A master switch couples Mg²⁺-assisted catalysis to domain motion in B. stearothermophilus tryptophanyl-tRNA Synthetase.
We demonstrate how tryptophanyl-tRNA synthetase uses conformation-dependent Mg(2+) activation to couple catalysis of tryptophan activation to specific, functional domain movements. Rate acceleration by Mg(2+) requires ∼-6.0 kcal/mol in protein⋅Mg(2+) interaction energy, none of which arises from the active site. A highly cooperative interaction between Mg(2+) and four residues from a remote, conserved motif that mediates the shear of domain movement (1) destabilizes the pretransition state conformation, thereby (2) inducing the Mg(2+) to stabilize the transition state for k(cat) by ∼-5.0 kcal/mol. Cooperative, long-range conformational effects on the metal therefore convert an inactive Mg(2+) coordination into one that can stabilize the transition state if, and only if, domain motion occurs. Transient, conformation-dependent Mg(2+) activation, analogous to the escapement in mechanical clocks, explains vectorial coupling.


Structure and antiinflammatory activity relationships of wogonin derivatives.
A number of wogonin derivatives have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE2 production. Wogonin derivatives modified at the B ring of wogonin were obtained from 2,4-Dihydroxy-3,6-dimethoxyacetophenone (1) via several steps. Most wogonin derivatives exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin. Alkylation of 5,7-phenol groups and substitution at the B ring of wogonin generally caused reduction of inhibitory activity.


Factors affecting the plasma membrane function of cooled-stored stallion spermatozoa.
The spermatozoon is a highly specified cell that has the abilities of active motility and fertilization of the ovum. Damage to the sperm plasma membrane results in the irreversible loss of its functions. Because of the high content of unsaturated fatty acids in the plasma membrane, mammalian sperm are sensitive to oxidative stress. While mild peroxidation appears to promote capacitation of the sperm cell, excessive peroxidation will damage the plasma membrane and results in loss of motility and fertility. The functional integrity of the sperm plasma membrane can be determined by functional tests (determination of motility, resistance against hypoosmotic media) or different staining methods. Today, fluorescent dyes that allow the evaluation of membrane-intact cells are preferred. Computer-assisted evaluation or the use of flow cytometry has improved the precision of these methods. The use of cooled-shipped semen has become a routine method in the equine industry and semen stored at 5 degrees C for about 24 h maintains fertility close to that of fresh semen. According to the suitability of their ejaculates for cooled-storage, stallions may be classified as "good coolers" or "poor coolers". Semen processing involves a number of factors that may damage the sperm plasma membrane. This includes addition of semen extender, centrifugation, cooling and storage at a temperature of 4-6 degrees C. Extender media and their ingredients protect the sperm plasma membrane against environmental influences, but unsuitable composition of the extender can also promote membrane damage. Recent advantages in extender composition are based on the substitution of undefined factors such as milk or egg yolk by more defined and stable components.


Incidence and levels of fumonisin contamination in Colombian corn and corn products.
A survey was conducted to determine the levels of fumonisins B1 and B2 in corn and corn-based products available in Colombia for human and animal consumption. A total of 120 samples were analyzed by acetonitrile-water extraction, cleanup with a strong-anion-exchange column, and liquid chromatography with o-phthaldialdehyde-2-mercaptoethanol derivatization and fluorescence detection. The samples of corn and corn-based products for animal intake were taken at different feed manufacturing plants, whereas the samples used for human foods where purchased from local retail stores. The number of positive samples for fumonisin B1 was 20.0% higher in corn and corn-based products for animal intake (75.0%) than in corn and corn-based products for human consumption (55.0%). The levels of fumonisin B1 were also higher in corn and corn-based products for animal intake (mean = 694 μg/kg; range = 32-2964 μg/kg), than in corn and corn-based products for human intake (mean = 218 μg/kg; range = 24-2170 μg/ kg). The incidence and levels of fumonisin B2 were lower than those for fumonisin B1. Corn and corn-based products for animal consumption had an incidence of fumonisin B2 of 58.3%, with a mean value of 283 μg/kg, and a range of 44-987 μg/kg. The incidence of fumonisin B2 in corn-based products for human intake was 35.0%, with a mean value of 118 μg/kg and a range of 21-833 μg/kg. The highest incidence and levels of fumonisins were found in samples of hominy feed, with concentrations ranging from 86 to 2964 μg/kg fumonisin B1 and 57 to 987 μg/kg fumonisin B2.


Energy expenditure during tennis play: a preliminary video analysis and metabolic model approach.
The aim of this study was to estimate, using video analysis, what proportion of the total energy expenditure during a tennis match is accounted for by aerobic and anaerobic metabolism, respectively. The method proposed involved estimating the metabolic power (MP) of 5 activities, which are inherent to tennis: walking, running, hitting the ball, serving, and sitting down to rest. The energy expenditure concerned was calculated by sequencing the activity by video analysis. A bioenergetic model calculated the aerobic energy expenditure (EEO2mod) in terms of MP, and the anaerobic energy expenditure was calculated by subtracting this (MP - EEO2mod). Eight tennis players took part in the experiment as subjects (mean ± SD: age 25.2 ± 1.9 years, weight 79.3 ± 10.8 kg, VO2max 54.4 ± 5.1 ml·kg(-1)·min(-1)). The players started off by participating in 2 games while wearing the K4b2, with their activity profile measured by the video analysis system, and then by playing a set without equipment but with video analysis. There was no significant difference between calculated and measured oxygen consumptions over the 16 games (p = 0.763), and these data were strongly related (r = 0.93, p < 0.0001). The EEO2mod was quite weak over all the games (49.4 ± 4.8% VO2max), whereas the MP during points was up to 2 or 3 times the VO2max. Anaerobic metabolism reached 32% of the total energy expenditure across all the games 67% for points and 95% for hitting the ball. This method provided a good estimation of aerobic energy expenditure and made it possible to calculate the anaerobic energy expenditure. This could make it possible to estimate the metabolic intensity of training sessions and matches using video analysis.


Perceptions of AI engaging in human expression.
Though humans should defer to the superior judgement of AI in an increasing number of domains, certain biases prevent us from doing so. Understanding when and why these biases occur is a central challenge for human-computer interaction. One proposed source of such bias is task subjectivity. We test this hypothesis by having both real and purported AI engage in one of the most subjective expressions possible: Humor. Across two experiments, we address the following: Will people rate jokes as less funny if they believe an AI created them? When asked to rate jokes and guess their likeliest source, participants evaluate jokes that they attribute to humans as the funniest and those to AI as the least funny. However, when these same jokes are explicitly framed as either human or AI-created, there is no such difference in ratings. Our findings demonstrate that user attitudes toward AI are more malleable than once thought-even when they (seemingly) attempt the most fundamental of human expressions.


[Primary hypothyroidism and postmenopause as the causes of delayed diagnosis of panhypopituitarism in a patient with nonfunctional pituitary adenoma].
Hypopituitarism is a state of complete or partial deficiency of pituitary hormones, including adrenal insufficiency, hypothyroidism, hypogonadism, growth hormone deficiency, and, rarely, diabetes insipidus.The article describes a clinical case of hypopituitarism due to a pituitary tumor in a postmenopausal woman. Difficulties in diagnosing hypopituitarism were due to a history of primary hypothyroidism. The first identified component of panhypopituitarism in the patient, (central hypothyroidism) had previously been seen as laboratory indications of medication-induced hyperthyroidism.The non-specific nature of the clinical symptoms, as well as a relatively rare combination of endocrine diseases, led to a long examination period and delayed diagnosis of the pituitary tumor.Whether the development of hypopituitarism in a patient with a nonfunctional pituitary tumor is an indication for transsphenoidal pituitary surgery remains a controversial issue. The decision for surgery is made taking into account the characteristics of the course of the disease in a particular patient. In this clinical case, a conservative tactic was chosen with hormone replacement therapy for glucocorticoid and thyroid deficiency.


Treatment of severe pediatric atopic dermatitis with methotrexate: A retrospective review.
Severe atopic dermatitis (AD) may require systemic immunomodulatory agents to control symptoms. A lack of evidence and guidelines for systemic AD therapy in children has led to variability in agents selected and uncertainty in their comparative efficacy and safety. Evaluation of the efficacy of methotrexate in children with severe AD was performed. We performed a retrospective chart review of 55 pediatric patients seen at Children's Hospital of Philadelphia that measured improvement using the Investigator's Global Assessment (IGA), a scale that rates AD symptoms from 0 to 5. About 76% of patients showed improvement with methotrexate. Mean baseline IGA of all patients was 4.18. After 6-9 months of treatment, this improved to 2.94. There was additional improvement to a mean IGA score of 2.39 after 12-15 months of treatment. At the final visit before each patient stopped methotrexate, the mean IGA score was 2.71. Approximately 50% of patients experienced minor side effects with gastrointestinal side effects the most common. In a diverse patient population, safety and efficacy of methotrexate was demonstrated. Significant improvement in IGA was noted for the majority after 6-9 months of therapy with further improvement when continuing treatment to 12-15 months. Methotrexate remains an important option for long-term symptom control with a favorable side effect profile and low cost.


Implication for the regulation of catabolism drawn from the single insulin-like growth factor binding domain protein (SIBD) gene in the mud crab, Scylla paramamosain.
Insulin-like growth factor (IGF) signaling system holds a central position in regulating growth and metabolism in vertebrates. As critical components of this system, the IGF-binding proteins (IGFBPs) play important roles in regulating the biological activities of IGFs. Recently, the single IGF-binding domain protein (SIBD) was identified in invertebrates and its sequence was highly homologous with the N-terminal domain of IGFBP. In view of the possible role as counterparts of vertebrate IGFBPs, SIBDs have attracted the ever-increasing attention. This study reports the identification of a 1284bp SIBD gene (Sp-SIBD) from a member of commercially important family of Portunidae. The tissue distribution analysis showed that Sp-SIBD was mainly expressed in the nervous tissues and hepatopancreas. RNA in situ hybridization analysis showed that the positive signals were predominantly distributed in the secretory cells of the hepatopancreas. Subsequently, we examined the effects of various stresses, including hyperosmotic stress, hyperthermia, activated stress and fasting, on glucose levels in the hemolymph and Sp-SIBD expressions in the hepatopancreas. Interestingly, we found that Sp-SIBD expression was strongly up-regulated in response to these catabolic circumstances. Given the previous findings of insulin-like peptides (ILPs) in invertebrates, we speculate that invertebrate ILPs and SIBDs promise to serve as a pair of counterparts of IGFs and IGFBPs from vertebrate species respectively. In this context, the combined results suggested, by analogy with IGFBP 1 from vertebrates, for the first time that SIBD might play a key physiological role by sequestering ILPs to inhibit energy-expensive growth until conditions are more favorable.


