in LR1000 and LR100 treatments whereas no acute toxicity was observed in any MR-RR treatment. RNA-seq was performed on all treatments of MC-LR and -RR. Differentially expressed genes and pathways associated with oxidative and endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) were highly enriched by both congeners as were inflammatory pathways. Genes associated with both apoptotic and inflammatory pathways were enriched in LR1000. We present a model of MC toxicity that immediately causes oxidative stress and leads to ER stress and the activation of the UPR. Differential activation of the three arms of the UPR and the kinetics of JNK activation ultimately determine whether cell survival or apoptosis is favored. Extracellular exosomes were enrichment of by both congeners, suggesting a previously unidentified mechanism for MC-dependent extracellular signaling. The complement system was enriched only in MC-RR treatments, suggesting congener-specific differences in cellular effects. This study provided an unbiased snapshot of the early systemic hepatocyte response to MC-LR and MC-RR congeners and may explain differences in toxicity among MC congeners.


Nursing home-acquired pneumonia presenting at the emergency department.
Nursing home-acquired pneumonia (NHAP) is one of the most common infections arising amongst nursing home residents, and its incidence is expected to increase as population ages. The NHAP recommendation for empiric broad-spectrum antibiotic therapy, arising from the concept of healthcare-associated pneumonia, has been challenged by recent studies reporting low rates of multidrug-resistant (MDR) bacteria. This single center study analyzes the results of NHAP patients admitted through the Emergency Department (ED) at a tertiary center during the year 2010. There were 116 cases, male gender corresponded to 34.5 % of patients and median age was 84 years old (IQR 77-90). Comorbidities were present in 69.8 % of cases and 48.3 % of patients had used healthcare services during the previous 90 days. In-hospital mortality rate was 46.6 % and median length-of-stay was 9 days. Severity assessment at the Emergency Department provided CURB65 index score and respective mortality (%) results: zero: n = 0; one: n = 7 (0 %); two: n = 18 (38.9 %); three: n = 26 (38.5 %); four: n = 30 (53.3 %); and five; n = 22 (68.2 %); and sepsis n = 50 (34.0 %), severe sepsis n = 43 (48.8 %) and septic shock n = 22 (72.7 %). Significant risk factors for in-hospital mortality in multivariate analysis were polypnea (p = 0.001), age ≥ 75 years (p = 0.02), and severe sepsis or shock (p = 0.03) at the ED. Microbiological testing in 78.4 % of cases was positive in 15.4 % (n = 15): methicillin-resistant Staphylococcus aureus (26.7 %), Pseudomonas aeruginosa (20.0 %), S. pneumoniae (13.3 %), Escherichia coli (13.3 %), others (26.7 %); the rate of MDR bacteria was 53.3 %. This study reveals high rates of mortality and MDR bacteria among NHAP hospital admissions supporting the use of empirical broad-spectrum antibiotic therapy in these patients.


ARF7 increases the endogenous contents of castasterone through suppression of BAS1 expression in Arabidopsis thaliana.
Homeostasis of brassinosteroids (BRs) maintained by the balance between their biosynthesis and inactivation is important to coordinate the diverse physiological and developmental responses of plants. Although BR signaling regulates the endogenous levels of BRs via negative feedback regulation, it remains largely unknown how the biosynthesis and inactivation of BR are triggered. BAS1 encodes CYP734A1, which inactivates the biologically active BRs via C-26 hydroxylation and is down-regulated by a BR-responsive transcription factor, BZR1. Here it is demonstrated that the expression of the BAS1 gene is regulated by auxin response factors (ARFs) in Arabidopsis thaliana. Two successive E-box motifs on the BAS1 promoter function as BZR1 binding sites and are essential for BR-regulated BAS1 expression. The expression of BAS1 is increased in the arf7 and arf7arf19 mutants. The endogenous level of bioactive BR, castasterone, is greatly decreased in those mutants. ARF7 can bind to the E-box motifs of the BAS1 promoter where BZR1 binds, suggesting that ARF7 and BZR1 mutually compete for the same cis-element of the BAS1 promoter. Additionally, ARF7 directly interacts with BZR1, which inhibits their DNA binding activities and regulation of BAS1 expression. In conclusion, auxin signaling via ARF7 directly modulates the expression of BAS1 by competition with BZR1, thereby increasing the level of castasterone and promoting growth and development in A. thaliana.


Evaluating a specialist education programme for nurses and allied health professionals working in older people care: A qualitative analysis of motivations and impact.
Developing clinical leaders is essential for high-quality, safe care for older people. Fundamental to achieving this is specialist continuing professional development for nurses and allied health professionals. To investigate the motivations of nurses and allied health professionals to undertake a national specialist gerontological programme, the Older Persons Fellowship, and its impacts on their development and on older people care. A qualitative descriptive design. Participants were nurses and allied health professionals undertaking a national specialist gerontological programme in England. A purposive sample of 63 participants was recruited. Twelve focus groups and four individual interviews were conducted between February 2015 and February 2019. Data were analysed using thematic analysis. Three themes were identified: credible gerontological experts; challenging ageism and suboptimal services; and legitimising gerontological practice as a speciality. Understanding the motivations to undertake a specialist gerontological programme and the impacts on practitioners and older people care and services will help inform the continuing professional development agenda for nurses and allied health professionals working in this field of practice. Policy makers, commissioners, managers, and educators can use the findings to inform continuing professional development priorities and provision for the gerontological workforce.


