Phorbol ester-induced inhibition of cyclic GMP formation mediated by muscarinic receptors in murine neuroblastoma cells.
The effects of phorbol 12-myristate 13-acetate (PMA) on carbamylcholine (CBC)-induced [3H]cyclic GMP formation in mouse neuroblastoma cells (clone N1E-115) were studied. PMA, but not 4 alpha-phorbol, suppressed muscarinic receptor-mediated cyclic GMP responses in a time-dependent and a concentration-dependent fashion with an IC50 of 68.8 +/- 20.2 nM. The inhibitory effects of PMA on CBC-induced cyclic GMP formation were of a mixed competitive and noncompetitive type, being characterized by a depression of maximal cyclic GMP response to CBC and a significant increase in its EC50. PMA also significantly reduced [3H]cyclic GMP formation induced by histamine, without affecting the responses elicited either by sodium azide or the calcium ionophore A23187. Although the inhibitory effects of PMA on CBC-induced cyclic GMP formation were not reversed by washing, these effects were significantly attenuated by H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], a protein kinase C inhibitor. PMA had no effect on binding of an antagonist ligand to muscarinic receptors, or on the binding characteristics of CBC to these receptors in intact cells. On the other hand, PMA competed for the specific binding of a labeled phorbol ester in intact cells with a potency similar to that of PMA in inhibiting muscarinic receptor-mediated [3H]cyclic GMP responses.


Prevalence and risk of chronic kidney disease in oral lichen planus: a large cross-sectional study from eastern China.
Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease which is frequently associated with comorbidities such as diabetes and cardiovascular diseases. However, little is known about the association of OLP with impaired kidney function. To elucidate the possible association of chronic kidney disease (CKD) with OLP and its severity, this study investigated the prevalence of CKD as well as its risk factors in patients with OLP. A large prospective cross-sectional study of 1,021 patients with OLP was carried out using questionnaires and laboratory tests available from an oral medicine clinic at a university in eastern China. According to the Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic guideline, CKD was classified based on the estimated glomerular filtration rate (eGFR, <60 mL/min/1.73 m2) or urinary albumin to creatinine ratio (UACR, >30 mg/g). The prevalence of CKD in the patients with OLP in this study was 14.3% (95% CI, 12.3-16.6%), which was higher than that in the general Chinese population (10.8%; 95% CI, 10.2-11.3%). The mean values of serum creatinine, eGFR, UACR, and urine N-acetyl-β-D-glucosidase in patients with CKD were significantly higher than those in patients without CKD (all P<0.01). Pearson's correlation analysis revealed that CKD stage and UACR were positively correlated with the severity of OLP (both P<0.001). Importantly, multivariate regression analysis revealed that age ≥58 years old, female sex, and hypertension were independent risk factors for incident CKD and abnormal UACR (>30 mg/g) in patients with OLP (all P<0.01). This study has reported for the first time that CKD is a comorbidity in patients with OLP. The occurrence and staging of incident CKD are associated with OLP and its severity.


Incisional herniation induces decreased abdominal wall compliance via oblique muscle atrophy and fibrosis.
The purpose of this study is to measure abdominal wall myopathic histologic and mechanical changes during incisional herniation and its effect on incisional hernia repairs. Unloaded skeletal muscles undergo characteristic atrophic changes, including change in fiber type composition, decreased cross-sectional area, and pathologic fibrosis. We hypothesize that these atrophic changes decrease muscle elastic properties and may contribute to the high laparotomy wound failure rate observed following incisional hernia repair. A rat model of chronic incisional hernia formation was used. Failing midline laparotomy incisions developed into incisional hernias. Controls were uninjured and sham laparotomy (healed) groups. Internal oblique muscles were harvested for fiber typing, measurement of cross-sectional area, collagen deposition, and mechanical analysis. Mesh hernia repairs were performed on a second group of rats with chronic incisional hernias or acute anterior abdominal wall myofascial defects. The hernia group developed lateral abdominal wall shortening and oblique muscle atrophy. This was associated with a change in the distribution of oblique muscle fiber types, decreased cross-sectional area, and pathologic fibrosis consistent with myopathic disuse atrophy. These muscles exhibited significant decreased extensibility and increased stiffness. The healed (sham) laparotomy group expressed an intermediate phenotype between the uninjured and hernia groups. Recurrent hernia formation was most frequent in the chronic hernia model, and hernia repairs mechanically disrupted at a lower force compared with nonherniated abdominal walls. The internal oblique muscles of the abdominal wall express a pattern of changes consistent with those seen in chronically unloaded skeletal muscles. The internal oblique muscles become fibrotic during herniation, reducing abdominal wall compliance and increasing the transfer of load forces to the midline wound at the time of hernia repair.


Serum and Glucocorticoid-Inducible Kinase 3/Nedd4-2 Signaling Pathway Participates in Podocyte Injury by Regulating the Stability of Nephrin.
Serum and glucocorticoid-inducible kinase 3 (SGK3) is involved in maintaining podocyte function by regulating the protein levels of podocin and CD2-associated protein. Nephrin is also one of the slit diaphragm proteins of podocytes, but whether SGK3 participates in podocyte injury by regulating the levels of nephrin remains unclear. In this study, we focused on whether SGK3 affects nephrin levels and the mechanisms involved in the same. In the kidneys of adriamycin (ADR)-induced podocyte injury mouse model, the protein levels of SGK3 and nephrin were significantly decreased. Furthermore, the expression of SGK3 was negatively correlated with the output of proteinuria, and positively correlated with the levels of nephrin. In ADR-treated conditionally immortalized mouse podocyte cells (MPCs), the protein levels of nephrin and SGK3 were inhibited, while the constitutive expression of SGK3 reversed the ADR-induced decline in nephrin protein levels. Furthermore, ADR treatment or SGK3 inactivation enhanced the ubiquitin-proteasome degradation of nephrin in MPCs, and dramatically activated downstream effector proteins of SGK3, neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2) and glycogen synthase kinase-3 β (GSK3β). Similarly, Nedd4-2 or GSK3β overexpression resulted in increased activity of Nedd4-2 or GSK3β, and significantly downregulated nephrin levels. Interestingly, ubiquitin-mediated protein degradation of nephrin was regulated by Nedd4-2, rather than by GSK3β. In summary, SGK3 inactivation downregulated the levels of nephrin by increasing Nedd4-2 and GSK3β activity in ADR-induced podocyte injury model; in particular, the SGK3/Nedd4-2 signaling pathway was found to be involved in ubiquitin-mediated proteasome degradation of nephrin.


Multi-aperture system approach for snapshot multispectral imaging applications.
We present an ultra-compact system approach for snapshot, multispectral imaging. It is based on a slanted linear variable spectral filter mounted in close proximity to the entrance pupil of a micro-optical, multi-aperture imaging system. A compact demonstration setup with a size of only 60 × 60 × 28 mm3 is developed, which enables the acquisition of 66 spectral channels in a single shot and offers a linear spectral sampling of approximately six nanometers over an extended wavelength range of 450-850 nm. The spatial sampling of each channel covers up to 400 × 400 pixels. First, the concept, the optical design and the fabrication are detailed. After the optical performance characterization, a comprehensive calibration strategy is developed and applied. An experimental demonstration is performed by acquiring the spatial and the spectral information of an imaged test scene.


Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment.
The development of immune checkpoint blockade (ICB) therapies has been instrumental in advancing the field of immunotherapy. Despite the prominence of these treatments, many patients exhibit primary or acquired resistance, rendering them ineffective. For example, anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-L1) treatments are widely utilized across a range of cancer indications, but the response rate is only 10%-30%. As such, it is necessary for researchers to identify targets and develop drugs that can be used in combination with existing ICB therapies to overcome resistance. The intersection of cancer, metabolism, and the immune system has gained considerable traction in recent years as a way to comprehensively study the mechanisms that drive oncogenesis, immune evasion, and immunotherapy resistance. As a result, new research is continuously emerging in support of targeting metabolic pathways as an adjuvant to ICB to boost patient response and overcome resistance. Due to the plethora of studies in recent years highlighting this notion, this review will integrate the relevant articles that demonstrate how tumor-derived alterations in energy, amino acid, and lipid metabolism dysregulate anti-tumor immune responses and drive resistance to anti-PD-1/PD-L1 therapy.


Order-disorder effects in structure and color relation of photonic-crystal-type nanostructures in butterfly wing scales.
In order to study local and global order in butterfly wing scales possessing structural colors, we have developed a direct space algorithm, based on averaging the local environment of the repetitive units building up the structure. The method provides the statistical distribution of the local environments, including the histogram of the nearest-neighbor distance and the number of nearest neighbors. We have analyzed how the different kinds of randomness present in the direct space structure influence the reciprocal space structure. It was found that the Fourier method is useful in the case of a structure randomly deviating from an ordered lattice. The direct space averaging method remains applicable even for structures lacking long-range order. Based on the first Born approximation, a link is established between the reciprocal space image and the optical reflectance spectrum. Results calculated within this framework agree well with measured reflectance spectra because of the small width and moderate refractive index contrast of butterfly scales. By the analysis of the wing scales of Cyanophrys remus and Albulina metallica butterflies, we tested the methods for structures having long-range order, medium-range order, and short-range order.


