Effect of cardiac rehabilitation on muscle mass, muscle strength, and exercise tolerance in diabetic patients after coronary artery bypass grafting.
The effects of cardiac rehabilitation (CR) on muscle mass, muscle strength, and exercise tolerance in patients with diabetes mellitus (DM) who received CR after coronary artery bypass grafting (CABG) have not been fully elucidated. We enrolled 78 consecutive patients who completed a supervised CR for 6 months after CABG (DM group, n=37; non-DM group, n=41). We measured mid-upper arm muscle area (MAMA), handgrip power (HGP), muscle strength of the knee extensor (Ext) and flexor (Flex), and exercise tolerance at the beginning and end of CR. No significant differences in confounding factors, including age, gender, ejection fraction, or number of CR sessions, were observed between the two groups. At the beginning of CR, the levels of Ext muscle strength and peak VO2 were significantly lower in the DM group than in the non-DM group. At the end of CR, significant improvement in the levels of muscle strength, HGP, and exercise tolerance was observed in both groups. However, the levels of Ext muscle strength, HGP, peak VO2, thigh circumference, and MAMA were significantly lower in the DM group than in the non-DM group. In addition, no significant improvement in thigh circumference and MAMA was observed in the DM group. At the end of CR, the levels of thigh circumference and MAMA correlated with Ext and Flex muscle strength as well as with HGP. Percent changes in the levels of Ext muscle strength were significantly correlated with those of MAMA and hemoglobin A1c. These data suggest that improvement in muscle strength may be influenced by changes in muscle mass and high glucose levels in DM patients undergoing CR after CABG. A CR program, including muscle mass intervention and blood glucose control, may improve deterioration in exercise tolerance in DM patients after CABG.


Characterization of Bacillus cereus sensu lato isolates from milk for consumption; phylogenetic identity, potential for spoilage and disease.
This study addresses the biodiversity of Bacillus cereus group population present along the value chain of milk for consumption. The B. cereus population did not grow and remained mainly unaltered during storage of milk at 4 °C while storage at a suboptimal temperature at 8 °C (representative of a broken cold chain) caused a major shift in its composition. Mesophilic strains dominated the B. cereus population in raw milk and after storage at 4 °C, while psycrotrophic strains dominated after storage at 8 °C. All psycrotrophic and mesophilic isolates (n = 368) demonstrated high spoilage potentials of the milk components. Fifteen out of 20 mesophilic isolates but only two out of 40 psychrotrophic isolates, exhibited vero cell toxicity. No genes encoding the emetic toxin cereulide were detected in the genomes of 100 milk isolates while 14 of them harbored the enterotoxin genes cytK1/cytK2. Both psycrotrophic and mesophilic isolates carried the enterotoxin genes nheA and hblA. Together, the results provide insight into the composition and properties, of the B. cereus population present in milk along the value chain and during storage at optimal refrigerated temperature and at suboptimal temperature. This knowledge is useful in the dairy industry's work to assure high quality products and for risk assessment.


University students' and educators' perceptions on the use of digital and social media platforms: A sentiment analysis and a multi-country review.
Due to Covid-19, an inevitable restructuring of higher education teaching and learning pedagogies ensuring the continuous and effective learning of students is deemed important. Despite such vitality, a prevalent disparity worldwide on the usages and gains of digital and social media integration is still noticeable. Following a Scoping Literature Review and using the Atlas.ti software for a Grounded Theory qualitative analysis, this study aims to ascertain the significance of digital and social media tools during and after the Covid-19 pandemic. The study explains the common challenges and opportunities both students and educators faced in thirty countries. Drawing on the sentiment analysis of these stakeholders, results indicate that despite the acceleration of digital education into a flexible, and student-centered didactic approach, various barriers in effectively fulfilling online learning still exist. Findings also revealed the lack of, and therefore need for, proper teaching and learning material and strategies suitable for digital education.


Prospective comparison of long term outcomes in patients with severe acute pancreatitis managed by operative and non operative measures.
Present study reports the long term functional and morphological changes following severe acute pancreatitis and compares patients managed by operative and non-operative methods. Association between morphological changes and functional parameters were studied. 35 patients with one year of follow up after recovery from attack of acute pancreatitis were evaluated. Etiology was alcohol in 19, gallstones in 11 and idiopathic in 5. Fourteen patients were managed non-operatively and 21 operatively. Patients in non-operative group had a mean follow-up of 18.4 ± 8.2 months while patients in necrosectomy group had 31.4 ± 20.6 months. 40% patients had exocrine insufficiency (abnormal fecal fat) while 48.5% patients (17/35) had new onset diabetes. 90% patients had morphological changes in pancreas. Exocrine abnormality was significantly higher in necrosectomy group compared to non-operative group (57.2% vs 14.1%, p = 0.01). Patients undergoing necrosectomy had higher incidence of endocrine dysfunction {61.9% in surgery and 28.5% in non-operative group (p = 0.053)}. Operative group had more number of patients with completely non-visualized main pancreatic duct (MPD) (p = 0.028) and non-operative group had significantly higher irregular MPD (p = 0.021). Exocrine dysfunction was more in patients with complete non-visualization of MPD and/or incompletely visualized MPD (p = 0.013). Patients managed non-operatively had significantly less exocrine and endocrine dysfunction compared to operated patients. Exocrine dysfunction was significantly associated with complete non-visualization of MPD and/or incompletely visualized MPD.


Risk of Kidney Dysfunction IN Nafld.
The timely identification of traditional and non-traditional precursors and risk factors for chronic kidney disease (CKD) (a common systemic disease defined as a decreased kidney function documented by reduced glomerular filtration rate, or markers of kidney damage, or both) is relevant in clinical practice, as CKD increases the risk of end-stage renal disease and other serious comorbidities. A possible relationship between non-alcoholic fatty liver disease (NAFLD) (which is to date the most common chronic disease worldwide) and CKD has recently gained significant attention of researchers. A systematic literature search using appropriate keywords was made in order to identify relevant articles that have investigated the association between NAFLD and CKD. Several observational studies and meta-analyses have reported the existence of an independent association between NAFLD and risk of CKD in patients with and without diabetes. However, whilst the association between NAFLD and risk of prevalent CKD is strong across various patient populations, whether NAFLD is independently associated with the development and progression of CKD is still debatable. Moreover, emerging evidence now suggests a potential association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 genotype (the most important genetic variant associated to NAFLD) and decreasing kidney function, independent of NAFLD. Convincing evidence now indicates that CKD is increased among patients with NAFLD. For this reason, patients with NAFLD should be regularly monitored for renal function and, on the other hand , NAFLD should be considered in all patients with CKD, especially if they are obese or have type 2 diabetes.


Distinguishing specific sexual and general emotional effects in fMRI-subcortical and cortical arousal during erotic picture viewing.
Sexual activity involves excitement with high arousal and pleasure as typical features of emotions. Brain activations specifically related to erotic feelings and those related to general emotional processing are therefore hard to disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we investigated regions that show activations specifically related to the viewing of sexually intense pictures while controlling for general emotional arousal (GEA) or pleasure. Activations in the ventral striatum and hypothalamus were found to be modulated by the stimulus' specific sexual intensity (SSI) while activations in the anterior cingulate cortex were associated with an interaction between sexual intensity and emotional valence. In contrast, activation in other regions like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala was associated only with a general emotional component during sexual arousal. No differences were found in these effects when comparing females and males. Our findings demonstrate for the first time neural differentiation between emotional and sexual components in the neural network underlying sexual arousal.


Regulatory T-cells and autoimmunity.
Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.


Estimation of the impact of combined sewer overflows on surface water quality in a sparsely monitored area.
Combined sewer overflows (CSOs) can have a severe negative, local impact on surface water systems. To assure good ecological surface water quality and drinking water production that meets the demands, the impact of sewer system overflows on the surrounding water bodies for current and future climate conditions needs to be assessed. Typically, integrated, detailed hydrological and hydrodynamic water quantity and quality models are used for this purpose, but often data and computational resource requirements limit their applicability. Therefore, an alternative computationally efficient, integrated water quantity and quality model of sewer systems and their receiving surface waters is proposed to assess the impact of CSOs on surface water quality in a sparsely observed area. A conceptual model approach to estimate CSO discharges is combined with an empirical model for estimating CSO pollutant concentrations based on waste water treatment plant influent observations. Both methods are compared with observations and independent results of established reference methods as to evaluate their performance. The methodology is demonstrated by modelling the current impact of CSOs on the water abstraction area of a major drinking water production centre in Flanders, Belgium. It is concluded that the proposed conceptual models achieve similar results for daily WWTP effluent and CSO frequency, whereby the accumulated CSO volume is similar to more detailed full hydrodynamic models. Further, the estimated pollutant concentrations correspond with another dataset based on high resolution sampled overflows. As a result, the proposed computational efficient method can give insights in the impact of CSOs on the water quality at a catchment level and can be used for planning monitoring campaigns or performing analyses of e.g. the current and future water availability for a data scarce areas.


Genetic disorders of potassium homeostasis.
Hereditary disorders of potassium homeostasis are an interesting group of disorders, affecting people from the newborn period to adults of all ages. The clinical presentation varies from severe hypotension at birth to uncontrolled hypertension in adults, often associated with abnormal potassium values, although many patients may have a normal serum potassium concentration despite being affected by the genetic disorder. A basic understanding of these disorders and their underlying mechanisms has significant clinical implications, especially in the few patients with subtle clinical signs and symptoms. We present a summary of these disorders, with emphasis on the clinical presentation and genetic mechanisms of these disorders.