Attachment theory in health care: the influence of relationship style on medical students' specialty choice.
Converging sources suggest that patient-provider relationships in primary care are generally of greater intensity and duration than those in non-primary care specialties. In this study, we hypothesised that Year 2 medical students whose close relationships were characterised by security and flexibility would be more likely than students who were less comfortable in close relationships to plan to pursue primary over non-primary care postgraduate training. We determined the relationship styles and demographic characteristics of 144 Year 2 medical students. We also gathered information regarding their predicted choices of postgraduate training, which were clustered into primary or non-primary care categories. We compared student choices with respect to their interpersonal relationship styles based on attachment theory. Prevalences of attachment styles were similar to those found in the general population, with 56% of students rating themselves as having a secure relationship style. Students with a secure style were more likely to choose primary care (61%) over non-primary care compared to those whose styles were characterised by self-reliance, support-seeking or caution (41% chose primary care). Compared to those with a secure relationship style, students with a cautious style [OR = 5.9 (1.9, 18.7)] and students with a self-reliant style [OR = 2.4 (0.96, 5.9)] were more likely to choose non-primary over primary care, after controlling for gender. Assessing relationship styles using attachment theory is a potentially useful way to understand and counsel medical students about specialty choice.


Biological effects of agglomerated multi-walled carbon nanotubes.
The physicochemical properties of nanomaterials play crucial roles in determining their biological effects. Agglomeration of nanomaterials in various systems is a common phenomenon, however, how agglomeration affects the biological consequence of nanomaterials has not been well investigated because of its complexity. Herein, we prepared variable sized agglomerates of oxidized multi-walled carbon nanotubes (O-MWCNTs) by using Ca(2+) and studied their cellular uptake and cytotoxicity in HeLa cells. We found the altered property of O-MWCNTs agglomerates could be controlled and adjusted by the amount of Ca(2+). Agglomeration remarkably facilitated the cellular uptake of O-MWCNTs at the initial contact stage, due to the easy contact of agglomerates with cells. But agglomeration did not induce evident cytotoxicity when the concentration of O-MWCNTs was less than 150μg/mL. That was assayed by cell proliferation, membrane integrity, apoptosis and ROS generation. This study suggests us that the biological behaviors of nanomaterials could be altered by their states of agglomeration.


The conventional doses of human chorionic gonadotropins may not always be sufficient to induce ovulation in all women: a reappraisal.
Failure of ovulation has occasionally been reported following the administration of conventionally recommended doses of exogenous human chorionic gonadotropins. A 25-year-old nulliparous woman with polycystic ovary syndrome underwent ovulation induction for primary infertility. Following successful ovarian stimulation, she failed to ovulate during two consecutive cycles in response to human chorionic gonadotropin doses of 5,000 and 10,000 IU. When challenged with a higher than conventional dose (15,000 IU) on the third cycle, she ovulated and conceived. Conventional doses of exogenous human chorionic gonadotropins occasionally fail to complete the ovulatory process in some women. Women with polycystic ovary syndrome appear to be particularly susceptible. Routine documentation of ovulation and individualization of the dose of exogenous human chorionic gonadotropins could therefore prove to be useful in some of these women in order to achieve the best treatment outcome.


Primary Tumor Resection Prolongs Survival in Spinal Chondrosarcoma Patients With Distant Metastasis.
Retrospective analysis. To investigate (1) whether resection of primary tumor improves survival of metastatic spinal chondrosarcoma patients and (2) which subgroups of metastatic spinal chondrosarcoma patients benefit more from primary tumor resection. Surgical resection is the mainstay of treatment for spinal chondrosarcoma, as chondrosarcoma is inherently resistant to radiotherapy and chemotherapy. However, evidence which justifies resection of the primary tumor for patients with metastatic spinal chondrosarcoma is still lacking. We retrospectively included 110 patients with metastatic spinal chondrosarcoma in the Surveillance, Epidemiology, and End Results database from 1983 to 2016. The association between primary tumor resection and survival was evaluated using Kaplan-Meier analyses, log-rank tests, and multivariable Cox analyses. The effect of primary tumor resection on survival was further assessed in subgroups stratified by histologic subtype, tumor grade, and age. Overall, 110 patients were divided into surgery group (n = 55, 50%) and nonsurgery group (n = 55, 50%). Primary tumor resection was associated with both prolonged overall survival (hazard ratio 0.262, 95% confidence interval 0.149-0.462, P < 0.001) and cancer-specific survival (hazard ratio 0.228, 95% confidence interval 0.127-0.409, P < 0.001). When we focused on surgical effects in subgroups, primary tumor resection conferred survival advantage on patients with conventional subtype, grade I to III malignancy, and an age younger than 70 years old (P < 0.001 for overall and cancer-specific survival). However, primary tumor resection brought limited survival benefit for patients with dedifferentiated subtype and patients over 70 years old. The present population-based study for the first time reports a clear association between primary tumor resection and prolonged survival in metastatic spinal chondrosarcoma patients. Specifically, primary tumor resection was associated with improved survival in patients with conventional subtype, grade I to III malignancy, and an age younger than 70 years old. 4.


