Venous Thromboembolic Prophylaxis in Foot and Ankle Surgery: A Review of Current Literature and Practice.
Venous thromboembolism (VTE) is a well-known and feared complication following foot and ankle surgery, as it is a source of morbidity and mortality in the perioperative phase. The most recent CHEST guidelines recommended against the use of chemoprophylaxis and the majority of the literature has found a low incidence of VTE following foot and ankle surgery. Some authors prefer screening patients for risk factors and recommend the use of chemoprophylaxis on a case-by-case basis. Interestingly, studies that found high incidence of VTE were unable to determine a statistically significant difference between the prophylaxis and placebo groups. Major limitations of retrospective reviews is they are only able to study symptomatic VTE because no routine screening is typically performed. In a survey study, up to 98% of foot and ankle surgeons responded that they use prophylaxis in high-risk patients. Despite evidence-based recommendations, a significant number of foot and ankle surgeons are routinely using some form of VTE prophylaxis without taking risk factors into account. Clinical, Level IV: Review Article.


[Interleukin-21 surface-modified MB49 cell vaccine for treatment of metastatic bladder in mice].
To develop a novel vaccine by immobilizing interleukin-21 (IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes (CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer. SA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine. C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine, soluble IL-21, GFP surface-modified MB49 cells, ethanol-fixed MB49 cells, or PBS. The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine. IL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response (P<0.05). At the same effector-target (E:T) ratio, the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells (P<0.05). With the protein-anchor technique, IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine. The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.


[Paraganglioma with multiple endocrine adenomas].
Report on a paraganglioma of the left division place of the carotid and the common occurrence with adenomas in other endocrine organs (hypophysis, thyroid gland, adrenal gland and pancrease) in the sense of an MEA-syndrome (multiple endocrine adenopathy) in a 75-year-old woman. Discussion of the morphologic findings as well as reference to the multiple occurrence of adenopathies from the APUD cell system.


AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families.
The phosphatidylinositol 3-kinase (PI3K)-AKT signal transduction pathway is critical to cell growth and survival. In vitro functional studies indicate that the candidate schizophrenia susceptibility gene DTNBP1 influences AKT signaling to promote neuronal viability. The AKT1 gene has also been implicated in schizophrenia by association studies and decreased protein expression in the brains of schizophrenic patients. The association of DTNBP1 in the Irish Study of High Density Schizophrenia Families (ISHDSF) prompted our investigation of AKT1 for association with disease in this sample. Eight single nucleotide polymorphisms spanning AKT1 were analyzed for association with schizophrenia across four definitions of affection and according to Operational Criteria Checklist of Psychotic Illness (OPCRIT) symptom scales. We examined expression of AKT1 messenger RNA from postmortem brain tissue of schizophrenic, bipolar, and control individuals. No single marker showed significant association, but the risk haplotype previously found over-transmitted to Caucasian schizophrenic patients was significantly under-transmitted in the ISHDSF (.01 < p < .05), across all OPCRIT symptom dimensions. Exploratory haplotype analysis confirmed association with schizophrenia toward the 5' end of AKT1 (.008 < p < .049, uncorrected). We found significantly decreased RNA levels in prefrontal cortex of schizophrenic individuals, consistent with reduced AKT1 protein levels reported in schizophrenic brain. The replication of association of AKT1 gene variants in a further Caucasian family sample adds support for involvement of AKT signaling in schizophrenia, perhaps encompassing a broader clinical phenotype that includes mood dysregulation. We show that AKT signaling might be compromised in schizophrenic and bipolar patients via reduced RNA expression of specific AKT isoforms.


A site-directed spin-labeling study of ligand-induced conformational change in the ferric enterobactin receptor, FepA.
The ferric enterobactin receptor, FepA, is a TonB-dependent gated porin that transports the siderophore ferric enterobactin across the outer membrane of gram-negative bacteria. We have created two site-directed mutants of Escherichia coli FepA, in both cases introducing a cysteine residue into the putative ligand-binding domain. The introduced cysteines were then modified with nitroxide spin labels for structural and dynamic studies using electron spin resonance (ESR) spectroscopy. The mutants were fully functional, as indicated by their ability to grow under iron-limiting conditions, their uptake of [59Fe]enterobactin, and their sensitivity to colicin B. Labeling of the mutant FepA receptors proceeded easily upon incubation with sulfhydryl-specific spin labels, e.g. MTSL, (1-oxy-2,2,5,5-tetramethylpyrrolidin-3-yl)methyl methanethiosulfonate. In contrast, spin labeling of the two native cysteines (Cys486 and Cys493) within wild-type FepA occurred only after treatment with a thiol reducing agent and partial denaturation in urea, suggesting that the native cysteines are disulfide-linked. ESR spectra showed a high degree of motional restriction for all three sites. Continuous wave (CW) saturation studies indicated that one of the mutationally introduced sites (Cys280) was surface-localized as evidenced by its exposure to the aqueous paramagnetic relaxation agent chromium oxalate and its low accessibility to O2. The other (Cys310) apparently occupies a site near the membrane/aqueous interface. The native cysteines occupy a site tightly packed within the protein structure with low accessibility to both CROX and O2. A shift in both conventional and saturation-transfer ESR spectra of MTSL-labeled E280C and E310C (but not MTSL-labeled wild type) FepA was observed upon addition of ferric enterobactin. The ESR spectral shift was dependent on ferric enterobactin concentration and did not occur with siderophores not recognized by FepA. Ferric enterobactin binding did not alter the CW saturation properties of MTSL bound to these sites, but did influence their accessibility to O2. These results provide consistent evidence for a ligand-specific conformational change in the surface peptides of FepA upon the binding of ferric enterobactin.


Valve replacement and myocardial revascularization. Results of combined operation in 59 patients.
Fifty-nine patients (mean age 57 years) underwent aortic valve replacement or mitral valve replacement combined with saphenous vein bypass grafting (39 single, 19 double, 1 triple) between May, 1970 and January, 1974. The hospital mortality for aortic valve replacement was 4.7% (2 of 43 patients) and for mitral valve replacement 6.3% (1 of 16 patients). There was a 21% incidence of postoperative myocardial injury in the patients with aortic valve replacement and a 6.2% incidence in the patients with mitral valve replacement. Variations in operative technique and in the methods of intraoperative myocardial preservation (coronary perfusion or profound hypothermic ischemic arrest) did not affect hospital mortality or the incidence of myocardial injury. Prolonged periods of ischemic arrest (greater than 50 minutes) were not used. The late mortality for aortic valve replacement was 16.3% (seven patients) and for mitral valve replacement 25% (four patients). There was symptomatic improvement in the majority of survivors. Operative mortality rates for the combined procedures are comparable to those from our institution for valve replacement alone.


A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients.
Fluoxetine, a selective serotonin reuptake inhibitor, was compared with mianserin and placebo in a double-blind study. In total, 81 depressed patients were included. Patients were rated weekly on the Hamilton Depression Rating Scale (HDRS) and the Montgomery & Asberg Depression Rating Scale (MADRS). The duration was 6 weeks, and 52 patients completed the study. Significantly more patients on fluoxetine improved than patients on placebo. For mianserin no significant differences were found with either fluoxetine or placebo. Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine, but not for mianserin, than placebo. Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3. Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7. Fluoxetine induced weight loss, while patients on mianserin gained weight. Side effects were present in most patients on the two active drugs; those on fluoxetine experienced nausea and vomiting, and those on mianserin drowsiness.


Differential detection of avian oncogenic viruses in poultry layer farms and Turkeys by use of multiplex PCR.
Avian oncogenic viruses include Marek's disease virus (MDV), a highly contagious herpesvirus, as well as retroviruses such as avian leukosis virus (ALV) subgroups A to J and reticuloendotheliosis virus (REV). In this study, we examined the incidence of these viruses in suspected samples collected from poultry layer farms of South India, mainly in the Namakkal district of Tamil Nadu, a highly dense poultry-growing area in India. The histopathology-positive tissue sections were identified and further confirmed by immunohistochemistry using virus-specific antibodies. The viruses belonging to all 3 groups (MDV, ALV, and REV) were isolated in a cell culture system and confirmed by immunofluorescence using virus-specific antibodies. PCR appeared to be the method of choice for rapid and accurate diagnosis of these viruses. The multiplex PCR primers specific to MDV, ALV, REV, and chicken DNA were designed for rapid differential diagnosis. The specificity of the primers was checked by amplification of DNA from virus-infected cell culture in comparison with uninfected samples, and sensitivity was evaluated by calculating the minimum copy number at which amplification occurs in the cloned PCR products. The sequences of the amplicons were compared by BLAST analysis. PCR tests demonstrated the presence of single, dual, or triple viruses in some of the samples. Of 169 samples screened by multiplex PCR, 9 samples were positive for MDV, 17 samples were positive for ALV, 12 samples were positive for REV, and 17 samples were positive for both ALV and REV. Three samples were positive for all three viruses. ALV-positive samples were further subjected to subgroup-specific PCR, which gave positive results for subgroups B and D but not for subgroup J. Multiplex PCR appeared to be a useful technique for rapid differential diagnosis of avian oncogenic viruses and detection of multiple infections of avian oncogenic viruses under field conditions.