Cyclic AMP stimulates Ca(2+)-ATPase-mediated Ca2+ extrusion from human platelets.
The effect of cAMP on active Ca2+ extrusion across the plasma membrane of intact human platelets was studied using quin2, a fluorimetric indicator of free Ca2+ in the cytoplasmic compartment ([Ca2+]cyt). Elevations of cAMP were achieved by incubation with dibutyryl-cAMP or by forskolin, which was found to selectively elevate cAMP without affecting cGMP levels. Progress curves of Ca2+ extrusion from quin2-overloaded platelets were measured. The rate vs. [Ca2+]cyt characteristic was calculated as previously described (Johansson, J.S. and Haynes, D.H. (1988) J. Membr. Biol. 104, 147-163). Forskolin, at a maximally effective concentration of 10 microM, was shown to stimulate Ca2+ extrusion by increasing by a factor of 1.6 +/- 0.5 the Vm of a saturable component, previously identified with a Ca(2+)-Mg(2+)-ATPase located in the plasma membrane. Neither the Km (80 nM) or Hill coefficient (1.7 +/- 0.3) of the Ca(2+)-ATPase was affected. Forskolin had no effect on the linear, non-saturable component of extrusion (previously identified with a Na+/Ca2+ exchanger) over the [Ca2+]cyt range examined (50-1500 nM). Dibutyryl-cAMP (Bt2-cAMP, 1 mM) stimulated the Ca(2+)-Mg(2+)-ATPase component of Ca2+ extrusion by a factor of 2.0 +/- 0.6. Separate experiments showed that 10 microM forskolin reduces the resting [Ca2+]cyt from 112 nM to 96 nM. Mathematical analysis showed that this can be accounted for by the above-mentioned increase in Vm of the pump, countered by a 37-74% increase in the rate constant for passive Ca2+ leakage across the plasma membrane. The results suggest two mechanisms by which prostacyclin-induced elevation of cAMP inhibits platelet aggregation: (a) lowering of resting [Ca2+]cyt and (b) increasing the rate of Ca2+ extrusion after the initial influx or triggered release event.


Infant Mortality and Life Expectancy: The Inequitable Loss of Potential Life.
Differences in life expectancy between racial and other subgroups of the population indicate inequities in the community. There are both societal and physical factors-including racism, poverty, and access to care-that must be resolved to increase and equalize life expectancy and decrease the infant mortality rate.


Antibacterial and cytotoxic activity of isoprenylated coumarin mammea A/AA isolated from Mammea africana.
The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 μg/ml), Streptococcus pneumoniae (MIC=0.25 μg/ml), and Clostridium difficile (MIC=0.25 μg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines.


Predictive equations to estimate spinal loads in symmetric lifting tasks.
Response surface methodology is used to establish robust and user-friendly predictive equations that relate responses of a complex detailed trunk finite element biomechanical model to its input variables during sagittal symmetric static lifting activities. Four input variables (thorax flexion angle, lumbar/pelvis ratio, load magnitude, and load position) and four model responses (L4-L5 and L5-S1 disc compression and anterior-posterior shear forces) are considered. Full factorial design of experiments accounting for all combinations of input levels is employed. Quadratic predictive equations for the spinal loads at the L4-S1 disc mid-heights are obtained by regression analysis with adequate goodness-of-fit (R(2)>98%, p<0.05, and low root-mean-squared-error values compared with the range of predicted spine loads). Results indicate that intradiscal pressure values at the L4-L5 disc estimated based on the predictive equations are in close agreement with available in vivo data measured under similar loadings and postures. Combinations of input (posture and loading) variable levels that yield spine loads beyond the tolerance compression limit of 3400 N are identified using contour plots. Ergonomists and bioengineers, faced with the dilemma of using either complex but more accurate models on one hand or less accurate but simple models on the other hand, have thereby easy-to-use predictive equations that quantifies spinal loads and risk of injury under different occupational tasks of interest.


Intravesical herniation of small bowel after bladder perforation.
Intravesical small bowel herniation is a rare complication of bladder perforation, with only 1 case reported previously. We describe 2 additional patients in whom the diagnosis of bladder perforation was delayed or made difficult because the herniated small bowel presented as a filling defect without significant extravasation of contrast medium on cystography. In both patients additional investigative procedures were necessary to establish the diagnosis preoperatively.


Recovered memories of trauma: phenomenology and cognitive mechanisms.
We outline four current explanations for the reported forgetting of traumatic events, namely repression, dissociation, ordinary forgetting, and false memory. We then review the clinical and survey evidence on recovered memories, and consider experimental evidence that a variety of inhibitory processes are involved in everyday cognitive activity including forgetting. The data currently available do not allow any of the four explanations to be rejected, and strongly support the likelihood that some recovered memories correspond to actual experiences. We propose replacing the terms repression and dissociation as explanations of forgetting with an account based on cognitive science.


One-Dimensional Perovskite Manganite Oxide Nanostructures: Recent Developments in Synthesis, Characterization, Transport Properties, and Applications.
One-dimensional nanostructures, including nanowires, nanorods, nanotubes, nanofibers, and nanobelts, have promising applications in mesoscopic physics and nanoscale devices. In contrast to other nanostructures, one-dimensional nanostructures can provide unique advantages in investigating the size and dimensionality dependence of the materials' physical properties, such as electrical, thermal, and mechanical performances, and in constructing nanoscale electronic and optoelectronic devices. Among the one-dimensional nanostructures, one-dimensional perovskite manganite nanostructures have been received much attention due to their unusual electron transport and magnetic properties, which are indispensable for the applications in microelectronic, magnetic, and spintronic devices. In the past two decades, much effort has been made to synthesize and characterize one-dimensional perovskite manganite nanostructures in the forms of nanorods, nanowires, nanotubes, and nanobelts. Various physical and chemical deposition techniques and growth mechanisms are explored and developed to control the morphology, identical shape, uniform size, crystalline structure, defects, and homogenous stoichiometry of the one-dimensional perovskite manganite nanostructures. This article provides a comprehensive review of the state-of-the-art research activities that focus on the rational synthesis, structural characterization, fundamental properties, and unique applications of one-dimensional perovskite manganite nanostructures in nanotechnology. It begins with the rational synthesis of one-dimensional perovskite manganite nanostructures and then summarizes their structural characterizations. Fundamental physical properties of one-dimensional perovskite manganite nanostructures are also highlighted, and a range of unique applications in information storages, field-effect transistors, and spintronic devices are discussed. Finally, we conclude this review with some perspectives/outlook and future researches in these fields.


Antimutagen from leaves of Carmona retusa (Vahl) Masam.
An antimutagenic principle was extracted from the leaves of Carmona retusa with ethyl alcohol. This was then purified by solvent partition and liquid chromatography. The micronucleus test, an in vivo method, using albino mice as the test system was used for monitoring the antimutagenic activity. At a dosage of 23.4 mg/kg body weight, the pure isolate reduced by 68.4% the number of micronucleated polychromatic erythrocytes induced by the mutagen tetracycline. Statistical analysis (one-way ANOVA) shows that the variance of the pure isolate differs significantly from that of tetracycline, a known mutagen.


Association between perfectionism and life satisfaction among a sample of the Lebanese population: The indirect role of social phobia and validation of the Arabic version of the Social Phobia Inventory.
To assess the psychometric properties of the Social Phobia Inventory (SPIN), and evaluate the indirect effect of social phobia between perfectionism and life satisfaction (LS). A cross-sectional study enrolled 683 Lebanese adults (April-May 2021). The confirmatory factor analysis results confirmed the one-factor solution of the SPIN items (Cronbach's alpha = 0.92). Social phobia had an indirect effect in the association between rigid, self-critical, and narcissistic perfectionism and life satisfaction. The study results confirm the psychometric properties of the SPIN to assess social phobia and constitute a preliminary database of the variables that interplay with LS in the Lebanese population. Future studies should suggest clinical tools and techniques to cope with anxiety or reduce perfectionism to enhance LS.


Cerebral blood flow and oxygen consumption during isoflurane and halothane anesthesia in man.
In 13 patients, the effects on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of isoflurane and halothane administered in a clinically relevant situation were studied. Measurements were performed during fentanyl/nitrous oxide (65%) anesthesia together with moderate hyperventilation (PaCO2 approx 4.5 kPa), and repeated after addition of 0.65 MAC of isoflurane (n = 6) or halothane (n = 7). CBF was measured after intravenous administration of 133xenon and CMRO2 was calculated from the arterial venous differences of oxygen content (AVDO2) determined in arterial and jugular venous bulb blood. CBF and CMRO2 (means +/- s.e. mean) determined prior to administration of volatile agents were 28 +/- 5 ml x 100(-1) x min-1 and 2.0 +/- 0.3 ml x 100 g-1 x min-1, respectively, in the isoflurane group. In the halothane group, CBF was 25 +/- 0.4 ml x 100 g-1 x min-1 and CMRO2 was 2.0 +/- 0.4 ml x 100 g-1 x ml-1. There were no significant intergroup differences. Isoflurane did not change CBF, whereas halothane produced an increase of 36% (P less than 0.05) compared to values obtained during fentanyl/N2O anesthesia. In addition, isoflurane caused a further decrease in CMRO2 of 12% (P less than 0.01) as compared to a 20% increase (P less than 0.05) with halothane. The cerebral metabolic depression caused by the short-acting anesthetic induction agents would be expected to decrease with time, and could partly explain the observed increase in CMRO2 produced by halothane. The study suggests that the cerebrovascular and metabolic properties of isoflurane differ from those of halothane, also in man.