Childhood psychological function and obesity risk across the lifecourse: findings from the 1970 British Cohort Study.
Psychological comorbidities of obesity are well recognised. However, the role of childhood psychological problems in the aetiology of later obesity has been little studied. Secondary analyses of a national birth cohort (1970 British Cohort Study). Logistic regression models to predict obesity risk at 26, 30 and 34 years related to hypothesised predictors: maternal and teacher reported child psychological function at 5 and 10 years (general behavioural, conduct, emotional or attentional/hyperactivity problems) and maternal psychological function. General behavioural problems at age 5 years increased the risk of obesity at 30 and 34 years. Persistence of these problems through childhood further increased the obesity risk. Inattention/hyperactivity at 10 years similarly increased risk of obesity at 30 years (adjusted odds ratios (AOR) 1.3). Chronic conduct problems at 5 and 10 years also increased the obesity risk at 30 years (AOR 1.6 (1.1, 2.4) P<0.05). Childhood emotional disorders and maternal psychological function were not associated with adult obesity. Children with early and persistent behavioural problems, particularly conduct problems, hyperactivity and inattention in early and mid-childhood are at an increased risk of obesity in adult life. The promotion of child and adolescent mental health and well-being may form an important part of future obesity prevention strategies. The promotion of healthy eating and activity should form part of secondary prevention and management strategies for children with disruptive behaviour disorders.


Asymmetric dimethylarginine accumulation under hyperglycemia facilitates β-cell apoptosis via inhibiting nitric oxide production.
Low concentrations of nitric oxide (NO) produced by constitutive NO synthase (cNOS) has been shown to suppress apoptosis in pancreatic β-cells. In the present study, the influence of asymmetric dimethylarginine (ADMA), the major endogenous inhibitor of NOS, on the apoptosis-suppressive effect of NO was investigated. The expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), an ADMA-metabolizing enzyme, in INS-1 β-cells and in mouse pancreatic islets was drastically reduced by in vitro exposure to high-concentration glucose (20 mM) and by in vivo treatment of mice with the insulin receptor blocker S661, which resulted in hyperglycemia, respectively. In line with this, a higher ADMA level was observed in INS-1 cells exposed to 20 mM glucose. The treatment of INS-1 cells with ADMA, similarly to with the NOS inhibitor NG-nitro-L-arginine methyl ester, significantly facilitated 20 mM glucose-induced increase in cleaved caspase-3 protein expression. Furthermore, increased protein expression of cleaved caspase-3 and CHOP was observed in INS-1 cells with knockdown of DDAH2. These results suggest that ADMA accumulation through a decrease in DDAH2 expression in β-cells, which is induced under hyperglycemic conditions, facilitates β-cell apoptosis through suppression of cNOS-mediated NO production.


Smooth-pursuit eye-movement dysfunction and motor control in schizophrenia: a follow-up study.
Smooth-pursuit eye-tracking data of 63 schizophrenic patients and 52 normal controls are presented and compared with data collected on the same subjects 2 years earlier. Despite considerable clinical stabilization of the patients the overall eye-tracking performance did not improve. Intrasubject stability over 2 years was moderate. Eye-tracking impairment was significantly correlated with number of psychomotor soft signs and with number of errors in an antisaccade task. The correlations indicate that impairment of smooth-pursuit eye movements is likely to be a consequence of deficient motor control.


Investigation of the occurrence of a contraceptive tetrapeptide in hamster embryos.
The synthetic tetrapeptide H-Thr-Pro-Lys-OH, the extract of two-cell hamster embryos, and the oviductal contents devoid of embryos failed to show any in vivo antifertility activity. In addition, the tetrapeptide was not found in the biologic preparations of embryo extract and remaining oviductal contents. These findings are not in agreement with those of previous reports.


Usefulness of resistant gene markers for predicting treatment outcome on second-line anti-tuberculosis drugs.
Mutations in rrs [nucleotide (nt) 1401], gyrA gene (codons 90, 91 or 94), tlyA, ethA and thyA genes of Mycobacterium tuberculosis (MTB) were evaluated for their usefulness in predicting treatment outcome of kanamycin (KM), capreomycin (CPM), ofloxacin (OFX), ethionamide (ETH) and para-aminosalicylic acid (PAS). DNA sequence analyses of these genes were performed against 188 MTB isolates obtained from patients put on second-line anti-TB drugs (SLDs) with well-documented clinical history and treatment outcome. Mutations in rrs and gyrA have 100% positive predictive value (PPV) in predicting treatment failure for KM and OFX, while 88·9 and 80% were obtained, respectively, when tlyA and rrs mutations were considered in CPM. For ETH and PAS, the PPV of using ethA and thyA mutations to predict treatment failure was 82·5 and 89·3%, respectively. Our study demonstrated high specificities of gene mutations in predicting poor treatment outcome; however, further technical advancement is required to make the molecular detection of resistances to other SLDs feasible in clinical laboratories. This is the first study to correlate different polymorphisms of major SLD resistance gene markers with predicted treatment outcome, using an international set of well-documented clinical MTB strains.


Influence of ionic environment on intestinal oxygen consumption.
The oxygen consumption of rat small intestine in vitro is influenced by the anions, chloride and bicarbonate, as well as by sodium.


Epitope mapping and characterization of monoclonal antibodies to human protein C.
Six monoclonal antibodies specific to human protein C were characterized. Epitopes of these antibodies were determined on isolated proteolytic peptides of protein C by immunological methods. Three antibodies bound light chain of protein C: PC01 bound the gamma-carboxyglutamic acid domain calcium-dependently, while PC02 and PC08 bound the first epidermal growth factor-like domain in calcium-dependent and independent manners, respectively. The other three antibodies bound the heavy chain of protein C: PC13 bound activation peptide, PC04 recognized the activation site and PC09 bound the region close to a disulfide bond connecting light and heavy chains. Activation of protein C with thrombin-thrombomodulin complex was inhibited strongly by PC04 and moderately by PC08, PC09 and PC13. PC04 and PC13 may directly block the activation site. On the other hand, epitopes of PC08 and PC09 may be involved in interaction between protein C and thrombin-thrombomodulin complex, or locate close to activation site on the tertiary structure of protein C. Anticlotting activity of protein C was inhibited strongly by PC01 and moderately by PC02, PC08 and PC09, while amidolytic activity was inhibited only by PC09. The epitopes described here may constitute part of protein-C-specific sites, which are important for the function of protein C.


Oxygen-induced retinopathy in the newborn rat: a scoring system for the evaluation of retinal vascular changes. Scoring system for OIR in the rat.
The authors describe a scoring system they have developed for evaluating damage produced in the retinal vascular network of the newborn rat by exposure to oxygen. India ink-injected retinal flat mounts are used. The scoring system provides for division of the retina into three concentric zones with the optic disk as a center point. Each retinal quadrant is then examined for the presence of the following lesions of progressive severity: vaso-obliteration of the capillary network, loss of the periarteriolar capillary-free zone, newly formed capillary tufts. When more than one type of lesion is present in a quadrant, only the most severe lesion is considered. The numerical score corresponding to that lesion is then multiplied by the factor corresponding to the concentric zone in which the lesion lies to give the quadrant score. The total retinal score is represented by the sum of the four quadrant scores. This type of system, if adopted by other investigators, can facilitate precise and systematic description of the results of different experimental protocols.


Acceptance and attitude of Lebanese lawyers and medical students toward surrogate pregnancy: a cross-sectional study.
Little is known about the acceptance of specific populations of decision makers in Lebanon regarding surrogacy. This study aimed to explore the acceptance and attitude of Lebanese Lawyers and Medical Students regarding surrogacy. In total 248 medical students and 204 lawyers completed a questionnaire to assess socio-demographic data, attitude toward surrogacy, and three different clinical scenarios to assess patterns of thinking. Finally, we validated a scale to assess the acceptance of surrogacy in these two populations. Concerning medical students, 54.8% reported they were supportive of surrogacy, 35.1% were neutral and 10.1% were against. For lawyers, 52.9% were supportive, 25% were neutral and 22.1% were against. Lawyers were more likely to be against surrogacy (p = 0.001). After conducting a multivariate analysis on the whole studied population to find predictors of acceptance of surrogacy, the best predictors were being single (OR 0.415; 95% CI 0.228, 0.753; p < 0.01), a supportive reported attitude regarding surrogacy (OR 5.464; 95% CI 3.65, 8.13; p < 0.001) and believing that surrogacy is a solution worth discussing in Lebanon (OR 4.186; 95% CI 1.709, 10.256; p < 0.01). Concerning the clinical scenarios, they showed that lawyers were more likely to oppose abortion regardless of the reason (p < 0.01). Also, in a case of gestational surrogacy, lawyers were more likely to give the right to the gestational carrier to keep the baby compared to medical students (p < 0.001). In conclusion, this study shows that only a minority of medical students and lawyers in Lebanon oppose surrogate pregnancy which warrants exploration of the perspective of other populations of decision makers in Lebanon to better guide legislations.


The lipoidal permeability barriers of the skin and alimentary tract.
The major routes of administration of drugs to humans involve transport either through the intestinal wall or through the skin. Both these barriers are nonpolar in nature and are subserved by membrane lipids. The lipid composition of the brush border of the intestinal wall is unusual, possessing unusually large quantities of glycosylceramide. The lipid composition of the stratum corneum of the skin is also unusual, possessing large quantities of ceramides and free fatty acids. These atypical membrane components are generally more ordered than the other common membrane lipids at body temperature and, thus, are suited for involvement in formation of barriers between the organism and its environment.