Is the plasma anti-Müllerian hormone (AMH) level associated with body weight and metabolic, and hormonal disturbances in women with and without polycystic ovary syndrome?
The aim of the study was to analyze interrelation between AMH levels and body weight, metabolic, and hormonal status in normal and overweight weight women with and without polycystic ovary syndrome (PCOS). Eighty-seven women (54 normal weight and 33 overweight) diagnosed with PCOS and 50 apparently healthy women - Non-PCOS (28 normal weight and 22 overweight) were enrolled. The body weight and height were measured and BMI was calculated. In addition to serum glucose, lipids, androgens, FSH, LH, SHBG and insulin, AMH were assessed in fasting state and free androgens index (FAI) was calculated. The insulin resistance was assessed based on the homeostasis model of assessment-insulin resistance (HOMA-IR). Plasma AMH levels were similar in normal weight and overweight PCOS groups (9.6±3.5 vs. 11.2±4.5ng/mL, respectively), and as expected markedly higher than in both Non-PCOS groups (2.5±0.8 and 2.3±0.7ng/mL, respectively). There were no correlations between BMI and AMH levels in all study groups. A significant positive correlation between HOMA-IR, free testosterone concentrations or FAI and AMH levels were found (R=0.31, p<0.001; R=0.91, p<0.001 and R=0.62, p<0.001, respectively). Moreover, there was positive correlation between total or LDL cholesterol and AMH levels (R=0.22, p<0.05 and R=0.31, p<0.05, respectively) and a negative one between HDL cholesterol and AMH levels (R=-0.17, p<0.05) in all study subjects. The plasma AMH level is associated with insulin resistance but not with BMI per se. Increased circulating AMH level seems to reflect the disturbances of gonadotrophins release in PCOS. It seems that AMH level may be used not only as new surrogate marker of ovarian hyperandrogenism in PCOS but also as a potential new cardiovascular risk factor.


Carcinoid heart disease revealed by cyanosis with both right and left valvular involvement: a case report.
Carcinoid heart disease is a frequent complication of carcinoid syndrome. It is related to the release by the carcinoid tumor and/or its metastases of bioactive substances such as serotonin. It is characterized by right-sided valvular involvement and can lead to right-sided heart failure. It is a prognostic factor of carcinoid syndrome. We report the case of a 53-year-old African woman with an endocrine tumor of her small intestine complicated by carcinoid heart disease, revealed by right-sided heart failure. The diagnosis was confirmed by transthoracic echocardiography, which showed a severe tricuspid regurgitation with a patent foramen ovale, and by increased serum chromogranin A and urinary 5-hydroxyindoleacetic acid. Initially she was treated with medical therapy (furosemide and injection of somatostatin). Afterwards she was proposed for surgery. The evolution of her treatment was good. Carcinoid syndrome is complicated in 60% of the cases of a heart disease, and is responsible for an important morbidity and mortality. The prognosis of patients with carcinoid heart disease has improved in recent years through somatostatin analogues and the cardiac surgery.


[Multinuclear neurons in the ganglia of the gastrointestinal tract].
Findings of light optical and electron microscopy studies on formation of multinuclear neurons in gastrointestinal tract myenteric plexus in mammals affected by extreme factors (vagotomy, modelling of portal hypertension. Hyperbaric oxygenation and hypergravitation) were presented. A model for original transformation of multinuclear neuron as a mechanism of new nerve cells formation in the course of the organism compensatory-adaptive reaction to extreme action was obtained.


Duration of excretion of virulent Newcastle disease virus following challenge of chickens with different titres of serum antibody to the virus.
Virulent Newcastle disease virus (NDV) was isolated from susceptible and immune chickens following intra-ocular challenge with the Essex '70 strain. Challenge virus was isolated from the trachea and cloaca of susceptible birds until they died 7 to 9 days after challenge. This virus was isolated from immunised chickens for up to 14 days after challenge. The duration of excretion was influenced by the prechallenge serum antibody titre to NDV. It persisted longest in chickens with titres of 2(3) to 2(7) and decreased in length and frequency from chickens with titres in the range 2(8) to 2(12). Chickens with pre-challenge titres of 2(3) to 2(5) developed 2- to 3- fold increases in post-challenge titres, whereas those with higher pre-challenge titres had smaller proportional increases in titre. Excretion of virulent virus from immunised birds should be considered in the development of Newcastle disease control programs.


Basement membrane and connective tissue proteins in intestinal mucosa of patients with coeliac disease.
Gluten ingestion in coeliac disease is associated with alterations of the intestinal mucosa, especially the expansion of the lamina propria. Antiendomysium and antireticulin antibodies may result from interactions between gliadin and extracellular matrix components. By behaving as autoantigens, connective tissue proteins could initiate mucosal damage. This study evaluates changes in the distribution of laminin, type IV collagen, and fibronectin in the mucosa of patients with coeliac disease in an attempt to explain the alterations of mucosal morphology. Intestinal biopsies were obtained from patients with coeliac disease on admission and while on a gluten free diet. The distribution of type IV collagen, laminin, fibronectin, and alpha-smooth muscle actin was evaluated by immunofluorescence and by immunogold labelling and electron microscopy. In patients with coeliac disease, the intensity of type IV collagen, laminin, and fibronectin immunofluorescent staining was decreased and less well defined than in controls, with frequent breaches in the basement membrane; fibronectin staining was weak in the distal third of the elongated crypts and absent under the flat surface. The distribution of smooth muscle fibre in the distal lamina propria of flat mucosae was altered. The distribution of these proteins was normal as assessed by immunoelectron microscopy. The intensity of staining of some components of the basement membrane is decreased in coeliac disease and the distribution of smooth muscle fibres is altered. These changes may result from interactions between gliadin and components of the extracellular matrix and may play a role in the genesis of mucosal lesions and in the damage to the epithelium.


Acetaldehyde as a Food Flavoring Substance: Aspects of Risk Assessment.
The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) has reviewed the currently available data in order to assess the health risks associated with the use of acetaldehyde as a flavoring substance in foods. Acetaldehyde is genotoxic in vitro. Following oral intake of ethanol or inhalation exposure to acetaldehyde, systemic genotoxic effects of acetaldehyde in vivo cannot be ruled out (induction of DNA adducts and micronuclei). At present, the key question of whether acetaldehyde is genotoxic and mutagenic in vivo after oral exposure cannot be answered conclusively. There is also insufficient data on human exposure. Consequently, it is currently not possible to reliably assess the health risk associated with the use of acetaldehyde as a flavoring substance. However, considering the genotoxic potential of acetaldehyde as well as numerous data gaps that need to be filled to allow a comprehensive risk assessment, the SKLM considers that the use of acetaldehyde as a flavoring may pose a safety concern. For reasons of precautionary consumer protection, the SKLM recommends that the scientific base for approval of the intentional addition of acetaldehyde to foods as a flavoring substance should be reassessed.


Prevalence, impact and management of postmenopausal symptoms among postmenopausal women in Rwanda.
This study aimed at evaluating the prevalence and management of postmenopausal symptoms among Rwandan women. A descriptive cross-sectional study was conducted at the four largest Rwandan referral hospitals from August 2017 to March 2018 among postmenopausal women. Data on postmenopausal symptoms were collected using the Modified Blatt-Kupperman Menopausal Index and score ranges of 0-6, 7-15, 16-30 and >30 were used to rate the degree of severity as none, mild, moderate, and severe, respectively. Six hundred participants were recruited. The mean age at natural menopause was 51.7 ± 5.6 years. Common symptoms were hot flushes (82%), sexual complaints (66%) and headache (61%). The mean Blatt-Kupperman index score was 21.2 (1-58). Participants' symptoms were classified as severe (35.8%), moderate (49.0%), mild (11.3%) and none (3.8%). Among 41.2% who had sought medical care, 1.7% were given hormonal replacement and 36% were given only pain medications. Age >50 years and lack of a male partner were significantly associated with higher scores. Postmenopausal symptoms remain a burden among Rwandan women and little consideration is given for optimal management. There is a need for health managers to consider this inevitable phase of life on the health policy agenda for equitable healthy aging.


Crystallization of charged gold particles mediated by nonadsorbing like-charged polyelectrolyte.
We report that the aqueous dispersions of negatively charged submicron-sized colloidal Au particles formed non-close-packed colloidal crystals by the addition of a like-charged linear polyelectrolyte, sodium polyacrylate (NaPAA). Au particles often form irregular aggregates in dispersions because of a strong van der Waals force acting between them. To prevent aggregation, we introduced negative electric charges on particle surfaces. By the addition of NaPAA, colloidal crystals were formed on the bottom of a sample cell because of the supply of Au particles by sedimentation and 2D diffusion even under very dilute conditions. Interparticle potential calculations demonstrated that the addition of NaPAA caused depletion attraction between the particles as well as a significant reduction in the interparticle repulsion because of the electrostatic screening effect. However, the electrostatic repulsion was strong enough to prevent the direct contact of particles in the excluded region between Au particles. Large-area crystals could be obtained by tilting the sample cell. By drying the sample, the Au particles came into contact and the non-space-filling crystals changed into closest packed crystals. These closest packed crystals exhibited a significant enhancement of Raman scattering intensity because of high hot-spot density.


Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.
The incidence of colorectal carcinoma has increased among patients <40 years of age for unclear reasons. In this study, we describe the clinical, pathologic, and molecular features of colorectal carcinomas that developed in young patients. We compiled a study group of 24 patients <40 years of age with colorectal carcinoma, and 45 patients > or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.