Angle-dependence and reproducibility of dual-beam vector doppler ultrasound in the common carotid arteries of normal volunteers.
Dual-beam vector Doppler has the potential to improve peak systolic blood velocity measurement accuracy by automatically correcting for the beam-flow Doppler angle. Using a modified linear-array system with a split receive aperture, we have assessed the angle-dependence over Doppler angles of 40 degrees -70 degrees and the reproducibility of the dual-beam blood maximum velocity estimate measured in the common carotid arteries (CCA) 1 to 2 cm prior to the bifurcation of 9 presumed-healthy volunteers. The velocity magnitude estimate was reduced by approximately 7.9% as the angle between the transmit beam and the vessel axis was increased from 40 degrees to 70 degrees. With repeat measurements made, on average, approximately 6 weeks apart, the 95% velocity magnitude limits of agreement were as follows: Intraobserver -41.3 to +45.2 cm/s; interobserver -29.6 to +46.8 cm/s. There was an 8.6 cm/s interobserver bias in velocity magnitude. We conclude that the dual-beam vector Doppler system can measure blood velocity within its scan plane with low dependence on angle and with similar reproducibility to that of single-beam systems.


24 hour ST segment analysis in transient left ventricular apical ballooning.
The etiologic basis of transient left ventricular apical ballooning, a novel cardiac syndrome, is not clear. Among the proposed pathomechanisms is coronary vasospasm. Long-term ST segment analysis may detect vasospastic episodes but has not been reported. 30 consecutive patients with transient left ventricular apical ballooning, left ventricular dysfunction and normal or near-normal coronary arteries were investigated. A 24-hour Holter ECG was obtained after emergency admission. ST segment analysis was performed automatically in 2 leads and confirmed by visual inspection. Criteria for an ischemic event were: 1. ST elevation or 2. horizontal or down-sloping ST segments ≥1 min duration and ≥100 µV J+80 point deviation corrected for baseline ST-deviation. Patients presented with ST segment elevation (n = 19) and/or T wave inversion (n = 20) on admission ECG. Ejection fraction was 50±12%. No transient ST elevations were observed during Holter ECG analysis. In 3 patients, 8 transient episodes of ST depression were recorded. Durations of episodes varied between 75 s and 790 s (mean 229 s). Maximal ST deviation averaged -191±71 µV. Ischemic burden was -1 to -22 mVs (mean -8 mVs). 27 patients showed no ischemic events. ST segment analysis of 24 h Holter recordings revealed minor ischemic events in only 10% of patients with transient left ventricular apical ballooning. Overall, ST segment changes were not indicative of recurrent coronary spasm playing a major role in the genesis of transient left ventricular apical ballooning.


[Retinal Detachment Part 1 - Epidemiology, Risk Factors, Clinical Characteristics, Diagnostic Approach].
This review article gives an overview of the epidemiology, relevant risk factors, clinical characteristics and the diagnostic approach of rhegmatogenous retinal detachment. Rhegmatogenous retinal detachment is an ophthalmologic emergency needing immediate surgical treatment. Main risk factors are retinal tears, myopia and previous cataract surgery. For patients with symptoms of posterior vitreous detachment, indirect ophthalmoscopy under pupil dilatation is necessary to diagnose retinal tears or retinal detachment. Differential diagnoses are tractive or exudative forms of retinal detachment or retinoschisis.


14-3-3 α and 14-3-3 ζ contribute to immune responses in planarian Dugesia japonica.
14-3-3 proteins are a family of highly conserved acidic proteins that regulate cellular processes. They act as a kind of important signaling molecules taking part in many crucial decisions throughout the development process. We have isolated and characterized two members of the 14-3-3 family, namely, Dj14-3-3 α and Dj14-3-3 ζ in the planarian Dugesia japonica. The Dj14-3-3 α and ζ genes encode polypeptides of 260 and 255 amino acids respectively. We have proved that the Dj14-3-3 α and ζ genes were especially expressed in the pharynx in adult and regenerating planarians by in situ hybridization and they were not involved in regeneration process. Besides, Dj14-3-3 α and ζ genes can compensate each other in planarians by RNA interference. The Dj14-3-3 α and ζ were significantly up-regulated expression when planarians were stimulated with the pathogen-associated molecular patterns including lipopolysaccharide (LPS), peptidoglycan (PGN), β-Glu and Poly (I:C), indicating that the Dj14-3-3 α and ζ may be involved in the immune responses.


NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors.
NF-Y, a trimeric transcription factor (TF) composed of two histone-like subunits (NF-YB and NF-YC) and a sequence-specific subunit (NF-YA), binds to the CCAAT motif, a common promoter element. Genome-wide mapping reveals 5000-15,000 NF-Y binding sites depending on the cell type, with the NF-YA and NF-YB subunits binding asymmetrically with respect to the CCAAT motif. Despite being characterized as a proximal promoter TF, only 25% of NF-Y sites map to promoters. A comparable number of NF-Y sites are located at enhancers, many of which are tissue specific, and nearly half of the NF-Y sites are in select subclasses of HERV LTR repeats. Unlike most TFs, NF-Y can access its target DNA motif in inactive (nonmodified) or polycomb-repressed chromatin domains. Unexpectedly, NF-Y extensively colocalizes with FOS in all genomic contexts, and this often occurs in the absence of JUN and the AP-1 motif. NF-Y also coassociates with a select cluster of growth-controlling and oncogenic TFs, consistent with the abundance of CCAAT motifs in the promoters of genes overexpressed in cancer. Interestingly, NF-Y and several growth-controlling TFs bind in a stereo-specific manner, suggesting a mechanism for cooperative action at promoters and enhancers. Our results indicate that NF-Y is not merely a commonly used proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve coassociation with FOS.


Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3-, CD3epsilon+, CD56+ phenotype and associated with the Epstein-Barr virus.
A novel interleukin-2 (IL-2)-dependent cell line, HANK1, was established from a patient with CD56+ NK/T-cell lymphoma arising in the retroperitoneum. Morphologically, HANK1 is a pleomorphic large cell line with irregular nuclei, which contains azurophilic granules in the cytoplasm. Immunophenotypic analysis showed that HANK1 expressed CD2, CD3epsilon, CD56, TIA-1, granzyme B, and HLA-DR, but no other T-lineage markers. These features were the same as seen in the original tumour, and are highly characteristic of nasal and 'nasal-type' NK/T-cell lymphoma as described in the proposed W.H.O. classification. Genotypically, this cell line also demonstrated the germline configuration of the T-cell receptor beta, gamma and the immunoglobulin heavy chain genes and clonal integration of the Epstein-Barr virus (EBV) together with antigen expression with a type II latency pattern (LMP-1+ and EBNA2-). Furthermore, Southern blot analysis using the EBV termini as probes confirmed its derivation from the original lymphoma, and revealed that it contained multiple copies of the EBV genome. Dose-dependent growth on IL-2 was observed in an in vitro study with a doubling time of 3 d at maximal stimulation. These data indicate that HANK1 seemed to preserve the biological characteristics of the original tumour and therefore may serve as a good model for the further analysis of unusual 'nasal-type' NK/T-cell lymphoma.


An observational study of emergency department intern activities.
To describe how intern time is spent, and the frequency of activities performed by interns during emergency department (ED) rotations. Prospective observational study of 42 ED interns from three Melbourne city teaching hospitals during 5 months in 2006. Direct observations were made by a single researcher for 390.8 hours, sampling all days of the week and all hours of the day. Proportion of time spent on tasks and number of procedures performed or observed by interns. Direct patient-related tasks accounted for 86.6% of total intern time, including 43.9% spent on liaising and documentation, 17.5% obtaining patient histories, 9.3% on physical examinations, 5.6% on procedures, 4.8% ordering or interpreting investigations, 3.0% on handover and 4.9% on other clinical activities. Intern time spent on non-clinical activities included 4.2% on breaks, 3.7% on downtime, 1.7% on education, and 1.3% on teaching others. Adjusted for an 8-week term, the ED intern would take 253 patient histories, consult more senior ED staff on 683 occasions, perform 237 intravenous cannulations/phlebotomies, 39 arterial punctures, 12 wound repairs and apply 16 plasters. They would perform chest compressions under supervision on seven occasions, observe defibrillation twice and intubation once, but may not see a thoracostomy. The ED exposes interns to a broad range of activities. With the anticipated increase in intern numbers, dilution of the emergency medicine experience may occur, and requirements for supervision may increase. Substitution of ED rotations may deprive interns of a valuable learning experience.