Rapid identification of mycobacteria by the Gen-Probe Accuprobe system.
Chemiluminescent acridinium ester-labelled (AE)-DNA probes (Gen-Probe, Inc., San Diego, Calif.) for the identification of Mycobacterium tuberculosis complex (MTBC) and the M. avium-M. intracellulare complex (MAC) were evaluated using 184 mycobacterial isolates cultured in BACTEC 12B vials (Becton Dickinson and Co., Towson, Md.). A 1.5 mL aliquot from BACTEC 12B vials containing acid-fast bacilli and a Growth Index of > 200 was concentrated 15-fold using a centrifugation step prior to performing the test procedure. When 184 mycobacterial isolates were tested (42MTBC/142 nontuberculous mycobacteria) using the AE-MTBC probe, there was 100% sensitivity and specificity when compared with conventional identification procedures. Criteria for using the AE-MAC probe were defined to optimize results whilst minimizing laboratory costs. Ninety-one (64%) of AE-MTBC probe negative isolates failed to meet selection criteria and were not tested. When 51 (36%) of the AE-MTBC-probe negative mycobacterial isolates were tested, the AE-MAC probe was found to be 88% sensitive and 100% specific. The non-isotopic Gen-Probe test is a rapid and practical alternative to current procedures for differentiation of mycobacteria.


Contrast computed tomography in the diagnosis of acute cholecystitis.
Computed tomography (CT) has the ability to detect small variations in tissue density. Meglumine diatrizoate was given intravenously to four patients with clinical acute cholecystitis as part of the CT scanning procedure. The enhancement of the thick gallbladder wall, together with an enlarged gallbladder and the presence of stones, confirmed the diagnosis of acute cholecystitis. Our present experience indicates that, after contrast medium administration, CT has a distinct place in the assessment of acute inflammation of the gallbladder.


Cytokinesis.
The actomyosin contractile-ring mechanism remains the paradigm for cytokinesis after 20 years of experimental testing. Recent evidence suggests that Ca2+ triggers the contraction and that cell-cycle kinases regulate the timing of cytokinesis. New work is required to identify the signals from the mitotic spindle that specify the position of the furrow.


Enzyme replacement in neuronal storage disorders in the pediatric population.
In the past 15 years, for select lysosomal storage diseases, there has been a shift from symptom management to disease modification in terms of treatment strategy, mainly related to use of enzyme replacement therapy (ERT). Yet the application of ERT is for very few diseases, and while beneficial, ERT does not represent a cure. For some disorders, the advent of ERT has made a dramatic impact, while for others, benefits have been much more modest. Understanding of the long-term effects as well as the appropriate time for initiation of ERT is under exploration in a number of diseases, while the feasibility of ERT is still being established for others. No definite effects of ERT on central nervous system manifestations of lysosomal storage diseases have been observed for any disease to date. New strategies, including intrathecal enzyme replacement, gene therapy and substrate reduction therapy are being developed in animal models and clinical trials, which hopefully will begin a new era of nervous system disease modification in neuronal storage disorders.


Age-dependent changes in 24-hour rhythms of thymic and circulating growth hormone and adrenocorticotropin in rats injected with Freund's adjuvant.
To analyze the 24-hour changes in thymic and serum concentration of growth hormone (GH) and adrenocorticotropin (ACTH) and their correlation with thymic concentrations of glutamate, aspartate, taurine and GABA in young and old rats during the acute phase of adjuvant's arthritis. Young (50-day-old) and old (18-month-old) rats were injected subcutaneously with Freund's adjuvant or its vehicle (paraffin oil containing 15% mannide monooleate). Eighteen days later, they were killed at six different time intervals throughout a 24-hour cycle. Serum and thymic levels of GH and ACTH were measured by radioimmunoassay. Thymic amino acid concentration was measured by HPLC. A quantitative assessment of arthritis was made in an independent group of rats by plethysmography. Old rats injected with Freund's adjuvant exhibited fewer clinical signs of inflammation than young rats. Significant 24-hour changes in thymic and serum GH occurred, except for serum GH in adjuvant's vehicle-treated old rats. Aging augmented thymic GH and decreased serum GH. Immunization with Freund's adjuvant did not modify GH concentration. Thymic and serum concentration of GH correlated negatively. Thymic ACTH varied significantly over 24 h with maxima during the dark phase, except in Freund's adjuvant-treated young rats. Maximal serum ACTH levels occurred in the late afternoon except in Freund's adjuvant-treated old rats which showed maxima at night. Immunization with Freund's adjuvant augmented thymic and circulating concentrations of ACTH. Thymic and serum concentration of ACTH correlated positively. Thymic concentration of glutamate, aspartate and taurine decreased in aged rats and correlated significantly with thymic ACTH. The results support the existence of a thymic compartment of GH and ACTH that may be independently regulated.


Early Post-transplant Lymphoproliferative Disease in the Donor Ureter Without Systemic Involvement: A Case Report.
Post-transplant lymphoproliferative disease is a serious complication of renal transplantation. Major risk factors include Epstein-Barr virus (EBV) seronegativity and induction immunosuppression with lymphocyte-depleting agents. We present a case of a 50-year year-old woman with very early onset PTLD confined to the donor ureter. Phenotypic studies on the tumor material reveal that the lymphoma was most likely of donor origin. A complete staging workup including the kidney allograft was negative for any other sites of involvement. This case, which had a fatal outcome, emphasizes the risk of renal transplantation in BV-negative individuals when given induction with lymphocyte-depleting drugs.


Learning curve for laparoscopic ventral hernia repair.
To test if there was any difference in the indications and early outcomes of laparoscopic ventral hernia repair (LVHR) during a 36-month period at a single institution. From August 1999 to August 2002, 64 consecutive, unselected patients underwent attempted LVHR. The patients were retrospectively divided into two groups: group 1 included the first 32 patients, and group 2 included the second 32 patients. Data regarding patient demographics, results, and postoperative follow-up were compared between the groups. Demographic characteristics, types of hernia, preoperative records, and hernia defects were well matched between the groups. Four patients in group 1 required conversion to laparotomy for bowel injuries, whereas no conversion was required in group 2 (12% vs 0%, P = 0.11 [NS]). The operative times and complication rates were similar, but bowel injuries were significantly more common in group 1 (19% vs 0%, P = 0.02), including the patients who were converted. The analgesic requirement was small and the hospital stay short in both groups; the differences were not significant. Three recurrences were noted in group 1 and none were noted in group 2, although follow-up was not comparable in the second group. A learning curve is needed to decrease conversions and bowel injuries during LVHR. The improved experience could permit the treatment of larger defects laparoscopically.


Primary bacterial intercostal pyomyositis diagnosis: A case report.
Pyomyositis is a microbial infection of the muscles and contributes to local abscess formation. Staphylococcus aureus frequently causes pyomyositis; however, transient bacteremia hinders positive blood cultures and needle aspiration does not yield pus, especially at the early disease stage. Therefore, identifying the pathogen is challenging, even if bacterial pyomyositis is suspected. Herein, we report a case of primary pyomyositis in an immunocompetent individual, with the identification of S aureus by repeated blood cultures. A 21-year-old healthy man presented with fever and pain from the left chest to the shoulder during motion. Physical examination revealed tenderness in the left chest wall that was focused on the subclavicular area. Ultrasonography showed soft tissue thickening around the intercostal muscles, and magnetic resonance imaging with short-tau inversion recovery showed hyperintensity at the same site. Oral nonsteroidal anti-inflammatory drugs for suspected virus-induced epidemic myalgia did not improve the patient's symptoms. Repeated blood cultures on days 0 and 8 were sterile. In contrast, inflammation of the soft tissue around the intercostal muscle was extended on ultrasonography. The blood culture on day 15 was positive, revealing methicillin-susceptible S aureus JARB-OU2579 isolates, and the patient was treated with intravenous cefazolin. Computed tomography-guided needle aspiration from the soft tissue around the intercostal muscle without abscess formation was performed on day 17, and the culture revealed the same clone of S aureus. The patient was diagnosed with S aureus-induced primary intercostal pyomyositis and was successfully treated with intravenous cefazolin for 2 weeks followed by oral cephalexin for 6 weeks. The pyomyositis-causing pathogen can be identified by repeated blood cultures even when pyomyositis is non-purulent but suspected based on physical examination, ultrasonography, and magnetic resonance imaging findings.


Cellular building unit integrated with microstrand-shaped bacterial cellulose.
In bottom-up tissue engineering, a method to integrate a pathway of nutrition and oxygen into the resulting macroscopic tissue has been highly desired, but yet to be established. This paper presents a cellular building unit made from microstrand-shaped bacterial cellulose (BC microstrand) covered with mammalian cells. The BC microstrands are fabricated by encapsulating Acetobacter xylinum with a calcium alginate hydrogel microtube using a double co-axial microfluidic device. The mechanical strength and porous property of the BC microstrands can be regulated by changing the initial density of the bacteria. By folding or reeling the building unit, we demonstrated the multiple shapes of millimeter-scale cellular constructs such as coiled and ball-of-yarn-shaped structures. Histological analysis of the cellular constructs indicated that the BC microstrand served as a pathway of nutrition and oxygen to feed the cells in the central region. These findings suggest that our approach facilitates creating functional macroscopic tissue used in various fields such as drug screening, wound healing, and plastic surgery.


A biosensor based on graphite epoxy composite electrode for aspartame and ethanol detection.
A gelatin membrane with carboxyl esterase and alcohol oxidase was subsequently integrated onto the surface of a graphite epoxy composite electrode (GECE). The developed biosensors showed linearity in the range of 2.5-400 microM for aspartame and 2.5-25 microM for ethanol with response times of 170 and 70s for each analyte, respectively. The resulting bienzyme biosensor was used for aspartame detection in diet coke samples and ethanol detection in beer and wine samples. From the obtained results, it can be concluded that the developed biosensor is a selective, practical and economic tool for aspartame and ethanol detection in real samples.