Soluble insulin analogs combining rapid- and long-acting hypoglycemic properties - From an efficient E. coli expression system to a pharmaceutical formulation.
The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD). The SOD gene was used as a signal peptide to enhance the expression of insulin. SOD::INS was manufactured in the form of insoluble inclusion bodies. After cleavage of the fusion protein with trypsin, the released insulin analogs were refolded and purified by reverse-phase high performance liquid chromatography (RP-HPLC). Elongation of chain A, described here for the first time, considerably improved the stability of the selected analogs. Their identity was confirmed with mass spectrometric techniques. The biological activity of the insulin derivatives was tested on rats with experimental diabetes. The obtained results proved that the new analogs described in this paper have the potential to generate prolonged hypoglycemic activity and may allow for even less frequent subcutaneous administration than once-a-day. When applied, all the analogs demonstrate a rapid onset of action. Such a combination renders the proposed biosynthetic insulin unique among already known related formulations.


Building an experimental model of the human body with non-physiological parameters.
New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10-6) microfluidic model of the human body.


Bisphenol A: developmental toxicity from early prenatal exposure.
Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development are not yet widely studied in human populations. This review presents research on the consequences for offspring of BPA exposure during pregnancy. Extensive work in laboratory rodents has evaluated survival and growth of the conceptus, interference with embryonic programs of development, morphological sex differentiation, sex differentiation of the brain and behavior, immune responsiveness, and mechanism of action. Sensitive measures include RAR, aryl hydrocarbon receptor, and Hox A10 gene expression, anogenital distance, sex differentiation of affective and exploratory behavior, and immune hyperresponsiveness. Many BPA effects are reported at low doses (10-50 µg/kg d range) by the oral route of administration. At high doses (>500,000 µg/kg d) fetal viability is compromised. Much of the work has centered around the implications of the estrogenic actions of this agent. Some work related to thyroid mechanism of action has also been explored. BPA research has actively integrated current knowledge of developmental biology, concepts of endocrine disruption, and toxicological research to provide a basis for human health risk assessment.


Vitamin D Deficiency Is a Predictor of Mortality in Elderly with Chronic Heart Failure.
The prevalence of both heart failure and vitamin D deficiency increases with age and is associated with poor outcome in the elderly. We aimed to investigate the relationship between all-cause mortality and vitamin D deficiency in elderly patients with chronic heart failure. It is a retrospective, observational cross-sectional study. Median follow-up time was 497 days. 302 patients aged ≥65 years heart failure patients was categorized into tertiles based on the 25-hydroxy-vitamin D levels. Clinical and laboratory parameters were evaluated according to tertiles. Hospitalization rates and overall survival were compared between tertiles. Independent predictors of all cause mortality were defined. Patients with low vitamin D tertile were mostly women (p=0.001), and had a worse NYHA functional class (p=0.005). During follow-up, deaths were more frequent in the first tertile (p = 0.001). All-cause mortality increased significantly with decreasing vitamin D tertiles (from third tertile 7.9%, to 11.9%, to 26%; log rank test p=0.003). No significant difference was observed at the composite endpoint of mortality or HF hospitalizations (P=0.451). Multivariate analysis supported that low vitamin D concentration was an independent predictor of all causes of mortality (HR 0.93; 95% CI 0.89-0.97; p=0.004). Low vitamin D levels were independent predictors of all-cause mortality in the elderly population with chronic heart failure.


Event-related potential maps depend on prestimulus brain electric microstate map.
The brain functional microstate immediately before each of about 3000 identical tone stimuli was classified using extracted reference-free descriptors (locations of maximal and minimal potential) of the landscape of the brain's momentary electric field, in 8 volunteers. Six prestimulus microstate map classes occurred more than 30 times in each subject, and were clustered into two map class types (totals of 242 and 283 cases, respectively, on the average per subject). Event-related potential (ERP) map series were averaged for each subject and prestimulus map class. Map descriptors were extracted from the ERP maps at times of maximal Global Field Power during the component time windows N100, P200 and P330. Discriminant functions were estimated; for the maps of N100 and P330, the discriminant scores differed significantly between the maps associated with the two prestimulus map class types (paired t-tests, df = 7, p = .014 and p = .005, respectively). The dominant axis of the poststimulus class type II ERP maps deviated clockwise from that of the type I ERP maps in all components. We conclude that subtle changes in the brain's spontaneous momentary functional microstate (as classified by spatial descriptors of a single map) influence event-related information processing by the brain, following common rules over subjects.


Implementation of automatic speech analysis for early detection of psychiatric symptoms: What do patients want?
Psychiatry is in dire need of a method to aid early detection of symptoms. Recent developments in automatic speech analysis prove promising in this regard, and open avenues for implementation of speech-based applications to detect psychiatric symptoms. The current survey was conducted to assess positions with regard to speech recordings among a group (n = 675) of individuals who experience psychiatric symptoms. Overall, respondents are open to the idea of speech recordings in light of their mental welfare. Importantly, concerns with regard to privacy were raised. Given that speech recordings are privacy sensitive, this requires special attention upon implementation of automatic speech analysis techniques. Furthermore, respondents indicated a preference for speech recordings in the presence of a clinician, as opposed to a recording made at home without the clinician present. In developing a speech marker for psychiatry, close collaboration with the intended users is essential to arrive at a truly valid and implementable method.


Lectin histochemistry of human skeletal muscle.
Biotinyl derivatives of seven plant lectins-concanavalin A (Con A), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA I), Ulex europeus agglutinin I (UEA I), soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), and wheat germ agglutinin (WGA)-were bound to cryostat sections of biopsied normal human muscle and visualized with avidin-horseradish peroxidase conjugates. A distinct staining pattern was observed with each lectin. The most general staining was observed with Con A, RCA I, and WGA, which permitted strong visualization of the plasmalemma-basement membrane unit, tubular profiles in the interior of muscle fibers, blood vessels, and connective tissue. PNA gave virtually no intracellular staining, while SBA and UEA I selectively stained blood vessels. DBA was unique in providing good visualization of myonuclei. In each case, lectin staining could be blocked by appropriate sugar inhibitors. Neuraminidase pretreatment of the cryostat sections altered the pattern of staining by all lectins except UEA I and Con A; staining with RCA I became stronger and that with WGA became less intense, while staining with PNA, SBA and DBA became stronger and more generalized, resembling that of RCA I. These effects of neuraminidase pretreatment are in conformity with the known structure of the oligosaccharide chains of membrane glycoproteins and specificities of the lectins involved.


Structural Analysis and Conformational Dynamics of STN1 Gene Mutations Involved in Coat Plus Syndrome.
The human CST complex (CTC1-STN1-TEN1) is associated with telomere functions including genome stability. We have systemically analyzed the sequence of STN and performed structure analysis to establish its association with the Coat Plus (CP) syndrome. Many deleterious non-synonymous SNPs have been identified and subjected for structure analysis to find their pathogenic association and aggregation propensity. A 100-ns all-atom molecular dynamics simulation of WT, R135T, and D157Y structures revealed significant conformational changes in the case of mutants. Changes in hydrogen bonds, secondary structure, and principal component analysis further support the structural basis of STN1 dysfunction in such mutations. Free energy landscape analysis revealed the presence of multiple energy minima, suggesting that R135T and D157Y mutations destabilize and alter the conformational dynamics of STN1 and thus may be associated with the CP syndrome. Our study provides a valuable direction to understand the molecular basis of CP syndrome and offer a newer therapeutics approach to address CP syndrome.


Cenozoic continental climatic evolution of Central Europe.
Continental climate evolution of Central Europe has been reconstructed quantitatively for the last 45 million years providing inferred data on mean annual temperature and precipitation, and winter and summer temperatures. Although some regional effects occur, the European Cenozoic continental climate record correlates well with the global oxygen isotope record from marine environments. During the last 45 million years, continental cooling is especially pronounced for inferred winter temperatures but hardly observable from summer temperatures. Correspondingly, Cenozoic cooling in Central Europe is directly associated with an increase of seasonality. In contrast, inferred Cenozoic mean annual precipitation remained relatively stable, indicating the importance of latent heat transport throughout the Cenozoic. Moreover, our data support the concept that changes in atmospheric CO2 concentrations, although linked to climate changes, were not the major driving force of Cenozoic cooling.


Embryonic trafficking of gammadelta T cells to skin is dependent on E/P selectin ligands and CCR4.
Dendritic epidermal T cells (DETC) express an invariant Vgamma3/Vdelta1 T-cell receptor, appear in fetal epidermis, and form a population of resident epidermal T cells. Their temporal development in the thymus has been studied extensively. However, little is known about the mechanisms involved in the embryonic trafficking of DETC from thymus to epidermis. We demonstrate that DETC in adult skin, as well as the DETC precursors in fetal thymus, express E and P selectin ligands (E- and P-lig). Mice deficient in alpha1,3 fucosyltransferases IV and VII (FTIV/VII) cannot synthesize the carbohydrate motifs that form key elements of these selectin ligands. The numbers of DETC in the epidermis of FTIV/VII(-/-) mice were dramatically reduced compared with normal mice. However, the development of DETC precursors in fetal thymus was identical in normal and FTIV/VII(-/-) mice, suggesting that the DETC precursors produced in FTIV/VII(-/-) mice could not traffic effectively to skin because they lack E- and P-lig. We tested this hypothesis by daily injection of blocking antibodies against E and P selectin into pregnant mice. Mice born from dams treated with anti-selectin antibodies, but not those born from dams treated with isotype control, had significantly diminished numbers of DETC. To test the role of chemokine receptors in DETC skin homing, we examined skin from CCR4(-/-) and CCR10(-/-) mice, respectively. DETC were significantly reduced in CCR4(-/-) mice but were present at normal levels in CCR10(-/-) mice. Our results present evidence for the crucial role of trafficking molecules in embryonic migration of DETC precursors to skin.