Human acellular dermis seeded with autologous fibroblasts enhances bronchial anastomotic healing in an irradiated rodent sleeve resection model.
The combination of neoadjuvant radiochemotherapy and parenchyma-preserving sleeve resection for lung cancer remains controversial because of potentially increased rate of anastomotic breakdown. We analyzed the effects of applying a decellularized human dermis transplant seeded with autologous fibroblasts in a rodent sleeve resection model with neoadjuvant radiotherapy. A total of 64 male Fisher rats underwent a transsection and surgical anastomosis of the left main bronchus and were randomized to receive plus/minus radiation treatment and plus/minus augmentation of the anastomosis with a fibroblast-seeded dermis transplant (2 × 2 factorial design). A μCT scan was performed at postoperative days 7 and 14, and the animals were sacrificed on day 14. Anastomotic bursting pressure and hydroxyproline concentration were measured. In the irradiated groups, the anastomotic bursting pressure was significantly higher in the augmented group at day 7 (100.9 ± 18.3 vs 141.3 ± 18.0 kPa, p = 0.0005) but not at day 14. Hydroxyproline levels showed a similar pattern in the irradiated group with significant differences at day 7 (7 days postoperative 158 ± 11.6 vs 198.2 ± 10.9 nmol/mg, p < 0.0001) but not at day 14 postoperatively. Augmentation of a bronchial anastomosis by a dermal matrix, seeded with autologous, viable fibroblasts improves early wound breaking strength. Fibroblast-enhanced dermal matrices provide a new and easily usable tool to prevent early anastomotic leakage after neoadjuvant chemoradiation in locally advanced lung cancer.


Prevention and Management of Serious Complications After Facial Fat Grafting.
Facial fat grafting is increasing worldwide. Although there are few reports in the literature on complications following facial lipofilling, rare but serious complications include embolic risk to local end organs such as the skin and eye, and the central nervous system. Treatment strategies are outlined. The key to prevention of complications is understanding the regional anatomy. It is imperative to adhere to the safe and efficacious techniques to minimize risk. Every surgeon who performs facial fat grafting should establish a systematic method to deliver safe, consistent, and long-term results for their patients.


A new hybrid system of QSAR models for predicting bioconcentration factors (BCF).
The aim was to develop a reliable and practical quantitative structure-activity relationship (QSAR) model validated by strict conditions for predicting bioconcentration factors (BCF). We built up several QSAR models starting from a large data set of 473 heterogeneous chemicals, based on multiple linear regression (MLR), radial basis function neural network (RBFNN) and support vector machine (SVM) methods. To improve the results, we also applied a hybrid model, which gave better prediction than single models. All models were statistically analysed using strict criteria, including an external test set. The outliers were also examined to understand better in which cases large errors were to be expected and to improve the predictive models. The models offer more robust tools for regulatory purposes, on the basis of the statistical results and the quality check on the input data.


Localization of the human aryl hydrocarbon hydroxylase gene to the 2q31----2pter region of chromosome 2.
Analysis of hybrid cells containing fragments of human chromosome 2 has resulted in the regional localization of a gene for aryl hydrocarbon hydroxylase (AHH). Hybrids prepared from a human cell line containing an established translocation have shown that AHH can be localized to the region 2q31----2pter.


Is randomization to placebo safe? Risk in placebo-controlled angina trials: angina risk meta-analysis.
It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing.


Knowledge of, and treatment strategies for, endometriosis among general practitioners.
Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis.


Physicochemical change and microparticle release from disposable gloves in the aqueous environment impacted by accelerated weathering.
The explosive growth of disposable gloves usage in cities around the world has posed a considerable risk to municipal solid management and disposal during the COVID-19 pandemic. The lack of the environmental awareness leads to glove waste being discarded randomly and ending up in the soil and/or the ocean ecosystem. To explore the physicochemical changes and environmental behaviors of disposable glove wastes in the aqueous environment, three kinds of glove (latex, nitrile and vinyl) were investigated. The results showed that the physicochemical characteristics of disposable gloves made of different materials were altered to different degrees by UV weathering. Nitrile gloves were more stable than latex and vinyl gloves after being exposed to weathering conditions. Although the chemical structures were not clearly demonstrated through FTIR after weathering, the SEM results showed significant microscopic changes on the surfaces of the gloves. Analysis of the leachate results showed that UV weathered gloves released leachable substances, including microparticles, organic matter, and heavy metals. Latex gloves were more likely to release microparticles and other substances into the water after UV weathering. The release of microparticles from gloves can also be impacted by sand abrasion. The appropriate strategy needs to be developed to mitigate the environmental impact caused by the discarded gloves.


Silent strokes in patients with heart failure.
The prevalence of asymptomatic strokes detected by brain imaging in a large cohort of patients with congestive heart failure (CHF) and reduced ejection fraction (EF) is unknown. The present study was conducted to assess the prevalence of cerebrovascular accidents (CVA) diagnosed by routine brain imaging in neurologically asymptomatic patients with CHF who were being evaluated for heart transplantation. A comprehensive review of clinical data in a consecutive case series of 168 adult patients being evaluated was conducted. Patients at a high risk of having cerebral infarction (ie, history of transient ischemic attack or stroke, paroxysmal or chronic atrial fibrillation, intracardiac thrombi, and prosthetic valves) were excluded. Brain imaging was performed as part of a routine pre-heart transplant evaluation protocol. The prevalence of silent ischemic strokes was 34%. Multiple logistic regression analysis revealed a 2.3 (95% CI 1.05-5.03) times increased risk of silent strokes if a patient was African American. Traditional risk factors such as age, gender, hypertension, and diabetes mellitus were not predictive of CVA in this population. Patients with CHF and a left ventricular EF less than 20% being evaluated for heart transplantation have a high prevalence of ischemic CVA. The role of anticoagulation in this high-risk group of patients should be further explored.


Follicular determinants of corpus luteum function in the human ovary.
The corpus luteum is a direct continuation of preovulatory follicle development. Growth and differentiation of a follicle to the preovulatory stage depends on certain endocrine changes taking place within the follicle itself (5). These endocrine changes markedly influence the viability, the rate of proliferation, and the biosynthetic potential of granulosa cells. Therefore, the sequence of endocrine events within the developing antral follicle is likely to be of considerable importance for the formation and secretory activity of the corpus luteum. If granulosa cells in developing antral follicles are exposed to certian hormones in the wrong sequence, the follicle may be prevented from developing into a normal corpus luteum. For example, if granulosa cells in antral follicles are not exposed to FSH, they are unable to generate high levels of oestrogen (Table 1). In the absence of oestrogen, granulosa cells do not increase in number. The same end result may also arise if the granulosa cells are exposed prematurely to elevated levels of LH or to high levels of prolactin: LH blocks granulosa cell mitoses even if the cells are exposed to oestrogen (1, 21); high levels of prolactin in antral fluid are associated with low levels of oestrogen and a reduced rate of granulosa cell proliferation. In women, it is likely that a fully functional corpus luteum is formed from a follicle that was exposed to the most favourable sequence of endocrine changes during its antral stages of development.


Pharmacokinetics of aminomethylpropanol in rats following oral and a novel dermal study design.
This study determined the oral and dermal ADME of 2-amino-2-methyl-1-propanol (AMP), a substituted aliphatic alcohol used in a number of industrial and consumer products. Groups of 4 male Fischer 344 rats received either a single bolus oral or dermal dose of 18 mg/kg (14)C-AMP in water. The dermal dose was applied to an area of 12 cm(2) on the back of the rats for 6h under semi-occluded conditions and fitted with rodent jackets to prevent grooming. Time-course blood and excreta were collected, radioactivity determined and blood and urine analyzed for AMP and metabolites. The orally administered (14)C-AMP was rapidly absorbed and eliminated in urine. Elimination of radioactivity from blood was biphasic with a rapid alpha phase (t(1/2 alpha) approximately 1h) followed by a slower beta phase (t(1/2 beta)=41+/-4h plasma and 69+/-34 h RBC). Total urinary elimination accounted for 87-93% of the dose, most (72-77%) within the first 48 h. Fecal elimination accounted for only 3-10%. Only 3-4% of the dose was found in tissues 168h post-dosing. The total dermal absorption of (14)C-AMP was 42% that included approximately 8% of the dose remaining at the application site 162 h after washing. Less than 1% of the applied dose remained in the stratum corneum and approximately 6% of the dose was found in tissues. Urinary elimination was 43% of the administered dose, most ( approximately 17%) within 48 h, and approximately 2% was eliminated in feces. It took much longer to reach plasma C(max) after dermal application (8.5+/-4.7 h in plasma and 4.0+/-2.8h in RBC) than the oral dose (0.3h) and the AUC(0-->alpha) for dermal dose was approximately 8-fold lower than with the oral dose. Again, elimination of the radioactivity from blood was biphasic with apparent t(1/2 alpha) of 9+/-6 and 2+/-1h for plasma and RBC, respectively. However, the alpha phase was "flipped-flopped" due to relatively slow dermal penetration and rapid elimination of the systemically absorbed dose, which was corrected to approximately 0.3 h after separating alpha elimination phase from the absorption. The slope of the beta phase became parallel to the oral route upon cessation of the absorption from the dose site skin, between 18 and 42 h post-washing. No metabolite of AMP was detected either in blood or excreta of any rat. Results of this study suggests that toxicologically significant concentrations of AMP are unlikely to be achieved in the systemic circulation and/or target tissues in humans as a result of dermal application of products containing AMP. Additionally, systemically absorbed dose will be rapidly eliminated from the body with little remaining at the application site.


The distribution and movements of carbon dioxide, carbonic acid and bicarbonate between blood and milk in the goat.
1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport.