The impact of serum magnesium and calcium on the risk of epilepsy: A mendelian randomization study.
To investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach. Single nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary-level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta-analysis was then conducted. The result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12-0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10-0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31-1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17-0.74, p = 0.006). The current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.


Periodic catatonia: a schizophrenic subtype with major gene effect and anticipation.
In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-degree relatives, we investigated age-specific morbidity risk according to Leonhard's clinical distinction between systematic and periodic catatonia. This dichotomy is based on different types of symptomatology, course, and outcome. In systematic catatonia the age-corrected morbidity risk was 4.6%. In periodic catatonia, however, there was an age-corrected morbidity risk with homogenous psychoses of 26.9%, and more parents than siblings were affected. This points strongly to a major gene effect in periodic catatonia. Furthermore, a pairwise comparison of patients and their parents revealed patterns of anticipation, i.e., the probands' age at the onset of disease was significantly earlier than that of their parents (P < 0.001). Similarly, anticipation was apparent in pedigrees with three successive generations affected. This inheritance pattern with homogenous psychoses and anticipation indicates that genes with trinucleotid repeat expansion or other repetitive elements affecting gene expression may be involved in the etiology of periodic catatonia. Thus, periodic catatonia as a specific clinical subtype of schizophrenia is a promising candidate for molecular genetic evaluation.


Tailgut cysts: report of two cases.
An illustration of the diagnosis and management of tailgut cysts. Two cases of tailgut cyst and a review of the literature. A female patient presented with acute urinary retention with a retrorectal mass felt during rectal examination and confirmed on ultrasound and magnetic resonance imaging underwent surgical resection and histology confirmed a chronically inflamed mucoid fluid-filled cyst partly lined by non-keratinised squamous epithelium. A male patient with ureteric obstruction and a prerectal cyst found on ultrasound scan underwent computed tomography with biopsies, but without reaching a conclusive diagnosis. Surgical resection was carried out and histology showed a chronically inflamed mucoid fluid-filled cyst partly lined with columnar epithelium. Tailgut cysts are a rare developmental abnormality arising from remnants of the embryological postanal gut. Usually presenting incidentally or with pressure symptoms in middle-aged females, tailgut cysts are often initially mistaken for other clinical entities. Magnetic resonance imaging helps to differentiate tailgut cysts from other retrorectal lesions and developmental cysts. Histologically, the cyst wall demonstrates a wide variety of epithelial types and has a malignant potential. Malignancy is difficult to rule out with imaging or biopsy. Magnetic resonance imaging is the favoured imaging modality and surgical resection is recommended to relieve pressure symptoms, provide a definitive diagnosis and rule out malignancy.


A comparative study of intralesional injection of Candida albicans antigen, bleomycin and 5-fluorouracil for treatment of plane warts.
Several therapeutic modalities for the treatment of verruca plana (VP) are available, but none has achieved complete cure in all cases with associated risk of side effects. To evaluate efficacy and safety of intralesional injection of Candida albicans (C. albican) antigen, bleomycin and 5-fluorouracil (5-FU) in treatment of VP. Sixty patients with VP were randomly divided into three equal groups who were treated using C. albicans antigen, bleomycin or 5- FU injections every 2 weeks till complete clearance of the lesions or for a maximum of four sessions and followed up for additional 8 weeks. A statistically significant higher incidence of complete response was achieved with bleomycin (85%) than C. albicans antigen (60%) which was higher than 5-FU (45%) with a significantly less number of required sessions to achieve best results with bleomycin and candida antigen than 5-FU. Candida albicans antigen, bleomycin and 5-FU are helpful modalities for treatment of VP. Bleomycin was the most effective, followed by C. albicans antigen then 5-FU (least effective). Single injection site, clearance of distant warts and decreased incidence of new lesion development - in situ or elsewhere - are additional merits of C. albicans immunotherapy. These modalities are cheap with only transient adverse effects.


Synthesis and elaboration of N-methylpyrrolidone as an acetamide fragment substitute in bromodomain inhibition.
N-Methylpyrrolidone is a solvent molecule which has been shown to compete with acetyl-lysine-containing peptides for binding to bromodomains. From crystallographic studies, it has also been shown to closely mimic the acetamide binding motif in several bromodomains, but has not yet been directly pursued as a fragment in bromodomain inhibition. In this paper, we report the elaboration of N-methylpyrrolidone as a potential lead in fragment-based drug design. Firstly, N-methylpyrrolidone was functionalised to provide points for chemical elaboration. Then, the moiety was incorporated into analogues of the reported bromodomain inhibitor, Olinone. X-ray crystallography revealed that the modified analogues showed comparable binding affinity and structural mimicry to Olinone in the bromodomain binding site.