IL-17A Has Some Nerve!
Sensory neurons are important in controlling cutaneous inflammation, but the role of neurons in host antimicrobial defense was relatively unknown. Kaplan and colleagues now demonstrate that nociceptive fibers within the dermis play a crucial role in antifungal defenses through their influence on dermal dendritic cells and induction of IL-17A.


Prevalence of depression, syndemic factors and their impact on viral suppression among female sex workers living with HIV in eThekwini, South Africa.
Over half of female sex workers (FSW) in South Africa are living with HIV and clinical depression has been frequently documented among FSW. Data characterizing structural determinants of depression and the role of syndemic theory, synergistically interacting disease states, on viral suppression among FSW in South Africa are limited. Between July 2018-March 2020, non-pregnant, cisgender women (≥ 18 years), reporting sex work as their primary income source, and diagnosed with HIV for ≥ 6 months were enrolled into the Siyaphambili trial in eThekwini, South Africa. Using baseline data, robust Poisson regression models were used to assess correlates of depression and associations between depression and syndemic factors on viral suppression. Of 1,384 participants, 459 (33%) screened positive for depression, defined as a score of ≥ 10 on the PHQ-9. Physical and sexual violence, drug use, alcohol use, anticipated stigma and internalized stigma were univariately associated with depression (all p's < 0.05) and included the multivariate model. In the multivariate regression, prevalence of depression was higher among participants experiencing sexual violence (PR = 1.47 95% CI:1.24,1.73), physical violence 5 times or more in < 6 months (PR = 1.38 95% CI:1.07, 1.80), using illicit drugs in the last month (PR = 1.23 95%:CI 1.04, 1.48), and reporting higher levels of internalized stigma (PR = 1.11, 95% CI:1.04,1.18). Depression in the absence of the Substance Abuse, Violence and AIDS SAVA syndemic factors was associated with increased prevalence of unsuppressed viral load (aPR 1.24; 95% CI:1.08,1.43), and the SAVA substance use and violence syndemic was associated with an increase in unsuppressed viral load among non-depressed FSW (aPR 1.13; 95% CI:1.01, 1.26). Compared to those experiencing neither factors, those jointly experiencing depression and the SAVA syndemics were at increased risk for unsuppressed viral load (aPR 1.15; 95% CI:1.02,1.28). Substance use, violence, and stigma were all associated with depression. Depression and syndemic factors (substance use + violence) were related to unsuppressed viral load; we did not observe higher unsuppressed viral load amongst those experiencing both depression and syndemic factors. Our findings point to the need to understand the unmet mental health needs of FSW living with HIV. Clinical Trial Number: NCT03500172.


Parkinsonian syndrome and central nervous system lymphoma involving the substantia nigra. A case report.
The clinical history and postmortem neuropathologic findings of a case of cerebral lymphoma revealed by a typical parkinsonian syndrome are reported. The clinical symptoms initially improved with dopa therapy. The tumor was classified as a diffuse, non-cleaved, large-cell lymphoma of B-cell origin producing monoclonal lambda light chains. The substantia nigra was infiltrated by the tumor and showed neuronal loss and extraneuronal pigment. The most striking histological feature was the presence of neuronophagic-like nodules composed of lymphomatous cells both in the locus niger and in the left thalamus. No tumoral mass effect and no histological stigmata of other etiologies of parkinsonian syndromes were observed. A hypothesis is that the neuronophagic-like nodules may reflect a neuronotoxic activity of the lymphoma and may be considered at the origin of parkinsonism.


A novel thiol oxidation-based mechanism for adriamycin-induced cell injury in human macrophages.
Adriamycin is a widely used antitumor antibiotic, but its use has been limited by its cytotoxicity in both cardiomyocytes and non-cardiac tissues. While adriamycin's ability to redox cycle via one-electron transfer reactions and generate ROS is thought to promote cardiotoxicity, the mechanisms involved in non-cardiac tissue injury are not clear. Here we show that prolonged exposure (48 h) of human monocyte-derived macrophages to adriamycin at concentrations as low as 1 microM promotes caspase-independent cell death. Treatment of cells with scavengers of superoxide and peroxyl radicals blocked adriamycin-induced oxidation of dichlorodihydrofluorescein (DCFH) but did not prevent macrophage injury. Macrophages treated with either adriamycin or the thiol oxidant diamide showed elevated levels of glutathione disulfide and increased protein-S-glutathionylation prior to cell injury, indicating that thiol oxidation is involved in adriamycin-induced macrophage death. Furthermore, inhibition of glutathione reductase (GR) with 1,3-bis[2-chloroethyl]-1-nitrosourea or transfection of macrophages with small inhibitory RNA (siRNA) directed against GR or glutaredoxin (Grx) potentiated adriamycin-induced macrophage injury. Thus, both GR and Grx appear to play a crucial role in protecting macrophages from adriamycin-induced cell injury. These findings suggest a new mechanism for adriamycin-induced tissue injury whereby thiol oxidation, rather than one-electron redox cycling and ROS generation, mediates adriamycin-induced cell damage.


Addressing hygiene needs of housing insecure populations: A qualitative analysis of Seattle and King County's mobile hygiene station intervention.
To evaluate the Seattle Public Utility mobile hygiene station program, a program deployed using public funds in response to the large-scale closures of public hygiene facilities due to COVID-19. We conduct a qualitative analysis using semi-structured interviews. We interviewed four Seattle Public Utility (SPU) and Public Health Seattle & King County (PHSKC) employees involved in the design, deployment, and management of the hygiene station intervention. Data were also collected from communications and reports released through SPU/PHSKC web sources. Our analysis revealed factors affecting the implementation of the hygiene program included the rental of hygiene trailers, community partnership to mediate between housed and housing insecure populations, funding source and cost-effectiveness, geographic location of the units, and maintenance of the units to continue population hygiene support. The SPU/PHSKC hygiene station was designed to support the housing insecure and homeless by compensating for the large-scale closures of public restrooms and showers. Several logistical and financing challenges need to be addressed to ensure the continuity of the program.


Immunohistochemical expression of CD117/KIT, HER2, and Erβ in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients.
Bladder carcinoma is an endemic problem in Egypt with schistosomiasis being an additional risk factor. Due to gender disparities, Erβ investigation and its role in modulating chemosensitivity are studied. CD117/KIT expression is also considered since the emergence of the targets of the tyrosine kinase inhibitor imatinib mesylate (Gleevec). HER2 is one of the established therapeutic targets in many cancers. We aimed to investigate CD117/KIT immunoexpression in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients and its relationship with HER2 and Erβ expressions, correlating it with pertinent variables that will help to provide better treatment options of possible combined targeted and hormonal therapy that might be effective against this aggressive malignancy. Sixty cases of bladder carcinoma were tested. Depending on the schistosomiasis association status of each case, two groups have been established with 30 cases each. CD117/KIT, HER2, and ERβ immunostaining were done and correlated with clinico- immuno-pathological parameters. CD117/KIT expression was seen in 71.7% of cases that correlated significantly with schistosomiasis (P = 0.01). In addition, a positive correlation was detected between schistosomiasis association and the percentage of immunostained cells and intensity score of CD117/KIT with P = 0.027, 0.01, respectively. 30% and 61.7% of cases were positively stained with HER2 and Erβ, respectively, with no significant relation with schistosomiasis. Due to the high expression, we found further clinical trials are needed to offer individualized targeted therapeutic options in urothelial tumors using anti-CD117/KIT, HER2, and ERβ other than limited traditional chemo- and nontargeted therapies.


A prospective, randomized, double-blinded placebo-controlled comparison of extended release oxybutynin versus phenazopyridine for the management of postoperative ureteral stent discomfort.
Ureteral stents commonly cause lower urinary tract and flank discomfort. We evaluated the use of extended release oxybutynin versus phenazopyridine versus placebo for the management of ureteral stent discomfort after ureteroscopy. Each of 60 patients who received a unilateral stent after ureteroscopy was given a blister pack containing 21 unmarked capsules of either extended release oxybutynin 10 mg, phenazopyridine 200 mg, or placebo in a prospective, randomized, and double-blinded fashion. Patients were instructed to take 1 capsule 3 times daily immediately after the procedure. Patients were given 50 tablets of oral narcotic to be taken as needed. Patients reported bothersome scores for flank pain, suprapubic pain, urinary frequency, urgency, dysuria, and hematuria on postoperative day 1, day 2, and the day of stent removal. Narcotic use was also recorded. Eight patients were excluded from the analysis for stent migration necessitating early removal (1), uncontrollable pain (1), failure to complete blister pack (4), and inability to contact for follow-up surveys (2). There was no difference in bothersome score among the groups for flank pain, suprapubic pain, urinary frequency, urgency, and dysuria. The phenazopyridine group reported less hematuria on postoperative day 1 when compared with placebo, which was statistically significant. The oxybutynin group required fewer narcotics, but this finding was not statistically significant. Although this study failed to show a significant difference in bothersome scores among the groups, the small sample size precludes definitive conclusion. Future studies pooling these data will determine the overall treatment effect and the optimal management of ureteral stent morbidity.


[Morbidity and mortality of military personnel at the Abidjan Military Hospital (AMH) in Côte d'Ivoire].
The purpose of this retrospective study was to document morbi-mortality in soldiers at the Abidjan Military Hospital (AMH). The medical files of soldiers treated at Abidjan Military Hospital from January 1 to December 31, 2004 were reviewed. During the study period, a total of 155 soldiers were treated for 259 pathologies including 208 infectious diseases (80.5%). The most common diseases were HIV infection (85 cases; 42%), pneumopathy (40 cases; 19%), cerebral toxoplasmosis (22 cases; 10.5%), malaria (18 cases; 9%) and tuberculosis (11 cases; 5%). Direct causes of death were cerebral toxoplasmosis (32%), pneumopathy (28%), tuberculosis (16%) and severe malaria (12%). The prevalence of HIV infection in soldiers who died was 76%. Morbi-mortality in military personnel at the AMH is due mainly to HIV infection and related complications. Specific prevention measures should be implemented for an effective control of this epidemic.


