Molecular hydrogen and water activation by transition metal frustrated Lewis pairs containing ruthenium or osmium components: catalytic hydrogenation assays.
The transition metal frustrated Lewis pair compounds [(Cym)M(κ3S,P,N-HL1)][SbF6] (Cym = η6-p-MeC6H4iPr; H2L1 = N-(p-tolyl)-N'-(2-diphenylphosphanoethyl)thiourea; M = Ru (5), Os (6)) have been prepared from the corresponding dimer [{(Cym)MCl}2(μ-Cl)2] and H2L1 by successive chloride abstraction with NaSbF6 and AgSbF6 and NH deprotonation with NaHCO3. Complexes 5 and 6 and the previously reported phosphano-guanidino compounds [(Cym)M(κ3P,N,N'-HL2)][SbF6] [H2L2 = N,N'-bis(p-tolyl)-N''-(2-diphenylphosphanoethyl) guanidine; M = Ru (7), Os (8)] and pyridinyl-guanidino compounds [(Cym)M(κ3N,N',N''-HL3)][SbF6] [H2L3 = N,N'-bis(p-tolyl)-N''-(2-pyridinylmethyl) guanidine; M = Ru (9), Os (10)] heterolytically activate H2 in a reversible manner affording the hydrido complexes [(Cym)MH(H2L)][SbF6] (H2L = H2L1; M = Ru (11), Os (12); H2L = H2L2; M = Ru (13), Os (14); H2L = H2L3; M = Ru (15), Os (16)). DFT calculations carried out on the hydrogenation of complex 7 support an FLP mechanism for the process. Heating 9 and 10 in methanol yields the orthometalated complexes [(Cym)M(κ3N,N',C-H2L3-H)][SbF6] (M = Ru (17), Os (18)). The phosphano-guanidino complex 7 activates deuterated water in a reversible fashion, resulting in the gradual deuteration of the three cymene methyl protons through sequential C(sp3)-H bond activation. From DFT calculations, a metal-ligand cooperative reversible mechanism that involves the O-H bond activation and the formation of an intermediate methylene cyclohexenyl complex has been proposed. Complexes 5-10 catalyse the hydrogenation of the CC double bond of styrene and a range of acrylates, the CO bond of acetophenone and the CN bond of N-benzylideneaniline and quinoline. The CC double bond of methyl acrylate adds to catalyst 9, affording complex 19 in which a new ligand exhibiting a fac κ3N,N',C coordination mode has been incorporated.


Insights Into Mechanisms of Oriented Division From Studies in 3D Cellular Models.
In multicellular organisms, epithelial cells are key elements of tissue organization. In developing tissues, cellular proliferation and differentiation are under the tight regulation of morphogenetic programs, that ensure the correct organ formation and functioning. In these processes, mitotic rates and division orientation are crucial in regulating the velocity and the timing of the forming tissue. Division orientation, specified by mitotic spindle placement with respect to epithelial apico-basal polarity, controls not only the partitioning of cellular components but also the positioning of the daughter cells within the tissue, and hence the contacts that daughter cells retain with the surrounding microenvironment. Daughter cells positioning is important to determine signal sensing and fate, and therefore the final function of the developing organ. In this review, we will discuss recent discoveries regarding the mechanistics of planar divisions in mammalian epithelial cells, summarizing technologies and model systems used to study oriented cell divisions in vitro such as three-dimensional cysts of immortalized cells and intestinal organoids. We also highlight how misorientation is corrected in vivo and in vitro, and how it might contribute to the onset of pathological conditions.


Comparative in vitro fermentation activity in the canine distal gastrointestinal tract and fermentation kinetics of fiber sources.
The current study aimed to evaluate the variation in fermentation activity along the distal canine gastrointestinal tract (GIT, Exp. 1). It also aimed to assess fermentation kinetics and end product profiles of 16 dietary fibers for dog foods using canine fecal inoculum (Exp. 2). For Exp. 1, digesta were collected from the distal ileum, proximal colon, transverse colon, and rectum of 3 adult dogs. Digesta per part of the GIT were pooled for 3 dogs, diluted (1:25, wt/vol), mixed, and filtered for the preparation of inoculum. A fructan, ground soy hulls, and native potato starch were used as substrates and incubated for cumulative gas production measurement as an indicator of the kinetics of fermentation. In addition, fermentation bottles with similar contents were incubated but were allowed to release their gas throughout incubation. Fermentation fluid was sampled at 4, 8, 12, 24, 48, and 72 h after initiation of incubation, and short-chain fatty acids and ammonia were measured. Results showed comparable maximal fermentation rates for rectal and proximal colonic inocula (P > 0.05). Production of short-chain fatty acids was least for the ileal and greatest for the rectal inoculum (P < 0.05). Therefore, for in vitro studies, fecal microbiota can be used as an inoculum source but may slightly overestimate in vivo fermentation. Experiment 2 evaluated the gas production, fermentation kinetics, and end product profiles at 8 and 72 h of incubation for citrus pectin, 3 fructans, gum arabic, 3 guar gums, pea fiber, peanut hulls, soy fiber, sugar beet fiber, sugar beet pectin, sugar beet pulp, wheat fiber, and wheat middlings. Feces of 4 adult dogs were used as an inoculum source. Similar techniques were used as in Exp. 1 except for the dilution factor used (1:10, wt/vol). Among substrates, large variations in fermentation kinetics and end product profiles were noted. Sugar beet pectin, the fructans, and the gums were rapidly fermentable, indicated by a greater maximal rate of gas production (R(max)) compared with all other substrates (P < 0.05), whereas peanut hulls and wheat fiber were poorly fermentable, indicated by the least amount of gas produced (P < 0.05). Sugar beet fiber, sugar beet pulp, soy fiber, and wheat middlings were moderately fermentable with a low R(max). Citrus pectin and pea fiber showed a similar low R(max), but time at which this occurred was later compared with sugar beet fiber, sugar beet pulp, soy fiber, and wheat middlings (P < 0.05). Results of this study can be used to formulate canine diets that stimulate dietary fiber fermentation along the distal GIT that may optimize GIT health and stimulate the level of satiety in dogs.


Subtypes of Personality and 'Locus of Control' in Bariatric Patients and their Effect on Weight Loss, Eating Disorder and Depressive Symptoms, and Quality of Life.
The present study subdivided personality types in a bariatric sample and investigated their impact on weight loss and psychopathology 6 and 12 months after surgery. One hundred thirty participants answered questionnaires on personality (NEO-FFI), 'locus of control' (IPC), depression severity (BDI-II), eating disorder psychopathology (EDE-Q), and health-related quality of life (HRQoL; SF-12). K-means cluster analyses were used to identify subtypes. Two subtypes emerged: an 'emotionally dysregulated/undercontrolled' cluster defined by high neuroticism and external orientation and a 'resilient/high functioning' cluster with the reverse pattern. Prior to surgery, the first subtype reported more eating disorder and depressive symptoms and less HRQoL. Differences persisted regarding depression and mental HRQoL until 12 months after surgery, except in the areas weight loss and eating disorders. Personality seems to influence the improvement or maintenance of psychiatric symptoms after bariatric surgery. Future research could elucidate whether adapted treatment programmes could have an influence on the improvement of procedure outcomes. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


A method for isolation of oligo(uridylic acid)-containing messenger ribonucleic acid from HeLa cells.
When cytoplasmic polyadenylated ribonucleic acid [poly(A+)RNA] from HeLa cells was treated with ribonuclease H (RNase H) and oligodeoxythymidylate [oligo(dT)] to remove its 3'-poly(A) tail, an increased binding to poly(A)-agarose was observed. The bound material, which comprised 4-6% of the initial RNA, contained 65-80% of the oligo(uridylic acid) [oligo(U)] sequences generated by RNase T1 digestion. Oligo(U) isolated from the bound fraction was shown to be 83% U and to have a U/G ratio of 33. In contrast, oligo(U) from the unbound material was 77% U and had a U/G ratio of 13, suggesting that it is shorter and less U rich than the oligo(U) in the bound fraction. On sucrose gradients, oligo(U+)RNA consistently sedimented with a larger s value than oligo(U-) RNA. The oligo(U) content of oligo(U+) RNA suggests one oligo(U) tract of 33 nucleotides per RNA molecule of 2000-3000 residues.


In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban.
Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.


Adaptive Laboratory Evolution as a Means To Generate Lactococcus lactis Strains with Improved Thermotolerance and Ability To Autolyze.
Lactococcus lactis subsp. lactis (referred to here as L. lactis) is a model lactic acid bacterium and one of the main constituents of the mesophilic cheese starter used for producing soft or semihard cheeses. Most dairy L. lactis strains grow optimally at around 30°C and are not particularly well adapted to the elevated temperatures (37 to 39°C) to which they are often exposed during cheese production. To overcome this challenge, we used adaptive laboratory evolution (ALE) in milk, using a setup where the temperature was gradually increased over time, and isolated two evolved strains (RD01 and RD07) better able to tolerate high growth temperatures. One of these, strain RD07, was isolated after 1.5 years of evolution (400 generations) and efficiently acidified milk at 41°C, which has not been reported for industrial L. lactis strains until now. Moreover, RD07 appeared to autolyze 2 to 3 times faster than its parent strain, which is another highly desired property of dairy lactococci and rarely observed in the L. lactis subspecies used in this study. Model cheese trials indicated that RD07 could potentially accelerate cheese ripening. Transcriptomics analysis revealed the potential underlying causes responsible for the enhanced growth at high temperatures for the mutants. These included downregulation of the pleiotropic transcription factor CodY and overexpression of genes, which most likely lowered the guanidine nucleotide pool. Cheese trials at ARLA Foods using RD01 blended with the commercial Flora Danica starter culture, including a 39.5°C cooking step, revealed better acidification and flavor formation than the pure starter culture. IMPORTANCE In commercial mesophilic starter cultures, L. lactis is generally more thermotolerant than Lactococcus cremoris, whereas L. cremoris is more prone to autolysis, which is the key to flavor and aroma formation. In this study, we found that adaptation to higher thermotolerance can improve autolysis. Using whole-genome sequencing and RNA sequencing, we attempt to determine the underlying reason for the observed behavior. In terms of dairy applications, there are obvious advantages associated with using L. lactis strains with high thermotolerance, as these are less affected by curd cooking, which generally hampers the performance of the mesophilic starter. Cheese ripening, the costliest part of cheese manufacturing, can be reduced using autolytic strains. Thus, the solution presented here could simplify starter cultures, make the cheese manufacturing process more efficient, and enable novel types of harder cheese variants.