History of the term prostate.
We comprehensively review the history of the word "prostate" and related terms from 600 BC to the present. Both medical and non-medical ancient texts were searched to clarify the term's etymology and use. Anatomy textbooks of the 16th through the 18th century were analyzed to identify descriptions, illustrations and various expressions used by contemporary authors to designate the prostate. In ancient Greek the masculine term "prostatēs" meant "president" and was exclusively used in a non-medical sense. It was not until the Renaissance that anatomists discovered the organ naming it "glandulous body." In 1600 the French physician du Laurens introduced the metaphoric denomination "prostatae." However he and his contemporaries misinterpreted the history of the organ and the term, choose the wrong gender when translating it into Latin, and believed that it designated a double organ. Only in the 1800s was this anatomical error corrected while the grammatical one lived on. The history of the term "prostate" is a prime example of the difficulties with which the development of a precise urologic terminology had to struggle. At the same time this retrospective view provides a stimulus to avoid linguistic ambiguity in the future.


Inadvertent corneal pigmentation following cosmetic blepharopigmentation.
To present a case of inadvertent corneal pigmentation as a complication of cosmetic eyelid tattooing. A 63 year old woman presented with left eye redness and irritation 3 days after undergoing permanent eyeliner tattooing of her upper and lower eyelids. On ocular examination a black pigmentation of the nasal cornea in her left eye was observed, with associated conjunctival injection. Initial slit lamp attempts of pigment removal were unsuccessful. A surgical attempt to scrape the pigment in the stroma was only partially successful due to the penetration of pigment particles in between stromal lamellae. Microanalysis spectroscopy was performed on a specimen of pigment taken from the eyelashes in order to attain the chemical properties of the material and assist with further therapeutic strategy. The analysis revealed an organic inert nature of the material (mostly carbon and oxygen) and ruled out presence of dangerous components such as copper and lead. Due to minimal inflammatory reaction and the non-central location of the corneal pigmentation, the patient remained under close observation, treated with lubrication and no further interventions, until complete resolution by 6 weeks. While the procedure of cosmetic blepharopigmentation is considered relatively safe, it bares many possible complications, ranging from mild dermal irritation to vision-threatening conditions. Our case of inadvertent keratopigmentation demonstrates the potential dangers of this procedure, and the importance of medical supervision and intervention in cases of complications. Vision preservation in this case was enabled by the midperipheral location of the pigment penetration.


[Effects of postural changes and volume depletion on renin-angiotensin system (author's transl)].
The effects of orthostatism and furosemide tests on different parameters of renin-angiotensin system have been studied in 14 normal human subjects. Both tests produced a significant increase in plasma renin activity and plasma renin concentration. Plasma substrate concentration was slightly, but significantly, increased on the furosemide test. Plasma aldosterone rose in both tests, while aldosterone urinary excretion decreased after orthostatism and increased after furosemide.


Arterial spin labeling in clinical pediatric imaging.
Arterial spin labeling (ASL) perfusion-weighted magnetic resonance imaging is the only approach that enables direct and non-invasive quantitative measurement of cerebral blood flow in the brain regions without administration of contrast material and without radiation. ASL is thus a promising perfusion imaging method for assessing cerebral blood flow in the pediatric population. Concerning newborns, there are current limitations because of their smaller brain size and lower brain perfusion. This article reviews and illustrates the use of ASL in pediatric clinical practice and discusses emerging cerebral perfusion imaging applications for children due to the highly convenient implementation of the ASL sequence.


Molecular epidemiological study of the G protein of human respiratory syncytial virus detected in patients with acute respiratory infections in Gyeonggi Province, South Korea.
To investigate the molecular characteristics of human respiratory syncytial virus (HRSV) detected in Gyeonggi Province from 2015/16 to 2017/18, 2331 specimens from patients with sporadic acute respiratory illness and 85 specimens from four HRSV outbreaks in the postpartum care center were analyzed by real-time reverse transcription PCR. HRSVs were detected in 97 of the 2416 (4.0%) specimens, and among the positive specimens, 38 (39.2%) were identified as HRSV-A and 59 (60.8%) as HRSV-B. During the study periods, HRSV-B predominated in all seasons, except in 2016/17 during which HRSV-A predominated. Depending on the age groups, HRSV prevalence was the highest in 0- to 2-year-old patients. Comparison of noninfected subjects with HRSV-infected subjects revealed that HRSV infection more frequently resulted in fever, nasal obstruction, and wheezing, although the frequency of sore throat was low; however, comparison of the symptoms between HRSV-A- and HRSV-B-infected patients revealed no significant differences in symptoms. Phylogenetic analysis showed that all HRSV-A patients had an ON1 genotype, and all HRSV-B patients had an BA9 genotype. These results provide a valuable reference regarding the circulating pattern and molecular characterization of HRSV. Continuous monitoring will be essential to detect newly emerging HRSV genotypes.