Structure of the conserved cytoplasmic C-terminal domain of occludin: identification of the ZO-1 binding surface.
Occludin is a transmembrane protein localized at tight junctions whose functions are complex yet poorly understood. Current evidence supports a role for occludin in both the formation of the paracellular barrier and in cell signaling. While the N-terminal extracellular domains of occludin mediate homotypic adhesion, the distal C-terminal cytoplasmic domain of occludin controls protein targeting and endocytosis. The C terminus can also bind to the scaffolding proteins ZO-1, ZO-2, ZO-3, cingulin, the membrane trafficking protein VAP33, and the cytoskeletal protein F-actin, suggesting an important role for this domain. This domain is highly homologous to an important functional domain in the C terminus of the ELL family of RNA polymerase II transcription factors. To explore the function of occludin, we determined the high-resolution crystal structure of its C-terminal distal cytoplasmic domain. The structure comprises three helices that form two separate anti-parallel coiled-coils and a loop that packs tightly against one of the coiled-coils. Using in vitro binding studies and site-directed mutagenesis, we have identified a large positively charged surface that contains the binding site for ZO-1, and this surface is required for proper localization of occludin to cell-cell junctions. On the basis of sequence conservation, we predict that occludin domains from different species and the C-terminal domain of the ELL transcription factors share a very similar structure. Our results provide a model to further test the function of occludin and its binding to other proteins.


The capture of oxidized mercury from simulated desulphurization aqueous solutions.
Elemental mercury in flue gases from coal combustion is difficult to control. However, oxidized mercury species are soluble in water and can be removed with a high degree of efficiency in wet flue gas desulphurization (WFGD) systems operating in coal combustion plants, provided that no re-emissions occur. In this article the mechanisms affecting the re-emission of oxidized mercury species in WFGD conditions via sulphite ions are discussed. The parameters studied include the operating temperature, the pH, the redox potential, the concentrations of mercury and oxygen in the flue gas and the concentration of reductive ions in the solution. The results show that temperature, pH and the concentration of mercury at the inlet of the WFGD systems are the most important factors affecting oxidized mercury removal. The results indicate that sulphite ions, not only contribute to the reduction of Hg(2+), but that they may also stabilize the mercury in the liquid fraction of the WFGD limestone slurry. Consequently, factors that increase the sulphite content in the slurry such as a low oxygen concentration promote the co-capture of mercury with sulphur.


Factors Predictive of Primary Resistance to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.
Primary resistance to immune checkpoint inhibitors (ICI) is observed in routine clinical practice. We sought to determine factors predictive of primary resistance to ICI monotherapy, defined by the Society for Immunotherapy of Cancer (SITC) as progression within 6 months of ICI treatment with patients receiving at least 6 weeks of ICI monotherapy, in patients with advanced non-small-cell lung cancer (NSCLC). Patients with stage IV NSCLC treated with at least 6 weeks of single-agent ICI at two tertiary hospitals in Singapore were included. A multivariate logistic regression model was utilised to elucidate factors predictive of primary resistance to ICI. Of the 108 eligible patients, 59 (54.6%) experienced primary resistance. The majority were male (65.7%), smokers (66.3%), Chinese (79.6%), had adenocarcinoma (76.9%), received Pembrolizumab (55.6%) and received immunotherapy treatment in the later line setting (≥2 lines) (61.1%). Female gender (aOR = 3.16, p = 0.041), a sixth-week neutrophil-to-lymphocyte ratio (NLR) of ≥3) (aOR = 3.454, p = 0.037) and a later line of immunotherapy treatment (≥2 lines) (aOR = 2.676, p = 0.040) were factors predictive of primary resistance to ICI monotherapy in patients with advanced NSCLC. Using SITC criteria, an elevated NLR (≥3) at 6 weeks, female gender and a later line of immunotherapy treatment (≥2 lines) were predictive factors of developing primary resistance to ICI monotherapy in patients with advanced NSCLC.


An analysis tool to calculate permeability based on the Patlak method.
Strokes are commonly diagnosed by utilizing images obtained from magnetic resonance imaging (MRI) technology. Nowadays, computer software can play a large role in analyzing these images and arriving at diagnoses quickly and accurately. Additionally, this software can reduce workload for medical personnel and lower misdiagnoses. In this paper a flexible permeability calculation tool called PCT based on the Patlak plot method is presented. Using the PCT we can calculate the permeability co-efficient of the Blood-Brain Barrier (BBB) function. The PCT tool offers both manual and automatic options for diagnosing the regions of the brain affected by stroke. Moreover, the PCT tool supports various extensions such as dicom, nifty and analyze.


Early differentiation of long-standing persistent atrial fibrillation using the characteristics of fibrillatory waves in surface ECG multi-leads.
We characterized the f-waves in atrial fibrillation (AF) in the surface ECG by quantifying the amplitude, irregularity, and dominant rate of the f-waves in leads II, aVL, and V1, and investigated whether those parameters of the f-waves could discriminate long-standing persistent AF (LPeAF) from non-LPeAF. A total of 224 AF patients were enrolled: 112 with PAF (87 males), 48 with PeAF (38 males), and 64 with LPeAF (47 males). The f-waves in surface ECG leads V1, aVL, and II, which reflect well electrical activity in the right atrium (RA), the left atrium (LA), and both atria, respectively, were analyzed. The f-waves for LPeAF had lower amplitudes in II and aVL, increased irregularity and a higher dominant rate in II and V1 compared to PAF and PeAF (all p < 0.02). In a multivariate analysis, a low amplitude in lead II (<34.6 uV) and high dominant rate in lead V1 (≧390/min) (p < 0.001) independently discriminated LPeAF from the other AF types. The f-waves combined with both a low amplitude in lead II and high dominant rate in lead V1 were significantly associated with LPeAF (OR 6.27, p < 0.001). Characteristics of the f-waves on the surface ECG could discriminate LPeAF from other types of AF.


Gelatin derivatives in blood: interference with the determination of inorganic phosphate in serum.
The method of Goldenberg and Fernandez (1966) Clin. Chem. 12, 871--882) for the determination of inorganic phosphate in serum is significantly influenced by turbidity after intravenous application of gelatin derivatives, even at low quantities. This turbidity can be eliminated by the addition of sodium dodecyl sulphate to the reaction solution.


Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nucleus.
In most mammals the cochlear nuclear complex (CN) contains a distributed system of granule cells (GCS), whose parallel fiber axons innervate the dorsal cochlear nucleus (DCN). Like their counterpart in cerebellum, CN granules are innervated by mossy fibers of various origins. The GCS is complemented by unipolar brush (UBCs) and Golgi cells, and by stellate and cartwheel cells of the DCN. This cerebellum-like microcircuit modulates the activity of the DCN's main projection neurons, the pyramidal, giant and tuberculoventral neurons, and is thought to improve auditory performance by integrating acoustic and proprioceptive information. In this paper, we focus on the rat UBCs, a chemically heterogeneous neuronal population, using antibodies to calretinin, metabotropic glutamate receptor 1alpha (mGluR1alpha), epidermal growth factor substrate 8 (Eps8) and the transcription factor T-box gene Tbr2 (Tbr2). Eps8 and Tbr2 labeled most of the CN's UBCs, if not the entire population, while calretinin and mGluR1alpha distinguished two largely separate subsets with overlapping distributions. By double labeling with antibodies to Tbr2 and the alpha6 GABA receptor A (GABAA) subunit, we found that UBCs populate all regions of the GCS and occur at remarkably high densities in the DCN and subpeduncular corner, but rarely in the lamina. Although GCS subregions likely share the same microcircuitry, their dissimilar UBC densities suggest they may be functionally distinct. UBCs and granules are also present in regions previously not included in the GCS, namely the rostrodorsal magnocellular portions of ventral cochlear nucleus, vestibular nerve root, trapezoid body, spinal tract and sensory and principal nuclei of the trigeminal nerve, and cerebellar peduncles. The UBC's dendritic brush receives AMPA- and NMDA-mediated input from an individual mossy fiber, favoring singularity of input, and its axon most likely forms several mossy fiber-like endings that target numerous granule cells and other UBCs, as in the cerebellum. The UBCs therefore, may amplify afferent signals temporally and spatially, synchronizing pools of target neurons.


Diabetes mellitus in a cohort of patients with acromegaly.
To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. This was a cross sectional study. Fifty-eight acromegalic patients were assessed. Only 29% met the criteria for cure, and 27% had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2%. Most of the diabetic patients (18 out of 22, 82%) did not meet criteria for cure. They were more often hypertensive [16/22 (73%) vs. 17/36 (46%), p = 0.04], and used statins more frequently [14/22 (64%) vs. 8/36 (21%), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95% CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95% CI: 0.03 - 0.78), p = 0.02]. The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes.


Contact allergy to colophony. (IV). The sensitizing potency of commercial products. An investigation of French and American modified colophony derivatives.
The sensitizing capacity of 15 commercial colophony products was studied experimentally in guinea pigs. The study included 8 French and 6 American colophony derivatives as well as French tall oil colophony. The results indicate that tall oil colophony is the strongest sensitizing material within the tested group and that the maleic-modified products and the zinc-calcium-resinate are moderate sensitizers. Most of the modified products show a higher sensitizing capacity than the genuine resin acids themselves. Cross-reactions between the resin acids and the derivatives are uncommon. Therefore, patch testing with high concentrations of colophony (e.g., 60%) will not help to detect patients with colophony-derivative allergy.