Exchange dynamics of nitric oxide in the human nose.
Nasal nitric oxide (NO) exchange dynamics are poorly understood but potentially are of importance, inasmuch as they may provide insight into the NO-related physiology of the bronchial tree. In healthy human volunteers, NO output was assessed by isolating the nasal cavity through elevation of the soft palate and application of tight-fitting nasal olives. Mean NO output was 334 nl/min and was a positive function of gas flow. With the use of a mathematical model and the introduction of nonzero concentrations of NO, the diffusing capacity for NO in the nose (DNO) and the mucosal NO concentration (Cw) were determined. DNO ranged from 0.52 to 2.98 x 10(-3) nl x s(-1) x ppb(-1) and Cw from 1,236 to 8,947 ppb. Cw declined with increasing gas flow, while DNO was constant. NO output declined with luminal hypoxia, particularly at oxygen tensions <10%. Measurement of nasal DNO and Cw is easy using this method, and the range of intersubject values of Cw raises the possibility of interindividual differences in NO-dependent nasal physiology.


Nicotinic acid adenine dinucleotide phosphate activates two-pore channel TPC1 to mediate lysosomal Ca2+ release in endothelial colony-forming cells.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most recently discovered Ca2+ -releasing messenger that increases the intracellular Ca2+ concentration by mobilizing the lysosomal Ca2+ store through two-pore channels 1 (TPC1) and 2 (TPC2). NAADP-induced lysosomal Ca2+ release regulates multiple endothelial functions, including nitric oxide release and proliferation. A sizeable acidic Ca2+ pool endowed with TPC1 is also present in human endothelial colony-forming cells (ECFCs), which represent the only known truly endothelial precursors. Herein, we sought to explore the role of the lysosomal Ca2+ store and TPC1 in circulating ECFCs by harnessing Ca2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide, and nigericin, which dissipates the proton gradient which drives Ca2+ sequestration by acidic organelles, caused endogenous Ca2+ release in the presence of a replete inositol-1,4,5-trisphosphate (InsP3 )-sensitive endoplasmic reticulum (ER) Ca2+ pool. Likewise, the amount of ER releasable Ca2+ was reduced by disrupting lysosomal Ca2+ content. Liposomal delivery of NAADP induced a transient Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store and by pharmacological and genetic blockade of TPC1. Pharmacological manipulation revealed that NAADP-induced Ca2+ release also required ER-embedded InsP3 receptors. Finally, NAADP-induced lysosomal Ca2+ release was found to trigger vascular endothelial growth factor-induced intracellular Ca2+ oscillations and proliferation, while it did not contribute to adenosine-5'-trisphosphate-induced Ca2+ signaling. These findings demonstrated that NAADP-induced TPC1-mediated Ca2+ release can selectively be recruited to induce the Ca2+ response to specific cues in circulating ECFCs.


There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes.
Lyme disease and relapsing fever are caused by various Borrelia species. Lyme disease borreliae, the most common vector-borne pathogens in both the U.S. and Europe, are transmitted by Ixodes ticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing fever borreliae, carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms of Borrelia spp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme disease borreliae that can be applied to relapsing fever borreliae. Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.


Radiation therapy alone for growth hormone-producing pituitary adenomas.
We present our experience in the treatment of growth hormone (GH)-producing pituitary adenomas using irradiation alone. Between 1983 and 1991, 21 patients suffering from GH-secreting pituitary adenomas were treated with radiotherapy alone. Two bilateral opposing coaxial fields were used in 10 patients and in the remaining 11 a third frontovertex field was added. Treatment was given in 1.8-2 Gy daily fractions and total dose ranged between 45 and 54 Gy. Treatment was given using a cobalt unit. Four patients treated with somatostatin prior to and 14 patients treated after the end of radiotherapy experienced symptom relief for 6-28 weeks. The 5-year actuarial rate of disease control was 72%. Five out of six failed patients had macroadenomas. Hypopituitarism was observed in 5/21 (24%) patients. Whereas RT alone is effective in the treatment of microadenomas, this is not true for large infiltrative macroadenomas.


State-to-state quantum mechanical calculations of rate coefficients for the D+ + H2 → HD + H+ reaction at low temperature.
The dynamics of the D(+) + H2 → HD + H(+) reaction on a recent ab initio potential energy surface (Velilla, L.; Lepetit, B.; Aguado, A.; Beswick, J. A.; Paniagua, M. J. Chem. Phys. 2008, 129, 084307) has been investigated by means of a time-independent quantum mechanical approach. Cross-sections and rate coefficients are calculated, respectively, for collision energies below 0.1 eV and temperatures up to 100 K for astrophysical application. An excellent accord is found for collision energy above 5 meV, while a disagreement between theory and experiment is observed below this energy. We show that the rate coefficients reveal a slightly temperature-dependent behavior in the upper part of the temperature range considered here. This is in agreement with the experimental data above 80 K, which give a temperature independent value. However, a significant decrease is found at temperatures below 20 K. This decrease can be related to quantum effects and the decay back to the reactant channel, which are not considered by simple statistical approaches, such as the Langevin model. Our results have been fitted to appropriate analytical expressions in order to be used in astrochemical and cosmological models.


mild Interlaminar decompression for the treatment of lumbar spinal stenosis: procedure description and case series with 1-year follow-up.
mild interlaminar decompression is a minimally invasive procedure for the treatment of patients with symptomatic lumbar spinal stenosis. This report describes the mild procedure and presents 1-year clinical outcomes of patients treated with mild. mild treats lumbar spinal stenosis by removing portions of the lamina and ligamentum flavum to restore space in the lumbar spine. The procedure is conducted under fluoroscopic guidance, and is performed with moderate sedation. One-year follow-up was obtained for 17 patients treated with the mild procedure. Clinical evaluations were conducted at baseline and at 1-year follow-up with the 10-point Visual Analog Score and Oswestry Disability Index. mild treatments were completed with no major device-related or procedure-related complications. The baseline mean Visual Analog Score of 7.6 improved at 1 year after the procedure to 2.3, a decrease of 5.4 cm points, or an average percentage decrease of 70.0%. Average baseline Oswestry Disability Index of 48.4 improved to 21.7 at 1 year, an improvement of 26.6 points. The mild technique provides an attractive early option for the treatment of symptomatic lumbar spinal stenosis after failed injection therapy, but before more invasive surgical treatment. For 17 patients with 1-year follow-up, the mild procedure provided significant pain relief and increased mobility. This procedure leaves no implants behind, and therefore does not limit subsequent, more invasive procedures that require implants.


Glycosaminoglycans and proteoglycans from different zones of the porcine knee meniscus.
Medial and lateral knee menisci were obtained from 20-week-old pigs, dissected into three zones of equal width, and analyzed for collagen and glycosaminoglycan content and for types of glycosaminoglycan and proteoglycan. The thin inner zones contained about 76% collagen and 8% glycosaminoglycan (by dry weight) and the outer zones, 93% collagen and 2% glycosaminoglycan. The most abundant glycosaminoglycan in all zones was chondroitin sulphate, accounting for about 80% of total glycosaminoglycan in the inner zones and 50-56% in the outer zones. Dermatan sulphate was the second most abundant glycosaminoglycan, present relative to chondroitin sulphate in a ratio of about 1:5-6 in the inner zones and 1:1.5 in the outer zones. Hyaluronic acid accounted for 4-5% of total glycosaminoglycan content in the inner zones and 10% in the outer zones. All compositional parameters for the middle zones were between those for the inner and outer zones. There were no statistically significant differences in composition between medial and lateral menisci. Proteoglycans were extracted and separated into two groups (large and small proteoglycans) by gel chromatography and were further characterized by gel electrophoresis. The large proteoglycans stained with use of monoclonal antibodies to chondroitin sulphate and keratan sulphate. Biglycan and decorin, two related dermatan sulphate proteoglycans, were identified in the small proteoglycan pool by their behaviour on gel electrophoresis and by immunostaining with specific antibodies. In the middle and inner zones, biglycan predominated. The observed lower electophoretic mobilities of dermatan sulphate proteoglycans from the inner zone compared with those from the outer zone were explained by the discovery of longer dermatan sulphate chains on the former. Collectively, these results show that the extracellular matrix of knee meniscus varies continuously across its width in a manner consistent with increased compressive loading on the thinner, inside aspect of the structure.