The prestige oil spill. I. Biodegradation of a heavy fuel oil under simulated conditions.
In vitro biodegradation of the Prestige heavy fuel oil has been carried out using two microbial consortia obtained by enrichment in different substrates to simulate its environmental fate and potential utility for bioremediation. Different conditions, such as incubation time (i.e., 20 or 40 d), oil weathering, and addition of an oleophilic fertilizer (S200), were evaluated. Weathering slowed down the degradation of the fuel oil, probably because of the loss of lower and more labile components, but the addition of S200 enhanced significantly the extension of the biodegradation. n-Alkanes, alkylcyclohexanes, alkylbenzenes, and the two- to three-ring polycyclic aromatic hydrocarbons (PAHs) were degraded in 20 or 40 d of incubation of the original oil, whereas the biodegradation efficiency decreased for higher PAHs and with the increase of alkylation. Molecular markers were degraded according to the following sequence: Acyclic isoprenoids > diasteranes > C27-steranes > betabeta-steranes > homohopanes > monoaromatic steranes > triaromatic steranes. Isomeric selectivity was observed within the C1- and C2-phenanthrenes, dibenzothiophenes, pyrenes, and chrysenes, providing source and weathering indices for the characterization of the heavy oil spill. Acyclic isoprenoids, C27-steranes, C1- and C2-naphthalenes, phenanthrenes, and dibenzothiophenes were degraded completely when S200 was used. The ratios of the C2- and C3-alkyl homologues of fluoranthene/pyrene and chrysene/benzo[a]anthracene are proposed as source ratios in moderately degraded oils. The 4-methylpyrene and 3-methylchrysene were refractory enough to serve as conserved internal markers in assessing the degradation of the aromatic fraction in a manner similar to that of hopane, as used for the aliphatic fraction.


The Marfan syndrome and cardiac surgery.
Of 31 patients with Marfan's syndrome and cardiovascular complications, 25 had ascending aortic aneurysms, five with aortic dissection; 26 had aortic regurgitation, two with aortic stenosis; and eight had mitral regurgitation, five with aortic regurgitation. Surgery included prosthetic aortic valve replacement in 24 patients and aortic valvular bicuspidization in two; 19 had resection of aneurysm with Dacron tube replacement, three had lateral aneurysmorrhaphy, and two had circumferential strip excision with end-to-end anastomosis. Four patients underwent mitral valve replacement. Operative complications occurred in 10 patients. There were nine (29 percent) hospital deaths, but only one death occurred in 12 patients operated upon since 1970. Late complications included prosthetic leak in six patients (23 percent) with reoperation in five; all survived. Five late deaths occurred (16 percent); one was unrelated and one was of unknown cause. Although risk of cardiac surgery remains high, our recent results support an aggressive surgical approach, particularly in patients with advanced or deteriorating cardiovascular complications.


Design, synthesis and structure-activity relationship of novel RXR-selective modulators.
The synthesis and in vitro characterization of novel RXR-selective ligands possessing various substituted 1-benzofuran or 1-benzothiophene moieties are described.


Elimination of P1 arginine 393 interaction with underlying glutamic acid 255 partially activates antithrombin III for thrombin inhibition but not factor Xa inhibition.
The mechanism for heparin activation of antithrombin III has been postulated to involve disruption of interactions between its reactive loop P1 residue and Glu(255) on the underlying protein surface. To test this hypothesis, the potential P1-constraining Arg(393)-Glu(255) hydrogen bond and ionic interactions were eliminated by converting Glu(255) to alanine. E255A and wild-type ATIIIs have identical reactive loop sequences (including the P1 and P14 residues), but differ in that Glu(255)-mediated, P1-constraining interactions with the underlying surface cannot form in the mutant. Relative to its wild-type parent, E255A had a 5-fold higher affinity for heparin and pentasaccharide. In the absence of cofactor, E255A exhibited a 5-fold activation of thrombin inhibition but no activation of factor Xa inhibition. Pentasaccharide addition elicited no further activation of thrombin inhibition but increased the factor Xa inhibition rate 100-fold. E255A heparin-dependent thrombin and factor Xa inhibition rates were 1000- and 2-fold faster, respectively, than pentasaccharide-catalyzed rates. Although "approximation" is the predominant factor in heparin activation of ATIII thrombin inhibition, and removal of the P1 constraint plays a distinct but minor role, the primary determinant for activation of factor Xa inhibition is the pentasaccharide-induced conformational change, with approximation making a further minor contribution, and removal of the P1 constraint playing no role at all.


Aspergillus nidulans 5S rRNA genes and pseudogenes.
The sequence of four Aspergillus nidulans 5S rRNA genes and of two pseudogenes has been determined. A conserved sequence about 100 bp upstream of the 5S rRNA coding sequences has been found in three genes and one pseudogene. The two pseudogenes correspond to the 5' half of the 5S rRNA coding sequence and their 3' flanking sequences which are not homologous to 5S rRNA are strongly conserved.