Lateral frontoethmoidal cell obstructing frontal sinus drainage pathway - report of six cases.
The European Anatomical Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses distinguishes anterior, posterior, medial and lateral frontoethmoidal cells. The lateral cells have not been characterized yet. Other classifications (Lee and Kuhn, International Frontal Sinus Anatomy Classification) neglect them. The aim of this study is to describe lateral frontoethmoidal cells in rhinosinusitis patients. Analysis of medical records and computed tomography (CT) examinations using multiplanar reconstruction with adjustable planes. The lateral cell extending between the frontal beak and the skull base pushing the frontal sinus drainage pathway medially/anteromedially was identified in 6 patients. These cells could not be classified as anterior, posterior or medial according to existing classifications. Four patients were operated on previously due to sinonasal symptoms. The lateral frontoethmoidal cell is an underestimated anatomical variation that may contribute to the persistence of inflammatory disease and can be easily overlooked preoperatively.


Lentropin: a factor in vitreous humor which promotes lens fiber cell differentiation.
An activity has been identified in chicken vitreous humor which stimulates embryonic chicken lens epithelial cells to elongate and specialize for lens crystallin synthesis. The activity is heat-labile and is destroyed by treatment with trypsin or agents that reduce disulfides. Gel filtration and ultrafiltration analyses indicate that it has an apparent molecular weight of approximately 60,000. Its properties differ from those of an activity present in serum which also can promote lens fiber cell formation in vitro. We call this material "lentropin" and suggest that it is responsible for stimulating lens fiber cell formation in vivo and, consequently, plays an important role in determining the shape and polarity of the lens.


Physician handling of prescription stimulants.
Good medical practices can significantly reduce the possibility of diversion and misuse of the stimulants commonly prescribed to treat ADHD. While the problems of misuse and abuse are real, they should not become a barrier to appropriate use of these medicines, which are safe and effective for the large majority of patients with ADHD using them. With appropriate care, physicians treating patients with ADHD can be confident that their treatments are safe, not only for the patients they treat, but also for the communities in which they live.


A single cell assay for the study of gamma-interferon formation in leprosy patients.
The number of gamma-interferon producing cells in the peripheral blood of leprosy (LL and BT) patients and controls was studied by the reversed protein A plaque assay before and after exposure in vitro to Mycobacterium leprae bacilli and Epstein-Barr virus (EBV). The level of spontaneous gamma-interferon production was significantly higher in BT patients compared to LL patients and controls. Mycobacterium leprae induced a specific gamma-interferon response in lymphocytes from BT patients and from healthy contacts whereas in LL patients and non-exposed controls the response was low or non-existing. There were no significant differences in the gamma-interferon response to EBV between the above groups.


A novel system to obtain addresses of out-patients--assessment in routine clinic practice in Madras, S. India.
A novel method of obtaining accurate home addresses from out-patients was introduced as a routine procedure in 6 chest clinics of Madras City, following highly satisfactory results under study conditions. In this method, the patient is given a card (the address card), and asked to get his exact address entered on it by any knowledgeable person of his choice such as a landlord or neighbour. An assessment of the system was undertaken after it had been in operation for about 8 months. A complete and legible address was available for 82% of 3956 patients, the range in the 6 clinics being 74% to 91%. The main causes for failure were: not giving address card to patient (7%), patient not reattending the clinic (6%), and patient reattending but not returning the address card (3%). Corrective measures have now been introduced, and a re-assessment will be undertaken in due course.


Cognitive psychopathology in Schizophrenia: Comparing memory performances with Obsessive-compulsive disorder patients and normal subjects on the Wechsler Memory Scale-IV.
Memory system turns out to be one of the cognitive domains most severely impaired in schizophrenia. Within the theoretical framework of cognitive psychopathology, we compared the performance of schizophrenia patients on the Wechsler Memory Scale-IV with that in matched patients with Obsessive-compulsive disorder and that in healthy control subjects to establish the specific nature of memory deficits in schizophrenia. 30 schizophrenia patients, 30 obsessive-compulsive disorder patients and 40 healthy controls completed the Wechsler Memory Scale-IV. Schizophrenia symptom severity was assessed by the Positive and Negative Syndrome Scale (PANSS). Performances on memory battery including Indexes and subtests scores were compared by a One-Way ANOVA (Scheffé post-hoc test). Spearman Rank correlations were performed between scores on PANSS subscales and symptoms and WMS-IV Indexes and subtests, respectively. Schizophrenia patients showed a memory profile characterized by mild difficulties in auditory memory and visual working memory and poor functioning of visual, immediate and delayed memory. As expected, schizophrenia patients scored lower than healthy controls on all WMS-IV measures. With regard to the WMS-IV Indexes, schizophrenia patients performed worse on Auditory Memory, Visual Memory, Immediate and Delayed Memory than Obsessive-compulsive disorder patients but not on Visual Working Memory. Such a pattern was made even clearer for specific tasks such as immediate and delayed recall and spatial recall and memory for visual details, as revealed by the lowest scores on Logical Memory (immediate and delayed conditions) and Designs (immediate condition) subtests, respectively. Significant negative correlations between Logical Memory I and II were found with PANSS Excitement symptom as well as between DE I and PANSS Tension symptom. Significant positive correlations between LM II and PANSS Blunted affect and Poor rapport symptoms as well as DE I and PANSS Blunted affect and Mannerism and Posturing symptoms, were found too. Memory damage observed in schizophrenia patients was more severe and wider than that of patients with obsessive-compulsive disorder, except for visual working memory. Memory dysfunction, mainly related to episodic memory damage and reduced efficiency of central executive, is intimately connected to the specific psychopathological processes characterizing schizophrenia. Implications for therapeutics and cognitive remediation techniques are discussed.


[Expression of metabotropic glutamate receptor 1alpha in different brain areas of the kindled epilepsia models of rats by Coriaria lactone].
To detect the expression of Metabotropic Glutamate Receptor 1alpha (MGLUR1alpha) in the different brain areas of the kindled epilepsia models of rats by Coriaria Lactone (CL). Thirty male SD rats were divided into 3 groups and were given intramuscular injections of 0.75, 1.0 and 1.25 ml/kg Coriaria Lactone respectively. 5 rats in the control group were given intramuscular injection of 1.0 ml/kg saline. After the kindling models were completed, the EcoG of all groups were recorded with the multi-electrophysiology recorder to view whether the EcoG of kindled rats accord with their seizures and to know whether there are differencees in EcoG among the kindled, non-kindled and control groups. The coronary sections of brain tissue were HE stained and MGLUR1alpha immunohistochemistry stained, and were observed under light microscope. The kindled rats had all grade (Simialowski scale) seizures after CL injection and their seizures accorded with their EcoG features. The MGLUR1alpha expression of kindled rats in hippocampus and temporal cortex outside hippocampus was stronger than that of non-kindled and control rats (P < 0.05); the strong expression was noted to be of no obvious difference between neuron and glia. The MGLUR1alpha expression of kindled rats in hippocampus and temporal cortex outside hippocampus is stronger than that of non-kindled and control. It is possible that MGLUR1alpha participates in epileptic seizures.


[Influences of enteral nutrition combined with probiotics on the gut microecology and barrier function of the rats with abdominal infection].
To investigate the influences of enteral nutrition (EN), parenteral nutrition (PN) and probiotics supplement on the intestinal microecology, and barrier function of the rats with abdominal infection. Twenty-one Sprague-Dawley (SD) rats with abdominal infection were randomly divided into three groups, and received PN (PN group, n=7), PN+ EN (PN+ EN group, n=7) or PN+ EN+ probiotics (probiotics group, n=7) respectively with isonitrogen and isocaloric nutrition. The rats were sacrificed after six days. The feces in cecum were cultured for anaerobic bacterial growth and DNA fingerprint spectrum was analyzed by randomly amplified polymorphic DNA technique. The transmembrane binding protein (occludin) and IgA levels in colon and terminal ileum were detected by immunohistochemistry method. The bacterial translocation rate and endotoxin level were also measured. The germ numbers of different species were both higher in PN+ EN and probiotic group than those in PN group. The bands of DNA fingerprint spectrum were significantly decreased in PN group, but the bands in both PN+ EN group and probiotic group were similar to that in the normal rats. The expression levels of occludin and IgA in the intestine and colorectum were higher in both PN+ EN group and probiotic group compared with those of PN group (P< 0.05, P< 0.01, respectively), the expression level of occludin was higher in probiotic group than that in PN+ EN group (P< 0.05). The overall bacterial translocation rates and endotoxin levels were significantly reduced in both probiotic and PN+ EN group (P< 0.05), but there was no difference between probiotic group and EN group. EN combined with probiotics can increase occluding and IgA expressions, improve the intestinal microecology,maintain the gut barrier function, and decrease the incidence of gut bacterial translocation.


Duodenal involvement by seminomatous tumors.
Testicular germ cell tumors, though rare (1%), represent the most common neoplasm among young men. Gastrointestinal involvement from these malignancies usually presents as bowel obstruction and digestive bleeding, but their frequency is low (5%). The patterns of this involvement are: infiltration from affected retroperitoneal lymph nodes or, less frequently, by peritoneal seeding and direct hematogenous spread. Particularly, infiltration of duodenum is also rare, though its real frequency is not well defined. Moreover, the affinity for GI tract differs among the histological types of GCT, being seminomatous tumors an exceedingly unfrequent cause of duodenal infiltration. We herein present a recent case in our institution of severe anemia due to gastrointestinal bleeding in the context of giant retroperitoneal bulky metastatic mass infiltrating duodenum as first manifestation of a testicular pure seminoma.