Visual outcome following cataract extraction in patients aged 90 years and older.
To analyse surgical outcomes following cataract surgery in patients aged 90 years and older. A retrospective case series of 78 patients aged 90 years or more (82 eyes) undergoing cataract extraction between 2000 and 2006 was performed. Age, sex, ocular comorbidities, surgical reports, preoperative and postoperative visual acuity (VA), and postoperative complications were recorded. A comparison of visual outcome between different ocular comorbidity groups was performed. Average age was 91.8 years. The most common comorbidities were dry AMD (47.4%) and open-angle glaucoma (24.4%). No ocular comorbidity was found in only 22 patients (28.2%). Posterior capsular tear (8.5%) was the most prevalent operative complication.Overall VA improvement was 67.8%, whereas unchanged VA and VA worsening rates were 16.1% each. A total mean improvement of 0.63 logMAR was achieved (from preoperative 1.36 logMAR to postoperative 0.73 logMAR), whereas patients with no comorbidity achieved as high as 0.8 logMAR improvement (1.42-0.62 logMAR). Almost 17% of patients achieved uncorrected VA of 20/40 or better at day 7, compared to 7% preoperatively. Final VA of 20/40 or better was achieved in 25% of the patients. AMD patients showed lower final improvement rates and higher rates of unchanged VA, as compared to the no comorbidity and glaucoma group (statistically significant at day 7). Overall, approximately 70% of very elderly patients can achieve VA improvement, which rises to 82% in those without ocular comorbidity. Although patients with AMD show less improvement and more unchanged VA outcome rates, 62.5% can still enjoy improvement in VA.


[Two cases of the rare Cronkhite-Canada syndrome].
Cronkhite-Canada syndrome (CCS) is a rare non-heritable condition characterized by gastrointestinal polyposis, dysgeusia, malnutrition, total alopecia and onychodystrophia. Two Danish cases of CCS (an 88-year-old female and a 69-year-old male) presented with signs of malnutrition, dyspepsia, vomiting, dysgeusia and hair loss. An upper endoscopy revealed marked oedema and polyposis in the stomach. Both patients developed colonic adenocarcinomas which were radically operated. Treatment consisted of hyperalimentation, prednisolone and azathioprine. Both patients went into remission - the first patient totally.


Influence of ethanol on methanol-induced oxidative stress and neurobehavioral deficits.
The present study examines the efficacy of ethanol as an antidote in methanol neurotoxicity in terms of its effect on antioxidant defense system and behavior. It was observed that acute methanol exposure (7.5 g/kg body weight) led to an increase in lipid peroxidation in various regions of brain. Ethanol administration (7.5 g/kg body weight), on the other hand, was found to accentuate methanol-induced lipid peroxidation. Glutathione levels in brain were significantly reduced in methanol-exposed animals. However, in the coexposed animals, the levels of glutathione were comparable to those observed in controls. The activities of superoxide dismutase and catalase were decreased in the brain following methanol exposure, whereas in methanol- and ethanol-coexposed animals there was no significant effect on these enzymes as compared to methanol-exposed animals. The activity of acetylcholinesterase was significantly reduced in the methanol-exposed animals. On the other hand, acetylcholinesterase activity was not affected in the coexposed animals in comparison to methanol-treated group. Neurobehavioral studies revealed impaired motor and cognitive functions following methanol exposure. In contrast, ethanol exposure ameliorated the behavioral deficits induced by methanol. The findings from the present study suggest the beneficial effect of ethanol on neurobehavioral deficits induced by methanol along with intensification of methanol-induced oxidative stress.


[MRI in the diagnosis of lissencephaly. Apropos of a case].
In a patient with clinical manifestations suggestive of brain malformation, CT showed lissencephaly with absent opercularization. The child had seizures but not a typical EEG of hypsarhythmia. MRI confirmed the diagnosis and showed heterotopic grey matter and abnormal basal ganglia. High grey-white matter contrast and the possibility of imaging the brain in sagittal, coronal and transverse planes make MRI the methode of choice for the evaluation of lissencephaly and other brain malformations.


Feasibility and efficacy of an attachment-based intervention in a maltreatment sample in residential care: A pilot study.
The effects of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline on improving maternal sensitivity and sensitive discipline were investigated using a randomized control design in a pilot sample of mothers at high risk of maltreatment. The study included 12 mothers and their 10- to 36-month-old children placed in parental residential care, due to a guardianship order issued by the Youth Court. Both at pretest and post-test, maternal sensitivity and sensitive discipline were assessed during mother-child interaction via observational measures. Mothers who received the intervention showed a significant reduction in dysfunctional strategies of maternal discipline. Results highlight the usefulness and feasibility of a brief residential care-based intervention in such a risk sample, with promising implications for the prevention of child maltreatment.


Contextualizing the immigrant experience: the role of food and foodways in identity maintenance and formation for first- and second-generation Latinos in Ithaca, New York.
This study examines the role of food and foodways in identity maintenance and formation for Latino individuals in Ithaca, New York. Preliminary results indicate that food provides a physical link that connects individuals to their heritage culture and local communities. Despite variability in the importance that immigrants attribute to food, it remains one of the most resilient tools that informants identified as central to identity formation and maintenance. Food can therefore be a useful tool for examining the degree to which immigrants are maintaining their cultural identity and connectedness with their community.


[Effect of vibrational factors on the evaluation of whole-body vibrational intensity].
The aim of this study is to obtain basic data useful to evaluate the riding comfort of railway vehicles. The apparatus used in the present experiment made it possible to simulate various vibrations of railway vehicles. Twenty-two adult subjects participated in this experiment. They were exposed to lateral vibration with varying peak and root mean square (rms) accelerations and frequencies. The types and ranges of vibrations used in this experiment approximated to the typical vibrations of railway vehicles. The subjects were asked to rate the intensity of each vibration given to them successively, using the 7-step rating scale. Results indicated that both peak and rms accelerations significantly affected for the evaluation, although the effect of frequency was not significant. As for interactions, it was found that there were significant interacting effects between frequency and peak acceleration, between frequency and rms acceleration, and between peak and rms accelerations. It was also found that the relationship between the rms acceleration and the evaluated score changed with varying peak accelerations.


Reliability of the Modified Mini-Mental State Examination in the context of a two-phase community prevalence study.
Data collected through the Canadian Study of Health and Aging were analyzed to estimate the reliability of the Modified Mini-Mental State (3MS) Examination when used in the context of a two-phase community prevalence study. During the screening phase of the study, subjects were tested in their home by a lay interviewer, either in English or French. All subjects scoring 77 or under on the 3MS and a sub-sample of those scoring over 77 were reassessed by a nurse during a clinical examination, following which subjects were classified as normal, cognitively impaired but not demented, or demented. Results indicate substantial reproducibility of the 3MS, slightly higher than that of the Mini-Mental State Examination from which it is derived. The english versions of these tests appear slightly more reproducible than their French counterparts.


Excited states of ladder-type π-conjugated dyes with a joint SOS-CIS(D) and PCM-TD-DFT approach.
First-principle simulations aimed at accurately reproducing the excited state properties of a large series of ladder-type π-conjugated organic molecules containing heteroatoms (Si, S, B, O, and N) have been performed. In particular, time-dependent density functional theory (TD-DFT) calculations relying on several global and range-separated hybrid functionals have been carried out in conjunction with three variations of the polarizable continuum model (PCM), namely, the linear-response (LR), corrected linear-response (cLR), and state-specific (SS) approaches. For this series of molecules, similar to many borate derivatives, the cLR-PCM-TD-M06-2X approach can be used to reproduce the auxochromic effects that tune the 0-0 energies. However, TD-DFT yields rather large absolute deviations with respect to the experimental 0-0 energies. These systematic errors can be reduced by more than 0.1 eV when scaled opposite spin-configuration interaction singles with a double correction [SOS-CIS(D)] vertical calculations are combined to the PCM-TD-DFT results. This study demonstrates that such a "hybrid" scheme, where the geometrical and vibrational parameters, as well as the solvation effects, are determined with PCM-TD-DFT, whereas the transition energies are obtained with a wavefunction-based method, offers a useful compromise between accuracy and computational cost.


Obesity: locus of control, body image, weight loss, and age-at-onset.
In a retrospective investigation designed to measure locus of control, body image, and weight loss in Overeaters Anonymous members who had childhood, adolescence, or adulthood onset of obesity, 116 subjects were grouped according to age at onset of obesity and the year they joined OA. A convenience, volunteer sample of OA members completed a demographic data questionnaire, Rotter's Social Reaction. Inventory, and Secord and Jourard's Body Cathexis Scale. Significant overweight percentage differences were not found when the three age-at-onset groups were compared. Significant differences emerged, however, for adolescent-onset group persons who were categorized as "old" members; they had a larger weight loss and were more satisfied with their body image. A positive linear relationship between greater perception of internal control and a good body image was found in the entire adulthood-onset group. Weight loss and good body image of the oldest adolescent-onset group probably was the outcome of their association with a self-help group i.e., OA. Assessment of developmental issues related to the time of initial weight gain may indicate which treatment regime would be most effective.


Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats.
Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis. Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature. Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression). Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.