Social Determinants of Health in Urban Transgender Patients: A Case Report.
The social determinants of health (SDOH) are a complex web of factors that influence the health of individuals throughout their lifetime. There are many drivers of health inequities within the SDOH, such as socioeconomic status, education, employment, gender, and race/ethnicity. It is possible that mental illness may develop when these factors negatively affect health. However, current research primarily focuses on SDOH in cisgender individuals leaving a scientific gap in transgender individuals who require unique considerations when providing comprehensive medical care. We present the case of a 20-year-old transgender female who was admitted for suicidal attempts during a methamphetamine overdose, and who had been struggling with mental illness and suicidal gestures since she was a young teenager. The significance of our findings is discussed in the context of the substantial lack of current research on SDOH in transgender individuals to underscore the need for clinical awareness and promote future research.


Environmental tobacco smoke: health effects and policies to reduce exposure.
The health hazards due to exposure to environmental tobacco smoke (ETS) are increasingly established. ETS contains thousands of chemicals including 43 known carcinogens. Known health effects of ETS exposure are lung cancer in nonsmokers, childhood disorders such as bronchitis, and perhaps, heart disease. Workplace exposure to ETS is widespread and is influenced strongly by the type of smoking policy in the workplace. To decrease ETS exposure, efforts to restrict public smoking have proliferated over the past decade. These restrictions have emanated from government as well as voluntary measures by various private industries. Bans on public smoking are effective in reducing nonsmokers' exposure to ETS. Workplace smoking bans also influence the intensity of smoking among employees and may increase quit smoking rates. In addition to the health benefits from smoke-free workplaces, there are likely cost savings to employers who implement such policies.


Improving well-being through psycho-education among voluntary counseling and testing seekers in Nigeria: a controlled outcome study.
The present study evaluated the efficacy of an individualized psycho-education (PE) program in reducing psychological distress and risky sexual behavior and enhancing self-disclosure associated with an HIV diagnosis among attendees of a walk-in non-governmental voluntary counseling and testing (VCT) center in Nigeria. Ninety-four consecutive individuals were asked to complete a pre-counseling, baseline questionnaire detailing their sociodemographic characteristics, psychopathology, sexual practices, self-disclosure intention and coping behaviors. They were screened for HIV and post-test counseled. Sixty-seven individuals (72.2%) who tested positive were consecutively randomly assigned to one of two groups: a PE program (four 60-minute weekly manual driven sessions) (N=34) and a wait-list (WL) control group (N=33). The major outcome measures used were the Crown Crisp Experiential Index (CCEI), the Beck Depression Inventory (BDI) (Beck et al., (1961), self-report sexual practices in past three months, self-disclosure intention and the brief COPE. At four weeks post-intervention, significant reductions on all measures as well as reduction in risky sexual practices were observed in the treatment group compared with the wait-list group. Treatment group members were also significantly more likely to disclose their serostatus and accept their HIV status as a way of coping, compared with the wait-list group. Overall, support was found for the efficacy of a manual-driven PE program for self-disclosure, reduction of depression and improvement in safe sexual practices.


'Untangling the web of critical incidents': Ethnography in a paediatric setting.
Critical incidents (CIs) are the elements that bring about an alert or wake up call for clinicians in hospital wards. They are considered critical because the safety of patients, staff or visitors is at risk. Not all CIs result in dire consequences, nor do they require Root Cause Analysis (RCA). Nonetheless, incidents affect patients and involve clinicians' interactions with each other. This paper describes the complexities embedded in two CIs in a major paediatric hospital in Australia. An anthropological ethnographic research approach enabled the researcher to observe, document, interpret and make sense of the activities of clinicians in two different clinical areas of the hospital, i.e., the Rehabilitation Unit and the Neonatal Unit (NU). Ethnographic research significantly exposes and highlights hospital dramas and shows the effects on clinicians' everyday lives. We suggest that CIs have two dimensions: a medical and a social. The medical dimension encompasses factors in the treatment and care of the patient. The social dimension encompasses the social relationships and the socio-affectivity (emotional responses and labour) of treating clinicians. Our main argument is that foregrounding of the socio-cultural dimensions of CIs informs and impacts on the medical dimensions. Our conclusions demonstrate that the social dimensions of CIs have important ramifications for clinical interactions in everyday practices and these impact on the positive learning of clinicians after a CI has occurred.


Discovery of a "true" aspirin prodrug.
Aspirin prodrugs formed by derivatization at the benzoic acid group are very difficult to obtain because the promoiety accelerates the rate of hydrolysis by plasma esterases at the neighboring acetyl group, generating salicylic acid derivatives. By tracing the hydrolysis pattern of the aspirin prodrug isosorbide-2,5-diaspirinate (ISDA) in human plasma solution, we were able to identify a metabolite, isosorbide-2-aspirinate-5-salicylate, that undergoes almost complete conversion to aspirin by human plasma butyrylcholinesterase, making it the most successful aspirin prodrug discovered to date.


Maternal nutritional status mediates the association between maternal age and birth outcomes.
Young maternal age during pregnancy is linked with adverse birth outcomes. This study examined the role of maternal nutritional status in the association between maternal age and small for gestational age (SGA) delivery and birth length. We used data from a birth cohort study in Ethiopia, involving women who were 15-24 years of age and their newborns. A mediation analysis was fitted in a sample of 1,422 mother infant dyads for whom data on birth length were available, and 777 dyads for whom gestational age and birth weight was measured. We used commands, medeff for the mediation analysis and medsens for sensitivity analysis in STATA 14. Maternal nutritional status, measured by mid-upper arm circumference, mediated 21% of the association between maternal age and birth length and 14% of the association with SGA delivery. The average direct effect (ADE) of maternal age on birth length was (β = 0.45, 95% CI [0.17, 0.99]) and the average causal mediated effect (ACME) was (β = 0.12, 95% CI [0.02, 0.15]). We also found an ADE (β = 0.31, 95% CI [0.09, 0.47]) and an ACME of (β = 0.05, 95% CI [0.003, 0.205]) of maternal age on SGA delivery. The sensitivity analysis suggests an unmeasured confounder with a positive correlation of 0.15 and 0.20 between the mediator and the outcome could explain the observed ACME for birth length and SGA, respectively. We cannot make strong causal assertions as the findings suggest the mediator partly explained the total effect of maternal age on both outcomes.


Military aviators with mitral valve prolapse: long-term follow-up and aeromedical endpoints.
Mitral valve prolapse (MVP) is a disqualifying condition for USAF aviators. Trained USAF aviators, and in recent years flying training applicants, may be granted waiver for initial or continued flying duties following extensive, periodic evaluation. This study examines the usefulness of the various tests performed in that evaluation process and provides long-term follow-up from 404 USAF flyers with MVP. We retrospectively reviewed 2-dimensional echocardiography, Holter monitoring, treadmill exercise, thallium imaging, coronary fluoroscopy, cardiac catheterization, and centrifuge testing results from 404 military aviators evaluated at the Aeromedical Consultation Service between 1 January 1972 and 31 October 1993. Follow-up was achieved through questionnaires (91%) and death certificates, etc. Mean follow-up was 8.6 yr (range 1-21 yr). Age at study entry was 21 to 64 yr (mean = 36 yr). The occurrence rate for suddenly incapacitating events (sudden cardiac death, syncope, pre-syncope, and cerebral ischemic episodes) was 0.32%/yr. Echocardiographic MVP in military aviators is associated with a low but statistically increased prevalence of "incapacitating" aeromedical events. Univariate predictors of adverse outcome included study entry with an enlarged left ventricle or left atrium, cardiovascular symptoms or findings, or MVP with thickened leaflets. Evaluation of coronary artery disease (CAD) in this population, absent specific indicators of CAD risk, is not indicated.


Natural radioactivity and element characterization in pit lakes in Northern Sweden.
Northern Sweden has been the object of intense metal mining in the last decades producing several water-filled open-pits, or pit lakes. Most of these pit lakes have been limed to maintain a good water quality and to prevent generation of acidic water that could leach the exposed rocks and release metals into water. The aim of this work was to examine the concentration of stable elements and naturally occurring radionuclides in water and sediment samples from pit lakes originating from non-uranium mining activities in Northern Sweden. Surface water and surface sediments were collected from 27 pit lakes in Northern Sweden. Water quality parameters, concentration of stable elements and radionuclides were measured by a water probe, ICP-MS and XRF, and alpha and gamma spectrometry, respectively. Furthermore, a multivariate statistical analysis (PCA) was performed on the water samples and sediments. In general, the quality of the surface water was good, but some lakes had low pH values (2.5-5.7), and high concentrations of Fe (up to 200 mg/L) and other metals (e.g. Zn, Cu). When relating the metal concentrations in sediments in pit lakes with the concentration found in natural lakes, some sites had relatively high levels of Cu, As, Cr and Pb. The activity concentration of 210Po, and U and Th isotopes in water and sediment samples were at environmental levels, as was the ambient dose equivalent rate at these sites (range 0.08-0.14 μSv/h).


Impaired sense of smell and altered olfactory system in RAG-1(-∕-) immunodeficient mice.
Immune deficiencies are often associated with a number of physical manifestations including loss of sense of smell and an increased level of anxiety. We have previously shown that T and B cell-deficient recombinase activating gene (RAG-1)(-∕-) knockout mice have an increased level of anxiety-like behavior and altered gene expression involved in olfaction. In this study, we expanded these findings by testing the structure and functional development of the olfactory system in RAG-1 (-∕-) mice. Our results show that these mice have a reduced engagement in different types of odors and this phenotype is associated with disorganized architecture of glomerular tissue and atrophy of the main olfactory epithelium. Most intriguingly this defect manifests specifically in adult age and is not due to impairment in the patterning of the olfactory neuron staining at the embryo stage. Together these findings provide a formerly unreported biological evidence for an altered function of the olfactory system in RAG-1 (-∕-) mice.