A portable gas chromatograph with simultaneous detection by mass spectrometry and electroantennography for the highly sensitive in situ measurement of volatiles.
Mating disruption is a sustainable method for the control of insect pests, involving the release of synthetic sex pheromones that disrupt the olfactory localization of females by males. However, the development and refinement of this strategy is hampered because current instruments lack the sensitivity to detect volatile organic chemicals in the field, and portable electroantennograms produce non-comparable relative units and distorted results in the presence of plant volatiles. To address the demand for more sensitive instruments that are suitable for the rapid in situ detection of airborne pheromones, we have developed a portable, automated needle trap device connected to a gas chromatograph, mass spectrometer, and electroantennographic detector (NTD-GC-MS/EAD) suitable for field applications. We tested the instrument by measuring the concentration of the sex pheromone (E,Z)-7,9-dodecadienyl acetate, which is used to disrupt the mating of the European grapevine moth Lobesia botrana (Lepidoptera: Tortricidae). Our data confirm that the instrument generates highly reproducible results and is highly sensitive, with a detection threshold of 3 ng/m(3) (E,Z)-7,9-dodecadienyl acetate in outside air.


Microsomal ethanol oxidation: activity in vitro and in vivo.
Studies by several investigators have confirmed that the microsomal fraction of mammalian liver oxidizes ethanol to acetaldehyde in a reaction that requires NADPH and oxygen. Efforts to identify the enzymes involved have produced conflicting opinions of the reaction mechanism, however. Initially, the microsomal mixed function oxidase system was assumed to be capable of oxidizing ethanol in a mechanism that did not involve either alcohol dehydrogenase or catalase. Later evidence suggested that the oxidative enzyme was, in fact, catalase, a contaminant of microsomal preparations and that the mixed function oxidase system merely furnished hydrogen peroxide to the reaction. Much current research supports the latter interpretation. Other workers provide evidence that favors a system in which catalase does not participate. Attempts to define the reaction process have involved studies with catalase inhibitors, kinetic studies of the different reaction systems, and physical separation of catalase from the microsomal components. Questions of the mechanism of microsomal ethanol oxidation may prove to be purely academic, however. Efforts to prove that the system has significant in vivo activity generally have not been successful.


Rheumatoid nodules. A lightmicroscopical study with special reference to fibrin and fibronectin.
The presence and localization of fibrin and fibronectin in rheumatoid nodules were studied using an indirect immunoperoxidase technique on tissue specimens fixed in formaldehyde, embedded in paraffin and pretreated with pepsin and testicular hyaluronidase. Three zones characteristic for rheumatoid nodules was recognized. Central area with necrosis, containing at least in part fibrinogen-antigenic material and fibronectin especially in the peripheral part of the necrotic area. Around the necrosis a layer of mesenchymal cells in a palisade arrangement was found. Especially in the external part of this layer fibronectin was demonstrated around and between the cells, where fibrin was absent. Peripherally, a zone of non-specific granulation tissue containing moderate amount of fibronectin decreasing towards the surround mature connective tissue, was seen. In the border of the cellular layer vessels were found in variable amount. In some of the vessels vasculitis was demonstrated with the presence of inflammatory cell infiltration, fibrin deposition and occasionally thrombosis. The pathogenesis of the inflammatory reaction in rheumatoid nodules is discussed.


Challenge in the management of infective endocarditis with multiple valvular involvement.
We describe the case of a 41-year-old man with congenital heart disease and infective endocarditis (IE), who presented multiple vegetations attached to the pulmonary, mitral, and aortic valves. Three valve replacements were performed, but the patient developed an abscess at the mitral-aortic intervalvular fibrosa and died due to sepsis. We briefly discuss the indications for surgery in IE, emphasizing its role in the treatment of uncontrolled infection.


Developmentally divergent effects of Rho-kinase inhibition on cocaine- and BDNF-induced behavioral plasticity.
Prefrontal cortical dendritic spine remodeling during adolescence may open a window of vulnerability to pathological stimuli that impact long-term behavioral outcomes, but causal mechanisms remain unclear. We administered the Rho-kinase inhibitor HA-1077 during three adolescent periods in mice to destabilize dendritic spines. In adulthood, cocaine-induced locomotor activity was exaggerated. By contrast, when administered in adulthood, HA-1077 had no psychomotor consequences and normalized food-reinforced instrumental responding after orbitofrontal-selective knockdown of Brain-derived neurotrophic factor, a potential factor in addiction. Thus, early-life Rho-kinase inhibition confers cocaine vulnerability, but may actually protect against pathological reward-seeking - particularly in cases of diminished neurotrophic support - in adulthood.


Intraoperative conversion from endoscopic to microscopic approach for the management of sellar pathology: incidence and rationale in a contemporary series.
The endoscopic transsphenoidal approach has become widely used for pituitary and extended skull base operations. Intraoperative conversion to a microscopic approach may be an important option in selected cases. We aim to characterize the operative situations in which such conversion occurred and facilitated the procedure. From April 2008 through August 2009, 148 planned endoscopic transsphenoidal approaches were performed. All cases were retrospectively reviewed to identify those patients converted to a microscopic approach. Clinical and operative characteristics, reasons for conversion, and patient outcomes were reviewed. Of the 148 endoscopic cases, conversion was undertaken in 27 (18%). Ten patients (37%) had undergone previous transsphenoidal surgery. Reasons for conversion in nonreoperation cases were atypical nasal anatomy (6 patients), acromegaly with distorted anatomy (5 patients), desire for binocular vision (3 patients), complex sphenoid sinus anatomy and difficulty visualizing sella/midline (2 patients), and obstructive mucosal bleeding (1 patient). Of the 10 reoperation procedures, conversions occurred in 3 patients with Cushing's disease and 2 with acromegaly. The primary reasons for conversion in reoperations were scarring with loss of anatomic landmarks (4 patients), mucosal bleeding (2 patients), acromegaly with distorted anatomy (2 patients), technical problem with visualization (1 patient), and desire for binocular surgery (1 patient). Although endoscopic transsphenoidal surgery provides superior visualization in most patients, conversion to a microscopic or endoscopic-assisted approach may provide essential visualization in selected patients. This may be especially true in patients undergoing reoperation and patients with acromegaly or Cushing's disease. Trainees learning the endoscopic transsphenoidal approach should become familiar with the benefits and limitations of the various transsphenoidal approaches.


Targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced by rapamycin in vitro and further improved by hyaluronan in vivo.
Gallbladder carcinoma (GBC) is highly lethal, and effective treatment will require synergistic anti-tumor management. The study is aimed at investigating the oncolytic value of myxoma virus (MYXV) infection against GBC and optimizing MYXV oncolytic efficiency. We examined the permissiveness of GBC cell lines to MYXV infection and compared the effects of MYXV on cell viability among GBC and control permissive glioma cells in vitro and in vivo after MYXV + rapamycin (Rap) treatment, which is known to enhance cell permissiveness to MYXV by upregulating p-Akt levels. We also assessed MYXV + hyaluronan (HA) therapy efficiency by examinating Akt activation status, MMP-9 expression, cell viability, and collagen distribution. We further compared hydraulic conductivity, tumor area, and survival of tumor-bearing mice between the MYXV + Rap and MYXV + HA therapeutic regimens. MYXV + Rap treatment could considerably increase the oncolytic ability of MYXV against GBC cell lines in vitro but not against GBC xenografts in vivo. We found higher levels of collagen IV in GBC tumors than in glioma tumors. Diffusion analysis demonstrated that collagen IV could physically hinder MYXV intratumoral distribution. HA-CD44 interplay was found to activate the Akt signaling pathway, which increases oncolytic rates. HA was also found to enhance the MMP-9 secretion, which contributes to collagen IV degradation. Unlike MYXV + Rap, MYXV + HA therapy significantly enhanced the anti-tumor effects of MYXV in vivo and prolonged survival of GBC tumor-bearing mice. HA may optimize the oncolytic effects of MYXV on GBC via the HA-CD44 interaction which can promote viral infection and diffusion.


Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India.
Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.


Recurrence of cutaneous squamous cell carcinoma at remote limb donor site.
Squamous cell skin cancer (SCC) is the second most common skin malignancy. The risk of metastasis is usually low and generally occurs through lymphatic spread. Surgical excision is the gold standard for treatment and subsequent reconstruction often involves a skin graft from a distant donor site. Our case highlights an incident in which metastatic spread of an SCC occurred in a distant skin graft donor site on the limb following free flap harvest.


[Experimental study on the activity of Staphyloccocal enterotoxin A liposome for inducing cytotoxicity of TIL from human hepatocellular carcinoma against tumor cells].
To investigate the activity of Staphyloccocal enterotoxin A liposome (L-SEA) for inducing cytotoxicity of tumor infiltrating lymphocytes (TIL) against tumor cells. TIL were isolated from the tumor tissues of five hepatocellular carcinoma patients. L-SEA, SEA and IL-2 were tested in vitro for their activity levels in stimulating TIL proliferation. The TNF-alpha and IFN-gamma secretion and cytotoxicity of TIL against HepG-2 liver cancer cells were estimated by ELISA and MTT, respectively. Both L-SEA and SEA significantly stimulated the proliferation of TIL. The cytokine secretion of L-SEA group was significantly higher than that of IL-2 group (P < 0.05). There was no significantly statistical difference in cytokine secretion between L-SEA group and SEA group (P > 0.05) except that IFN-gamma secretion of L-SEA group was lower than that of SEA group at day 4 (P < 0.05). Both L-SEA and SEA had potent ability to induce TIL cytotoxicity against HepG-2 cells. And no significant difference was observed between these two groups (P > 0.05). These results suggest that L-SEA is as efficient as SEA in activating TIL.