Pseudo-pulseless electrical activity in the emergency department, an evidence based approach.
A great deal of the literature has focused specifically on true pulseless electrical activity (PEA), whereas there is a dearth of research regarding pseudo-PEA. This narrative review evaluates the diagnosis and management of patients in pseudo-PEA and discusses the impact on emerging patient outcomes. Pseudo-PEA can be defined as evidence of cardiac activity without a detectable pulse. Distinguishing pseudo-PEA from true PEA is important for emergency physicians as the prognosis and management of these patients differ. POCUS is the tool most commonly used to diagnose pseudo-PEA and there are varying treatment strategies to manage these patients. Identifying patients in pseudo-PEA can help guide resuscitation decisions, and ultimately impact emergency response systems, patients, and families. The incidence of pseudo-PEA is increasing. Effective care of these patients begins with early diagnosis of this condition and immediate treatment to warrant the greatest chance of survival. There is a need for further prospective studies surrounding pseudo-PEA as evidenced by the lack of research in the current literature.


The benefits of low anterior en bloc resection as part of cytoreductive surgery for advanced primary and recurrent epithelial ovarian cancer patients outweigh morbidity concerns.
The aim of this study was to assess the safety, efficacy and impact on survival of low anterior resection and primary anastomosis at the time of en bloc resection for primary and recurrent epithelial ovarian carcinoma. We performed a retrospective review of 46 primary and 14 recurrent epithelial ovarian carcinoma patients who underwent procedures between April 2001 and May 2005 in our center. Data were obtained from patient medical records and the cancer registry. Parameters for safety, efficacy and survival were considered as primary endpoints. For primary advanced ovarian cancer patients, 43.5% showed no visible tumor at the completion of surgery and optimal cytorection (residual tumor [RT] less than or equal 5 mm) was achieved in 89.2%. Complications associated with en bloc resection occurred in two patients (1 leakage of anastomosis site and 1 rectovaginal fistula), and these were managed with diversion colostomy. Patients with no visible residual tumor had longer disease-free survival compared to those with visible RT (median, 30 vs. 7 months; P=0.0082) and longer overall survival (3-year survival rate, 82.03% vs. 66.63%; P=0.0437). Patients with rectal invasions up to the serosa/subserosa had longer disease-free survival than those with rectal invasion up to the muscle/mucosa (P=0.0176) but did not differ significantly in terms of overall survival (P=0.0880). For recurrent ovarian cancer patients, 42.9% showed no visible tumor at the completion of surgery and optimal cytorection was achieved in 64.3%. One patient experienced an en-bloc-resection-associated complication (a rectovaginal fistula), which was managed conservatively. Patients with no visible residual tumor (RT) had longer disease-free survival than visible RT patients (median, not reached vs. 5 months; P=0.0156) but did not differ significantly in terms of overall survival (median, 32 months for no visible RT vs. 24 months for visible RT patients; P=0.0833). There were no surgery-related deaths among the overall 60 primary and recurrent ovarian cancer patients. En bloc resection of primary and recurrent epithelial ovarian carcinomas with low anterior resection permits a high rate of complete debulking with acceptable morbidity and mortality rates. Patients with no visible RT after surgery had a survival advantage over patients with visible RT.


'There is no sea, only fish': effects of United States policy on the health of the displaced in El Salvador.
The poor health status of El Salvador's displaced is a direct result of government policy which defines civilians as legitimate military targets. The effects of this 'strategic hamlet' policy on health is vividly seen in five areas of concern: war related trauma, infectious diseases, malnutrition and insufficient health services due to the repression of health providers and lack of resources. This report documents the major causes of mortality and morbidity among the 500,000 displaced in El Salvador and discusses the efforts of government and private organizations to meet their health needs. Health services for the displaced are primarily provided by private voluntary organizations which base their work on active neutrality. However, neutrality has become almost as dangerous as active opposition. The active repression of health workers by government security forces has exacerbated the already severe shortage of health care services for the displaced.


An unusual metastatic site of tongue carcinoma: shoulder muscles.
The incidence of skeletal muscle metastases is reported to be less than 1% of metastases of haematogenous origin. Distant skeletal muscle metastases from head and neck squamous cell carcinomas are exceedingly rare. Only a case with tongue carcinoma metastasized to paravertebral muscles, has been reported so far. The reasons for the rarity of metastatic involvement of skeletal muscle are still unclear. The presence of skeletal muscle metastases in the setting of disseminated disease offers no hope for curative treatment. We report an unusual case of a 63-year-old patient with tongue carcinoma metastasizing to the left shoulder muscles. To our knowledge, this is the first such case to be reported in the English medical literature.


Segmenting and accessing the market in consultation-liaison psychiatry.
Although the importance of consultation-liaison (C-L) psychiatry is increasingly recognized, obstacles to acceptance of the specialty persist in many service delivery settings. These can be countered by identifying specific consumers of C-L services and demonstrating that products of the specialty will meet consumers' needs. Once access to the market is gained, it is important to monitor potential sources of competition in the interest of ensuring continued high quality patient care.


Deficits in social behavior in autism and their modification by a synthetic adrenocorticotrophic hormone (4-9) analog.
When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4-9) analog ORG 2766.