High-Throughput Structural and Functional Characterization of the Thin Film Materials System Ni-Co-Al.
High-throughput methods were used to investigate a Ni-Co-Al thin film materials library, which is of interest for structural and functional applications (superalloys, shape memory alloys). X-ray diffraction (XRD) measurements were performed to identify the phase regions of the Ni-Co-Al system in its state after annealing at 600 °C. Optical, electrical, and magneto-optical measurements were performed to map functional properties and confirm XRD results. All results and literature data were used to propose a ternary thin film phase diagram of the Ni-Co-Al thin film system.


Using geminal dicationic ionic liquids as solvents for high-temperature organic reactions.
[reaction: see text] Several organic reactions conducted at high temperatures, including the isomerization reaction, the Claisen rearrangement, and the Diels-Alder reaction, were investigated in three geminal dicationic ionic liquids with high thermal stability. High to moderate yields of the products for most entries were obtained. Advantages of these approaches are discussed. These ionic liquids were shown to be recyclable. The utility of these ionic liquid solvents for high-temperature organic reactions was demonstrated.


Persistence of camptothecin analog-topoisomerase I-DNA ternary complexes: a molecular dynamics study.
Topoisomerase I (top1) is the sole chemotherapeutic target for the anticancer alkaloid camptothecin and its analogs (CPTs). The CPTs mediate cytotoxicity by binding reversibly to transient top1-DNA covalent complexes. There is significant variation in the persistence of the resultant CPTs-top1-DNA ternary complexes formed. Presently, there is no reliable method that can be used to predict the persistence of the ternary complexes, significantly limiting formulation of structure-activity relationships. Here, we used molecular dynamics simulations to probe the properties of several CPTs that form ternary complexes of greatly variable persistence. Our study reveals that correlated motions primarily occur between the CPTs and the flanking base pairs. We envision that the nature and strength of the interactions between the CPTs and the flanking base pairs are of key importance and can shed light on the mechanistic basis for the differing persistence of the ternary complexes. Our 'flanking base pairs' models further reveal that the most persistent CPTs (i) have higher calculated free-energy barriers for drug dissociation from the flanking base pairs, (ii) are less sensitive to changes in the rotation angles of the flanking base pairs, (iii) form stronger van der Waals and hydrophobic interactions, and (iv) have larger stacking areas with the flanking base pairs. Collectively, our study demonstrates that molecular dynamics simulations can be used to gain mechanistic insight into the molecular basis for the persistence of the ternary complexes and predict the persistence of such complexes during the drug discovery process.


Effect of daily milk supplementation on serum and umbilical cord blood folic acid concentrations in pregnant Han and Mongolian women and birth characteristics in China.
Many studies have demonstrated the efficacy of folic acid (FA) supplementation in prevention of neural tube defects (NTDs), although the extent of NTDs varies among individuals of different races and ethnic origin. China is a multi-ethnic country with no standard practice for FA-fortified food. Milk is consumed by women, but little is known about the effects of milk on folate concentration in maternal blood and neonatal umbilical cord blood in Han and Mongolian women after stopping taking the supplement for a month and five month, respectively. The objective of this study was to determine whether only daily consumption of liquid milk can increase the blood folate concentration in pregnant women and whether there are differences in blood folate concentrations between Han and Mongolian women after cessation of FA supplementation. Of the 4052 women enrolled in the parallel group design study. Three thousand five hundred and twenty-six women had confirmed pregnancies and were randomized to receive liquid milk or not until delivery. Women who consumed the liquid milk had significantly increased serum folate concentrations at 16 and 32 weeks of gestation as well as cord blood at birth compared to control groups in both ethnic groups. Infants born to women drinking milk also had better the term birth weight and height, which may be related to the increased concentration of folate. In conclusion, daily consumption of milk can increase the serum folate concentration in pregnant Han and Mongolian women in China (differences in the efficacy of FA and milk supplementation) and may enhance birth outcomes.


Advances in Somatic Embryogenesis of Banana.
The cultivation of bananas and plantains (Musa spp.) holds significant global economic importance, but faces numerous challenges, which may include diverse abiotic and biotic factors such as drought and various diseases caused by fungi, viruses, and bacteria. The genetic and asexual nature of cultivated banana cultivars makes them unattractive for improvement via traditional breeding. To overcome these constraints, modern biotechnological approaches like genetic modification and genome editing have become essential for banana improvement. However, these techniques rely on somatic embryogenesis, which has only been successfully achieved in a limited number of banana cultivars. Therefore, developing new strategies for improving somatic embryogenesis in banana is crucial. This review article focuses on advancements in banana somatic embryogenesis, highlighting the progress, the various stages of regeneration, cryopreservation techniques, and the molecular mechanisms underlying the process. Furthermore, this article discusses the factors that could influence somatic embryogenesis and explores the prospects for improving the process, especially in recalcitrant banana cultivars. By addressing these challenges and exploring potential solutions, researchers aim to unlock the full potential of somatic embryogenesis as a tool for banana improvement, ultimately benefiting the global banana industry.


Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model.
Tay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the α subunit of the lysosomal β-hexosaminidase enzyme (HEXA). Abnormal GM2 ganglioside accumulation causes progressive deterioration in the central nervous system in Tay-Sachs patients. Hexa-/- mouse model failed to display abnormal phenotype. Recently, our group generated Hexa-/-Neu3-/- mouse showed severe neuropathological indications similar to Tay-Sachs patients. Despite excessive GM2 ganglioside accumulation in the brain and visceral organs, the regulation of autophagy has not been clarified yet in the Tay-Sachs disease mouse model. Therefore, we investigated distinct steps of autophagic flux using markers including LC3 and p62 in four different brain regions from the Hexa-/-Neu3-/- mice model of Tay-Sachs disease. Our data revealed accumulated autophagosomes and autophagolysosomes indicating impairment in autophagic flux in the brain. We suggest that autophagy might be a new therapeutic target for the treatment of devastating Tay-Sachs disease.


Time course of rod influences on hue perception.
Stimulation of dark-adapted rods can shift the hues associated with specific wavelengths throughout the spectrum: Rods exert a green bias (strengthen green relative to red) at longer wavelengths and a blue bias (strengthen blue relative to yellow) at short-to-middle wavelengths. A third rod influence at shorter wavelengths is more complicated because it has been shown to reverse direction with change of stimulus duration. Thus, for 30-ms stimuli, rods exert a green bias like that observed at longer wavelengths. However, for 1-s stimuli, rods exert a red bias that is observed nowhere else in the spectrum. We examined the latency (time course) of rod hue biases by measuring the shifts of the three spectral unique hues under dark-adapted versus bleached (cone plateau) conditions. The rod green bias at unique yellow (mean 10 nm) and, in contrast to some prior studies, the rod blue bias at unique green (mean 21 nm) were not systematically affected by test stimulus duration. A quick rod green bias (mean 5 nm) was shown at unique blue for two of three observers but was dominated by a slower rod red bias (mean 11 nm) after 30-50 ms of rod stimulation. These opposing rod influences may reflect competing effects of rod signals on ML-cone and S-cone pathways.


ABO blood types and postpartum depression among Chinese women: A prospective cohort study in Tianjin, China.
Postpartum depression is associated with adverse consequences for mother and offspring. The heritable ABO blood group has been associated with multiple diseases, including mental illness and diabetes. We explored the association of ABO blood group and postpartum depressive symptoms (PPDS) in a population-based cohort of pregnant Chinese women. From 2010 to August 2012, we recruited 8842 pregnant women with a mean age of 28.5 years (SD: 2.94) and mean body mass index of 22.4kg/m2 (SD: 3.45) in Tianjin, China. We used the Mainland Chinese version of the Edinburgh Postnatal Depression Scale after delivery with a cutoff score of 10 to define PPDS. Odds ratios (ORs) and 95% confidence intervals (CIs) for PPDS were obtained using binary logistic regression. Of 8842 women, 8.5% (n = 747) developed PPDS. Compared to those with blood group B, women with blood groups A, AB or O had a higher odds of PPDS (adjusted ORs: 1.23 (95% CI: 1.13-1.40), 1.31 (95% CI: 0.98-1.74), and 1.30(95% CI:1.03-1.60), respectively). Blood group B was associated with reduced odds of PPDS in pregnant Chinese women. If replicated in other studies, non-blood group B may be a useful risk factors for PPDS in Chinese pregnant women.


New Determination Method of Two Bioactive Saponins in Lysimachia capillipes Hemsl. by Quantitative Analysis of Multi-Components by Single-Marker.
Capilliposide B (CPS-B) and Capilliposide C (CPS-C), as the key components in Lysimachia capillipes Hemsl., increasingly aroused the interest and research concern of many researchers due to the good bioactivities. Nowadays, the reference standards of CPS-B and CPS-C yield were very limited. Due to the deficit of reference standards, the determination could be difficult to carry out, and the quality control and evaluation would be restrained afterwards. To solve this urgent problem, a quantitative analysis of multi-components by single-marker (QAMS) method was proposed and established based on high-performance liquid-chromatography tandem evaporative light-scattering detector. In this QAMS method, the content of the two bioactive components could be calculated by buddlejasaponin IV, which is applied as an external standard and readily obtained. And the methodological experiments were evaluated and indicated accuracy, stability and feasibility of this QAMS method. Therefore, in this study, this built method would properly meet the requirement of determination of CPS-B, CPS-C and quality control of the L. capillipes Hemsl. plant.


Practical points in the care of the obstetric surgical patient.
Although not all PACUs provide care to patients postcesarean section, most PACUs do provide care to patients who are either pregnant for nonobstetric surgery or for patients terminating pregnancy. Although all of these patients will have postanesthetic priorities of airway, oxygenation, and cardiac stability, these priorities are intensified because of the physiological changes associated with pregnancy. Knowledge of these physiological changes can help increase the PACU nurse's ability to understand and meet the needs of the obstetric patient in the PACU.


KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway.
Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.


P-glycoprotein (Mdr1a/1b) and breast cancer resistance protein (Bcrp) decrease the uptake of hydrophobic alkyl triphenylphosphonium cations by the brain.
Mitochondrial dysfunction contributes to degenerative neurological disorders, consequently there is a need for mitochondria-targeted therapies that are effective within the brain. One approach to deliver pharmacophores is by conjugation to the lipophilic triphenylphosphonium (TPP) cation that accumulates in mitochondria driven by the membrane potential. While this approach has delivered TPP-conjugated compounds to the brain, the amounts taken up are lower than by other organs. To discover why uptake of hydrophobic TPP compounds by the brain is relatively poor, we assessed the role of the P-glycoprotein (Mdr1a/b) and breast cancer resistance protein (Bcrp) ATP binding cassette (ABC) transporters, which drive the efflux of lipophilic compounds from the brain thereby restricting the uptake of lipophilic drugs. We used a triple transgenic mouse model lacking two isoforms of P-glycoprotein (Mdr1a/1b) and the Bcrp. There was a significant increase in the uptake into the brain of two hydrophobic TPP compounds, MitoQ and MitoF, in the triple transgenics following intra venous (IV) administration compared to control mice. Greater amounts of the hydrophobic TPP compounds were also retained in the liver of transgenic mice compared to controls. The uptake into the heart, white fat, muscle and kidneys was comparable between the transgenic mice and controls. Efflux of hydrophobic TPP compounds by ABC transporters contributes to their lowered uptake into the brain and liver. These findings suggest that strategies to bypass ABC transporters in the BBB will enhance delivery of mitochondria-targeted antioxidants, probes and pharmacophores to the brain.


Transpulmonary angiotensin II formation in patients with chronic stable cor pulmonale.
The activity of the renin-angiotensin (RA) system and the ability of the lungs to generate angiotensin II (AII) were studied in 11 patients with stable cor pulmonale and respiratory failure caused by chronic obstructive bronchitis and emphysema. Angiotensin I concentrations (18.7 +/- 8.3 pmol/L) were normal, and transpulmonary AII formation rates (TRAIIFR) (14.2 +/- 18.1 pmol/min) were not significantly different from those recorded in nonedematous cardiac subjects (19.9 +/- 20.1 pmol/min), matched for sex, age, and diuretic therapy. The main determinant of TPAIIFR was the mixed venous AI concentration. Administration of oxygen for 30 min led to a small increase in TPAIIFR in the majority of patients. This increase could not be accounted for by changes in mixed venous AI. There was no correlation between serum angiotensin-converting enzyme levels and either the TPAIIFR or the systemic arterial AII concentrations.


The effect of hyperemesis gravidarum on the 75 g oral glucose tolerance test screening and gestational diabetes mellitus.
To clarify the effect of hyperemesis gravidarum (HG) on the 75 g oral glucose tolerance test (OGTT) and gestational diabetes mellitus. This retrospective cohort study was conducted via an evaluation of the hospital database medical records of 700 pregnant women. Of these, 60 were included in the study group as a result of hospitalization due to HG, 41 were excluded, and the remaining 599 formed a control group. The body mass index (BMI), urine ketone levels, and ages of all participants were separately recorded, both in the initial examination and during the 75 g OGTT. At initial examination, no significant differences in maternal age and BMI were observed between the two groups. There was a significant decrease in BMI after 75 g OGTT in the study group. No significant difference in fasting serum glucose levels was found between the two groups, but significant differences in first and second hour serum glucose levels were observed. HG may improve in many women in the late second trimester, and loss of fatty tissue may affect the 75 g OGTT screening results. The appropriate cutoff value of 75 g OGTT for HG should be reevaluated following future, larger, studies.


Secretion of functional antibody and Fab fragment from yeast cells.
We have constructed yeast strains that secrete functional mouse-human chimeric antibody and its Fab fragment into the culture medium. For chimeric whole antibody, cDNA copies of the chimeric light-chain and heavy-chain genes of an anti-tumor antibody were inserted into vectors containing the yeast phosphoglycerate kinase promoter, invertase signal sequence, and phosphoglycerate kinase polyadenylylation signal. Simultaneous expression of these genes in yeast resulted in secretion of properly folded and assembled chimeric antibody that bound to target cancer cells. Yeast chimeric antibody exhibited antibody-dependent cellular cytotoxicity activity but not complement-dependent cytotoxicity activity. For production of Fab fragments, a truncated heavy-chain (Fd) gene was created by introducing a stop codon near the codon for the amino acid at which papain digestion occurs. Simultaneous expression of the resulting chimeric Fd and light-chain genes in yeast resulted in secretion of properly folded and assembled Fab fragment that bound to target cancer cells.


Myocardial color scan with 43K in ischemic heart disease.
The value of myocardial scanning with 43K was assessed in 64 consecutive patients undergoing coronary arteriography, and in five young volunteers. Myocardial scans at rest detected only 16 of the 35 transmural infarcts documented on electrocardiograms, 11 of 11 anterior infarcts and five of 24 in other sites. Myocardial scans were obtained immediately after a graded exercise test in the five normal volunteers, in nine patients with normal coronary arteriograms and in 25 patients with atherosclerotic narrowing greater than 75% involving the left anterior descending artery, with or without disease of other coronary vessels. All patients with normal coronary arteriograms had normal myocardial scans. A regional perfusion deficit was observed after exercise in all six patients with single vessel disease, but in only 11 of the 19 patients with disease involving two or three vessels. Although the technique was specific, it lacked sensitivity, due mostly to poor resolution and the location of the disease.


Erythropoietin-induced metallothionein gene expression: role in proliferation of K562 cells.
Recent evidence has demonstrated an appreciable expression of metallothionein (MT) in erythrocytes. However, the induction of the MT protein by hematopoietic growth factors and its subsequent functional significance on clonal expansion or differentiation of erythroid progenitor cells remain elusive. We therefore examined the effects of growth factors erythropoietin (EPO), granulocyte-monocyte colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3) on MT gene expression in erythroid progenitor K562 cell line. EPO, but not IL-3 or GM-CSF, induced a 3-fold increase in MT transcripts in K562 cells. MT induction was associated with EPO-induced cellular proliferation, suggesting a specific role for MT induction by EPO in erythroid progenitor cells. However, EPO- or sodium butyrate-induced differentiation as monitored by hemoglobin formation was inhibited in K562 cells stably transfected with an expression vector containing human MT-IIA gene. This inhibition of differentiation was partially reversed in these cells by an MT antisense phosphorothioate oligonucleotide. Furthermore, the MT-induced inhibition of differentiation was associated with downregulation of EPO receptor transcripts in K562 cells. These data suggest that, among growth factors required for erythropoiesis, EPO is a potent inducer of MT, and that MT may plays a significant role in EPO-induced proliferation, but not in the erythroid-specific differentiation of the progenitor cells.


Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.
The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the ability to avoid Fe deficiency nevertheless appeared to be the same in both breeds.


Comparison of cefpimizole with cefotaxime and penicillin G for treatment of uncomplicated gonorrhea.
One hundred sixteen patients (92 men and 24 women) with suspected uncomplicated gonorrhea were randomized in a double-blind manner to receive intramuscular treatment with 1.0 g of cefpimizole, 1.0 g of cefotaxime, or 4.8 x 10(6) units of aqueous procaine penicillin G (APPG) with 1 g of oral probenecid. Seventeen percent were nonassessable (cultures negative, co-existing syphilis, etc.). Infection sites in 96 assessable patients were urethra (78), cervix (17), pharynx (two), and rectum (two). Of 52 patients treated with cefpimizole, 46 (88%) were bacteriologically cured, as compared with 100% (24 of 24) treated with APPG (P = 0.18) and 90% (18 of 20) treated with cefotaxime (P greater than 0.20). On a weight basis the in-vitro activity of cefpimizole against Neisseria gonorrhoeae was similar to that of APPG. Pain at the injection site was reported by 52% of patients treated with cefpimizole as compared with 27% of those given cefotaxime (P = 0.008) and 17% of those given APPG (P = 0.002). No major organ toxicity was found with cefpimizole, cefotaxime, or APPG. Thus, for acute uncomplicated gonorrhea cefpimizole is similar in efficacy to cefotaxime and APPG but has a higher frequency of pain at the injection site.


Spatial Analyses of Specialized Metabolites: The Key to Studying Function in Hosts.
Microbial communities contribute to a wide variety of biological functions in hosts and have the ability to specifically influence the health of those organisms through production of specialized metabolites. However, the structures or molecular mechanisms related to health or disease in host-microbe interactions represent a knowledge gap. In order to close this gap, we propose that a combinatory approach, pulling from microbiology and analytical chemistry, be considered to investigate these interactions so as to gain a better understanding of the chemistry being produced. We hypothesize that bacteria alter their chemistry in order to survive and induce specific states in their host organisms. Our lab makes use of imaging mass spectrometry and other analytical techniques to study this chemistry in situ, which provides actionable information to test hypotheses.