Spinal cord compression injury in guinea pigs: structural changes of endothelium and its perivascular cell associations after blood-brain barrier breakdown and repair.
This study examines morphological changes of the blood-brain barrier (BBB) after spinal cord compression. The lowest thoracic segment (T13) of female guinea pigs was injured and the BBB was tested from 7 days to 5.5 months postinjury using intravenously injected horseradish peroxidase (HRP) as a tracer. Tracer leakage in the injured segment was verified with the light microscope and the fine structure of capillaries was examined. Diffuse tissue staining was observed at T13 up to 2 weeks following injury. A leaky BBB correlated with expected changes in the fine structure of endothelial cell junctions. These were predominantly nonoverlapping cell junctions which, in many instances, were separated by clefts between adjacent cells. At early survival times, numerous capillary profiles with juxtaposed astrocyte foot processes were noted in addition to altered cell associations. Complete sealing of the BBB against interstitial HRP leakage was not observed until 17 days postinjury. After the first week, some of the endothelial cells were contacted by macrophages, processes of perivascular microglia, and processes of swollen and degenerating astrocytes. Perivascular spaces varied in extent and contained amorphous deposits of extracellular materials in addition to supernumerary layers of basal lamina. The early changes were followed by profound tissue restructuring due to loss of both neurons and glia. At longer survival times the BBB to HRP repaired. Endothelial cells formed complex overlapping junctions with zonulae occludentes. Most of the capillaries in the injured segment were no longer in direct contact with astrocyte foot processes, although reactive astrocytes constituted the predominant cell type in the remaining gray matter. Substantial expansion of perivascular spaces was evident. The cytoplasm of endothelial cells had numerous pinocytotic vesicles. Perivascular spaces contained layers of assembled collagen arranged perpendicularly to each other in addition to amorphous matrix materials. The findings suggest that decoupling of astrocyte foot processes from endothelial cell surfaces does not prevent reformation of tight junctions. It remains to be examined what effects the larger perivascular spaces, extracellular matrix deposits, and changes of cell associations may have on transport systems and ionic buffering. The data are relevant for estimating an opportune time for application of barrier-impermeable drugs to the lesion area.


[Comorbidity in the migraine: depression, anxiety, stress and insomnia].
Migraine is frequently associated to other pathologies or factors. To analyze the migraine's profile in a neurologic consultation and to determinate its comorbidity. 155 patients (36 men and 119 women) were studied in a neurologic consultation of the University Hospital of Salamanca during the year 2005. Migraine was diagnosed according the International Headache Society criteria, and associated disorders were measured using the Goldberg's Anxiety and Depression Scale, the Perceived Stress Questionnaire and the Oviedo Sleep Questionnaire. 99 patients suffered from migraine without aura and 56 with aura; mean age was 36 years; age at onset 20.64 years. 43 migraneurs had depression, anxiety 34, insomnia 58, stress 79, none of these pathologies 62 (40%). Depression and dream upheavals were close to equal between the migraine subtypes (although depression was something more common in migraine without aura), while anxiety and stress were more frequent in migraine with aura (RR: 1.42; 95% CI: 0.92-2.2; and RR: 1.38; 95% CI: 0.9-2.12, respectively). Depression and insomnia were more likely among women with nonsignificant differences (RR: 1.3; 95% CI: 0.95-1.34; and RR: 1.13; 95% CI: 0.95-1.34, respectively), whereas anxiety and stress were similar in both genders. Another associations were found between: migraine's family-history and migraine with aura (OR: 1.31; 95% CI: 0.63-2.71); some dietary factors and migraine without aura (OR: 2.27; 95% CI: 0.57-9.07). 60% of our migraneurs had at least one of the following disorders: depression (27.74%), anxiety (21.94%), stress (50.97%) or insomnia (37.42%); can trigger or worsen migraine attacks.


Trisomy 7 and Potter syndrome.
A patient with mosaic trisomy 7 and features of Potter syndrome is described. The patient was the product of a 35-week gestation and survived fourteen hours, demise being attributed to respiratory insufficiency. Autopsy confirmed pulmonary hypoplasia and renal agenesis. Additional findings included malformed, low-set ears, a flattened nasal bridge, redundant nuchal skin, positional deformation of the extremities, rocker-bottom feet, and clitorimegaly. Cytogenetic study of peripheral blood and skin fibroblast culture revealed mosaicism for full trisomy 7, the skin showing 12% of the cells to have an extra 7. Comparison with one previously confirmed case of trisomy 7 and two cases of trisomy C suggests a correlation between trisomy 7 and Potter syndrome.


Short- and long-term outcomes of ileal pouch-anal anastomosis for ulcerative colitis.
Ileal pouch-anal anastomosis was an important advancement in the treatment of ulcerative colitis. The aim of this study was to determine whether early complications of ileal pouch-anal anastomosis in patients with ulcerative colitis are associated with poor late functional results. Eighty patients were operated on from 1986 to 2000, 62 patients with ileostomy and 18 without. The early and late complications were recorded. Specific emphasis has been placed on the incidence of pouchitis with prolonged follow-up. The ileostomy was closed an average of 9.2 months after the first operation. Fourteen patients were excluded from the long-term evaluation; 6 patients were lost to regular follow-up, 4 died, and 4 patients still have the ileostomy. Of the 4 patients that died, 1 died from surgical complications. Early complications after operation (41) occurred in 34 patients (42.5%). Late complications (29) occurred in 25 patients as follows: 16 had pouchitis, 3 associated with stenosis and 1 with sexual dysfunction; 5 had stenosis; and there was 1 case each of incisional hernia, ileoanal fistula, hepatic cancer, and endometriosis. Pouchitis occurred in 6 patients (9.8%) 1 year after ileal pouch-anal anastomosis, 9 (14.8%) after 3 years, 13 (21.3%) after 5 years, and 16 (26.2%) after more than 6 years. The mean daily stool frequency was 12 before and 5.8 after operation. One pouch was removed because of fistulas that appeared 2 years later. Ileal pouch-anal anastomosis is associated with a considerable number of early complications. There was no correlation between pouchitis and severe disease, operation with or without ileostomy, or early postoperative complications. The incidence of pouchitis was directly proportional to duration of time of follow-up.


[Daunomycin-human albumin microspheres (dau-ha-ms)--preparation, characterization and use in experimental cancer therapy].
For the purpose of enhancing the therapeutic index and reducing the toxic effect of chemotherapeutic drugs, Dau-HA-Ms was prepared, mostly as monodispersed microspheres with a mean diameter of 52 +/- 16 microns, ranging from 29 to 194 microns, being suitable for the use of transarterial embolization (TAE) therapy. Dau released effectively in physiological saline solution from microspheres without burst release. The spectrophotometric characteristics and cytotoxic effect in vitro of the released Dau remained unchanged, retaining the original physicochemical and biological properties. It was demonstrated that 30% of mice bearing S-180 sarcoma ascites treated with intraperitoneal injection of Dau-HA-MS survived longer than 6 months, while all tumor bearing control mice and Dau treated tumor bearing mice died within 21 and 14 days, respectively. The results show that Dau-HA-MS is therapeutically more effective and less toxic than Dau, Dau-HA-MS can possibly be used in TAE therapy for human liver cancer.


Surgical indication of pediatric Rathke's cleft cyst based on a 20-year retrospective cohort.
Rathke's cleft cyst (RCC) is the most commonly encountered pituitary incidentaloma in children. Because RCC is not frequently diagnosed in children, there are few reports on pediatric RCCs. The natural course of the disease and appropriate treatments are still obscure. The present study aimed to elucidate the natural history and surgical indications of RCCs in children. The authors retrospectively reviewed the clinical presentations, imaging features, ophthalmological evaluations, endocrine evaluations, and surgical outcomes of pediatric RCCs at a single institution from January 2000 to October 2022. Clinical outcomes between the surgery and observation groups were compared. Among 93 patients, there were 41 patients in the surgery group and 52 patients in the observation group. The mean age at diagnosis was 10.9 years, and the mean follow-up period was 5.6 years. Headache fully or partially improved after surgery (86.2%), but the rate of improvement was not different from that of the observation group (70.0%). Ophthalmological abnormalities were effectively improved by surgical treatment (93.3%). Both the improvement and deterioration rates of endocrine abnormalities were significantly higher in the surgery group (p = 0.026 and p < 0.001, respectively), but the deterioration rate (43.9%) was higher than the improvement rate (14.6%). In the surgery group, the recurrence rate was 17.1% and the reoperation rate was 4.9%. Compared with total cyst wall resection, cyst fenestration with partial wall resection was associated with a higher recurrence rate (26.9%, p = 0.035) but a lower rate of endocrine abnormalities (30.8%, p = 0.049). Pediatric RCCs of ≥ 10 mm in size were analyzed. Ophthalmological abnormalities are the major surgical indications for pediatric RCCs. Headache and partial endocrine abnormalities may be improved with surgery, but they are not absolute indications for surgery. Cyst fenestration with partial wall resection via an endoscopic endonasal approach is the most recommended surgical method. Follow-up is essential to monitor for the occurrence of visual field defects and the recurrence of cysts.


The case for integrating grounded theory and participatory action research: empowering clients to inform professional practice.
Grounded theory and participatory action research methods are distinct approaches to qualitative inquiry. Although grounded theory has been conceptualized in constructivist terms, it has elements of positivist thinking with an image of neutral search for objective truth through rigorous data collection and analysis. Participatory action research is based on a critique of this image and calls for more inclusive research processes. It questions the possibility of objective social sciences and aspires to engage people actively in all stages of generating knowledge. The authors applied both approaches in a project designed to explore the experiences of female survivors of childhood sexual abuse with physical therapy and subsequently develop a handbook on sensitive practice for clinicians that takes into consideration the needs and perspectives of these clients. Building on this experience, they argue that the integration of grounded theory and participatory action research can empower clients to inform professional practice.