Moral distress in midwifery practice: A Delphi study.
Moral distress is a psychological concept that describes the harm associated with actions or inactions that oppose an individuals' moral beliefs. Moral distress is linked to moral compromise in the workplace that may negatively impact mental wellbeing. Current tools available to assess moral distress are not specific for the Australian health care system or midwifery practice. The aim of this study was to develop a list of situational and outcome statements associated with moral compromise and levels of moral distress in midwifery to inform the development of a tool to measure levels of moral distress in midwives. This e-Delphi study was the third stage of a sequential exploratory mixed-methods study. Using an online strategy, three iterative rounds of e-Delphi were collected and analysed for consensus on situations leading to moral distress and the associated psychological outcomes. Twenty participants contributed across the three rounds. Consensus was met in 40 morally compromising situation statements. The highest level of consensus related to excessive workloads and the associated negative impact of this on women and families. Consensus on outcomes following exposure to morally distressing situations led to the development of a continuum scale from moral frustration to moral injury. This is the first study to use a consensus method to establish different levels of moral compromise, frustration, distress, and injury in midwifery practice. The findings of this study contribute to a growing body of literature that supports the concept of moral distress occurring across a continuum.


Intraoperative angiography with indocyanine green injection for precise localization and resection of small bowel bleeding.
Bleeding in the small bowel rarely occurs, and its treatment is challenging. Surgery is sometimes required in unstable patients; however, intraoperative identification of the bleeding site is extremely difficult. Many methods have been reported, but no standard strategy has been established yet. Here, we aimed to assess the safety and feasibility of intraoperative angiography with indocyanine green staining to accurately identify small bowel bleeding sites. This retrospective study analyzed contrast-enhanced computed tomography images of patients (n = 8) with small bowel extravasation who underwent surgery. If extravasation or other vessel abnormalities that were potential bleeding sites were detected on intraoperative angiography, a microcatheter was placed as close as possible to the extravasation site. Laparotomy was carried out, and 3-5 mL indocyanine green was injected through the microcatheter. The green-stained segment of the small bowel was resected. Seven of the eight patients had positive angiographic findings and underwent bowel resection. The eighth patient had no abnormalities and hence did not undergo laparotomy. The rate of hemostatic success among the resected cases was 85.7% (six of seven cases). The resected specimens showed pathologic features in six of the seven patients (85.7%), all of whom achieved hemostasis. One patient had pneumonia and congestive heart failure that required longer hospital stay, but no mortality occurred. Intraoperative angiography with indocyanine green injection, followed by resection for massive small bowel bleeding is effective. This can be a therapeutic option for hemodynamically unstable patients.


Mast cell density, angiogenesis, blood clotting, and prognosis in women with advanced ovarian cancer.
To determine clinical or biological associations between mast cell density, blood clotting, angiogenesis, and survival of patients with advanced ovarian cancer. Tumor tissue sections were assessed for mast cell density by staining for mast cell tryptase, blood clotting by staining of thrombosed blood vessels, and angiogenesis by CD34 expression. Chi-square, Kaplan-Meier, and Cox proportional hazard statistical analyses were used. 44 women with stage III-IV ovarian cancers had tumor blocks available for immunohistochemical analysis. Higher mean vessel density (MVD) (>11 vessels/400x field) predicted for better survival than lower MVD (< or =11 vessels/400x field) (P = 0.004). Women whose tumors had low levels of peri-tumoral mast cell infiltration had a mean survival of 40.6 months compared to 50.6 months in those whose tumors had high levels (P = 0.47). Tumors with higher MVD and high peri-tumoral mast cell infiltration had a mean survival of 80.3 months compared to 37.8 months in those with low mast cell density or low MVD (P = 0.015). Patients with tumors showing a low degree of blood clotting had a mean survival of 45.5 compared to 45.1 months in those with tumors showing a high degree of blood clotting (P = 0.91). There was no significant association between angiogenesis and mast cell density (P = 0.123). In multivariate analysis, higher MVD remained as a significant prognostic factor for improved survival after adjusting for clotting and mast cell density. Our data suggest that peri-tumoral mast cell infiltration in tumors with high MVD predicts for improved survival in women with advanced epithelial ovarian cancer.


Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates.
To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11-13 weeks' gestation in the prediction of small-for-gestational age (SGA) neonates. Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls. In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4-93.4 ng/mL vs 94.9, IQR 56.7-131.2 ng/mL, p=0.002) and IGFBP-1 (58.2, IGR 39.8-84.9 ng/mL vs 81.4, IGR 57.3-105.5 ng/mL, p=0.002) but not IGFBP-3 (54.5, IGR 45.6-61.5 ng/mL vs 55.4, IGR 47.4-64.9 ng/mL, p=0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA. Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.


Enhanced degradation of 2,4-dichlorophenol by ultrasound in a new Fenton like system (Fe/EDTA) at ambient circumstance.
This study investigated the effect of ultrasound (US) enhancement on the degradation of 2,4-DCP in a new Fenton like system. An obviously synergistic effect was observed after introduction of US into the Fe/EDTA system. Good correspondences with pseudo-first-order kinetic were found in each reaction system. It was demonstrated that the degradation rate constant (kobs) of DCP in US/Fe/EDTA was 7 and 32 times higher than those in Fe/EDTA and US system alone. Simultaneously, lower first-order kobs was also obtained in the investigation of decomposition of EDTA. At 60 min reaction time, Removals of 81% TOC, complete DCP and 89% EDTA were achieved. Low molecular weight organic acids are identified as the main products, which contribute to the solution self-buffer at about pH 6.5 along with the reaction. In addition, the effect of initials condition, i.e., iron addition, EDTA dosage, DCP concentration and US input power as well as reaction temperature were studied and reaction activation energy (Ea) was also calculated.


Effectiveness of the soft-shell technique in patients with Fuchs' endothelial dystrophy.
To evaluate the protective ability of the soft-shell technique in patients with senile cataract and Fuchs' dystrophy having phacoemulsification with intraocular lens (IOL) implantation. Department of Ophthalmology, Railway Hospital, Katowice, Poland. Sixty-one eyes of 54 patients (37 women, 17 men) with clinically confirmed Fuchs' dystrophy and cataract had clear corneal phacoemulsification and implantation of an intracapsular posterior chamber IOL with sodium hyaluronate 1% (Healon) or chondroitin sulfate 4%-sodium hyaluronate 3% (Viscoat) in combination with sodium hyaluronate 1% (Provisc) in 1 package (DuoVisc). The central corneal thickness (CCT), measured with a Pocket Precision ultrasonic pachymeter (Quantel Medical, Inc.), was compared preoperatively and 1 day, 1 week, and 1 and 6 months postoperatively. The mean preoperative CCT was 549.5 microm +/- 29.3 (SD). The postoperative increase in CCT over preoperative pachymetry measurements remained statistically significant in both ophthalmic viscosurgical device groups throughout the entire follow-up, from the first day to the sixth month after surgery (P<.0001). The maximum increase in CCT in both groups was on the first postoperative day, and it was significantly higher in the Healon group. Six months postoperatively, patients in the Healon group had a significantly greater CCT increase (P = .008). The soft-shell technique effectively protected the compromised endothelium in patients with Fuchs' dystrophy, proving its advantages in eyes with moderately damaged endothelium.


Exploring the mechanism of lipid transfer during biosynthesis of the acidic lipopeptide antibiotic CDA.
The non-ribosomally synthesized lipodepsipeptide CDA belongs to the group of acidic lipopeptide antibiotics, whose members feature a fatty acid side chain that strongly affects their antimicrobial activity. This study elucidates the N-acylation of the N-terminal serine in the CDA peptide chain. This reaction is referred to as lipoinitiation and is shown to be catalyzed by the dissected starter C domain found at the N-terminus of Cda-PSI. The recombinantly produced C domain specifically interacts with 2,3-epoxyhexanoyl-S-ACP and catalyzes the transfer of the fatty acid moiety onto the amino group of PCP-bound serine with high selectivity for both carrier protein bound substrates at the donor and acceptor site.


A multicenter, cross-platform clinical validation study of cancer cytogenomic arrays.
Cytogenomic microarray analysis (CMA) offers high resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multiplatform, multicenter clinical validation project to compare the reliability and inter- and intralaboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms-from Affymetrix, Agilent, and Illumina. Each microarray platform was employed at two independent test sites. The results were compared in a blinded manner with current standard methods, including karyotype, FISH, or morphology. Twenty-nine chronic lymphocytic leukemia blood, 34 myelodysplastic syndrome bone marrow, and 30 fresh frozen renal epithelial tumor samples were assessed by all six laboratories. Thirty formalin fixed paraffin embedded renal tumor samples were analyzed at the Affymetrix and Agilent test sites only. All study samples were initial diagnostic samples. Array data were analyzed at each participating site and were submitted to caArray for central analysis. Laboratory interpretive results were submitted to the central analysis team for comparison with the standard-of-care assays and for calculation of intraplatform reproducibility and cross-platform concordance. The results demonstrated that the three microarray platforms 1) detect clinically actionable genomic changes in cancer compatible to standard-of-care methods; 2) further define cytogenetic aberrations; 3) identify submicroscopic alterations and loss of heterozygosity (LOH); and 4) yield consistent results within and between laboratories. Based on this study, the CGC concludes that CMA is a sensitive and reliable technique for copy number and LOH assessment that may be used for clinical oncology genomic analysis.


Fractions and transformation of organic phosphorus in sediments from a eutrophic lake in China.
Several organic phosphorus compounds (Po) in sediment from a representative eutrophic lake were surveyed using a sequential fractionation procedure, which included microbial biomass phosphorus (Biomass-P), fulvic acid phosphorus (FA-P), humic acid phosphorus (HU-P), and residual phosphorus (Res-P). In addition, several organic compounds including orthophosphate monoesters, orthophosphate diesters, and pyrophosphate were simultaneously measured using 31P nuclear magnetic resonance (31P NMR). Results showed that Po contributed over 50% of total phosphorus (TP), and the average concentration of Po species generally decreased from Res-P > FA-P > HU-P > Biomass-P. Additionally, the relative proportions of phosphorus compounds in the sediment followed the decreasing order of orthophosphate monoesters > orthophosphate diesters > pyrophosphate. In general, Po was the dominant phosphorus species. Residual P was not a single species but comprised of a group of species, and tended to be stable. Although orthophosphate monoesters had the highest concentrations and ratios in Po, orthophosphate diesters displayed a more distinct remineralization trend. Principal component analysis (PCA) coupled with correlation analysis suggested that a greater amount of orthophosphate diesters resided in Res-P, than HU-P or FA-P.