Aggregation of influenza virus haemagglutinin in the presence of detergents.
In the haemagglutinin (HA) detergent mixtures coexist various protein complexes. Using 125I-HA tracer, gel chromatography, and centrifugation techniques we found protein aggregates comprising up to eight HA trimers. Formation of these structures seemed to be a function of the protein storage medium only. By contrast, special properties of the detergent as well as physicochemical conditions during the protein/detergent interaction had nearly no influence.


alpha-Aminoadipate aminotransferase from an extremely thermophilic bacterium, Thermus thermophilus.
The extremely thermophilic bacterium Thermus thermophilus HB27 synthesizes lysine through alpha-aminoadipate (AAA). In this study, a T. thermophilus gene encoding the enzyme that catalyses transamination of AAA was cloned as a mammalian kynurenine/AAA aminotransferase (Kat2) gene homologue. A T. thermophilus mutant with disruption of the Kat2 homologue required a longer lag phase for growth and showed slower growth in minimal medium. Furthermore, addition of AAA or lysine shortened the lag phase and improved the growth rate. The Kat2 homologue was therefore termed lysN. LysN recognizes not only 2-oxoadipate, an intermediate of lysine biosynthesis, but also 2-oxoisocaproate, 2-oxoisovalerate and 2-oxo-3-methylvalerate, intermediates of leucine, valine and isoleucine biosyntheses, respectively, along with oxaloacetate, a compound in the TCA cycle, as an amino acceptor. These results suggest multiple roles of LysN in several cellular metabolic pathways including lysine and branched-chain amino acid biosyntheses.


Diagnostic challenges in celiac disease.
Diagnosis of celiac disease in adults is currently based on serologic tests in combination with histopathological assessment of small intestinal biopsy specimens. High titers of celiac-specific antibodies in immunocompetent patients with villous atrophy in a good quality biopsy sample allow us to state a confident diagnosis. The relief of symptoms and histological improvement after embarking on a gluten free diet further support the initial diagnosis. However, in some cases, these conditions are not fulfilled, which requires a critical evaluation of laboratory and histopathology results and a consideration of other potential causes for the observed pathologies. To avoid diagnostic uncertainty, both biopsy and laboratory testing should be performed on a diet containing gluten. Immune deficiency, cross reaction of antibodies and possibilities of seronegative or latent celiac disease should be considered while evaluating serology results. Uneven distribution and variable intensity of histopathological changes in the small intestine along with multiple disorders presenting a similar specimen image may lead to invalid biopsy results. Additional laboratory testing and careful examination of a patient's history may deliver important data for a differential diagnosis and a more specific biopsy evaluation. Persistence or recurrence of symptoms, despite the ongoing treatment, requires a revision of the initial diagnosis, an evaluation of the gluten free diet and a search for concurrent disorders or complications.


A peptide mimic of an antigenic loop of alpha-human chorionic gonadotropin hormone: solution structure and interaction with a llama V(HH) domain.
The X-ray structure of a ternary complex between human chorionic gonadotropin hormone (hCG) and two Fvs recognizing its alpha and beta subunits has been recently determined. The Fvs recognize the elongated hCG molecule by its two ends, one being the Leu-12-Cys-29 loop of the alpha subunit. We have designed and synthesized a 17-amino-acid peptide (named PepH14) derived from the sequence of this antigenic loop with the purpose of mimicking its three-dimensional structure and its affinity for antibodies. We have determined the solution structure of PepH14 by homonuclear NMR spectroscopy and derived distance restraints. Comparison of this structure with that of the corresponding antigenic loop of alpha-hCG reveals strong conformational similarities. In particular, the two pairs of residues that establish crucial contacts with the Fv fragment share the same conformation in PepH14 and in the authentic hormone loop. We propose a three-dimensional model of interaction of PepH14 with a llama V(HH) (V(HH)-H14) fragment cloned from a single-chain llama immunoglobulin raised against alpha-hCG. This model has been constrained by the chemical shift variations of the H14 1HN and 15N resonances monitored upon binding with PepH14. Mapping of the backbone chemical shift variations on the V(HH) structure determined by NMR indicates that PepH14 binds to V(HH)-H14 and forms a complex using the three complementary determining regions (CDRs). They define a shallow groove encompassing residues Thr-31, Ala-56, Tyr-59 and Trp-104 which have been shown to be in conformational exchange [Renisio, Pérez, Czisch, Guenneugues, Bornet, Frenken, Cambillau and Darbon (2002) Proteins 47, 546-555] and also Phe-37 and Ala-50. This groove is close to the hydrophobic interface area observed between VH and VL domains in Fvs from classical antibodies, which explains the rather lateral binding of PepH14 on the V(HH).


The mechanisms of spatial and temporal patterning of cell-edge dynamics.
Adherent cells migrate and change their shape by means of protrusion and retraction at their edges. When and where these activities occur defines the shape of the cell and the way it moves. Despite a great deal of knowledge about the structural organization, components, and biochemical reactions involved in protrusion and retraction, the origins of their spatial and temporal patterns are still poorly understood. Chemical signaling circuitry is believed to be an important source of patterning, but recent studies highlighted mechanisms based on physical forces, motion, and mechanical feedback.


Solid state concentration quenching of organic fluorophores in PMMA.
In this study the concentration quenching phenomenon is explored for seven organic singlet emitters (Rhodamine 6G, Pyridine 2, Lumogen F Red 305, Perylene, Coumarin 102, DCM and DCJTB) in an inert host of poly(methyl methacrylate) (PMMA). Combining fluorescence lifetime and quantum yield measurements on samples of different molecular separation allows a deep decay rate analysis to be performed yielding, for each fluorophore, a monomial power law that indicates the strength and type of interaction. The fluorophores studied exhibit interactions in between that of FRET-like dipole-dipole (R(-6)) and surface-surface (R(-2)) with many lying close to that expected for surface-dipole (R(-3)) interactions. With no observed dependence on molecular structure it is concluded that the concentration quenching rate in singlet emitters follows a power law as kCQ = aR(-3.1±0.7) with aggregation expected to increase the magnitude of the observed power.


Haemodynamic effects of chronic octreotide and tetrandrine administration in portal hypertensive rats.
Octreotide is an effective portal hypotensive drug in the control of variceal bleeding. Tetrandrine is a type of calcium channel blocker recently reported to reduce portal hypertension. The present study was undertaken to investigate the haemodynamic effects of octreotide and tetrandrine, alone and in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 mL/day), octreotide group (100 microg/kg per 12 h), tetrandrine group (20 mg/kg per 12 h), and octreotide (100 microg/kg per 12 h) plus tetrandrine (20mg/kg per 12 h) group. Tetrandrine or saline was administered by gavage, and octreotide by subcutaneous injection. The drug was given for 8 consecutive days, starting 1 day before ligation and continuing onwards. Haemodynamic parameters were measured thereafter, using the radioactive microsphere method. The portal venous pressure and portal tributary blood flow were significantly reduced, while portal territory and renal vascular resistances were significantly enhanced, by octreotide, tetrandrine, or octreotide plus tetrandrine in portal hypertensive rats, compared with the vehicle group. Our results showed that long-term administration of octreotide, tetrandrine, or octreotide plus tetrandrine led to portal hypotensive effects in portal hypertensive rats, but octreotide alone exerted better anti-hyperdynamic effects compared with tetrandrine alone. A combination of octreotide and tetrandrine offered no major beneficial anti-hyperdynamic effects compared with octreotide alone.


[In vivo imaging of corneal innervation in the human using confocal microscopy].
To date, descriptions of the structure of corneal innervation have only been possible on the basis of histological techniques. Confocal microscopy represents a new method for the structural examination of the cornea in vivo. Through our examinations we first defined the control group and then proceeded to record the reinnervation of donor tissue after perforating keratoplasty. We used the confocal slit-scanning video-microscope Microphthal to examine 40 corneas from 20 normal volunteers, 15 donor corneas and 5 eyes after enucleation for ocular tumors. These results were compared to our findings from postoperative checks on 14 patients after perforating keratoplasty (from 1 month to 2 years). With this system we were able to see nerves in the middle and in the superficial stroma. The course of these nerves can be followed, as well as their branching in the subepithelial plexus. Nerve fibers from superficial stromal nerves penetrate Bowman's membrane and create the basal epithelial plexus in the region of the basal epithelium. Seven months after perforating keratoplasty the first stromal nerves could be seen in the central corneal area. The first central reinnervation in the region of Bowman's membrane as well as in the basal epithelium was not detected until 15 months after operation. With confocal microscopy we have the potential to study the morphology of corneal innervation in vivo and in fresh donor tissue. For the first time it is possible to perform non-invasive morphological studies of reinnervation of the human cornea after surgical treatment.


Needle in a Haystack: Acute Intermittent Porphyria, an Often-missed Differential Diagnosis of Abdominal Pain.
Acute intermittent porphyria (AIP) is a rare disease that arises due to deficiency of the biosynthetic enzyme porphobilinogen deaminase (PBGD) involved in heme synthesis. Acute attacks can present with abdominal pain and neurological symptoms, although vague in nature. Recurrent hospitalizations for idiopathic intermittent abdominal pain should warrant investigation for AIP. Posterior reversible encephalopathy (PRES) presents with visual disturbances and seizure-like activity and can be, although rarely, associated with AIP. It is noteworthy to know that antiepileptic medication used in management of PRES can in turn worsen AIP.


[The endovascular treatment of the aortic trauma].
Traumatic injuries of the thoracic aorta are very frequent during motor vehicle accidents with sudden deceleration. Spiral CT has become the modality of choice for evaluating significant blunt trauma and grading system for aortic injury has been developed. Immediate diagnosis, introduction of antihypertensive therapy and endovascular treatment by means of stentgraft give a better chance for patients with blunt aortic injury. Prospective evaluation of results of endovascularly treated patients with blunt aortic injury. We prospectively followed patients after endovascular treatment of acute aortic injury. Diagnosis was based on chest x-ray and CT examination. Stentgrafts were placed under fluoroscopic guidance and patients were routinely followed by CT and clinical visit. Between December 1999 and September 2004 we endovascularly treated seven patients (6 men, 1 woman, mean age 41.7 years) for blunt aortic injury of the thoracic aorta. Stentgraft was implanted between 5 hours and 6 days (mean 3.2 days) after injury. Seven stentgrafts were implanted in 7 patients in total. One patient died due to failure of endovascular technique for collapsed stentgraft. A new onset of lower legs paraparesis was detected in one patient. Other five patients are regularly followed (3-55 months, mean 30.7 months) without any complications. Endoluminal technique can be used successfully in the immediate repair of aortic trauma. At present time in our center, treatment by means of the stentgraft placement is the first line therapy in injured patients. It allows rapid stabilization of aortic trauma and further treatment of other injuries.