Nontargeted homologue series extraction from hyphenated high resolution mass spectrometry data.
A large proportion of polar anthropogenic compounds routinely released into the environment comprises homologue series, i.e., sets of chemicals differing in a repeating chemical unit. Using analytical techniques such as liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), these compounds are readily measurable as signal sets with characteristic differences in mass and typically retention time. However, and despite such distinct characteristics, no computational approach for the direct, simultaneous and untargeted detection of all such signal sets comprising both LC and HRMS information has to date been presented. A fast two-staged approach has been developed to extract LC-HRMS signal patterns which can be indicative of homologous analytes. In a first stage, a k-d tree representation of picked LC-HRMS peaks is used to extract all feasible 3-tuples of peaks with restrictions in, e.g., mass defect differences. A second stage then recombines these 3-tuples to larger series tuples while ensuring smooth changes in their retention time characteristics. This unsupervised approach was evaluated for ten effluent samples from Swiss sewage treatment plants (STPs), in both positive and negative electrospray-ionization. Beside recovering all continuous series of previously identified homologues, substantial fractions of nontargeted peaks could subsequently be assigned into very diverse peak series, although assignments were often not unique. The latter ambiguities were resolved by a self-organizing map technique and revealed both distinctive series meshing and rivaling combinatorial solutions in the presence of isobaric or gapped series peaks. When comparing STPs, several ubiquitous yet partially low-frequent series mass differences emerged and may prioritize future identification efforts. The presented algorithm is freely available as part of the R package nontarget and as a user-friendly web-interface at www.envihomolog.eawag.ch.Graphical AbstractSearch for systematic series indicative of homologous compounds is based on a partitioned representation of LC-HRMS signal characteristics. This nontargeted search first extracts series triplets in a nearest-neighbour walk and then recombines them to larger ones. For illustration, the two dimensions involving mass defect characteristics are represented by one only.


Genotype by environment interaction for stayability of Red Angus in the United States.
Bulls are used across a wide variety of environments through the use of artificial insemination. However, not all bulls rank the same for genetic merit in all environments. Sire selection could be more accurate via improved methods of characterization. The objective of this study was to evaluate the presence of genotype by environment (GxE) interaction for stayability in Red Angus in the United States. Environments were defined as nine regions within the continental United States with similar temperature-humidity indices. Stayability was defined as having a calf at age 4 given that the cow had a calf at age 2. A probit sire model was used to determine the heritability on the underlying scale. The percentage of females that calved at age 2 that also calved at age 4 ranged from 32.9 to 58.5% across regions and was 55.0% for the national data set. The heritability of stayability ranged from 0.10 to 0.57 across regions and was 0.12 for the national data set. Genetic correlations were estimated for stayability between all pairs of regions. An estimate of less than 0.80 indicates GxE at a level for concern. Genetic correlations between regions ranged from 0.32 to 0.87 and were <0.80 for 29 of 36 region pairs.


Self-assembly of random networks of zirconium-doped manganese oxide nanoribbons and poly(3,4-ethylenedioxythiophene) flakes at the water/chloroform interface.
Owing to their magnificent chemical and physical properties, transition metal-based heterostructures are potential materials for applications ranging from point-of-care diagnostics to sustainable energy technologies. The cryptomelane-type octahedral molecular sieves (K-OMS-2) are extensively studied porous materials with a hollandite (2 × 2 tunnel of dimensions 4.6 × 4.6 Å2) structure susceptible to the isovalent substitution of metal cations at the framework of MnO6 octahedral chains. Here we report a facile in situ synthesis of framework-level zirconium (Zr)-doped K-OMS-2 nanoribbons in poly(3,4-ethylenedioxythiophene) (PEDOT) nanoflakes at a water/chloroform interface at ambient conditions. An oxidant system of KMnO4 and ZrOCl2·8H2O initiated the polymerisation at temperatures ranging from 5° to 50 °C. The lattice distortions arising from the framework-level substitution of Mn4+ by Zr4+ in the K-OMS-2 structure were evidenced with powder X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and N2 adsorption-desorption studies. Transmission electron microscopic and mapping images confirmed that PEDOT/Zr-K-OMS-2 comprises a highly crystalline random network of two-dimensional PEDOT flakes and Zr-doped K-OMS-2 nanoribbons. In this regard, the proposed interfacial strategy affirms an in situ method for the morphological tuning of heterostructures on polymer supports at low temperatures.


Posterior Vitreous Structures Evaluated by Swept-source Optical Coherence Tomography with En Face Imaging.
To evaluate posterior vitreous structures using swept-source (SS) optical coherence tomography (OCT) with en face imaging. We retrospectively reviewed OCT images of healthy individuals who did not have intra-ocular disease. We obtained high-definition horizontal and vertical line scans crossing the fovea and 3D scans using SS-OCT, with the 3D scan centered between the fovea and the optic-nerve head. An enhanced vitreous visualization function was used to highlight vitreous structures. En face mode was used to measure the area of Martegiani (AM) and bursa premacularis (BP). We performed all measurements using a built-in function of the viewing software. We enrolled 24 eyes from 12 healthy individuals. The mean patient age was 28.7 ± 4.6 years (range, 24 to 39 years). The mean AM and BP areas were 5.73 ± 0.88 and 18.76 ± 6.95 mm², respectively. In en face imaging, AM shape was most frequently a vertical oval (18 / 22, 81.8%), while the predominant BP shape was round (16 / 20, 80.0%). AM was in contact with the optic disc, either at the temporal-disc margin (13 eyes, 59.1%) or the nasal optic-disc margin (9 eyes, 40.9%). Posterior vitreous structures, such as AM and BP, were readily visualized using en face imaging with SS-OCT. Investigating normal vitreous configuration might help in understanding changes in vitreous structures associated with retinal pathology.


1,3,4-Thiadiazole Based Anticancer Agents.
In recent years, researchers like medicinal chemists in the field of medicinal chemistry have widely utilized the 1,3,4-thiadiazole nucleus to investigate its biological and pharmacological effects. This heterocyclic structure has demonstrated various bioactivities such as antifungal, antimicrobial, antiviral, antileishmanial, anti-inflammatory, antihypertensive, antiepileptic, and anticancer effects among others. Anticancer activity is one of its promising effect as five membered heterocyclic rings have widely been investigated by researchers in the recent years. Herein, we reviewed the chemical structures bearing 1,3,4-thiadiazole template exerting anticancer activity.


Fibula-Only Fixation for a Very Distal Tibia-Fibula Fracture: A Case Report.
A 70-year-old patient with multiple medical problems presented to us with displaced closed very distal tibia and fibula fractures and a prior total knee replacement on the affected extremity. We treated the patient with an isolated fibula open reduction and internal fixation. At a 1-year follow-up, both the tibial and fibular fractures had healed, and the patient had an excellent outcome. "Fibula-only" fixation of very distal tibia-fibula fractures appears to be a viable option to manage these difficult fractures. The novelty of the case report lies in that this technique has not been described previously in the literature.


Continuity of care of Swiss residents aged 50+: a longitudinal study using claims data.
Continuity of care (COC) should be measured for healthcare quality monitoring and evaluation and is a key process indicator for integrated care. Measurement of COC using routinely collected data is widespread, but there is no consensus on which indicator to use and the relevant time horizon to apply. Information about COC is especially warranted in highly fragmented healthcare systems, such as in Switzerland. Our study aimed to compare COC measures in Swiss residents aged 50+ obtained with various indices and time horizons. Using insurance claims data, we computed and compared several commonly used visit-based Continuity of Care Indices (COCIs): Bice-Boxerman Index, Usual Provider of Care, Herfindahl-Hirschman Index, Modified, Modified Continuity Index and Modified Continuity Index, based on all doctor visits and on primary care (PC) visits only. Indices were computed over short (1 year) and medium (4 years) terms. The mean indices based on all visits varied between 0.51 and 0.77, while PC indices presented less variation with a median of 1.00 for all but one index. Indices focusing on a variety of individual providers decreased with time horizon, while indices focusing on the overall number of visits and providers showed the opposite trend. These findings suggest fundamental differences in the interpretation of COCIs. Broad COC appeared moderately low in Switzerland, although comparable to other countries, and PC COC was close to one. The choice of indices and time horizon influenced their interpretation. Understanding these differences is key to select the appropriate index for the monitoring of COC.


The dependence of detergent-induced cell dissociation in non-palmo-plantar stratum corneum on endogenous proteolysis.
We have recently shown that cell cohesion in plantar stratum corneum is mediated to a significant extent by protein structures, and that endogenous proteolysis plays an important role in desquamation in this tissue. This paper is a report of our investigations into whether similar mechanisms for cell cohesion and desquamation can be found in non-palmo-plantar stratum corneum. Biopsies of non-palmo-plantar human skin were incubated at 37 degrees C, pH 8, in a buffer with and without additions of detergents (a mixture of N,N-dimethyldodecylamine oxide and sodium dodecyl sulphate), ethylene diamine tetraacetate (EDTA), and the proteinase inhibitor aprotinin. Released cells were examined by phase contrast microscopy and counted. The incubated biopsies were examined by light microscopy. As has been previously shown by others, we found that in the presence of detergents there was a dissociation of stratum corneum cells. This dissociation was stimulated by EDTA and inhibited by aprotinin. After 36 h of incubation the entire stratum corneum and, on some parts of the biopsies, the stratum granulosum had dissociated. There was no evidence of cell dissociation in the spinous or basal epidermal layers. We conclude that the detergent-induced cell dissociation in non-palmo-plantar human stratum corneum is dependent on the action of proteinases present in the tissue on protein structures. These structures may be of significant importance for non-palmo-plantar stratum corneum cell cohesion.