A Systematic Review and Meta-Analysis of Non-database Comparative Studies on Cemented Versus Uncemented Femoral Stems in Primary Elective Total Hip Arthroplasty.
Cemented and uncemented femoral stems have shown excellent survivorship and outcomes in primary total hip arthroplasty (THA). Cementless stems have become increasingly common in the United States; however, multiple large database studies have suggested that elderly patients may have fewer complications with a cemented stem. As conclusions from large databases may be limited due to variations in data collection, this study investigated femoral stem survivorship and complication rates based on cement status in non-database studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilized to identify articles for inclusion up until June 2021. Included articles directly compared outcomes and complications between patients undergoing primary THA without femoral stem cementing to those with cementing. Studies were excluded if they utilized large databases or consisted of patients with a preoperative diagnosis of trauma. Of the 1700 studies, 309 were selected for abstract review and nineteen for full-text review. A total of seven studies were selected. Meta-analyses indicated substantial heterogeneity between studies. There were no differences in revision rates (cementless: 5.53% vs. cemented 8.91%, P = .543), infection rates (cementless: 0.60% vs. cemented: 0.90%, P = .692), or periprosthetic fracture rates (cementless: 0.52% vs. cemented: 0.51%, P = .973) between groups. There is scarce literature comparing outcomes and complications between cemented and cementless femoral stems in primary elective THA without utilizing a database methodology. In our study, there were no differences in complications detected on meta-analyses. Given previous findings in database studies, additional high-quality cohort studies are required to determine if selected patients may benefit from a cemented femoral stem.


Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.
The influence of the addition of magnesium on myocardial protection with intermittent antegrade warm blood hyperkalaemic cardioplegia in patients undergoing coronary artery surgery was investigated and compared with intermittent antegrade warm blood hyperkalaemic cardioplegia only. Twenty-three patients undergoing primary elective coronary revascularization were randomized to one of two different techniques of myocardial protection. In the first group, myocardial protection was induced using intermittent antegrade warm blood hyperkalaemic cardioplegia. In the second group, the same technique was used except that magnesium was added to the cardioplegia. Intracellular substrates (ATP, lactate and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. There were no significant changes in the intracellular concentration of ATP or free amino acid pool in biopsies taken at the end of the period of myocardial ischaemia. However, the addition of magnesium prevented the significant increase in the intracellular concentration of lactate seen with intermittent antegrade warm blood hyperkalaemic cardioplegia. Upon reperfusion there was a significant fall in ATP and amino acid concentration when the technique of intermittent antegrade warm blood hyperkalaemic cardioplegia was used but not when magnesium was added to the cardioplegia. This work shows that intermittent antegrade warm blood hyperkalaemic cardioplegia supplemented with magnesium prevents substrate derangement early after reperfusion.


Incidence, characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression, a study on 22 cases.
Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.


Predicting treatment outcomes for bilinguals with aphasia using computational modeling: Study protocol for the PROCoM randomised controlled trial.
Bilinguals with aphasia (BWA) present varying degrees of lexical access impairment and recovery across their two languages. Because both languages may benefit from therapy, identifying the optimal target language for treatment is a current challenge for research and clinical practice. Prior research has demonstrated that the BiLex computational model can accurately simulate lexical access in healthy bilinguals, and language impairment and treatment response in bilingual aphasia. Here, we aim to determine whether BiLex can predict treatment outcomes in BWA in the treated and the untreated language and compare these outcome predictions to determine the optimal language for rehabilitation. The study involves a prospective parallel-group, double-blind, randomised controlled trial. Forty-eight Spanish-English BWA will receive 20 sessions of semantic treatment for lexical retrieval deficits in one of their languages and will complete assessments in both languages prior and after treatment. Participants will be randomly assigned to an experimental group receiving treatment in the optimal language determined by the model or a control group receiving treatment in the language opposite to the model's recommendation. Primary treatment outcomes include naming probes while secondary treatment outcomes include tests tapping additional language domains. Treatment outcomes will be compared across the two groups using 2×2 mixed effect models for repeated measures Analysis of variance (ANOVA) on metrics of treatment effects commonly employed in rehabilitation studies (ie, effect size and percentage change). All procedures included in this protocol (protocol number 29, issue date: 19 March 2019) were approved by the Boston University Charles River Campus Institutional Review Board at Boston, Massachusetts (reference number: 4492E). The results of this study will be published in peer-reviewed scientific journals and will be presented at national and international conferences. NCT02916524.


Bioabsorbable Unsintered Hydroxyapatite/Poly-l-Lactic Acid Pin Fixation of Osteochondritis Dissecans in Adolescents: Initial Experiences.
This study sought to retrospectively evaluate the clinical and magnetic resonance imaging (MRI) outcomes of u-HA/PLLA pin (u-HA/PLLA: hydroxyapatite/poly-L-lactic acid) pin fixation of unstable osteochondritis dissecans (OCD) lesions of the knee. Seven adolescent patients (four females and three males) with arthroscopically unstable OCD lesions of the knee were included. The mean age at diagnosis was 13.1 years. Clinical results were evaluated preoperatively and during follow-up using the Ogilvie-Harris score (0 - 15 points). MRI scans were performed preoperatively and during follow-up, with results evaluated using the Dipaola classification (grades 1 - 4). Mean follow-up time was 29 months. The median Ogilvie-Harris score improved from 13 points (range: 10 - 14 points) to 15 points (range: 13 - 15 points). Separately, the median Dipaola score improved from 3 points (range: 2 - 4 points) to 1 point (range: 1 - 4 points). No complications such as infection, synovitis, or intra-articular adhesion were observed. Initial experiences using bioabsorbable u-HA/PLLA pins for the refixation of unstable OCD lesions in adolescents in the knee are promising, and MRI provides excellent monitoring of healing.