Suppression of experimental autoimmune myasthenia gravis by autologous T regulatory cells.
Adoptive transfer of regulatory T (Treg) cells have been employed effectively for suppression of several animal models for autoimmune diseases. In order to employ Treg cell therapy in patients, it is necessary to generate Treg cells from the patient's own cells (autologous) that would be able to suppress effectively the disease in vivo, upon their reintroduction to the patient. Towards this objective, we report in the present study on a protocol for a successful immune-regulation of experimental autoimmune myasthenia gravis (EAMG) by ex vivo--generated autologous Treg cells. For this protocol bone marrow (BM) cells, are first cultured in the presence of GM-CSF, giving rise to a population of CD11c(+)MHCII(+)CD45RA(+)CD8(-) DCs (BMDCs). Splenic CD4(+) T cells are then co-cultured with the differentiated BM cells and expand to 90% of Foxp3(+) Treg cells. In vitro assay exhibits a similar dose dependent manner in the suppression of T effector cells proliferation between Treg cells obtained from either healthy or sick donors. In addition, both Treg cells inhibit similarly the secretion of IFN-γ from activated splenocytes. Administration of 1 × 10(6) ex-vivo generated Treg cells, I.V, to EAMG rats, modulates the disease following a single treatment, given 3 days or 3 weeks after disease induction. Similar disease inhibition was achieved when CD4 cells were taken from either healthy or sick donors. The disease suppression was accompanied by reduced levels of total AChR specific antibodies in the serum. Moreover, due to the polyclonality of the described Treg cell, we have examined whether this treatment approach could be also employed for the treatment of other autoimmune diseases involving Treg cells. Indeed, we demonstrated that the ex-vivo generated autologous Treg cells suppress Adjuvant Arthritis (AA) in rats. This study opens the way for the application of induced autologous Treg cell therapy for myasthenia gravis, as well as for other human autoimmune diseases involving Treg cells.


The use of tranquilizers in the treatment of mixed drug abuse.
If the abuse potential of tranquilizers, and particularly benzodiazepines, is examined by their administration as a therapeutic agent to persons dependent on alcohol, alcohol and drugs, or drugs alone, these substances are found to be potentially dependence producing with similar mechanisms to those of other hypnotics and sedatives. However, their abuse potential varies from one substance to another, and on the whole is relatively small. At all events, with constant medical supervision, patients who were previously dependent on a drug of barbiturate type do not independently increase their intake so as to become dependent on the tranquilizers. These experiments on persons with an inherent susceptibility to dependency show that tranquilizers must represent only a very small risk to the general population. The view that benzodiazepines are not potentially dependence producing has no more scientific foundation than the exaggerated fears of this potential. Important is that the uncontrolled supply of highly potent tranquilizers, and above all those with a strong sedative component, leads to dependence in a considerable percentage of cases in the treatment of mixed abuse. No conclusions in absolute terms on the risk presented by tranquilizers (and above all benzodiazepines) may be drawn from observations made in the uncontrolled administration of these substances in case of polytoxicomania. It follows that tranquilizers, which, as far as their therapeutic effect is concerned, are a valuable aid in the treatment of drug abuse, can be safely given when there is constant medical supervision combined with psychotherapy. The basic principle to be followed in the use of tranquilizers for the treatment of drug-dependent persons, is, therefore, their periodic administration in limited doses with constant medical supervision. In principle, however, because of the abuse potential which is nevertheless present, the same mode of administration is also to be recommended for other patient groups. Uncontrolled long-term administration is to be rejected in all circumstances, and supply should be strictly on prescription only in order to prevent uncontrolled acquisition. The various experiments carried out by us on the administration of benzodiazepines to patients with simple or mixed drug dependence show that the habit forming potential of benzodiazepines must, on the whole, be considered as being relatively small; at all events, this group of substances is the least hazardous of all known sedatives. This is of considerable importance, since the neuroleptics and antidepressants (which in themselves present no risk of abuse) are generally poorly tolerated and refused by patients with an inherent tendency towards drug dependence.


Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC.
Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC. RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.


Vaccination guidelines for gay and bisexual men.
While gay and bisexual men should be vaccinated according to the most recent guidelines, this population also has needs that extend beyond those guidelines. This article explores current vaccination recommendations for gay and bisexual men and provides strategies to reduce barriers to vaccination in this population.


Combined free autologous bladder mucosa/skin tube for urethral reconstruction: an update.
A combined free autologous bladder mucosa/skin graft was used to reconstruct the urethra in 23 patients. Although the complication rate remains high (61%), the results represent a significant improvement over the use of complete mucosal tubes to the tip of the penis. The technique is recommended for those patients with failed hypospadias surgery, where sufficient skin is not available for urethral reconstruction.


Relationship Between Vitamin D Deficiency and Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study From a Tertiary Care Center in Northern India.
Background Vitamin D levels are strongly associated with myocardial infarction, coronary artery disease, heart dysfunction, and even mortality. Non-alcoholic fatty liver disease (NAFLD) is a prevalent hepatic illness whose incidence has grown dramatically over the past several decades. Methodology This observational, cross-sectional study was conducted over 1.5 years (January 2019 to June 2020) at the Department of General Medicine of a tertiary care hospital in northern India on 100 adult patients with NAFLD admitted to the emergency ward, intensive care unit, and medical ward. Results In our study, of the 100 patients, 45.0%, 16.0%, and 39.0% of patients exhibited vitamin D deficiency, insufficiency, and sufficiency, respectively. Vitamin D deficiency was the highest among those aged 41-50 (54.2%) and lowest among those aged 30-40 (29.0%). We observed that vitamin D deficiency was less prevalent in people with a normal body mass index (39.1%) than in those who were overweight (91.7%). There was a significant (p < 0.05) association between the severity of vitamin D deficiency and the presence of hepatomegaly, splenomegaly, and ascites. Overall, the incidence of fatty liver was 49% among patients. There was a significant (p = 0.0001) correlation between fatty liver and serum vitamin D levels. The association between the proportion of patients with fatty liver and the degree of vitamin D deficiency was found to be significant (p = 0.04). The relationship between the distribution of patients according to insulin resistance and the degree of vitamin D deficiency was also statistically significant (p < 0.001). Conclusions Vitamin D deficiency is associated with an increased risk of NAFLD, as well as with the severity of NAFLD.


Ten-eleven translocation 1 functions as a mediator of SOD3 expression in human lung cancer A549 cells.
Superoxide dismutase (SOD) 3, one of the SOD isozymes, plays a pivotal role in extracellular redox homeostasis. The expression of SOD3 is regulated by epigenetics in human lung cancer A549 cells and human monocytic THP-1 cells; however, the molecular mechanisms governing SOD3 expression have not been elucidated in detail. Ten-eleven translocation (TET), a dioxygenase of 5-methylcytosine (5mC), plays a central role in DNA demethylation processes and induces target gene expression. In the present study, TET1 expression was abundant in U937 cells, but its expression was weakly expressed in A549 and THP-1 cells. These results are consistent with the expression pattern of SOD3 and its DNA methylation status in these cells. Moreover, above relationship was also observed in human breast cancer cells, human prostate cancer cells, and human skin fibroblasts. The overexpression of TET1-catalytic domain (TET1-CD) induced the expression of SOD3 in A549 cells, and this was accompanied by the direct binding of TET1-CD to the SOD3 promoter region. Furthermore, in TET1-CD-transfected A549 cells, the level of 5-hydroxymethylcytosine within that region was significantly increased, whereas the level of 5mC was decreased. The results of the present study demonstrate that TET1 might function as one of the key molecules in SOD3 expression through its 5mC hydroxylation in A549 cells.


Severity of sarcopenia is associated with postural balance and risk of falls in community-dwelling older women.
Background/Study context: Falls represent the leading cause of accidental deaths in the elderly. Sarcopenia is a geriatric syndrome defined as the loss of muscle mass and strength. However, the association between falls and sarcopenia is still unclear. Thus, the aim of the present study was to investigate the association between different stages of sarcopenia and postural balance, risk of falls, and fear of falling in community-dwelling older women. A total of 196 women (68.6 ± 6.5 years) underwent body composition (Dual-energy X-ray Absorptiometry), muscle strength (isokinetic), and functional (Timed Up-and-Go) assessments. Sarcopenia was classified according to European Working Group on Sarcopenia in Older People. Center of pressure (CoP) sway, risk, and fear of falling were assessed through force platform, QuickScreen, and Falls Efficacy Scale, respectively. ANOVA models and chi-squared were used to compare groups. Severe sarcopenic subjects presented higher risk of falling when compared to the other stages (p < 0.01). Regarding CoP sway, both mean speed and mediolateral range were significantly higher in severe sarcopenia when compared to both nonsarcopenia and presarcopenia (p < 0.05). Fear of falling was higher in all sarcopenia stages when compared to nonsarcopenic individuals (p < 0.05). Sarcopenia negatively affects balance, and both risk and fear of falling in community-dwelling older women. Moreover, this study provides evidence that sarcopenia severity is further associated to reduced balance and imposes an even greater risk of falls in the elderly.