The un-natural history of an adolescent with combined congenital and acquired heart disease.
This study describes the un-natural history of a 16-year-old patient, presenting with a critical bicuspid aortic valve stenosis, who was initially treated in the neonatal period and later with a valvuloplasty. This focused the attention on palliative interventions that, in young adulthood or middle age, are usually related to several complications, until heart transplantation. The other important aspect of this case is the presence of a coronary atherosclerotic plaque producing a significant obstruction, in the setting of haemodynamic acute postoperative failure caused by the sudden aortic valve laceration and insufficiency. This favoured the transmural myocardial antero-septal evolution of the myocardial ischaemic-reperfusion damage. This case is peculiar in that it presents two unrelated entities in their natural history. The coronary lesion was an unexpected finding in an adolescent with congenital heart disease. The severity of the coronary lesion became haemodynamically significant as a combination of the hypoperfusion due to the massive aortic valve regurgitation following the acute failure of the aortic valve plasty and the vasoconstriction of the eccentric speared segment. Once again, the complete understanding of grown-up patients with congenital hart disease is mandatory together with the point that a close collaboration of a multidisciplinary team is essential for appropriate operative timing and planning the most suitable treatment option. Acquired heart diseases can rarely present in association in this group of patients and need to be taken into account.


[The importance of a careful examination of all persons in close contact with newly diagnosed infectious tuberculosis].
The diagnosis of infectious pulmonary tuberculosis was made in a 53-year-old Macedonian man. A careful examination of all persons in close contact with him according to the guidelines of the Swiss respiratory society was performed. Pulmonary tuberculosis was diagnosed in his 22-year-old son, in his 20-year-old daughter and in his 3-year-old granddaughter. Seven persons had isoniazid preventive treatment for latent tuberculosis. These data shows very clearly that a careful examination of all persons in close contact with contagious tuberculosis is very important.


Filling the gap: strategies for improving oral health.
As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened, with the Children's Dental Health Project (CDHP), a select group of grantmakers and national experts who have made a major commitment to improving oral health. This Issue Dialogue - held on May 16,2001, in Washington, DC - explored current challenges related to oral health in the United States, and highlighted public and private sector initiatives to overcome these challenges. The roundtable also illustrated current activities and future opportunities for foundations in the area of oral health. This Issue Brief synthesizes key points from the day's discussion with a background paper previously prepared for Issue Dialogue participants. It includes quantitative and qualitative information on oral health as well as profiles of public sector, private sector, and grantmaker strategies for promoting improvements.


Cloning of a LEU gene and an ARS site of Rhodotorula glutinis.
Genomic library of DNA from an extracellular protease-producing yeast strain, Rhodotorula glutinis K-24, was constructed, using Escherichia coli plasmid vector PBR322. A LEU gene from R. glutinis was cloned, and found to complement leu- mutations in E. coli and Saccharomyces cerevisiae. In E. coli, the LEU gene in the cloned yeast DNA fragment was efficiently expressed when inserted into the vector in one orientation. In S. cerevisiae, the R. glutinis LEU gene was efficiently expressed when inserted into a shuttle vector YEP13 in both orientations, suggesting that the isolated R. glutinis DNA fragment contains a promotor sequence of R. glutinis in front of the LEU gene. In addition, our data suggests that the cloned LEU fragment also contains an ARS (autonomously replication sequence) site of R. glutinis that could function in S. cerevisiae.


Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision.
The transcription factor recombination signal binding protein-J (RBP-J) functions immediately downstream of the cell surface receptor Notch and mediates transcriptional activation by the intracellular domain of all four kinds of Notch receptors. To investigate the function of RBP-J, we introduced loxP sites on both sides of the RBP-J exons encoding its DNA binding domain. Mice bearing the loxP-flanked RBP-J alleles, RBP-J(f/f), were mated with Mx-Cre transgenic mice and deletional mutation of the RBP-J gene in adult mice was induced by injection of the IFN-alpha inducer poly(I)-poly(C). Here we show that inactivation of RBP-J in bone marrow resulted in a block of T cell development at the earliest stage and increase of B cell development in the thymus. Lymphoid progenitors deficient in RBP-J differentiate into B but not T cells when cultured in 2'-deoxyguanosine-treated fetal thymic lobes by hanging-drop fetal thymus organ culture. Competitive repopulation assay also revealed cell autonomous deficiency of T cell development from bone marrow of RBP-J knockout mouse. Myeloid and B lineage differentiation appears normal in the bone marrow of RBP-J-inactivated mice. These results suggest that RBP-J, probably by mediating Notch signaling, controls T versus B cell fate decision in lymphoid progenitors.


[Measuring facial paralysis using the three-dimensional dynamic quantitative analysis system of facial motion: correlation with subjective grading systems].
The aim of this study was to measure the facial motion of patients with facial paralysis using a three-dimensional dynamic quantitative analysis system of facial motion (3D ASFM) and analyze its correlation with subjective grading systems. We included 30 healthy volunteers and 50 patients with unilateral facial paralysis. After placing landmarks on the faces, the facial motions of the patients were measured using the 3D ASFM. The regional symmetry ratios(SRs) and gross scores of different parameters were calculated. Then a comparison with four subjective grading systems(House-Brackmann, Sunnybrook, Facial Nerve Grading System 2.0, Fisch) was performed. The entire test could be completed within five minutes. The normal range of healthy volunteers were obtained, the gross score of which was 91.9±1.5. The SRs of the maximal moving distance(MMD) were most strongly correlated with regional subjective grading systems, followed by the SRs of the maximal moving velocity (MMV). The SRs of the maximal moving acceleration (MMA) were either poorly correlated or uncorrelated with the subjective grading systems. Moreover, the Spearman coefficients with four subjective grading systems were -0.630(House-Brackmann), -0.728(Facial Nerve Grading System 2.0), 0.697(Sunnybrook), and 0.617(Fisch)respectively(P<0.05). The 3D ASFM is a convenient method to rapidly assess facial paralysis. It not only overcomes the shortcomings of conventional subjective grading systems, but also correlates well with them.


Psychotherapy 2.0: MySpace blogging as self-therapy.
A survey conducted by America Online (AOL) in 2005 reported the startling finding that almost 50% of those posting entries on internet logs (weblogs or blogs), use them as a form of self-therapy. This finding went relatively unnoticed by psychotherapists and other mental health professionals. Given the rather significant global population of bloggers (those who post internet journal entries) and readers, and the seemingly intractable problem of mental illness worldwide (according to the World Health Organisation, the global burden of mental illness accounts for more than the burden of all cancers put together), the possibility of blogging as self-therapy deserves greater attention. Research investigating the health possibilities of blogs holds particular promise, at least for those disposed to writing and those working with patients who write. This paper addresses the question of how one might blog within a social network as a form of self-therapy. Based on an interview conducted with a blogger in May 2007, we construct a portrait of an individual who uses a blog as self-therapy.


Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation.
Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. In 3,310 individuals (mean age 58 ± 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809). Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement.


Extended (10-Day) Real-Time Monitoring by Dexamethasone-Enhanced Microdialysis in the Injured Rat Cortex.
Intracerebral microdialysis has proven useful for chemical monitoring in patients following traumatic brain injury. Recent studies in animals, however, have documented that insertion of microdialysis probes into brain tissues initiates a foreign-body response. Within a few days after probe insertion, the foreign body response impedes the use of microdialysis to monitor the K+ and glucose transients associated with spreading depolarization, a potential mechanism for secondary brain injury. Herein, we show that perfusing microdialysis probes with dexamethasone, a potent anti-inflammatory glucocorticoid, suppresses the foreign body response and facilitates the monitoring of spontaneous spreading depolarizations for at least 10 days following controlled cortical injury in the rat. In addition to spreading depolarizations, results of this study suggest that a progressive, apparently permanent, decline in pericontusional interstitial glucose may be an additional sequela of brain injury. This study establishes extended dexamethasone-enhanced microdialysis in the injured rodent cortex as a new paradigm for investigating trauma-induced metabolic crisis.


Morphometric analysis of the internal auditory canal by computed tomography imaging.
Many clinical and experimental studies have been done to analyze the anatomical and functional aspects of the internal auditory canal (IAC) in human beings since there are great inter-individual variability and structural variations that may occur regarding the other adjacent structures. The purpose of this study was to characterize the morphology of the internal auditory canal (IAC) during development using high resolution computed tomography (CT) and to analyze its dimensions, which will be determined by measuring the nearby areas and structures using a system of digital image processing. CT images of the IAC of 110 normal subjects aged 1 to 92 years (mean age, 46.5 years) of both genders were reviewed to determine the shape, area, opening width (OW), longitudinal length (LL), vertical diameter (VD) and distance from the vestibular aqueduct. The shapes observed in children and adults were funnel-shaped (74% and 58.3%, respectively), cylindrical (22% and 30.9%, respectively) and bud-shaped (4% and 10.8%, respectively). The measurements by CT in children were: area= 50.30 mm(2), OW = 7.53 mm, length = 11.17 mm, VD = 4.82 mm and the distance between the IAC and the vestibular aqueduct (VA) = 12.63 mm. In adults, the measurements were: area = 44.64 mm(2), OW = 7.10 mm, length = 9.84 mm, VD = 4.47 mm and the distance between IAC and VA = 11.17 mm. CT images showed that the IAC has different shapes and when the measurements obtained for children were compared with those of adults, the parameters that presented statistically significant differences in either gender were length and diameter.