Magnitude and determinants of adverse treatment outcomes among tuberculosis patients registered under Revised National Tuberculosis Control Program in a Tuberculosis Unit, Wardha, Central India: A record-based cohort study.
Deaths, defaults, relapses, and treatment failures have made the control of TB difficult across the globe. This study is a record-based follow-up of a cohort of patients registered under Revised National Tuberculosis Control Program in the year 2014 in Wardha Tuberculosis Unit, India. Data was collected from the records available at the District Tuberculosis Office. Data of 510 patients was analyzed. The sputum conversion rate was 88%. The overall treatment success rate was 81.9%, and rates of any adverse outcome, deaths, defaults, failure, and shift to Category IV regimen were 32.60/100 person years at risk (PYAR), 16.88/100 PYAR, 11.12/100 PYAR, 3.45/100 PYAR, and 1.15/100 PYAR, respectively. The median times for the above outcomes were 81days, 110days, 66days, 118days, and 237days, respectively. The cumulative probability of occurrence at 6months of any adverse outcome, deaths, default, failure, and shift to Category IV regimen was 0.145, 0.056, 0.088, 0.002, and 0.004, respectively. On multivariate analysis, the determinant of any adverse outcome was age >45years, whereas extrapulmonary disease was protective. The hazard of defaulting was also significantly higher in male patients and those aged >45years. Appropriate interventions and program implementation to reduce the adverse treatment outcomes and interruptions will help in improving program performance.


Meta-Analysis of the Incidence, Prevalence, and Correlates of Atrial Fibrillation in Rheumatic Heart Disease.
To estimate the incidence, prevalence, and correlates of atrial fibrillation (AF) in a global population with rheumatic heart disease (RHD). Bibliographic databases were searched to identify all published studies providing data on AF in patients with RHD. Random-effects meta-analysis method was used to pool estimates. Eighty-three studies were included, reporting data from 75,637 participants with RHD in 42 countries. The global prevalence of AF in RHD was 32.8% (range: 4.3%-79.9%). It was higher in severe valvular disease (30.8% vs 20.7%, p = 0.009), in severe mitral valve disease compared to severe aortic disease (30.4% vs 6.3%, p = 0.038). The global cumulative incidence of AF in patients with RHD was 4.8%, 11.4%, 13.2%, and 30.8% at 1, 2, 5, and 10 years of follow-up, respectively. From comparison between patients with and without AF, AF was associated with increased age (mean difference [MD]: 9.5 years; 95% CI: 7.8-1.3), advanced heart failure (odds ratio [OR]: 4.4; 95% CI 2.1-9.3), tricuspid valve involvement (OR: 4.0; 95% CI: 3.0-5.3), history of thromboembolism (OR: 6.2; 95% CI: 3.4-11.4), highly sensitive C-reactive protein (MD: 5.5 mg/dL; 95% CI: 1.2-9.8), systolic pulmonary arterial pressure (MD: 3.6 mmHg; 95% CI: 0.8-6.3), right atrium pressure (MD: 1.5 mmHg; 95% CI: 1.0-2.0), and left atrium diameter (MD: 8.1 mm; 95% CI: 5.5-10.7). About one-third of patients with RHD have AF, with an incidence which almost triples every five years after diagnosis. Factors associated with AF include age, advanced heart failure, thromboembolism, and few cardiac hemodynamics parameters.


Lack of inotropic effect of nitric oxide on the rat myocardium.
1. Nitric oxide (NO) is an important mediator of contractile function in the heart. However, isolated papillary muscle preparations appear to lack NO responsiveness in certain animal species. Although cat, guinea-pig and ferret models have been NO responsive, there have been mixed results in the rat papillary muscle. In null form, we tested three separate hypotheses in rat papillary muscle, specifically that the NO donor sodium nitroprusside (SNP) would not affect the contractility of: (i) the isolated papillary muscle; (ii) papillary muscle prestimulated with the beta-adrenoceptor agonist isoprenaline; and (iii) papillary muscle subjected to 15 min anoxia followed by 45 min reoxygenation. 2. Male Sprague-Dawley rats were used. The left ventricular papillary muscle was mounted and maintained at 30 degrees C and was stimulated at 10 b.p.m. Each experiment was performed in parallel with a control papillary muscle from the same animal. Papillary muscles were exposed to increasing concentrations of SNP (10(-9) to 10(-5) mol/L) either alone or following pretreatment with 10(-7) mol/L isoprenaline. Anoxia/reoxygenation was simulated by 15 min anoxia followed by 60 min reoxygenation in the presence or absence of 10(-7) mol/L SNP. 3. Both isometric and isotonic parameters were assessed. As expected, isoprenaline had a significant positive inotropic response. Similarly, contractility was impaired during anoxia and partially recovered during reoxygenation. Nitric oxide did not alter either isotonic or isometric parameters in the three experimental protocols. 4. The rat isolated papillary muscle has no measurable response to exogenous NO. The inotropic effects of beta-adrenoceptor stimulation and anoxia/reoxygenation are NO independent.


[Lumbar microdiscectomy. Technique and results in 80 cases].
The results of treatment for 80 patients with lumbar disc disease who undergone microdiscectomy were reviewed. Low rate of post-operative complications, short hospital stay and early return of the patients to their normal activities were observed.


Defective immunometabolism pathways in cystic fibrosis macrophages.
Mitochondria play a key role in immune defense pathways, particularly for macrophages. We and others have previously demonstrated that cystic fibrosis (CF) macrophages exhibit weak autophagy activity and exacerbated inflammatory responses. Previous studies have revealed that mitochondria are defective in CF epithelial cells, but to date, the connection between defective mitochondrial function and CF macrophage immune dysregulation has not been fully elucidated. Here, we present a characterization of mitochondrial dysfunction in CF macrophages. Mitochondrial function in wild-type (WT) and CF F508del/F508del murine macrophages was measured using the Seahorse Extracellular Flux analyzer. Mitochondrial morphology was investigated using transmission electron and confocal microscopy. Mitochondrial membrane potential (MMP) as well as mitochondrial reactive oxygen species (mROS) were measured using TMRM and MitoSOX Red fluorescent dyes, respectively. All assays were performed at baseline and following infection by Burkholderia cenocepacia, a multi-drug resistant bacterium that causes detrimental infections in CF patients. We have identified impaired oxygen consumption in CF macrophages without and with B. cenocepacia infection. We also observed increased mitochondrial fragmentation in CF macrophages following infection. Lastly, we observed increased MMP and impaired mROS production in CF macrophages following infection with B. cenocepacia. The mitochondrial defects identified are key components of the macrophage response to infection. Their presence suggests that mitochondrial dysfunction contributes to impaired bacterial killing in CF macrophages. Our current study will enhance our understanding of the pathobiology of CF and lead to the identification of novel mitochondrial therapeutic targets for CF.


Deaths from accidental steam inhalation during traditional therapy.
Death from accidental steam inhalation is quite a rare occurrence. Two cases of children who died during the inhalation of superheated steam in a closed room are reported. To our knowledge this is the first case report where children died from the injurious effects of steam while inhaling steam. At autopsy, petechial haemorrhages in brain, lungs, heart, and congestion of epiglottis, congestion and oedema of lungs were seen macroscopically. Microscopically, trachea showed swelling and oedema of mucosa and sub mucosa, focal loss of mucosal epithelium and coagulative necrosis with scanty inflammatory reaction, lungs showed congestion, oedema and haemorrhages. It is considered that these findings caused hypoxia and cause of death in these cases was accidental inhalation of superheated steam. It indicates that mucosa of respiratory tract is vulnerable to the effects of vapors of superheated steam. Moreover it would seem that fatal hypoxia occurs within a few minutes from the effects of inhalation of steam in a closed space.


Hydrogen metabolism and nitrogen fixation in wild type and Nif- mutants of Rhodopseudomonas acidophila.
N2 fixation, C2H2 reduction and H2 production in Rhodopseudomonas acidophila DSM 137 were shown to be stoichiometrically related in ratios of 1:2.8:2.8. The highest possible H2 oxidation rate has been calculated to be about 6 fold higher in Rhodopseudomonas acidophila DSM 137 than the maximum rate of H2 production. Nif- mutants were isolated and tested; all of them had lost their ability of reduce C2H2 and to produce H2. In two nif- mutants hydrogenase activity and the capacity for autotrophic growth with H2 were also strongly diminished. Nif+ revertants not only regained their ability for C2H2 reduction and H2 production but also their full capacity for autotrophic growth with H2.


Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals.
Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. Multicenter, randomized, controlled trial. The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. A total of 5059 asymptomatic men and women aged 50 to 69 years. Colonoscopy. Prevalence of serrated polyps and their association with synchronous advanced neoplasia. Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.


Hippocampal dysfunction and behavioral deficit in the water maze in mice: an unresolved issue?
Dysfunction of the hippocampal formation manifests as impaired relational learning and memory in humans and animals. One of the most frequently applied relational learning paradigms in animals is the Morris water maze (MWM), in which the subject is required to learn complex spatial relationships of visual cues. MWM has been employed as a diagnostic tool to investigate effects of drugs and mutations. However, the validity of this test and its ability to properly detect hippocampal dysfunction have been questioned. In order to corroborate the role of hippocampus in spatial learning, we employed ibotenic acid lesioning and ablated the hippocampus bilaterally or unilaterally in mice, as ascertained by magnetic resonance imaging. We found a significant impairment in response to hippocampal disruption that was more pronounced in mice with bilateral lesion than with unilateral lesion. However, the results also indicated that even the mice with bilateral lesion could improve their performance, which confirms the notion that the MWM has an important non-hippocampal component. It is thus possible that experimental alteration of brain function does not manifest as modified performance in MWM, even when hippocampal function is modified (false-negative finding), or manifest as altered performance without varying hippocampal function (false-positive finding), possibilities that have important implications for studies using genetic and pharmacological manipulation of the brain.