Improving inference for aerial surveys of bears: The importance of assumptions and the cost of unnecessary complexity.
Obtaining useful estimates of wildlife abundance or density requires thoughtful attention to potential sources of bias and precision, and it is widely understood that addressing incomplete detection is critical to appropriate inference. When the underlying assumptions of sampling approaches are violated, both increased bias and reduced precision of the population estimator may result. Bear (Ursus spp.) populations can be difficult to sample and are often monitored using mark-recapture distance sampling (MRDS) methods, although obtaining adequate sample sizes can be cost prohibitive. With the goal of improving inference, we examined the underlying methodological assumptions and estimator efficiency of three datasets collected under an MRDS protocol designed specifically for bears. We analyzed these data using MRDS, conventional distance sampling (CDS), and open-distance sampling approaches to evaluate the apparent bias-precision tradeoff relative to the assumptions inherent under each approach. We also evaluated the incorporation of informative priors on detection parameters within a Bayesian context. We found that the CDS estimator had low apparent bias and was more efficient than the more complex MRDS estimator. When combined with informative priors on the detection process, precision was increased by >50% compared to the MRDS approach with little apparent bias. In addition, open-distance sampling models revealed a serious violation of the assumption that all bears were available to be sampled. Inference is directly related to the underlying assumptions of the survey design and the analytical tools employed. We show that for aerial surveys of bears, avoidance of unnecessary model complexity, use of prior information, and the application of open population models can be used to greatly improve estimator performance and simplify field protocols. Although we focused on distance sampling-based aerial surveys for bears, the general concepts we addressed apply to a variety of wildlife survey contexts.


Manifestation of plasmonic response in the detection of sub-terahertz radiation by graphene-based devices.
We report on the sub-terahertz (THz) (129-450 GHz) photoresponse of devices based on single layer graphene and graphene nanoribbons with asymmetric source and drain (vanadium and gold) contacts. Vanadium forms a barrier at the graphene interface, while gold forms an Ohmic contact. We find that at low temperatures (77 K) the detector responsivity rises with the increasing frequency of the incident sub-THz radiation. We interpret this result as a manifestation of a plasmonic effect in the devices with the relatively long plasmonic wavelengths. Graphene nanoribbon devices display a similar pattern, albeit with a lower responsivity.


Interferon-gamma induces a decrease in the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells.
We studied the effect that treating two types of glioblastoma cell lines, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their susceptibility to lysis by lymphokine-activated killer (LAK) cells. We also examined the participation of cell-adhesion molecules and major histocompatibility complex (MHC) class I and II antigens present on the target cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml) for 48 hours resulted in the increased expression of both intercellular-adhesion molecule 1 and MHC class I antigens on tumor cells. In addition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affected by IFN-gamma treatment. These changes in expression were accompanied by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further inhibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-gamma increased their susceptibility to lysis by LAK cells. These findings suggest that treatment of glioblastoma cells with IFN-gamma decreased their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expression of MHC class I antigen on target cells.


Genetic and environmental variation in political orientation in adolescence and early adulthood: A Nuclear Twin Family analysis.
Political orientation is often assumed to be shaped by socialization processes; however, previous studies have shown substantial genetic variance components in party affiliation, political attitudes and behaviors, or closely related personality traits. The majority of these studies have relied on the Classical Twin Design, which comes with restrictive assumptions, some of which are easily violated. Moreover, most analyses lack a perspective of age-group differences. In this study, we investigated political orientation in adolescents (age: 16-18) and young adults (age: 21-25) in a cross-sectional Nuclear Twin Family Design. We used data of the German TwinLife project, including data from same-sex twins reared together, their biological parents, and nontwin full siblings. We found genetic variation in political orientation, which was significant in the older cohort, possibly indicating an increasing importance of active gene-environment correlation from adolescence to adulthood. Individual differences in political orientation because of passive gene-environment correlation and shared environmental effects were larger in the younger cohort, substantiating the same theoretical consideration and the importance of shared socialization contexts for adolescents' political views. By running Nuclear Twin Family model analyses, and considering age-group differences, as well as the relationship of political orientation with the Big Five personality traits, our study extended previous work, and resulted in more robust and fine-grained estimates of genetic and environmental sources of variance in political orientation. Therefore, it contributed to a better understanding of the complex nature-nurture interplay that forms political orientation in emerging adulthood. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Use of propofol for anesthesia in cats with primary hepatic lipidosis: 44 cases (1995-2004).
OBJECTIVE-To determine morbidity and fatalities in cats with hepatic lipidosis that received propofol to facilitate placement of a feeding tube. STUDY DESIGN-Retrospective case series. ANIMALS-44 Cats with presumed primary hepatic lipidosis anesthetized for placement of a feeding tube. PROCEDURES-Medical records from January 1995 through December 2004 were reviewed to identify cats that matched the inclusion criteria (histologic confirmation of hepatic lipidosis, anesthetized for placement of feeding tube, complete intensive care unit [ICU] records, and recorded outcome). Data extracted included age, body weight, sex, anesthetic drugs, drug dosages, type of feeding tube, duration of anesthesia, number of hours in ICU, administration of blood products, and survival until discharge from ICU. RESULTS-44 Cats (21 females and 23 males) were included in the analysis. Age range was 3 to 15 years (median, 8 years), and body weight ranged from 1.8 to 9.0 kg (4.0 to 19.8 lb), with a median of 4.8 kg (10.6 lb). Twenty-seven cats were administered propofol. There was no significant association between the use of propofol or the dosage of propofol and any risk factor, need for blood products, number of hours in the ICU, or survival. There was no significant difference between cats that received propofol and cats that did not receive propofol with regard to interval until discharge from the ICU. CONCLUSIONS AND CLINICAL RELEVANCE-The use of propofol did not increase morbidity or fatalities in cats with primary hepatic lipidosis. Thus, propofol can be used in these cats for placement of a feeding tube.


HIV-1 p55-gag protein induces senescence of human bone marrow mesenchymal stem cells and reduces their capacity to support expansion of hematopoietic stem cells in vitro.
Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the BM mesenchymal stem cells (BMSCs) can be impacted by HIV proteins that are released by infected cells within BM. In this study, we tested whether HIV protein p55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with p55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon ). Then, we analyzed the hematopoietic support function of BMSCcon and BMSCgag by determining cellular proliferation, colony-forming ability, and primitive hematopoietic populations of hematopoietic progenitors grown on the BMSCs. In addition, we compared the gene expression patterns for supporting hematopoiesis of BMSCcon and BMSCgag. The results show that when compared to BMSCcon , BMSCgag reduced their proliferative activity and underwent senescence. The ability of BMSCgag to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired, while the expression of genes associated with maintaining and enhancing hematopoiesis appeared to be decreased in treated BMSCs compared to control BMSCs. In conclusion, senescence induced by p55-gag resulted in decreased hematopoietic support function of BMSCs through reducing a series of hematopoietic cytokine expression.


Benefits and risks of combined oral contraceptives.
The use of combined oral contraceptives carries a number of well-established major non-contraceptive benefits. Of these, the most important protective effects are suppression of the risk of epithelial cancer of the ovary and cancer of the endometrium. Also of great importance is a reduction in the risk of pelvic inflammatory disease. Needless to say, there are also some established risks of combined oral contraceptives. The most important of these are the vascular ones, comprising effects on acute myocardial infarction, thrombotic stroke, haemorrhagic stroke, and venous thrombosis and embolism. Possible risks which are still under evaluation include an adverse effect on breast cancer and, likewise, on carcinoma of the cervix. More information is needed about both these conditions. A number of authors have provided analyses of varying degrees of complexity in which they have attempted to weigh the benefits and risks of combined oral contraceptives. Results from some of these studies are presented in the paper. On the whole, the findings are reasonably reassuring.


A de novo transcriptomic analysis to reveal functional genes in Apolygus lucorum.
The widespread planting of genetically engineered cotton producing the Cry1Ac toxin has led to significantly reduced pesticide applications since 1997. However, consequently, the number of green mirid bugs (GMB), Apolygus lucorum (Meyer-Dür) has increased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera (Hübner), has become the major pest in the transgenic Bt cotton field and has influenced cotton yield. Disproportionately, only a few studies on GMB at molecular level have been reported. Libraries from both third instar nymphs and adults were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 unigenes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes (42.01%) matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes (DEGs) strategy between the two developmental stages: nymph and adult. The results demonstrated that thousands of genes were significantly differentially expressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding.


Dedifferentiation of oncocytic epithelial-myoepithelial carcinoma to mucoepidermoid carcinoma in parotid gland: A rare case report.
Epithelial-myoepithelial carcinomas (EMCs) account for <1% of all salivary gland malignancies. Till now, 23 cases of dedifferentiated EMC have been reported to the best of our knowledge. However, dedifferentiation of oncocytic EMC to mucoepidermoid carcinoma is extremely rare. A 38-year-old female presented with right post aural swelling 4 cm × 2 cm in size for 6 months. Surgical excision was carried out, and we received partly skin-covered tissue 5 cm × 2 cm in size. Sections examined showed features of oncocytic EMC dedifferentiating into mucoepidermoid carcinoma. Myoepithelial component showed oncocytic change which was highlighted by p63.