Cultural Barriers Influencing Midwives' Sexual Conversation with Menopausal Women.
The present study aimed to determine the barriers influencing the sexual conversation. In this descriptive cross-sectional study, 200 midwives were selected through convenience sampling method from private and public clinics in Mashhad, North East of Iran. A self-structured questionnaire was used to collect the study data. The mean age of subjects was 39.58 ± 8.12 years with 13.49 ± 7.59 years of work experience. A number of cultural conditions act as an inhibitory force for the midwives to address sexual issues with menopausal women. Menopausal women visit a doctor at the acute stage when emotional and physical problems make sexual discussion difficult for the midwives (86.5%). Other related causes for not having proper sexual conversation were insufficient knowledge (51.4%), inadequate education provided via public media through health providers (83.5%), midwives or their patient's shame (51.5%), and attempt to get help from traditional healers, friends, relatives and supplicants instead of midwifery staff (78.5%). Also, we found that sexual workshops, communication workshops, and work experiences had a significant influence in changing the views of midwives. Cultural barriers prevent the patients and providers from communicating effectively with each other, thus highlighting the need for sexual and communication workshops for the health care providers.


Validation of the Ottawa Knee Rule in Iran: a prospective study.
This study was designed to determine the accuracy of the Ottawa Knee Rule (OKR) when applied to patients with acute knee injury in the Iranian population of the Imam Hospital Emergency Department (ED) at. This prospective cohort validation study included a convenience sample of all patients with a blunt knee injury sustained in the preceding 7 days presenting to the ED of a tertiary care teaching hospital during the study period. Patients were assessed for the five variables comprising the OKR, and a standardised data form was completed for each patient. Standard knee radiographs were ordered on all patients irrespective of the determination of the rule. The rules were interpreted by the primary investigator on the basis of the data sheet and the final orthopaedist radiograph reading. Outcome measures of this study were: sensitivity, specificity, positive predictive value and negative predictive value of the OKR. A total of 283 patients were enrolled in the study. 22 fractures (7.77%) were detected. The decision rule had a sensitivity of 0.95 (95% CI 0.77 to 0.99), and a specificity of 0.44 (95% CI 0.37 to 0.50). The potential reduction in use of radiography was estimated to be 41%. The OKR missed only one fracture. Prospective validation has shown that the OKR is a highly sensitive tool for detecting knee fractures and has the potential to reduce the number of radiographs in patients with acute knee injuries.


Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS-SOD1 mice.
We have investigated the expression of Hsp25, a heat shock protein constitutively expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness. This decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as identified by cellulose acetate filtration and Western blot analysis. In contrast to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT-PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels occurs post-transcriptionally. In view of the cytoprotective properties of Hsp25 and the temporal relationship between decreased Hsp25 expression and the onset of motoneuron death, it is feasible that reduced Hsp25 concentration contributes to the degeneration of motoneurons in G93A mice. These data are consistent with the idea that mutant SOD1 may reduce the availability of the protein quality control machinery in motoneurons.


[A role of the retinal pigment epithelium in the involution of subretinal neovascularization].
We clarified a role of the retinal pigment epithelium (RPE) in the regression of experimentally induced subretinal neovascularization (SRN) in monkey. Eight eyes of 5 rhesus monkeys were used in this study. Two weeks after intense krypton laser photocoagulation to the posterior pole of the fundus, 0.5M l-ornithine hydrochloride solution 0.03 ml was injected intravitreously for the purpose of selective RPE damage. After ornithine injection, SRN continued without any evidence of spontaneous regression over 8 weeks following photocoagulation. Histopathologically, SRN developed with wide lumen in the subretinal space accompanied with serous detachment of the sensory retina, and new vessels were not enveloped completely by the proliferating RPE cells. We already showed that experimentally induced subretinal neovascularizations naturally regress spontaneously by envelopment of RPE cells 5 to 8 weeks after photocoagulation. Our results suggested that SRN persist actively without regression due to incomplete enclosure by RPE by selective damage of RPE at the active stage of SRN. We have confirmed that the RPE cells played an important role at the involution stage of SRN.


Ewings Sarcoma: A Case of Respiratory Distress and Opacification That Was not Pneumonia.
The Ewing sarcoma family of tumors typically appears in the second decade of life with regional pain and swelling of a long bone. The following case presents a pediatric patient, aged 4 years, given a diagnosis of Ewing sarcoma of the rib with the initial presentation of respiratory distress, hypoxia, and pleural effusion. Respiratory distress accounts for a large majority of emergency department visits annually, so it is the distinct responsibility of the emergency department physician to avoid premature closure in attributing the most common diagnoses to account for the presenting symptoms. In this case, the careful study of the initial radiographic findings led to further identification and characterization of the mass through thoracic computed tomography to suggest Ewing sarcoma, despite the patient's unlikely demographics and presentation.


Edges of Layered FePSe3 Exhibit Increased Electrochemical and Electrocatalytic Activity Compared to Basal Planes.
Transition metal trichalcogenphosphites (MPX3), belonging to the class of 2D materials, are potentially viable electrocatalysts for the hydrogen evolution reaction (HER). Many 2D and layered materials exhibit different magnitudes of electrochemical and electrocatalytic activity at their edge and basal sites. To find out whether edges or basal planes are the primary sites for catalytic processes at these compounds, we studied the local electrochemical and electrocatalytic activity of FePSe3, an MPX3 representative that was previously found to be catalytically active. Using scanning electrochemical microscopy, we discovered that electrochemical processes and the HER are occurring at an increased rate at edge-like defects of FePSe3 crystals. We correlate our observations using optical microscopy, confocal laser scanning microscopy, scanning electron microscopy, and electron-dispersive X-ray spectroscopy. These findings have profound implications for the application of these materials for electrochemistry as well as for understanding general rules governing the electrochemical performance of layered compounds.


Improving the communication between farmers and veterinarians to enhance the acceptability of bovine tuberculosis eradication programmes.
France and Spain have been fighting against bovine tuberculosis (bTB) for years, even though new outbreaks continue to appear on both sides of the border, generating misconceptions about the disease and social distrust in the eradication programme and competent authorities. The perceived disease risk and the commitment of all interested parties are key factors for the successful implementation of control programmes, as they might influence the acceptability of recommended measures. Effective communication can contribute to increasing knowledge, trust and stakeholders' engagement, thus ensuring the acceptability of the eradication programme. This study was conducted in Catalonia (Spain) and Pyrenees-Atlantiques (France) in the frame of the INNOTUB project (https://innotub.eu/) to characterise the communication on bTB in the trans-Pyrenees region and provide recommendations to improve it. The communication on bTB was characterised by analysing 153 (Spain) and 66 (France) online freely available texts, published between 2018 and 2020, through Content Analysis and Critical Metaphor Analysis. Moreover, six farmers and four veterinarians were in-depth interviewed in each area to gather information about the communication on bTB. Interviews were made in original languages and analysed using a qualitative thematic approach. A pilot participatory intervention inspired by the Systematic Tool for Behavioural Assumption Validation and Exploration (STAVE) method was used to develop a list of proposals to improve communication and to promote the creation of territorial networks/committees on bTB prevention and control. It included three focus groups with farmers and veterinarians, a meeting with representatives of the regional veterinary services, and a final deliberative workshop. Results highlight the existence of a controversial debate on bTB and a heterogeneous understanding between stakeholders. Institutional and scientific communication mainly focus on bTB detection and control while other aspects are left in the background. On the contrary, farmers extend their communication to a greater variety of topics. The metaphorical framing strongly differed among actors, while veterinary services and researchers "fight" against bTB and "progress" toward the eradication, farmers place themselves in a framework of "sacrifice" and, particularly in Spain, they play a passive role. The proposals developed by the participants to improve the current communication on bTB included: (i) create participatory meeting spaces to share opinions and information; (ii) improve data accessibility (on epidemiological situations); (iii) develop clearer and written protocols and informative visual material; (iv) redesign the training courses (v) increase the stakeholders' participation in the design of protocols.


[New trends in providing home care for elderly clients].
A progressive form of long-term care of old people with reduced self-sufficiency is home care. It is an alternative of in-patient care and provides services in the client's home. It combines the advantages of lower cost with the possibility to remain in the domestic environment and keep up social contacts. The most important factors which will substantially increase the need of home care are demographic development, the declining availability of potential care providers and possibilities of the family to ensure care, economic pressure and clients' preference. The present state of home care provision does not meet the demands of society nor individual demands of clients. It is important to create a new model of home care which will form an integral part of the social and health care policy of the state. The author discusses in particular the main principles of this care based on principles of state regulated pluralism.