Assessment of the corpus callosum size in male individuals with high intelligence quotient (members of Mensa International).
The aim of this study was to assess the size of the corpus callosum in members of Mensa International, which is the world's largest and oldest high-intelligence quotient (IQ) society. We performed T2-weighted magnetic resonance imaging (Repetition Time, TR = 3200 ms, Time of Echo, TE = 409 ms) to examine the brain of members of Mensa International (Polish national group) in order to assess the size of the corpus callosum. Results from 113 male MENSA members and 96 controls in the age range of 21-40 years were analyzed. The comparative analysis showed that the mean length of the corpus callosum and the thickness of the isthmus were significantly greater in the Mensa members compared to the control groups. A statistically significant difference was also identified in the largest linear dimension of the brain from the frontal lobe to the occipital lobe. The mean corpus callosum cross-sectional area and its ratio to the brain area were significantly greater in the Mensa members. The results show that the dimensions (linear measures and midsagittal cross-sectional surface area) of the corpus callosum were significantly greater in the group of Mensa members than in the controls.


Transient left ventricular basal dysfunction without coronary stenosis in acute cerebral disorders: a novel heart syndrome (inverted Takotsubo).
Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. We report 4 cases where, in the context of acute cerebral disorder, the echocardiograms revealed an extensive left ventricular circumferential akinesis except at the apex. Besides, for three of those cases no coronary disease has been highlighted. Recognition of such a pattern of LV dysfunction should lead to the search for an acute cerebral disease.


Spectral properties of a novel cytochrome P-450 of a Saccharomyces cerevisiae mutant SG1. A cytochrome P-450 species having a nitrogenous ligand trans to thiolate.
An altered cytochrome P-450 (SG1 P-450) was partially purified from Saccharomyces cerevisiae mutant SG1 which is defective in lanosterol 14 alpha-demethylation. Oxidized SG1 P-450 showed a Soret peak at 422 nm and the alpha peak was lower than the beta peak. This spectrum was considerably different from those of known low-spin P-450s, indicating a unique ligand structure of SG1 P-450. The absorption spectrum of ferric SG1 P-450 was superimposable on that of the imidazole complex of ferric P-450, suggesting the presence of a nitrogenous ligand such as histidine of the apoprotein at the 6th coordination position. SG1 P-450 was immunochemically indistinguishable from cytochrome P-450 of S. cerevisiae catalyzing lanosterol 14 alpha-demethylation (P-45014DM) but had no lanosterol 14 alpha-demethylase activity.


Recruiting people with severe mental illness through community pharmacies: real-world experiences from a UK study.
Proxy recruitment of patient participants through community pharmacies may be a valuable strategy to maximise participation. This paper focuses on the feasibility of such a recruitment strategy for research involving people who experience severe mental illness. Fifty-three community pharmacies, including 50 'Research Ready' pharmacies, were asked to recruit people with severe mental illness for participation in research. Pharmacists were asked to provide participant information to anyone presenting a prescription meeting specific criteria. Thirteen recruitment sites (25%) (from 4 distinct organisations) were approved to recruit patient participants. Eighty-five percent (n = 11) failed to recruit any potential participants. Proxy recruitment of people with severe mental illness through community pharmacies was challenging with challenges in both pharmacy- and participant-recruitment. Further investigation into supporting community pharmacists' engagement with recruiting patients with SMI as research participants is required.


[The Dachau multidisciplinary treatment program for chronic pain. Efficacy data of a diagnosis-independent multidisciplinary treatment program for back pain and other types of chronic pain].
Data on the efficacy of the Dachau multidisciplinary treatment program for chronic pain is presented. The treatment is administered in a primary care day clinic and the treatment period is 5 weeks plus 5 booster days 6 months later. The program is characterized by high treatment intensity (122.5 h over 5 weeks) and is aimed at patients where outpatient pain therapy proved to be insufficient. The treatment plan is applicable to different types of chronic pain and the main treatment objective is functional restoration. Outcome criteria were pain intensity, disability, vitality, depression, catastrophizing, and employment status. The data was assessed at the beginning of treatment, after 5 weeks and 6 months after therapy. The patient population consisted of 189 chronic pain patients. All outcome criteria showed a significant and stable improvement over 6 months. Effect sizes demonstrated medium and high treatment effects. The back to work rate was 63% at 6 months follow-up. The Dachau multidisciplinary treatment for chronic pain achieved significant improvements which remained stable for 6 months after treatment.


Ankle block in forefoot reconstruction before or after inflation of tourniquet--Does timing matter?
Forefoot surgery causes postoperative pain frequently requiring strong painkillers. Regional blocks are now increasingly used in order to control postoperative pain especially in the first 24h when the pain is at its worst. We conducted a prospective study to see if timing of ankle block i.e. before or after inflation of tourniquet showed any difference in efficacy in postoperative pain control in first 24h. A prospective randomised study was conducted between September 2010 and August 2011 involving 60 patients. Group A (n=30) had the ankle block administered after and Group B (n=30) had a block before inflation of a thigh tourniquet. Patients were given assessment forms to chart their pain on visual analogue scale (VAS) score at 4h and 24h postoperatively. Both groups demonstrated good postoperative pain control. Average VAS pain score at four and twenty fours after surgery was 2.5 and 4.5 in Group A and 3.9 and 6.3 in Group B respectively. Pain control, both at 4 and 24h surgery was better in Group A but this was statistically significant only at 24h. A regional anaesthetic ankle block should be routinely used in forefoot surgery to control postoperative pain. The ankle block should be applied after the inflation of tourniquet as this appears to provide better pain control.


Pediatric infectious disease emergencies.
Infectious diseases are the cause of the majority of pediatric emergency visits, although only a minority constitute true emergencies. Progress in identifying the true emergencies continues.


[Organ specific water-soluble cerebral cortex proteins; possible participation in physiological functions and pathologic manifestations].
The spectre of active antigens in brain is studied. The presence of 3 protein and 3 glycoprotein brain specific antigens is demonstrated. The possible participation of brain specific antigens in increased antibody formation in schizophrenics, multiple sclerosis and lateral ammiotrophic sclerosis is studied. The data obtained indicate the role of brain specific antigens to autoimmunity in those patients. The possible participation of one of the specific antigens of the brain, sialoglycoprotein GP-350, in physiological processes connected with the mechanism of memory is also studied. In experiments of inbred trained rats an activation of the synthesis of GP-350 is observed.


Gemfibrozil and Mediterranean diet for patients with high plasma levels of lipoprotein [Lp(a)] and cholesterol--pilot study.
Plasma levels of lipoprotein-a [Lp(a)] > 30 mg/dl represent an independent risk factor for cardiovascular diseases with both proatherosclerotic and prothrombotic activity. The results of dietary or pharmacological treatment are not encouraging and are often controversial. We have evaluated a combination of medical treatment with Gemfibrozil (600 mg bid) and a Mediterranean diet for 2 months in 15 patients with both hypercholesterolemia (> 240 mg/dl) and high levels of Lp(a) (> 30 mg/dl). Three patients dropped out within the first 2 weeks, complaining of epigastric pain and burning; the remainder (5 females and 7 males, mean age 70 years) completed the treatment without any side effects. The median values of Lp(a) decreased from 36.5 to 8.4 mg/dl (p < 0.0002) and total cholesterol from 254.5 to 208.0 mg/dl (p < 0.0001). The small number of patients does not permit any definitive conclusion on effectiveness to be drawn, but the results indicate further randomized studies might prove worthwhile.


The detection of smooth muscle antibodies reacting with intermediate filaments of desmin type.
Some human smooth muscle antibodies (SMA) react with cytoskeletal intermediate filament (IMF) antigens. The smooth muscle tissue contains two types of IMF: vimentin and desmin filaments. In this study, SMA of anti-IMF type in 52 patients' sera have been classified into anti-vimentin filament and anti-desmin filament types according to their immunofluorescence staining patterns on rat testis. This classification is based on the fact that the arterial walls of testis contains both vimentin and desmin whereas the myoid cell layer surrounding the seminiferous tubuli contains only desmin. Four out of the 52 sera gave the anti-desmin staining pattern and 40 sera showed the anti-vimentin type of staining. Thirty-two sera were further classified by using cultured human rhabdomyosarcoma (RD) cells as targets. Nine sera reacted with the intermediate filaments of the RD cells. Among these were 3 out of the 4 sera that gave the anti-desmin filament staining pattern. The anti-desmin specificity of SMA was confirmed in 1 serum by the immunoblotting technique. These results indicate that while human anti-desmin filament antibodies exist, most human SMA of anti-IMF type react with vimentin filaments.


New data on temperature optimum and temperature changes in energy crop digesters.
As a result of self-heating in anaerobic digesters when using energy crops in the feedstock, the influence of temperature on the digestion process came back into focus. The aim of this study was to investigate the impact of such temperature increases on process stability. Furthermore, different strategies for the transition from mesophilic to thermophilic conditions and the resulting methane yields at different temperature levels were evaluated. Two main effects were identified with different bio-slurries from agricultural biogas plants: (1) a failure of methane production connected to changes in the microbial community; and (2), a slow but continuous accumulation of propionic acid, though without an immediate effect on methane production. All strategies for increasing the operating temperature showed negative effects on digester performance, some with serious economic consequences for the operator. It was shown that methane yields at different temperature levels in the mesophilic and sub-thermophilic ranges are similar.


Small-diameter (2 mm) laparoscopy in the evaluation of liver disease.
Percutaneous liver biopsy fails to demonstrate cirrhosis in approximately 32% of cases when compared with laparoscopy with liver biopsy. The aim of this study is to determine the usefulness of small-diameter (2 mm) laparoscopes compared with larger laparoscopes. Patients undergoing diagnostic laparoscopy for various liver diseases were evaluated with small-diameter (2 mm) laparoscopes either alone or in combination with a 5 or 10 mm laparoscope. Twenty patients were enrolled in this study. Small-diameter laparoscopes provided appropriate visualization of the abdominal organs and proper guidance to liver biopsy in 9 cases. In the remaining 11 cases a larger laparoscope was used for the following reasons: short length of the trocar/introducer in a morbidly obese patient (1), liver mass located in the anterosuperior aspect of the liver precluding good visualization with forward lenses (1), and inability to properly visualize the anterosuperior aspect of the liver (9). No complications were noted with the use of the small-diameter laparoscopes alone. There is a need for an oblique-viewing minilaparoscope that allows visualization comparable to the larger laparoscopes.