Lipoprotein lipase activity in skeletal muscle and adipose tissue of marathon runners after simple and complex carbohydrate-rich diets.
A comparison of the influence of simple and complex carbohydrate (CHO) consumption on adipose tissue- and skeletal muscle-lipoprotein lipase activity (AT-LPLA, SM-LPLA) was examined. Twenty male marathon runners were divided into two equal dietary groups: simple-CHO and complex-CHO. Half of the subjects in each group consumed either a low-CHO (15% energy [E] intake), or a mixed diet (50% CHO) for 3 days. Immediately following this dietary period, the subjects consumed a CHO-rich diet (70% E intake) predominant in simple-CHO or in complex-CHO for an additional 3 days. Thereafter, all subjects returned to a normal mixed diet. Skeletal muscle biopsies, adipose tissue aspirations, and venous blood samples were obtained prior to dietary manipulation (PRE), upon completion of the 6 day diet (POST I), and 2 weeks after returning to a normal diet (POST II). The samples were analysed for AT-LPLA, SM-LPLA, serum insulin, and free fatty acids (FFA), and blood glucose, and lactate. SM-LPLA fell 71% from PRE values of 0.39 +/- 0.30 mu mol.g-1.h-1 to POST I values of 0.11 +/- 0.09 mu mol.g-1.h-1 (means +/- SD) (p less than 0.05), after a complex-CHO diet. However, the simple-CHO diet did not alter SM-LPLA. AT-LPLA similarly decreased (p less than 0.05) after the complex-CHO diet, and no significant decrease was noted after the simple-CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)


[Postoperative deposits on a second-generation silicone lens].
In the literature there have often been reports about deposits (hydroxyapatite) in hydrophilic or hydrophobic intraocular lenses (IOLs). We report, for the first time, about deposits on a silicone IOL of the second generation. A silicone IOL (Allergan, type SI-40) which was extracted due to gradual visual loss, has been examined. The examination with the scanning electron microscope (SEM) showed crystalline precipitations in the anterior surface of the IOL while the X-ray analysis showed the existence of calcium and carbon, whereas no phosphorus was found. It could be hypothesised that metabolic disorders in aqueous humor (i. e., in patients with diabetes mellitus), the quality of the production of the lens, and not the IOL material, are the main cause for deposits in the IOL surface.


Lesions of the vertical lobe impair visual discrimination learning by observation in Octopus vulgaris.
We investigated whether lesions of the vertical lobe of the supraesophageal nervous mass of Octopus vulgaris impair discrimination learning acquired by observation of conspecific behavior. When tested alone, observer octopuses with about 50% of the vertical lobe removed showed a deficit in their learning by observation performance. The level of learning improved 24 h after the observational phase, when observer Octopus vulgaris showed a visual discriminatory performance significantly in agreement with the observed one. Control animals that had no brain tissue removed, did not show any impairment in the discriminative performance they had acquired vicariously. Removal of the vertical lobe of the octopus 'brain' has been reported to induce learning and memory deficits of visual discrimination in direct learning by conditioning experiments. Our findings support the conclusion that the removal of such brain center impairs short-term recall, but does not impair acquisition nor retention of 'observational' long-term memory.


The outcome of one-stage hypospadias repairs.
Hypospadias is an increasingly common condition, and many procedures have been described for operative correction. We reviewed our experience of different techniques of one-stage hypospadias repair. We retrospectively reviewed 107 hypospadic boys who were younger than 15 years between January 1986 and June 2003. We included all patients who underwent one-stage hypospadias repair. All patients were evaluated for age, type of hypospadias, associated anomalies, surgical technique, and morbidity rate. The functional and cosmetic results were evaluated at 1 month, 6 months and 1 year postoperatively. Univariate analysis was done to identify those variables that might serve as interdependent predictors of postoperative complications. The median age was 7 years (6 months to 13 years). Severe chordee was observed in 15 patients. The majority of cases were anterior hypospadias (53%), while the majority of complications were observed in the middle group (62%). Cosmetic and functional results were satisfactory in the majority of the patients. Complications included 16 fistulae (15%) and 11 meatal stenoses (10%). Some prognostic factors such as age, insertion of a suprapubic cystostomy tube, suture structure, and time of catheter removal did not significantly affect the risk of complication, whereas some other factors such as associated anomalies, severe chordee, middle and posterior hypospadias, and use of a pedicle island flap were significant in their relation to the complication rate. Such possible risk factors as severe chordee, middle and posterior localized hypospadias, and use of a pedicle island flap may increase the postoperative complication rate. There is no gold-standard technique for hypospadias repair; the procedure of choice should depend on the individual anatomy of the penis. The long-term outcome after puberty has to be awaited.