Eighteen to 37 hours' preservation of major organs using a new autoperfusion multiorgan preparation.
A new autoperfusion preparation was used to preserve six major organs simultaneously. In 7 Yorkshire white swine, the heart and lungs were separated and removed with the liver, pancreas, duodenum, and both kidneys en bloc while they were self-perfused. Fresh blood, glucose, electrolytes, heparin sodium, methylprednisolone, and a fat emulsion (Soyacal) were infused through the portal vein. No inotropic drugs were necessary. The organs survived for 18 to 37 hours (average survival, 24.6 +/- 2.7 hours [+/- standard error of the mean]). Aortic systolic pressure ranged from 78.5 +/- 5.5 to 98.7 +/- 11.8 mm Hg. Arterial oxygen tension ranged from 206 +/- 23 to 266 +/- 15 mm Hg and arterial carbon dioxide tension, from 20.1 +/- 2.7 to 32.1 +/- 4.9 mm Hg. Blood lactic acid levels decreased from 8.75 +/- 2.06 to 5.50 +/- 2.45 mmol/L at 24 hours. Urine output ranged from 25 to 82 mL/h. Blood urea nitrogen levels decreased from 9.17 +/- 0.59 to 4.67 +/- 1.08 mg/dL. Blood creatinine levels decreased from 1.34 +/- 0.10 to 0.57 +/- 0.22 mg/dL. Serum glutamicoxaloacetic transaminase levels increased from 73.4 +/- 26.3 to 194 +/- 179.5 U/L and serum glutamic-pyruvic transaminase levels, from 44.8 +/- 5.7 to 91 +/- 66.4 U/L. Red blood cell count ranged from 6.94 +/- 0.58 to 13.23 +/- 2.30 x 10(6)/microliters. Lung wet/dry weight ratios changed from 5.79 +/- 0.17 at the beginning to 6.25 +/- 0.16 at 24 hours. The technique for simultaneous multiorgan preservation presented here is simple, effective, and highly reproducible. This study appears to have produced one of the longest average survival times for autoperfusion.


Short-latency EMG potentials elicited by head taps in sternocleidomastoid muscles: a study on normal human subjects and patients with central or vestibular lesions.
The aim of the present study was to determine whether a tap on the forehead evokes a vestibulospinal reflex in sternocleidomastoid muscles in normal human subjects and patients with central or vestibular lesions. While first positive-negative short-latency EMG potentials with a mean positive potential peak of about 12 ms and a mean negative potential peak of about 17 ms were found in the bilateral sternocleidomastoid muscles in normal subjects, they disappeared or were attenuated in patients with central or peripheral vestibular lesions.


Hysterectomy with ovarian conservation: effect on bone mineral density.
A cross-sectional study was undertaken in 58 consecutive women with premenopausal hysterectomy and ovarian conservation (Group 1) and 59 randomly selected women with natural menopause (Group 2) to determine the effect of hysterectomy on bone mineral density (BMD). Subjects were similar in age, height, weight, body mass index (BMI), exercise levels, family history of osteoporosis and smoking levels, but not years since hysterectomy or menopause (Group 1 = 14.9 +/- 10.8 years versus Group 2 = 9.8 +/- 8.7 years; p = 0.005), age at hysterectomy or menopause (Group 1 = 42.3 +/- 7.3 years versus Group 2 = 45.9 +/- 6.9 years; p = 0.008) or current alcohol consumption (Group 1 = 13.8% versus Group 2 = 39%; p = 0.002). Dual X-ray absorptiometry of the raw (unadjusted) lumbar spine and femoral neck BMD were similar for the 2 groups: lumbar spine = 0.947 +/- 0.179 g/cm2 (Group 1) versus 0.958 +/- 0.203 g/cm2 (Group 2) (p = 0.76) and femoral neck = 0.825 +/- 0.127 g/cm2 (Group 1) versus 0.815 +/- 0.146 g/cm2 (Group 2) (p = 0.71). Multivariate linear regression revealed that factors other than hysterectomy were associated with lumbar spine and femoral neck BMD. Thus, prior hysterectomy with ovarian conservation has no adverse effect on lumbar spine or femoral neck BMD.


[Study on the effect of integrin on human sperm activation].
This study was aimed to disclose whether the VLA-5 integrin on human sperm membrane takes part in the activation of human spermatozoa. Fluo-3/AM was coincubated with human spermatozoa. The change of intracellular calcium([Ca2+]i) was determined by flow cytometry when human sperms were exposed to Fibronectin(Fn) as the specific ligand of integrin VLA-5. Human sperm acrosome reaction(AR) rate was evaluated by triple-stain technique. Fn significantly raised the AR rate (P < 0.05) and the level of [Ca2+]i (P < 0.01) in the spermatozoa of fertile men. But there was no significant rise in the level of [Ca2+]i in the spermatozoa of infertile men. The VLA-5 integrin on human sperm membrane plays a role in the activation of sperm.


A return to responsibility: A critique of the single actor strategic model of CSR.
Any functional utility gained through corporate social responsibility (CSR) depends on "responsibility" as the governing principle between "corporate" and "social" interests. We argue that Porter and Kramer's highly popularised notion of "shared value" has been pivotal to the erosion of responsibility as a moderating concept in CSR. Under this approach, "strategic" CSR becomes an instrument to leverage corporate advantage, rather than fulfil social responsibilities and address business-related harms. In mining, this approach has supported shallow, derivative ideas including the wellknown CSR artefact: "social license to operate" (SLTO). We argue that CSR, and the related concept corporate social irresponsibility (CSI), suffer from the single actor problem, where the corporation too easily becomes the exclusive focus of analysis. We advocate for a reinvigorated debate about mining and social responsibility in which the corporation is but one actor in the (ir)responsibility landscape.


Control-relevant modeling of the antitumor effects of 9-nitrocamptothecin in SCID mice bearing HT29 human colon xenografts.
The mathematical model structure selected to describe system behavior is at least partially dependent on the proposed use of the model. In this paper, a pharmacokinetic(PK)/pharmacodynamic (PD) model for use in drug delivery algorithm synthesis is developed. The antitumor agent 9-nitrocamptothecin (9NC) was administered orally to severe combined immunodeficient (SCID) mice bearing subcutaneously implanted HT29 human colon xenografts, and the effect of 9NC on those xenografts was characterized. Different PK model structures were considered in characterizing the dynamics of the drug concentration in the plasma. Akaike's Information Criterion (AIC) was used to select the model structure maximizing fit accuracy while simultaneously minimizing the number of model parameters. The resulting PK model was a set of coupled linear ordinary differential equations able to describe the nonlinear dynamic behavior (e.g. plateauing, etc.) of the drug concentrations observed in the plasma. Pharmacodynamics were modeled by characterizing tumor growth in both the untreated and drug-treated animals. The resulting PK/PD model related drug administration to effect, and this model has a structure that facilitates future control algorithm synthesis. Control algorithms in this context would directly utilize PK/PD model predictions. These predictions would be used to determine the amount and frequency of drug administration in order to reduce the tumor burden without violating clinically relevant constraints. This methodology could then be used to aid the clinician in selecting dose levels and schedules, and extension to patient tailored treatment may eventually be feasible with this approach.


Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.
Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea.


A method for simultaneous determination of the two possible products of acetohydroxy acid synthase.
A method for the simultaneous assay of 2-acetolactate and 2-aceto-2-hydroxybutyrate formation catalyzed by acetohydroxy acid synthase in the presence of its substrates pyruvate and 2-ketobutyrate is described. The method, appropriate for the study of the physiologically and mechanistically significant competition between the two reactions, involves oxidative decarboxylation of the acetohydroxy acids to the corresponding 2,3-diketones, transfer of the volatile diketones to methanol, and gas chromatographic analysis with electron-capture detection. Oxidative decarboxylation by air requires catalytic activation, and addition of iron salts is crucial to the success of the method with purified enzymes.


Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis.
The etiology of schizophrenia (SCZ), as a serious mental illness, is unknown. The significance of genetics in SCZ pathophysiology is yet unknown, and newly identified mechanisms involved in the regulation of gene transcription may be helpful in determining how these changes affect SCZ development and progression. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the olfactory epithelium (OE) samples in order to better understand the molecular regulatory processes implicated in SCZ disorders in living individuals. The Gene Expression Omnibus database was used to obtain the OE microarray dataset (GSE73129) from SCZ sufferers and control subjects, which contained information about both lncRNAs and mRNAs. The limma package of R software was used to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). RNA interaction pairs were discovered using the Human MicroRNA Disease Database, DIANA-LncBase, and miRTarBase databases. In this study, the Pearson correlation coefficient was utilized to find positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Eventually, lncRNA-associated ceRNA axes were developed based on co-expression relations and DElncRNA-miRNA-DEmRNA interactions. This work found six potential DElncRNA-miRNA-DEmRNA loops in SCZ pathogenesis, including, SNTG2-AS1/hsa-miR-7-5p/SLC7A5, FLG-AS1/hsa-miR-34a-5p/FOSL1, LINC00960/hsa-miR-34a-5p/FOSL1, AQP4-AS1/hsa-miR-335-5p/FMN2, SOX2-OT/hsa-miR-24-3p/NOS3, and CASC2/hsa-miR-24-3p/NOS3. According to the findings, ceRNAs in OE might be promising research targets for studying SCZ molecular mechanisms. This could be a great opportunity to examine different aspects of neurodevelopment that may have been hampered early in SCZ patients.


Treatment volume shaping with selective beam blocking using the Leksell gamma unit.
The Leksell gamma unit at the University of Pittsburgh uses 201 highly focused 60Co beams arranged in a hemispherical array. Selective beam blocking can be used to modify the treatment volume into ellipsoid shapes oriented in different directions to match better the shape of the target volume. Dose distributions for different blocking patterns were calculated using specially developed computerized 3-D treatment planning software. The changes in dose distribution with different blocking patterns predicted by computer were verified by film densitometry. Techniques for using selective beam blocking to match more closely the treatment volume to the intended target volume have the potential of reducing the likelihood of complications for radiosurgery with the Leksell gamma unit and need to be further developed.