Refractory ventricular arrhythmia: the role of intraoperative electrophysiological study.
Thirty patients with drug refractory ventricular tachycardia (RVT) were studied between 1 week and 5 years after myocardial infarction with coronary agniography and left ventriculography. They were divided into four groups: (1) inoperable, five patients; (2, a) operated, with primary left ventricular failure, five patients; (2, b) operated with primary RVT, not mapped, 15 patients; (2, c) operated, with mapping, five patients. The mortality rate in group 1 was 100%, and in group 2, a it was 80%. In group 2, b, despite aggressive drug therapy and operation, including aneurysmectomy, coronary revascularization, and intra-aortic balloon pumping when appropriate, the mortality rate wad intraoperative mapping in group 2, c. Arrhythmogenic foci were identified and removed in four. There was one operative death (20%) and four patients are alive from 12 to 27 months after operation, three of whom are asymptomatic. Intraoperative epicardial mapping is an important adjunct to surgery for RVT.


A re-annotation of the Anopheles darlingi mobilome.
The mobilome, portion of the genome composed of transposable elements (TEs), of Anopheles darlingi was described together with the genome of this species. Here, this mobilome was revised using similarity and de novo search approaches. A total of 5.6% of the A. darlingi genome is derived of TEs. Class I gypsy and copia were the most abundant superfamilies, corresponding to 22.36% of the mobilome. Non-LTR elements of the R1 and Jockey superfamilies account for 11% of the TEs. Among Class II TEs, the mariner superfamily is the most abundant (16.01%). Approximately 87% of the A. darlingi mobilome consist of short, truncated and/or degenerated copies of TEs. Only three retrotransposons, two belonging to gypsy and one to copia superfamilies, are putatively active elements. Only one Class II element, belonging to the mariner superfamily, is putatively active, having 12 copies in the genome. The TE landscape of A. darlingi is formed primarily by degenerated elements and, therefore, somewhat stable. Future applications of TE-based vectors for genetic transformation of A. darlingi should take into consideration mariner and piggyBac transposons, because full length and putatively active copies of these elements are present in its genome.


Evaluation of the Association between CD4, CD8 and CD25 Cell Counts and SLE in Active Disease and in Remission.
To evaluate the correlation between the levels of CD4, CD8 and CD25 cells and SLE disease in active phase and in remission. A total of 25 SLE patients, aged between 18-60 years, and fulfilling the ACR criteria with preferential Renal and CNS involvement were included in this study. Baseline CD4/CD8 and CD25 counts, lab parameters etc were conducted. Approximately at the end of 6 months with the settlement of the disease activity blood sample was drawn for the CD4, CD8 and CD25 counts and other lab parameters. ESR showed a statistical significant decrease while the SLEDAI score and proteinuria showed a decreasing trend as the patients underwent remission. The C3 showed an increasing trend, while the C4 showed more or less a stable pattern. Rise in %CD4 and %CD25 count was statistically significant. There was negative correlation between % CD4 count and SLEDAI score, while positive correlation between % CD25 count and SLEDAI score. %CD4 count is a sensitive, specific, reliable and valid marker of active disease in SLE and can be used to follow disease activity. %CD25 count can also be used as a marker to follow disease activity.


Bilateral Osteochondritis Dissecans of the Talar Posterior Calcaneal Articular Surface in a Professional Soccer Player: A Case Report.
Preferred sites of osteochondritis dissecans (OCD) are the distal femur and humerus, and the dome of the talus. We report a rare case of a professional soccer player with bilateral OCD of the talar posterior calcaneal articular surface. The left talus showed a loose but not displaced fragment, and pain was relieved with 3 months of conservative treatment. The right had two loose fragments that were displaced from their beds in the talar posterior calcaneal articular surface. The loose bodies were surgically excised. The player remains symptom free 4 years after the operation and participates in professional games. Thus, although OCD of the talar posterior calcaneal articular surface remains a relatively uncommon injury, we suggest that treatment methods tailored to the OCD stage as per Berndt and Harty classification may be successful. The exact causes and establishment of a treatment protocol in these cases will depend on the investigation of future cases. Since this case of OCD of the talar posterior calcaneal articular surface was bilateral, we hypothesized that it may have been caused by microtrauma in the sense of repetitive, excessive compression of the subchondral bone, or by a vascular etiology.


Prevalence of Normal Weight Obesity and Health Risk Factors for the Female Collegiate Dancer.
Brown, AF, Alfiero, CJ, Brooks, SJ, Kviatkovsky, SA, Smith-Ryan, AE, and Ormsbee, MJ. Prevalence of normal weight obesity and health risk factors for the female collegiate dancer. J Strength Cond Res 35(8): 2321-2326, 2021-The purpose of this study was to investigate the prevalence of normal weight obesity (NWO) and evaluate the relationship between NWO and health risk factors in a collegiate dancer population. Reanalysis of data of female dancers (N = 42) from 2 larger studies was used to assess prevalence and health risk factors of NWO. Dancers completed a dual-energy x-ray absorptiometry scan to assess fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT) and a 3-day food record. Normal weight obesity was defined as a body mass index (BMI) of 18.5-24.9 kg·m-2 and body fat (BF) ≥30%. Twenty-five (60%) dancers were classified as normal weight lean (NWL), and 17 dancers (40%) were classified as NWO. Significant differences were observed for BMI (NWL: 21.1 ± 1.7, NWO: 23.1 ± 1.6, p < 0.001), LM (NWL: 71.0 ± 2.9%, NWO: 62.5 ± 2.7%, p < 0.001), %BF (NWL: 24.8 ± 3.1%, NWO: 33.9 ± 2.6%, p < 0.001), and VAT (NWL: 130.6 ± 43.0 g, NWO: 232.3 ± 70.8 g, p < 0.001) between NWL and NWO. A significant difference was observed for carbohydrate intake (NWL: 4.7 ± 1.8 g·kg-1, NWO: 3.7 ± 1.0 g·kg-1, p = 0.020) between groups. Significant positive correlations with FM were observed between carbohydrate (kcal, p = 0.048), fat (kcal, p = 0.018; g·kg-1, p = 0.040), and total calories (p = 0.019) in NWO. Normal weight obesity in collegiate dancers may be more prevalent than previously perceived and may be significantly related to important health risk factors. The current study demonstrates the need for body composition assessments and emphasizing on promoting overall health in collegiate dancers.


Endopolyploidy in irradiated p53-deficient tumour cell lines: persistence of cell division activity in giant cells expressing Aurora-B kinase.
Recent findings including computerised live imaging suggest that polyploidy cells transiently emerging after severe genotoxic stress (and named 'endopolyploid cells') may have a role in tumour regrowth after anti-cancer treatment. Until now, mostly the factors enabling metaphase were studied in them. Here we investigate the mitotic activities and the role of Aurora-B, in view of potential depolyploidisation of these cells, because Aurora-B kinase is responsible for coordination and completion of mitosis. We observed that endopolyploid giant cells are formed via different means in irradiated p53 tumours, by: (1) division/fusion of daughter cells creating early multi-nucleated cells; (2) asynchronous division/fusion of sub-nuclei of these multi-nucleated cells; (3) a series of polyploidising mitoses reverting replicative interphase from aborted metaphase and forming giant cells with a single nucleus; (4) micronucleation of arrested metaphases enclosing genome fragments; or (5) incomplete division in the multi-polar mitoses forming late multi-nucleated giant cells. We also observed that these activities can release para-diploid cells, although infrequently. While apoptosis typically occurs after a substantial delay in these cells, we also found that approximately 2% of the endopolyploid cells evade apoptosis and senescence arrest and continue some form of mitotic activity. We describe here that catalytically active Aurora-B kinase is expressed in the nuclei of many endopolyploid cells in interphase, as well as being present at the centromeres, mitotic spindle and cleavage furrow during their attempted mitotes. The totally micronucleated giant cells (containing sub-genomic fragments in multiple micronuclei) represented only the minor fraction which failed to undergo mitosis, and Aurora-B was absent from it. These observations suggest that most endopolyploid tumour cells are not reproductively inert and that Aurora-B may contribute to the establishment of resistant tumours post-irradiation.


I₂-catalyzed oxidative C(sp³)-H/S-H coupling: utilizing alkanes and mercaptans as the nucleophiles.
By using alkanes and mercaptans as the nucleophiles with di-tert-butyl peroxide (DTBP) as the oxidant, I2-catalyzed oxidative C(sp(3))-H/S-H coupling was achieved. This protocol provides a novel process to construct C(sp(3))-S bonds from commercially available hydrocarbons and mercaptans.


Living well in care homes: a systematic review of qualitative studies.
research in care home settings is often negatively focused, portraying life as sterile and devoid of meaningful experiences. Care homes have the potential to influence people's lives socially, physically and psychologically. It is important to understand what factors contribute to this. to conduct a systematic qualitative review of care home life and provide practical recommendations to enhance residents' quality of life. the following databases were searched: PsycINFO, Medline, Web of Science, EMBASE, Allied and Complementary Medicine Database and Cumulative Index to Nursing and Allied Health Literature. References from appropriate journals and individual articles were checked. Papers that fitted our selection criteria were selected. Two independent reviewers assessed methodological study quality. Thematic analysis and meta-ethnographic methods were adapted to synthesise findings. thirty-one studies were identified. People in care homes voiced concerns about lack of autonomy and difficulty in forming appropriate relationships with others. Four key themes were identified: (i) acceptance and adaptation, (ii) connectedness with others, (iii) a homelike environment, (iv) caring practices. positive experiences in care homes can occur and are important for residents' quality of life. The review supports literature highlighting the need for relationship-centred approaches to care and emphasises the importance of understanding the resident's attitude towards living in care homes.