Obsessive Compulsive Disorder and Bipolar Disorder Comorbidity: A Comparative Study.
Objective: One of the difficult comorbidity of Obsessive-Compulsive disorder (OCD) to manage is bipolar disorder (BD). Results of previous studies on OCD-BD comorbidity may have been affected by different clinical definitions of OCD-BD, small or different sample sizes, different thresholds for including BD patients and different accuracies in OCD diagnosing. We tried to reduce limitations of previous studies and hypothesized that the OCD-BD group is a unique category and can be associated with greater levels of severity, episodic course of illness, more hostility and suicidal behaviors and different dimensions of OC symptoms. Method : We compared 44 OCD-BD patients with 94 OCD patients who had completed at least a 24-month follow-up period. Clinical interviews and rating scales, and obtaining information from clinical charts were used to assess the patients. Life chartings of OCD and BD course were made for each patient and were categorized into four groups based on the clinical course of OCD. Results: OCD-BD was characterized by a more continuous course, higher dysfunction, suicide and hostility scores. OC aggressive symptoms, having first-degree relatives with OCD and comorbidity of any anxiety disorders were associated with a reduction in odds of belonging to the OCD-BD group. Conclusion: OCD-BD can be considered a unique category with greater morbidity and a more episodic course of OCD. Further research is recommended for exploring potential biological, social and psychological factors along with OCD-BD comorbidity.


Medical outreach to homeless substance users in New York City: preliminary results.
An innovative, experimental, medical out-reach initiative, using a fully-equipped mobile medical van with a staff of 2 part-time physicians, a physician assistant, a social worker, and a driver/medical aid serving the needs of 1048, mostly male, minority group, high-level, homeless New York City substance users with infectious diseases is described. The study sample (N = 250) was divided into experimental S's who received Intensive case management and a control group who could choose to refer themselves to the SW. Biological tests revealed high rates of cocaine use and infectious diseases. Preliminary 4-month outcomes (N = 128) showed reductions in drug use, homelessness and health complaints in both groups; experimental subjects compared with controls received more Public Assistance and had fewer emergency room visits.


Ground state of a large number of particles on a frozen topography.
Problems consisting in finding the ground state of particles interacting with a given potential constrained to move on a particular geometry are surprisingly difficult. Explicit solutions have been found for small numbers of particles by the use of numerical methods in some particular cases such as particles on a sphere and to a much lesser extent on a torus. In this paper we propose a general solution to the problem in the opposite limit of a very large number of particles M by expressing the energy as an expansion in M whose coefficients can be minimized by a geometrical ansatz. The solution is remarkably universal with respect to the geometry and the interaction potential. Explicit solutions for the sphere and the torus are provided. The paper concludes with several predictions that could be verified by further theoretical or numerical work.


[Blood, teeth and hair: 3 different materials used to evaluate exposure to lead and cadmium in children living in an industrial zone].
There is a general agreement that children are a population at increased risk with respect to lead and cadmium exposure and to adverse health effects resulting from increased exposure. Different biological indicators such as blood hair and teeth have been used to evaluate lead and cadmium exposure in humans. However, up to date, it has not been established which is the best indicator to provide an assessment of internal exposure. The aim of the present study was to examine the levels of lead and cadmium in hair, blood and teeth of children living from birth in an industrialized area near Modena. The relationship between these indicators of exposure and children characteristics such as sex, weight, height, blood pressure and smoking habits of parents was also examined. 142 children (71 males and 71 females) representing 20.8% of those aged 6-7 years living in Sassuolo (Modena) have been included in the study. The geometric means of lead in blood, hair and teeth were 11.2 micrograms/dl, 7.24 micrograms/g and 6.16 micrograms/g, respectively. Hair lead were significantly related to both blood and teeth values (r = 0.226, p = 0.007 and r = 0.186, p = 0.027, respectively). Mean cadmium concentrations were 0.47 mu/l in blood, 0.17 micrograms/g in hair and 47.9 ng/g in teeth and no significant correlation was observed between the three biological matrixes examined. Significant correlations were found between lead and cadmium in both hair (r = 0.427, p = 0.000) and teeth (r = 0.224, p = 0.007). In addition, for lead content in teeth, a significant difference between boys and girls was observed; females showed higher values than males (6.77 micrograms/g vs 5.61 micrograms/g; t = 2.23 p = 0.028). Taking into account the individual characteristics of children, a negative relationship was found between Pb levels in teeth and height (r = -0.217, p = 0.024). Systolic blood pressure values were positively associated to cadmium hair levels in males but not in females (r = 0.281; p = 0.053). From the results of the present study it appears that blood, hair and teeth provide different information to predict lead and cadmium exposure of children. Hair seem to be a useful global indicator of total environmental pollution.


Immunohistochemical expression of thymidine phosphorylase in human endometrial cancer.
To investigate correlations between the expression of thymidine phosphorylase (TP) by endometrial cancer cells and the density of microvessels within the tumor, the clinicopathologic features, and the prognosis. We examined tumor specimens obtained from 46 patients with endometrial cancer (9 FIGO stage IA, 16 stage IB, 8 stage IC, 1 stage IIA, 6 stage IIB, and 6 stage IIIC). The cellular expression of TP and the intratumoral density of microvessels were determined by immunohistochemistry using monoclonal antibodies to TP and factor VIII-related antigen, respectively. We investigated the relationship between the cellular expression of TP and the following factors: clinicopathologic features (menopausal status, histologic type, tumor size, histologic grade, myometrial invasion, cervical invasion, and metastasis), the microvessel count, and the disease-free survival period. Of the 46 tumors, 19 (41%) were TP-positive. The microvessel count was significantly higher in TP-positive tumors than in TP-negative tumors (P = 0.01, Mann-Whitney U test). There was no significant correlation between TP expression and clinicopathologic features, and there was no significant difference in the disease-free survival period between patients with TP-positive tumors and patients with TP-negative tumors. TP expression was not correlated with clinicopathologic features or prognosis, but was associated with an increased density of microvessels in endometrial cancer. These findings suggest that TP may play an important role in angiogenesis and may be involved in the tumorigenesis of endometrial cancer.


The use of genetically altered astrocytes to provide nerve growth factor to adrenal chromaffin cells grafted into the striatum.
Transplantation of adrenal chromaffin cells into the striatum of Parkinson's disease patients is unlikely to become a reliable therapy unless techniques are devised to improve cell survival. To address this issue, we investigated the use of genetically altered astrocytes that constitutively secrete beta-nerve growth factor (NGF) to provide trophic support for adrenal chromaffin cells grafted into the dopamine-denervated striatum of the rat. Primary rat astrocytes were altered genetically in vitro by infection with a retroviral vector harboring a mouse beta-NGF transgene under constitutive long terminal repeat transcriptional control. Confluent cultures of these genetically altered astrocytes secrete NGF into their culture medium at a rate of approximately 9 pg/10(5) cells/h. This rate of NGF secretion is at least 10-fold higher than that of confluent sister cultures of uninfected astrocytes. The effects of the NGF-secreting astrocytes on the survival and neuronal transformation of dissociated adrenal chromaffin cells were assessed in vitro and following transplantation into the dopamine-denervated striatum of the adult rat. In vitro experiments demonstrated that neuritic outgrowth is stimulated when postnatal day 12 chromaffin cells are grown on a monolayer of the genetically altered astrocytes. When co-grafted with genetically altered astrocytes, young postnatal chromaffin cells displayed extensive neuritic outgrowth within the host brain 2 weeks postimplantation, whereas chromaffin cells grafted alone or with normal astrocytes retain an endocrine-like morphology. Survival of the chromaffin cells is also enhanced 3-6-fold when co-grafted with the genetically altered astrocytes. In addition, the neuronally transformed chromaffin cells appear to lose adrenergic properties as assessed by diminished immunoreactivity to the adrenergic marker, phenylethanolamine-N-methyltransferase. Although their survival is also enhanced approximately 4-fold relative to controls, adult chromaffin cells do not convert to a neuronal morphology when co-grafted with the genetically altered astrocytes. These studies demonstrate that rat astrocytes carrying a mouse NGF transgene provide trophic support for intrastriatal chromaffin cell grafts.


[Is there still a place for surgery in the treatment of communicating pseudocyst in chronic pancreatitis?].
The purpose of this study was to evaluate the results of long term percutaneous catheter drainage in the treatment of chronic pancreatic pseudocysts communicating with pancreatic ducts. Since 1986, 13 consecutive patients with symptomatic pseudocysts were treated prospectively. All pseudocysts were associated with chronic pancreatitis. The location was head (n = 8), body (n = 3) or tail (n = 2). The procedure included fine needle aspiration under ultrasonic control, percutaneous drainage along a guide wire and closed suction aspiration. A radiological control was performed weekly and the catheter was left in place until total resolution of pseudocyst. Immediate relief of pain and resolution of pseudocyst were obtained in all 13 patients. The average length of hospital stay was 12.2 +/- 8 days (1 to 23). The average duration of drainage was 36 days. There was no mortality of morbidity related to the drainage. There were two asymptomatic recurrences, but long-term follow-up (mean 3 years) showed that all 13 patients were symptom-free. The clinical results of such a long-term catheter drainage seem better in our study than in other previous series. It is a simple and innocuous procedure, and could be carried out in an outpatient unit. Such drainage represents an efficient alternative to endoscopic or surgical treatment of chronic pancreatic pseudocyst with ductal communication. In our experience surgery is no longer indicated.


Urinary tract anomalies in patients with hypospadias.
Fifty-five patients with hypospadias were reviewed. Intravenous urography was carried out on 80%. The incidence of upper urinary tract anomalies was 22%. This was independent of the severity of the hypospadias. Patients with hypospadias and undescended testis were reviewed as a separate group. The incidence of upper urinary tract anomaly here was 31%. Again, the incidence was not influenced by the severity of the hypospadias. None of the upper urinary tract anomalies required surgical intervention. It is concluded that routine IVU is not indicated in all cases of hypospadias.