Differences in lipid and lipoprotein concentrations of capillary and venous blood samples.
The concentrations of lipids and lipoproteins measured in capillary blood serum taken from young adults were significantly lower than in venous blood, although they correlated satisfactorily. These differences may reflect differences in the morphological and hemodynamic conditions existing either in large veins or in the peripheral circulatory system. It was concluded that venous and capillary blood serum cannot be used interchangeably for these estimations.


Pathogenic Role of an IL-23/γδT17/Neutrophil Axis in Coxsackievirus B3-Induced Pancreatitis.
Coxsackievirus B is a common cause of viral myocarditis and pancreatitis. IL-17A is intensively involved in the pathogenesis of viral myocarditis. Whether IL-17A plays a role in Coxsackievirus B-induced pancreatitis, characterized by acinar cell destruction and immune infiltration, remains largely unknown. We found a significant, but transient, increase of IL-17A expression and γδT influx in the pancreas of C57BL/6J mice within 3 d following CVB3 infection. The pancreatic IL-17A was mainly produced by Vγ4 γδ T cells, to a lesser extent by CD4+ Th17 cells. IL-17A-/- and TCRδ-/- mice both reduced their susceptibility to CVB3 infection and pancreatitis severity when compared with the wild-type mice, without altering viral load. mAb depletion of Vγ4γδ T cells significantly improved mice survival and pancreatic pathology via decreasing Th17 expansion and neutrophil influx into the pancreas compared with isotype-treated mice. Transfer of Vγ4γδ T cells from wild-type, but not IL-17-/-, mice reconstituted TCRδ-/- mice to produce IL-17 and develop pancreatitis to the level of wild-type mice during CVB3 infection, indicating γδ T IL-17A is required for the onset of viral pancreatitis. IL-23 was robustly induced in the pancreas within the first day of infection. Administration of exogenous rIL-23 to mice increased CVB3 pancreatitis through in vivo expansion of IL-17+γδT17 cells at 12 h postinfection. Our findings reveal a key pathogenic role for early-activated γδT17 cells in viral pancreatitis via promoting neutrophil infiltration and Th17 induction. This IL-23/γδT17/neutrophil axis is critically involved in the onset of CVB3 pancreatitis and represents a potential treating target for the disease.


Antibiotic resistance markers in genetically modified plants: a risk to human health?
Cotransformation with an antibiotic-resistance marker is often necessary in the process of creating a genetically modified (GM) plant. Concern has been expressed that the release of these markers in GM plants may result in an increase in the rate of antibiotic resistance in human pathogens. For such an event to occur, DNA must not be totally degraded in field conditions, and the antibiotic-resistance marker must encounter potential recipient bacteria and be taken up by them, before being integrated into the bacterial genome, and the genes then expressed. In addition, the new recombinant must overcome the physiological disadvantage of acquisition of a piece of foreign DNA, probably in conditions where the new gene does not provide a selective advantage. We review each of these stages, summarising the investigations that have followed each of these steps. We contrast the potential increase in the antibiotic resistance reservoir created by antibiotic-resistance markers in GM plants with the current situation created by medical antibiotic prescribing. We conclude that, although fragments of DNA large enough to contain an antibiotic-resistance gene may survive in the environment, the barriers to transfer, incorporation, and transmission are so substantial that any contribution to antibiotic resistance made by GM plants must be overwhelmed by the contribution made by antibiotic prescription in clinical practice.


Postprandial triacylglycerol metabolism is modified by the presence of genetic variation at the perilipin (PLIN) locus in 2 white populations.
Several perilipin (PLIN) polymorphic sites have been studied for their potential use as markers for obesity and the metabolic syndrome. We aimed to examine whether the presence of polymorphisms at the perilipin (PLIN) locus (PLIN1, 6209T-->C; PLIN4, 11482G-->A; PLIN5, 13041A-->G; and PLIN6, 14995A-->T) influence postprandial lipoprotein metabolism in 2 white populations. Eighty-eight healthy Spanish men and 271 healthy US subjects (men and women) underwent an oral-fat-load test in 2 independent studies. Blood samples were taken in the fasting state and during the postprandial phase at regular intervals. Total cholesterol and triacylglycerol and triacylglycerol in triacylglycerol-rich lipoproteins (TRL, large and small) were measured. Carriers of the minor C allele at the PLIN1 variant displayed lower postprandial concentrations of large-TRL triacylglycerol (Spanish subjects: P = 0.024; US subjects: P = 0.005) than did subjects carrying the T/T genotype. The same pattern was observed in the Spanish population at the PLIN4 locus (P = 0.015), and both SNPs were in strong linkage disequilibrium. In both populations, subjects carrying the minor C and A alleles at PLIN1 and PLIN4, respectively, had significantly lower postprandial concentrations of plasma triacylglycerol (P < 0.05) and lower concentrations of small-TRL triacylglycerol than did those who were homozygous for the major alleles at PLIN1 and PLIN4 (Spanish subjects: P = 0.020 and 0.008, respectively; US subjects: P = 0.021 and 0.035, respectively). These 2 studies suggest that the presence of the minor C and A alleles at PLIN1 and PLIN4, respectively, are associated with a lower postprandial response that may result in lower atherogenic risk for these persons.


The selective response to adenosine of renal microvessels from hamster explants.
The present study was undertaken to investigate the effect of adenosine on the microvasculature of the hamster kidney and the possibility of angiotensin II mediation. Renal tissue from neonatal hamsters was grafted into the cheek pouch of 33 adult hamsters. Seven to twelve days later the renal microcirculation was studied. Adenosine was tested on the pre- and postglomerular arterioles as well as on cheek pouch arterioles before and after applying an AII antagonist, saralasin. Adenosine dilated the cheek pouch arterioles and constricted the preglomerular arterioles in a dose-dependent manner. Adenosine had no effect on postglomerular arterioles. The renal vasoconstriction persisted as long as adenosine was present. Theophylline reduced the adenosine-mediated vasoconstriction of the afferent arteriole in a dose-dependent manner. These changes were not altered in the presence of saralasin at various doses, one of which was 20-fold greater than that required to abolish the vasoconstrictor response of a test dose of angiotensin II. This study indicates that the adenosine-mediated vasoconstriction of the preglomerular microvessels is not mediated via the renin-angiotensin system but may be a direct effect of adenosine.


Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats.
Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress, we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201+/-5 vs. 163+/-7 mm Hg in diabetic rats untreated and treated with lercanidipine, respectively; P<0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P<0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P<0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P<0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2/TIMP-2 expression.


Inbreeding, eugenics, and Helen Dean King (1869-1955).
Helen Dean King's scientific work focused on inbreeding using experimental data collected from standardized laboratory rats to elucidate problems in human heredity. The meticulous care with which she carried on her inbreeding experiments assured that her results were dependable and her theoretical explanations credible. By using her nearly homozygous rats as desired commodities, she also was granted access to venues and people otherwise unavailable to her as a woman. King's scientific career was made possible through her life experiences. She earned a doctorate from Bryn Mawr College under Thomas Hunt Morgan and spent a productive career at the Wistar Institute of Anatomy and Biology in Philadelphia where she had access to the experimental subjects which made her career possible. In this paper I examine King's work on inbreeding, her participation in the debates over eugenics, her position at the Wistar Institute, her status as a woman working with mostly male scientists, and her involvement with popular science.


Subarachnoid Hemorrhage: Updates in Diagnosis and Management.
Subarachnoid hemorrhage (SAH) is a neurologic emergency due to bleeding into the subarachnoid space. Mortality can reach 50%. The clinical presentation is most often in the form of headache, classically defined as maximal at onset and worst of life. The most common cause is traumatic; approximately 80% of nontraumatic SAH are due to aneurysmal rupture, with the remainder from idiopathic peri-mesencephalic hemorrhage or other less common causes. Noncontrast brain computed tomography (CT) performed within 6 hours of symptom onset has sensitivity approaching 100%. Lumbar puncture may be considered after this period for definitive diagnosis if initial CT is normal.


Lerner's homeostasis and blood pressure.
Lerner's concept of developmental homeostasis, formerly elaborated with regard to the study of morphological traits, is proposed as a way of analysing the heritability of blood pressure. The important and controversial contribution of the autonomic nervous system to blood pressure regulation is also discussed with the aid of the hyperkinetic state, an entity described by Julius and Schork, and considered as an etiological factor in the occurrence of borderline hypertension. Experimental support through an analysis of a study performed on 87 pedigrees of normal healthy individuals is provided. The analysis calculates the heritabilities of systolic and diastolic blood pressure as well as heart rate. A classification in four categories, taking into account the hyperkinetic state, using the combined values of heart rate and mean arterial blood pressure is proposed, and its value regarding the categorization of normal individuals is emphasized and discussed simultaneously with the heritabilities calculated, in an attempt to explain the contribution of Lerner's theory to the inheritance of blood pressure.