Historical climate controls soil respiration responses to current soil moisture.
Ecosystem carbon losses from soil microbial respiration are a key component of global carbon cycling, resulting in the transfer of 40-70 Pg carbon from soil to the atmosphere each year. Because these microbial processes can feed back to climate change, understanding respiration responses to environmental factors is necessary for improved projections. We focus on respiration responses to soil moisture, which remain unresolved in ecosystem models. A common assumption of large-scale models is that soil microorganisms respond to moisture in the same way, regardless of location or climate. Here, we show that soil respiration is constrained by historical climate. We find that historical rainfall controls both the moisture dependence and sensitivity of respiration. Moisture sensitivity, defined as the slope of respiration vs. moisture, increased fourfold across a 480-mm rainfall gradient, resulting in twofold greater carbon loss on average in historically wetter soils compared with historically drier soils. The respiration-moisture relationship was resistant to environmental change in field common gardens and field rainfall manipulations, supporting a persistent effect of historical climate on microbial respiration. Based on these results, predicting future carbon cycling with climate change will require an understanding of the spatial variation and temporal lags in microbial responses created by historical rainfall.


Identification of a Novel Mutation in the PAH Gene in an Iranian Phenylketonuria Family: A Case Report.
Phenylketonuria (PKU) is an inborn error of amino acid metabolism with an autosomal recessive inheritance caused in most cases by mutations in the phenylalanine hydroxylase (PAH) gene. PKU has wide allelic heterogeneity. Here we report a novel heterozygous substitution (c.1223G>T (p.Arg408Leu)) in the PAH gene in an Iranian PKU family. The patient was 19-yr-old female with diagnosis of moderate PKU referred to Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran for genetic counseling/analysis in April 2015. We used PCR-Sequencing to identify any sequence variations in the PAH gene.


[Effect of physical activity on bone turnover in young boys].
To evaluate the effect of the physical activity on bone turnover in young male soccer players at the Tanner's stage of 1-2. 61 young soccer players (13,4 +/- 0,3 years old) who actively participated in soccer since 3,7 +/- 0,7 years were compared to 60 age and sex- matched non active subjects. Bone mineral density (BMD) of whole body, and in specific skeleton sites, fatty body mass (FBM) and lean body mass (LBM) were determined by a dual energy X-ray absorptiometry (DXA). Total plasma alkaline phosphatase (ALP) and plasma bone alkaline phosphatase (BALP), plasma osteocalcin (OC) and plasma collagen type I cross-linked C-telopeptide (CTX) were measured. BMD of the whole body and at the lumbar spine (L2-L4), femoral, lower limbs and LBM were significantly higher in young soccer players than in controls. The biochemical markers of bone turnover: ALP (6,7%), BALP (8,9%), OC (3%) and CTX (3,1%) were not significantly higher in sportsmen than in controls. The calcium was significantly higher in sportsmen than in controls. These results suggest that soccer practice induced an increase of bone mass in boys. The increase in the level of bone turnover evaluated by the new biochemical markers was not significant in the sportsmen.


Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews.
Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs. We defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected. We selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional "childhood" diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination. Within each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers.


[Urolithiasis in HIV-positive patients: prevalence and risk factors].
Today, the total number of people living with the human immunodeficiency virus (HIV) is 43.8 million. From the moment of infection to the terminal stage of the disease, the risk of stone formation progressively increases. A prevalence and role of individual risk factors for urolithiasis in patients with HIV are reviewed in the article. It is shown that in HIV-positive individuals, urolithiasis takes a leading position among renal diseases, with a prevalence ranging from 8 to 27%. The main risk factors for urolithiasis in HIV are: dietary factors, age, comorbid pathologies, use of protease inhibitors, changes in the ionic composition of urine, etc.


Feasibility and scalability of spring parameters in distraction enterogenesis in a murine model.
Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model. A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology. Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm (P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm (P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine. Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future.


Intestinal parasitoses and environmental factors in a rural population of Argentina, 2002-2003.
We evaluate the prevalence of intestinal parasites in 504 people and the degree of association between environmental variables and parasites found in population, soil and water in a rural area of Argentina during 2002-2003. A structured survey was used to evaluate the environmental variables and fecal-human, soil and water samples were analyzed. The prevalence of parasites was 45.4%. Most prevalent protozoa were Blastocystis hominis (27.2%) and Giardia lamblia (6.9%), while the most prevalent helminth was Ascaris lumbricoides (3.8%). The analyzed environmental variables showing association (p < 0.05) with presence of parasites in population were: cardboard-tin or wooden house, dirt floor, home or communal water pump, faucet outside the house or public faucet and cesspool or latrine. Parasite forms were found in 82.3% of the soil samples and in 84.2% of the water samples. In both samples we found parasites that were also found in people. In this study we have found deficient sanitary conditions associated with presence of parasites in population and we have evidenced that contaminated soil and water were the source of these parasites.


Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Data Set of Metabolic Mixtures.
Nuclear magnetic resonance (NMR) spectroscopy has tremendous advantages of minimal sample preparation and interconvertibility of data among different institutions; thus, large data sets are frequently acquired in metabolomics studies. Previously, we used a novel analytical strategy, named signal enhancement by spectral integration (SENSI), to overcome the low signal-to-noise ratio (S/N ratio) problem in (13)C NMR by integration of hundreds of spectra without additional measurements. In this letter, the development of a SENSI 2D method and application to >1000 2D JRES NMR spectra are described. Remarkably, the obtained SENSI 2D spectrum had an approximate 14-fold increase in the S/N ratio and 80-250 additional peaks without any additional measurements. These results suggest that SENSI 2D is a useful method for assigning weak signals and that the use of coefficient of variation values can support the assignment information and extraction of features from the population characteristics among large data sets.


Distribution of Aromatic Amino Acid Residues in Substrate-Binding Regions Modulates Substrate Specificity of Microbial Debranching Enzymes.
Debranching enzymes (DBEs) directly hydrolyze α-1,6-glucosidic linkages in glycogen, starch, and related polysaccharides, making them important in the starch processing industry. However, the ambiguous substrate specificity usually restricts synergistic catalysis with other amylases for improving starch utilization. Herein, a glycogen-debranching enzyme from Saccharolobus solfataricus (SsGDE) and two isoamylases from Pseudomonas amyloderamosa (PaISO) and Chlamydomonas reinhardtii (CrISO) were used to investigate the molecular mechanism of substrate specificity. Along with the structure-based computational analysis, the aromatic residues in the substrate-binding region of DBEs played an important role in binding substrates. The aromatic residues in SsGDE appeared clustered, contributing to a small substrate-binding region. In contrast, the aromatic residues in isoamylase were distributed dispersedly, forming a large active site. The distinct characteristics of substrate-binding regions in SsGDE and isoamylase might explain their substrate preferences for maltodextrin and amylopectin, respectively. By modulating the substrate-binding region of SsGDE, variants Y323F and V375F were obtained with significantly enhanced activities, and the activities of Y323F and V375F increased by 30 and 60% for amylopectin, and 20 and 23% for DE4 maltodextrin, respectively. This study revealed the molecular mechanisms underlying the substrate specificity for SsGDE and isoamylases, providing a route for engineering enzymes to achieve higher catalytic performance.


Baicalein ameliorates ischemic brain damage through suppressing proinflammatory microglia polarization via inhibiting the TLR4/NF-κB and STAT1 pathway.
Microglial polarization mediated neuroinflammation plays an important role in the pathological process of stroke. The aim of this study is to determine whether baicalein indirectly ameliorates neuronal injury through modulating microglial polarization after stroke and if so, then by what mechanism. The effects of baicalein on microglial polarization were revealed through the middle cerebral artery occlusion mouse model (MCAO, n = 6), the lipopolysaccharide (LPS) + interferon-γ (IFN-γ) and oxygen-glucose deprivation (OGD) induced neuroinflammatory microglia model (BV2, n = 3), respectively. Mice were treated with baicalein (100 mg/kg, i.g.) after reperfusion, and followed by daily administrations for 3 days. Results showed that the infarct volumes at 3 d in vehicle and baicalein-treated MCAO mice were 91.18 ± 4.02% and 55.36 ± 4.10%. Baicalein improved sensorimotor functions (p < 0.01) after MCAO. Real-time PCR revealed that baicalein decreased proinflammatory markers expression (p < 0.05), while elevated the anti-inflammatory markers (p < 0.05) in vivo and in vitro. Both western blot and immunofluorescent staining further confirmed that baicalein reduced proinflammatory marker CD16 levels (p < 0.01) and enhanced anti-inflammatory marker CD206 or Arg-1 levels (p < 0.05). Notably, baicalein suppressed the release of proinflammatory cytokines (p < 0.05) and nitric oxide (NO, p < 0.001). Mechanistically, baicalein prevented increases in TLR4 protein levels (p < 0.001), the phosphorylation of IKBα and p65 (p < 0.01), and the nuclear translocation of NF-κB p65 (p < 0.05). The NF-κB inhibitor, BAY 11-7085, enhanced the inhibitory effect of baicalein on the proinflammatory microglial polarization. Baicalein also inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1, p < 0.001). A microglia-neuron co-culture system revealed that baicalein driven neuroprotection against OGD induced neuronal damage through modulating microglial polarization (p < 0.05). Baicalein indirectly ameliorates neuronal injury after stroke by polarizing microglia toward the anti-inflammatory phenotype via inhibition of the TLR4/NF-κB pathway and down-regulation of phosphorylated STAT1, suggesting that baicalein might serve a potential therapy for stroke.


PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth.
Akt/protein kinase B critically regulates the balance between cell survival and apoptosis. Phosphorylation of Akt at two key sites, the activation loop and the hydrophobic motif, activates the kinase and promotes cell survival. The mechanism of dephosphorylation and signal termination is unknown. Here, we identify a protein phosphatase, PH domain leucine-rich repeat protein phosphatase (PHLPP), that specifically dephosphorylates the hydrophobic motif of Akt (Ser473 in Akt1), triggering apoptosis and suppressing tumor growth. The effects of PHLPP on apoptosis are prevented in cells expressing an S473D construct of Akt, revealing that the hydrophobic motif is the primary cellular target of PHLPP. PHLPP levels are markedly reduced in several colon cancer and glioblastoma cell lines that have elevated Akt phosphorylation. Reintroduction of PHLPP into a glioblastoma cell line causes a dramatic suppression of tumor growth. These data are consistent with PHLPP terminating Akt signaling by directly dephosphorylating and inactivating Akt.


Clinical Outcome and Prognostic Variables of Second-line Therapy for Patients With Castration-resistant Prostate Cancer After Failure of First-line Androgen Receptor Axis-targeted Therapy.
Despite the rapid introduction of androgen receptor-targeted agents (ARTA) into clinical practice for castration-resistant prostate cancer (CRPC), the optimal treatment strategy after first-line ARTA remains unclear. The object of this study was to clarify clinical outcomes of second-line therapy for CRPC after first-line ARTA. The medical records of 130 consecutive patients with CRPC with disease progression during first-line ARTA and who started second-line therapy at our Institution between 2014 and 2020 were analyzed. A total of 130 patients with CRPC were identified. Ninety patients underwent ARTA-ARTA treatment, and 40 patients underwent ARTA-docetaxel treatment. The median observation period after second-line ARTA or docetaxel administration was 14.2 months. The prostate-specific antigen response rates overall, and after second-line ARTA, and docetaxel were 26.8%, 24.7%, and 31.6%, respectively. The median progression-free survival (PFS) and 1- and 2-year PFS rates of second-line therapy were 7.9 months and 34.6% and 15.4%, respectively. The median overall survival (OS) and 1- and 2-year OS rates were 27.4 months and 81.8%, and 54.9%, respectively. Multivariate analyses for OS disclosed that a C-reactive protein over the upper limit of normal and time from first-line ARTA to progression under 12 months were associated with shorter OS. Prostate-specific antigen response, PFS and OS of second-line therapy were not significantly different between second-line ARTA and docetaxel. There was no significant difference in OS between ARTA-ARTA and ARTA-docetaxel groups in the present study, suggesting that second-line ARTA might be the preferred treatment after initial failure of ARTA.


MicroRNA-15 suppresses viability, migration and invasion of the human MG-63 osteosarcoma cells via inhibition of cyclin dependent kinase 6 (CDK6).
MicroRNA-15a-3p (miR-15) acts as tumor-suppressor in different human cancers including osteosarcoma. Nonetheless, the molecular function of miR-15 in osteosarcoma via suppression of cyclin dependent kinase 6 (CDK6) is yet to be studied. The results showed significant downregulation of miR-15 in osteosarcoma tissues and cell lines. Overexpression of miR-15 inhibited the proliferation and colony formation of the MG-63 osteosarcoma cells via induction of apoptosis. Moreover, miR-15 inhibited the migration and invasion of MG-63 osteosarcoma cells. The tumor-suppressive functional role of miR-15 was shown to be exerted via suppression of CDK6. The expression of CDK6 was upregulated in osteosarcoma and its silencing could exert growth inhibitory effects on human osteosarcoma cells. However, overexpression of CDK6 could nullify the tumor-suppressive effects of miR-15 on the MG-63 osteosarcoma cells. Taken together, miR-15 negatively regulates growth, migration and invasion of osteosarcoma cells by targeting CDK6 at post-transcriptional level. These findings suggest the therapeutic potential of miR-15/CDK6 in human osteosarcoma.


The effect of Imuran on implantation and early embryonic development in rats.
Pregnant rats were injected daily with 2, 4, and 20 mg/kg of Imuran from the first day of gestation until sacrificed on Days 6-12. Gravid uteri, as well as maternal organs, were removed and examined histologically. According to the histologic findings, the treatment with the high dose of 20 mg/kg/day Imuran induced injuries to the blastocyst. Starting from Day 8, the trophoblastic layer lost its continuity and maternal blood invaded into the blastocystic cavity resulting in destruction of embryonic tissues. This degeneration progressed until evident resorption on Day 12. Smaller doses, such as 2 or 4 mg/kg of Imuran, did not result in early trophoblastic damage. The effect seemed to be the result of the antimetabolic effect of Imuran acting on the proliferating trophoblast through the maternal blood.


A new acute inflammatory syndrome related to the introduction of mycophenolate mofetil in patients with Wegener's granulomatosis.
Mycophenolate mofetil (MMF) is increasingly used for prevention of allograft rejection and to treat immune disorders. We report the development of an acute inflammatory syndrome in two patients with Wegener's granulomatosis after MMF was introduced, because of persistent renal and systemic disease activity despite cyclophosphamide treatment. Within 1 week both patients developed an acute inflammatory syndrome, characterized by fever, arthralgias and muscle pain. No infection could be detected and no indications for increased Wegener's activity were present. MMF was stopped resulting in a rapid and complete resolution of the syndrome. A rechallenge with 2 g of MMF in the second patient resulted in a relapse of the syndrome within 4 days. There was an association between symptoms and increased levels of mycophenolic acid (MPA) acyl glucuronide and serum interleukin-6, suggesting the induction of inflammatory cytokines by MPA acyl glucuronide as the cause of the syndrome. Therefore, special attention should be given to side effects such as fever, arthralgias and muscle pain when treating patients with Wegener's granulomatosis during the active phase. Because this side effect of MMF may also occur after solid organ transplantation and in other immune disorders, pharmacokinetic profiling of MPA and MPA acyl glucuronide is needed in future studies with MMF.


Further SEM observation of human scalp hair: statistical research.
Scalp hair of 100 somalian subjects (50 males and 50 females) were examined with SEM at standard magnification (X 1.000). On each specimen, the hair diameter, mean scale height (M.S.H.), scale index (S.I.), mean scale number (M.S.N.) and mean scale width (M.S.W.) were searched. The statistical elaboration of the obtained data indicates that: i) the hair diameter and M.S.N. are greater in the males, while the other parameters (M.S.H., M.S.W. and S.I.) are prevalent in the females; ii) the hair diameter is directly correlated with M.S.W. and M.S.N., while M.S.H. shows a direct correlation with M.S.W. and an inverse on with M.S.N.. From the comparison between these results and those previously obtained in 100 subjects of white race it results that: a) the mean hair diameter as well as M.S.W. are greater in the white subjects; b) M.S.N., M.S.H. and S.I. are prevalent in the somalians.


Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism and affects amastigotes by increasing total iron bound capacity.
American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoa of the genus Leishmania. The high toxicity, high costs and resistance of some strains to current drugs has prompted the search for therapeutic alternatives for the management of this disease. Sphagneticola trilobata is a plant that has diterpenes as main constituents, including grandiflorenic acid (GFA) that has antiinflammatory, antiprotozoal, antibacterial and antinociceptive activity. The aim of our study was to determine the effect of GFA on both the promastigotes and the amastigotes of Leishmania amazonensis. Isolation by chromatographic methods and chemical identification of GFA, then evaluation of the in vitro leishmanicidal activity of this compound against Leishmania amazonensis promastigotes and L. amazonensis infected peritoneal Balb/c macrophages, as well its action and microbicide mechanisms. GFA treatment significantly inhibited the proliferation of promastigotes. This antiproliferative effect was accompanied by morphological changes in the parasite with 25 nM GFA. Afterwards, we investigated the mechanisms involved in the death of the protozoan; there was an increase in the production of reactive oxygen species (ROS), phosphatidylserine exposure, permeabilization of the plasma membrane and decreased mitochondrial depolarization. In addition, we observed that the treatment caused a reduction in the percentage of infected cells and the number of amastigotes per macrophage, without showing cytotoxicity in low doses to peritoneal macrophages and sheep erythrocytes. GFA increased IL-10 and total iron bound to transferrin in infected macrophages. Our results showed that GFA treatment acts on promastigote forms through an apoptosis-like mechanism and on intracellular amastigote forms, dependent of regulatory cytokine IL-10 modulation with increase in total iron bound to transferrin. GFA showed in vitro antileishmanial activity on L. amazonensis promastigotes forms and on L. amazonensis-infected macrophages.


A new method for calibrating indicator dilution curves.
A technique is proposed and experiments carried out to validate an in vivo method of calibrating ascorbate dilution curves. Cardiac output measured by the proposed method (COi) was compared to cardiac output measured by electromagnetic flowmeter (COe). COe averaged 1,281 mg/min and COi averaged 1,284 ml/min (P greater than 0.90). Correlation between the two methods was 0.92. It is concluded that the proposed method measures CO with reasonable accuracy and provides a number of advantages over the usual method of measuring blood flow by means of indicators.


Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation.
GABA is catabolized in the mitochondrial matrix through the GABA shunt, encompassing transamination to succinic semialdehyde followed by oxidation to succinate by the concerted actions of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), respectively. Gamma-hydroxybutyrate (GHB) is a neurotransmitter and a psychoactive drug that could enter the citric acid cycle through transhydrogenation with α-ketoglutarate to succinic semialdehyde and d-hydroxyglutarate, a reaction catalyzed by hydroxyacid-oxoacid transhydrogenase (HOT). Here, we tested the hypothesis that the elevation in matrix succinate concentration caused by exogenous addition of GABA, succinic semialdehyde or GHB shifts the equilibrium of the reversible reaction catalyzed by succinate-CoA ligase towards ATP (or GTP) hydrolysis, effectively negating substrate-level phosphorylation (SLP). Mitochondrial SLP was addressed by interrogating the directionality of the adenine nucleotide translocase during anoxia in isolated mouse brain and liver mitochondria. GABA eliminated SLP, and this was rescued by the GABA-T inhibitors vigabatrin and aminooxyacetic acid. Succinic semialdehyde was an extremely efficient substrate energizing mitochondria during normoxia but mimicked GABA in abolishing SLP in anoxia, in a manner refractory to vigabatrin and aminooxyacetic acid. GHB could moderately energize liver but not brain mitochondria consistent with the scarcity of HOT expression in the latter. In line with these results, GHB abolished SLP in liver but not brain mitochondria during anoxia and this was unaffected by either vigabatrin or aminooxyacetic acid. It is concluded that when mitochondria catabolize GABA or succinic semialdehyde or GHB through the GABA shunt, their ability to perform SLP is impaired.


Ethambutol-induced lichenoid eruption.
The tuberculostatic drug ethambutol is an infrequent skin offender. A lichenoid skin eruption restricted to the light-exposed areas in a 67-year-old male was proved by withdrawal and challenge to be caused by ethambutol. Patch tests with ethambutol 0.1%, 0.5% and 1% in watery solution were negative.


Septins: new microtubule interacting partners.
Originally characterized as regulators of cytokinesis, septins were later implicated in other cellular processes. Recent studies show that septins have a broader role in microtubule-dependent processes, such as karyokinesis, exocytosis, and maintenance of cell shape. Many members of the septin family have been shown to colocalize or interact with the microtubule cytoskeleton, suggesting that these might be general properties of septins. Septins could play an important role in regulating microtubule dynamics by interacting with microtubule-associated proteins (MAPs) that modulate microtubule stability. Being able to associate with both microtubules and actin, septins can play an important role as adaptors between the two cytoskeletons and as regulators of processes in which both actin and microtubules are involved. As septins are associated with various neurodegenerative diseases and cancer, a better understanding of the biology of septins and their interactions with microtubules is important in order to develop possible therapeutic strategies for these diseases.


[Acute renal failure--clinical aspects and morphology].
This study reports the pathological-anatomical diagnoses in 180 cases in which a diagnosis of acute renal failure (ARF) had been made on clinical grounds. The clinical and pathological diagnoses were in agreement in 43.3% of the cases. In 56.7%, the pathological-anatomical diagnosis differed from the clinical diagnosis. Glomerulonephritis (GN) was particularly often concealed behind ARF, in particular rapidly progressive GN, but also acute interstitial nephritis or hemolyticuremic syndrome. In addition, the clinical diagnoses in cases with a pathological-anatomical diagnosis of ARF are presented. Finally, the clinical diagnoses made in cases with a pathological-anatomical diagnosis of GN with ARF are reported. It is thus shown that the pathologist is in a position to distinguish GN with true compensated retention from GN with transient ARF simulating compensated retention.


Applications of near-infrared spectroscopy in "anaerobic" diagnostics - SmO2 kinetics reflect PCr dephosphorylation and correlate with maximal lactate accumulation and maximal pedalling rate.
We investigated the relationship of the time-dependent behaviour of muscle oxygen saturation SmO2(t), phosphagen energy supply WPCr(t) and blood lactate accumulation ΔBLC(t) during a 60-s all-out cycling sprint and tested SmO2(t) for correlations with the end of the fatigue-free state tFf, maximal pedalling rate PRmax and maximal blood lactate accumulation rate v̇Lamax. Nine male elite track cyclists performed four maximal sprints (3, 8, 12, 60 s) on a cycle ergometer. Crank force and cadence were monitored continuously to determine PRmax and tFf based on force-velocity profiles. SmO2 of the vastus lateralis muscle and respiratory gases were measured until the 30th minute after exercise. WPCr was calculated based on the fast component of the post-exercise oxygen uptake for each sprint. Before and for 30 minutes after each sprint, capillary blood samples were taken to determine the associated ΔBLC. Temporal changes of SmO2, WPCr and ΔBLC were analysed via non-linear regression analysis. v̇Lamax was calculated based on ΔBLC(t) as the highest blood lactate accumulation rate. All models showed excellent quality (R2 > 0.95). The time constant of SmO2(t) τSmO2 = 2.93 ± 0.65 s was correlated with the time constant of WPCr(t) τPCr = 3.23 ± 0.67 s (r = 0.790, p < 0.012), v̇Lamax = 0.95 ± 0.18 mmol · l-1 · s-1 (r = 0.768, p < 0.017) and PRmax = 299.51 ± 14.70 rpm (r = -0.670, p < 0.049). tFf was correlated with τSmO2 (r = 0.885, p < 0.001). Our results show a time-dependent reflection of SmO2 kinetics and phosphagen energy contribution during a 60-s maximal cycling sprint. A high v̇Lamax results in a reduction, a high PRmax in an increase of the desaturation rate. The half-life of SmO2 desaturation indicates the end of the fatigue-free state.


Ought we to sentence people to psychiatric treatment?
In principle, there seem to be three main ways in which society can react when people commit crimes under influence of mental illness. (1) The standard model. We excuse them. If they are dangerous they are detained in the interest of safety of the rest of the citizens. (2) The Swedish model. We hold them responsible for their criminal offence, we convict them, but we do not sentence them to jail. Instead, we sentence them to psychiatric treatment. (3) My model. We sentence them to jail, but offer them (voluntary) psychiatric treatment. The advantages of my model are obvious. We get a clear delineation of roles. We allow the psychiatrist to be just a doctor, not a warden. We liberate psychiatry of the objective of deciding whether people who were mentally ill when they committed criminal offences 'could have acted otherwise' -- a hopeless task. We allow that psychiatrists live up to their professional ethical code (The Hawaii Declaration). We treat psychically ill persons as 'normal', we allow them to repent their crimes, which renders easier their recovery. However, two objections to my model come to mind. First of all, is it not unfair to sentence people to jail who could not help doing what they did? And, secondly, the question of fairness set to one side, is it not inhumane to sentence mentally ill persons to jail? Is it not inhumane to the mentally ill persons themselves, and does it not mean that they will be a burden to other prisoners? In my paper I show that, if our system of criminal punishment takes a civilised form, neither of these objections carries any weight.


[M-mode echocardiography in dressage horses, class S jumping horses and untrained horses].
Heart structures of 45 warmblooded horses were measured by M-mode-echocardiography. The current training level of 15 dressage horses (group I) and 15 show-jumping horses (group II) was category "S". In the third group were 15 untrained horses. Four standardized transducer positions were determined for the m-mode echobeam, calibrated according to the two-dimensional real time technique. End systolic and end diastolic diameters of left ventricle, right ventricle, aortic root, interventricular septum and left ventricular wall, as well as motion pattern of heart wall, mitral valve and aortic valve of all horses were measured. The dressage horses showed a significant thickening of interventricular septum and left-ventricular wall compared with the show-jumping horses and the untrained horses. The end diastolic left ventricle diameter of the show-jumping horses was significantly larger than in the other groups. Compared to the untrained horses the show-jumping horses showed a significantly larger end systolic left ventricular wall diameter measured at the level of papillary muscle. It can be concluded, that an increase in heart mass in category "S" sport horses is attributed to their level of training.


Livedo reticularis, developmental delay and stroke-like episode in a 7-year-old male.
Livedo reticularis is a vascular abnormality of the skin resulting in an erythematous reticular rash. The combination of livedo reticularis and stroke-like episodes in adults is known as Sneddon syndrome [Sneddon, IB (1965). Br J Dermatol 77:180-188]. A similar combination of stroke-like episodes and livedo reticularis has been reported to occur in children [Baxter P et al. (1993). Dev Med Child Neuro 35:917-926]. We present here a 7-year-old male with congenital livedo reticularis, obesity, developmental delay, stroke-like episode, hypertension and cystic kidneys. We summarize our patient's findings and family history, and compare his disorder to other possibly related conditions.


Cementoenamel defects in an unusual location.
An unusual case involving cementoenamel defects was discussed. These defects appeared as vertical grooves at the cervical margins on the facial surfaces of the maxillary incisors. They have caused no pulpal or periodontal problems.


A micro gas chromatography column with a micro thermal conductivity detector for volatile organic compound analysis.
In this paper, a micro gas chromatography (μGC) system contained a μGC column and a micro thermal conductivity detector (μTCD) was proposed. In order to reduce the volume of the system, some micro heaters were integrated on the surface and backside of the GC column, which could provide a robust temperature programming capability and rapidly increase the temperature of the μGC column. In addition, a silicon-glass μTCD with four-thermistor thermal conductivity cells that can offer significant advantages over previously reported designs including low dead volume, good thermal isolation, and elimination of the thermal noise was proposed in this paper. Experimental results have indicated that the μGC system with a detection limit of several ppm concentration levels separated and detected the benzene, toluene, and styrene in less than 3 min, and the μGC system also exhibited a good linear response in the test range.