Unusual tomographic findings of complicated necrotizing pancreatitis.
Acute pancreatitis (AP) is a potential life-threatening disease, which originates from inflammatory involvement of the pancreas and surrounding tissues. Serious complications eventuate and treatment is difficult. AP is classified in both interstitial edematous pancreatitis, which occurs in 70-80% of patients, and necrotizing pancreatitis, which occurs in 20-30% of patients. Diagnosis is based on the presence of two of the following criteria: abdominal pain, increased serum determination of amylase and/or lipase more than three times the reference value, and characteristic tomographic findings. Among the latter, there is the pancreatic and surrounding tissue damage as well as that related to distant organ involvement. This case report shows the fatal case of a male patient with a history of heavy alcoholic abuse admitted with the diagnosis of necrotizing pancreatitis. The authors call attention to the unusual tomographic findings; namely, a huge duodenal hematoma and a large hemoperitoneum, ischemic involvement of the spleen and kidneys, as well as pancreatic and peripancreatic necrosis.


Higher urinary bisphenol A concentration and excessive iodine intake are associated with nodular goiter and papillary thyroid carcinoma.
In the present study, we investigated whether bisphenol A (BPA) levels and excessive iodine intake were associated with papillary thyroid carcinoma (PTC) and nodular goiter (NG). We determined total BPA concentrations (TBC) in paired serum and urine samples, and urinary iodine concentrations (UIC) in urine samples collected from PTC patients, NG patients, and healthy individuals, then compared BPA concentrations and UIC within and between each patient group. The results showed that there were no gender-specific differences in serum TBC and UIC in each group, and no differences across all patient groups. Urinary BPA concentrations (UBC) were higher in the NG and PTC groups compared with the control group. UBC showed gender-specific differences in the NG and PTC group. Furthermore, UIC were higher in the NG and PTC groups compared with the control group. Higher UBC and excessive iodine intake were risk factors for NG and PTC according to multivariate logistic regression analysis. There was a significant correlation between UBC and UIC in each group. These data suggested that higher UBC and excessive iodine intake are associated with NG and PTC. The metabolic and functional pathways between BPA and iodine are potentially linked to the pathogenesis and progression of NG and PTC.


Total Mesorectal Excision Technique-Past, Present, and Future.
While the treatment of rectal cancer is multimodal, above all, a proper oncological resection is critical. The surgical management of rectal cancer has substantially evolved over the past 100 years, and continues to progress as we seek the best treatment. Rectal cancer was historically an unsurvivable disease, with poor understanding of the embryological planes, lymphatic drainage, and lack of standardized technique. Major improvements in recurrence, survival, and quality of life have resulted from advances in preoperative staging, pathologic assessment, the development and timing of multimodal therapies, and surgical technique. The most significant contribution in advancing rectal cancer care may be the standardization and widespread implementation of total mesorectal excision (TME). The TME, popularized by Professor Heald in the early 1980s as a sharp, meticulous dissection of the tumor and mesorectum with all associated lymph nodes through the avascular embryologic plane, has shown universal reproducible reductions in local recurrence and improvement in disease-free and overall survival. Widespread education and training of surgeons worldwide in the TME have significantly impact outcomes for rectal cancer surgery, and the procedure has become the gold standard for curative resection of rectal cancer. In this article, we discuss the evolution of the standard abdominal approach to the TME, with emphasis on the history, relevant anatomy, standard procedure steps, oncologic outcomes, and technical evolution.


[Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study].
Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.


Effects of annexin A1 on apoptosis and cell cycle arrest in human leukemic cell lines.
Recent studies suggest that annexin A1 (ANXA1) promotes apoptosis in cancerous cells. This study aims to investigate the effects of ANXA1 on apoptosis and cell cycle arrest in K562, Jurkat and U937 cells and peripheral blood mononu-clear cells (PBMC). Cells were treated with ANXA1 and cyclophosphamide prior to flow cytometry analysis for apoptosis and cell cycle arrest induction. At 2.5µM, ANXA1 induced significant apoptosis in K562 (p ≤ 0.001) and U937 (p ≤ 0.05) cells, with EC50 values of 3.6 and 3.8 µM, respectively. In Jurkat cells, induction was not significant (EC50, 17.0 µM). No significant apoptosis induction was observed in PBMC. ANXA1 caused cycle arrest in the G0/G1 phase in K562 and U937 cells with p ≤ 0.001 for both, and (p ≤ 0.01) for Jurkat cells. ANXA1 induced apoptosis and cycle arrest in the G0/G1 phase in K562 and U937 cells, causing only cell cycle arrest in Jurkat cells.


A randomized controlled trial to determine the effects of music and relaxation interventions on perceived anxiety in hospitalized patients receiving orthopaedic or cancer treatment.
Nonpharmacological interventions, including combinations of music, education, coping skills, and relaxation techniques, have been found to have a positive effect on patients' perceived anxiety in many settings. However, few research studies have assessed and compared the effectiveness of music and relaxation interventions in reducing the anxiety levels of orthopaedic and oncology patients. We conducted a prospective, randomized, controlled study to examine the effectiveness of music and relaxation interventions on perceived anxiety during initial hospitalization for patients receiving orthopaedic or cancer care treatment at a Midwestern teaching hospital. This was a pre-test/post-test study design utilizing the State-Trait Anxiety Inventory. One hundred twelve patients were randomized into 3 study groups. Thirty-eight subjects (34%) were randomized in the music-focused relaxation group, 35 subjects (31%) in the music and video group, and 39 (35%) subjects in the control group. Fifty-seven (51%) were orthopaedic patients and 55 (49%) were oncology patients. Comparison of the 3 study groups showed no statistically significant differences with regard to patients' demographics. Although reduced anxiety levels were reported for all 3 groups postintervention, the differences were not statistically significant (p > .05). Also, there was no significant difference found between the perceived anxiety levels of patients admitted to the orthopaedic and oncology care units (p > .05). Finally, the results of the intragroup comparisons (regardless of the group assignment) showed a significant decrease in anxiety levels reported by all patients postintervention (p < .001). Music and relaxation interventions could be an additional tool in assisting patients to become less anxious during their hospital stay. Music focused relaxation and music and video are both valuable and cost-effective strategies that can assist the orthopaedic and oncology patient population. Identifying opportunities to make these interventions easily accessible to healthcare professionals can assist in the management of patient anxiety during hospitalization.


Coenzyme-A-Independent Transacylation System; Possible Involvement of Phospholipase A2 in Transacylation.
The coenzyme A (CoA)-independent transacylation system catalyzes fatty acid transfer from phospholipids to lysophospholipids in the absence of cofactors such as CoA. It prefers to use C20 and C22 polyunsaturated fatty acids such as arachidonic acid, which are esterified in the glycerophospholipid at the sn-2 position. This system can also acylate alkyl ether-linked lysophospholipids, is involved in the enrichment of arachidonic acid in alkyl ether-linked glycerophospholipids, and is critical for the metabolism of eicosanoids and platelet-activating factor. Despite their importance, the enzymes responsible for these reactions have yet to be identified. In this review, we describe the features of the Ca2+-independent, membrane-bound CoA-independent transacylation system and its selectivity for arachidonic acid. We also speculate on the involvement of phospholipase A2 in the CoA-independent transacylation reaction.


Monitoring on-line desalted lignocellulosic hydrolysates by microdialysis sampling micro-high performance anion exchange chromatography with integrated pulsed electrochemical detection/mass spectrometry.
An on-line system based on microdialysis sampling (MD), micro-high performance anion exchange chromatography (micro-HPAEC), integrated pulsed electrochemical detection (IPED), and electrospray ionization mass spectrometry (MS) for the monitoring of on-line desalted enzymatic hydrolysates is presented. Continuous monitoring of the enzymatic degradation of dissolving pulp from Eucalyptus grandis as well as degradation of sugar cane bagasse in a 5-mL reaction vessel was achieved up to 24 h without any additional sample handling steps. Combining MD with micro-HPAEC-IPED/MS and on-line desalting of hydrolysates enabled injection (5 microL) of at least 23 samples in a study of the sequential action of hydrolytic enzymes in an unmodified environment where the enzymes and substrate were not depleted due to the perm-selectivity of the MD membrane (30 kDa cut-off). Xylanase, phenolic acid esterase and a combination of endoglucanase (EG II) with cellobiohydrolase (CBH I) resulted in the production of DP 1 after the addition of esterase, DP 2 and DP 3 after the addition of EG II and CBH I, from the dissolving pulp substrate. Similar sequential enzyme addition to sugar cane bagasse resulted in DP 1 production after the addition of esterase and DP 1, DP 2 and DP 3 production after the addition of the EG II and CBH I mixture. Combining MS on-line with micro-HPAEC-IPED proved to be a versatile and necessary tool for such a study compared to conventional methods. The mass selectivity of MS revealed complementary information, including the co-elution of saccharides as well as the presence of more than one type of DP 2 in the case of dissolving pulp and several types of DP 2 and DP 3 for sugar cane bagasse. This study demonstrates the limitation of the use of retention time alone for confirmation of the identity of saccharides especially when dealing with complex enzymatic hydrolysates. In situ sampling and sample clean-up combined with on-line desalting of the chromatographic effluent, provides a generic approach to achieve real time monitoring of enzymatic hydrolysates when they are detected by a combination of IPED and MS.