Chronic allograft vasculopathy: new strategies for drug development.
Chronic rejection reflects cumulative trauma to the allograft regardless of its origin. The main histologic feature in chronic rejection in all allografts is proliferative allograft vasculopathy. According to the current paradigm, chronic rejection can be prevented by more intensive and selective immunosuppression. Experimental retransplantation to donor strain suggests that elimination of histoincompatibility does not prevent progression of the disorder after the initial stimulus has been sufficiently strong or long-lasting. In order to design additional sites for intervention after this point of no return, attention has focused on the regulation of the synthesis and/or action of smooth muscle cell growth factors. In several preclinical models, the blocking of growth factor synthesis, blocking of the binding of the growth factors to their receptors, and/or growth factor signaling downstream of the receptor, have successfully been used in the inhibition of the intimal response and allograft vasculopathy. Inhibition of proteolytic enzymes, necessary for smooth muscle cell locomotion, may provide additional sites of intervention. However, on most occasions, the inhibitory effect is incomplete only 30% to 50% of maximal. The future will demonstrate whether several approaches must be applied concomitantly, or whether genes regulating several of these ligands and their receptors simultaneously can be identified and exploited.


Lymphomatosis cerebri masquerading as the Marburg variant of multiple sclerosis.
Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma with few cases reported. Here, we describe the case of a patient with clinical presentation, imaging, and biopsy in keeping with aggressive multiple sclerosis (MS) such as that in Marburg variant. He deteriorated clinically over 9 months. Post-mortem examination yielded a diagnosis of LC with B-cell lymphoma. LC is notoriously difficult to diagnose, as it can present in various ways and biopsy of unaffected areas will be non-diagnostic. In our case, diagnosis was made more challenging by the patient's dramatic response to treatment with steroids and cyclophosphamide.


Multidimensional Risk Factors of Age-Related Hearing Loss Among Malaysian Community-Dwelling Older Adults.
This study evaluates the prevalence of and the multidimensional risk factors associated with age-related hearing loss (ARHL) among community-dwelling older adults in Malaysia. A total of 253 participants aged 60 years and above participated in this cross-sectional study. The participants were subjected to pure tone audiometric assessment. The hearing threshold was calculated for the better ear and classified into pure-tone average (PTA) for the octave frequencies from 0.5 to 4 kHz and high-frequency pure-tone average (HFA) for the octave from 2 to 8kHz. Then, the risk factors associated with PTA hearing loss (HL) and HFAHL were identified by using multivariate logistic regression analysis. The prevalence of ARHL based on PTA and HFA among the community-dwelling older adults was 75.5% and 83.0%, respectively. Following multifactorial adjustments, being older (OR: 1.239; 95% CI: 1.062-1.445), having higher waist circumference (OR: 1.158; 95% CI: 1.015-1.322), lower intake of niacin (OR: 0.909; 95% CI: 0.831-0.988) and potassium (OR: 0.998; 95% CI: 0.996-1.000), and scoring lower in RAVLT T5 (OR: 0.905; 95% CI: 0.838-0.978) were identified as the risk factors of PTAHL. Meanwhile, being older (OR: 1.117; 95% CI: 1.003-1.244), higher intake of carbohydrate (OR: 1.018; 95% CI: 1.006-1.030), lower intake of potassium (OR: 0.998; 95% CI: 0.997-0.999), and lower scores on the RAVLT T5 (OR: 0.922; 95% CI: 0.874-0.973) were associated with increased risk of having HFAHL. Increasing age, having higher waist circumference, lower intake of niacin and potassium, higher intake of carbohydrates and having lower RAVLT T5 score were associated with increased risk of ARHL. Modifying these risk factors may be beneficial in preventive and management strategies of ARHL among older persons.


Development of anaerobic fecal flora in healthy newborn infants.
Stool samples from 196 healthy infants less than ten days of age were cultured to delineate bacterial colonization patterns of the intestine. By one week of age, isolation rates of Bacteroides fragilis and other anaerobic bacteria in term infants following vaginal delivery and formula feeding approach that of adults. Differences in gestational age, type of delivery, and type of feeding are associated with significantly different colonization patterns of anaerobic and aerobic bacteria in the first week after birth.


[Disturbances of micturition after general surgical operations (author's transl)].
Impaired micturition after general surgical operations can be due to three causes, which occur individually or in combination. The first comprises side effects of anesthetics upon the autonomic nervous system. Inhibition of the abdominopelvic reflex, initiating micturition, due to the operative trauma represents the scond cause. Both the vegetative and the mechanical traumas, lead to decompensation of the urinary bladder, whose function is impaired by neuropathic factors and outflow obstruction. Pulmonary, cerebral, and abdominal insufficiency prolong the effects of both traumas. The third cause is direct operative injury of the sacroplexus pelvus.--Approximately 25% of all patients undergoing surgery will shown voiding disturbances in the postoperative period. The treatment consists sympatholytic therapy. In cases of neuropathic and obstructed bladders, the treatment of choice is transurethral correction of the bladder outlet.


Homotypic and heterotypic serum neutralizing antibody response to rotavirus proteins following natural primary infection and reinfection in children.
Worldwide trials of rotavirus vaccines are currently in progress, but the basis of cross-reactive immunity between rotavirus serotypes is yet to be elucidated. The involvement of the outer capsid proteins, VP7 and VP4, in the production of cross-reactive neutralizing antibody (N-Ab) is unclear, and may be important for the success of animal rotavirus-based candidate vaccines that lack a VP4 of human rotavirus origin. In this study, VP7- and VP4-specific N-Ab was assayed in sera from children experiencing primary (27 children) and/or secondary (14 children) rotavirus infections using human-animal reassortant strains. These reassortants contained genes encoding the major G- and P-types found in human infection, including G1, 2, 3, and 4; or P1A[8], 1B[4], and 2[6]. After primary infection, the N-Ab response to VP7 was generally serotype-specific, whereas the response to VP4 was heterotypic. After reinfection (with the same or different serotypes) there was a significant increase (P=0.0313) in the number of VP7 serotypes seroconverted against with no broadening of cross-reactivity to VP4. Increases in homotypic N-Ab titer, following both primary and secondary infection, were greater against VP7 than VP4, with the seroconversion against VP7 being significantly greater upon reinfection than following primary infection (P=0.0280). In summary, heterotypic N-Ab produced following primary infection appears to be primarily against VP4. However, upon reinfection, VP7 becomes increasingly immunodominant both in terms of cross-reactive N-Ab production and increases in N-Ab titer.


1,2-Bis(2,4-di-nitro-phen-yl)disulfane.
In the title mol-ecule, C12H6N4O8S2, the dihedral angle between the benzene rings is 77.00 (8)°. The mean planes of the nitro groups are twisted slightly from the benzene rings, forming dihedral angles in the range 2.3 (2)-8.6 (3)°. The S-S bond length is 2.0458 (7) Å. Each S atom is essentially coplanar with the benzene ring to which it is attached, with deviations from the ring planes of 0.0163 (5) and 0.0538 (5) Å. In the crystal, mol-ecules are linked through weak C-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (001).


Surgical resection of hepatic metastases from gastric cancer: outcomes from national series in England.
The objectives of this national study were to examine the short-term safety and long-term survival benefit associated with surgical resection of hepatic metastases from gastric cancer. Patients from the Hospital Episode Statistics database were classified by disease and treatment approach. Gastric cancer: 1. Without liver metastases treated by gastrectomy (GG). 2. With liver metastases treated by gastrectomy and hepatectomy (GGH). 3. With liver metastases treated by gastrectomy without hepatectomy (GGNH). 4. With liver metastases treated with no surgery (GNS). Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. During the study period, 87,482 were patients diagnosed with gastric cancer, of whom 13,841 underwent partial or total gastrectomy. Of those who underwent gastrectomy, 336 had a diagnosis of liver metastases and 78 of these had a hepatectomy. Propensity-matched analysis showed no significant differences in 30- or 90-day mortality between the GGH and GG groups. The GGH group had significantly improved 1-year mortality (35.9 % vs. 50.0 %, p = 0.049) and 5-year mortality (61.5 % vs. 75.7 %, p = 0.031) compared to the GGNH group, and compared to the GNS group, the GCH group had 1-year mortality (35.9 % vs. 84.6 %, p < 0.001) and 5-year mortality (61.5 % vs. 90.8 %, p < 0.001). This study showed that hepatectomy for synchronous gastric cancer hepatic metastases may carry survival benefits in selected patients. The data presented should not be a rationale to change current clinical practice but rather a stimulus to prospectively study the role of surgery in a selected group of patients who are currently treated with palliative chemotherapy.


JPEG vs. JPEG2000: benchmarking with dermatological images.
Despite the importance of images in the discipline and the diffusion of digital imaging devices, the issue of image compression in dermatology was discussed only in few studies, which yielded results often not comparable, and left some unanswered questions. To evaluate and compare the performance of the JPEG and JPEG2000 algorithms for compression of dermatological images. Nineteen macroscopic and fifteen videomicroscopic images of skin lesions were compressed with JPEG and JPEG2000 at 18 different compression rates, from 90% to 99.5%. Compressed images were shown, next to uncompressed versions, to three dermatologists with different experience, who judged quality and suitability for educational/scientific and diagnostic purposes. Moreover, alterations and quality were evaluated by calculation of mean 'distance' of pixel colors between compressed and original images and by peak signal-to-noise ratio, respectively. JPEG2000 was qualitatively better than JPEG at all compression rates, particularly highest ones, as shown by dermatologists' ratings and objective parameters. Agreement between raters was high, but with some differences in specific cases, showing that different professional experience can influence judgement on images. In consideration of its high qualitative performance and wide diffusion, JPEG2000 represents an optimal solution for the compression of digital dermatological images.