Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
Osteoarthritis (OA) has been recognized as the most common chronic age-related disease. Cartilage degeneration influences OA therapy. Here we report that hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is essential for OA development. Elevated HPIP levels are found in OA patients. Col2a1-CreERT2/HPIPf/f mice exhibit obvious skeletal abnormalities compared with their HPIPf/f littermates. HPIP deficiency in mice protects against developing OA. Moreover, intra-articular injection of adeno-associated virus carrying HPIP-specific short hairpin RNA in vivo attenuates OA histological signs. Notably, in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles identify that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes. Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Furthermore, HPIP potentiates the transcriptional activity of LEF1 and acetylates histone H3 lysine 56 in the promoters of Wnt targets, suggesting that HPIP is an attractive target in OA regulatory network.


Temporal requirements of the fragile X mental retardation protein in the regulation of synaptic structure.
Fragile X syndrome (FraX), caused by the loss-of-function of one gene (FMR1), is the most common inherited form of both mental retardation and autism spectrum disorders. The FMR1 product (FMRP) is an mRNA-binding translation regulator that mediates activity-dependent control of synaptic structure and function. To develop any FraX intervention strategy, it is essential to define when and where FMRP loss causes the manifestation of synaptic defects, and whether the reintroduction of FMRP can restore normal synapse properties. In the Drosophila FraX model, dFMRP loss causes neuromuscular junction (NMJ) synapse over-elaboration (overgrowth, overbranching, excess synaptic boutons), accumulation of development-arrested satellite boutons, and altered neurotransmission. We used the Gene-Switch method to conditionally drive dFMRP expression to define the spatiotemporal requirements in synaptic mechanisms. Constitutive induction of targeted neuronal dFMRP at wild-type levels rescues all synaptic architectural defects in Drosophila Fmr1 (dfmr1)-null mutants, demonstrating a presynaptic requirement for synapse structuring. By contrast, presynaptic dFMRP expression does not ameliorate functional neurotransmission defects, indicating a postsynaptic dFMRP requirement. Strikingly, targeted early induction of dFMRP effects nearly complete rescue of synaptic structure defects, showing a primarily early-development role. In addition, acute dFMRP expression at maturity partially alleviates dfmr1-null defects, although rescue is not as complete as either early or constitutive dFMRP expression, showing a modest capacity for late-stage structural plasticity. We conclude that dFMRP predominantly acts early in synaptogenesis to modulate architecture, but that late dFMRP introduction at maturity can weakly compensate for early absence of dFMRP function.


Suberin lamellae in the hypodermis of maize (Zea mays) roots; development and factors affecting the permeability of hypodermal layers.
The development of suberin lamellae in the hypodermis of Zea mays cv. LG 11 was observed by electron microscopy and the presence of suberin inferred from autoliuorescence and by Sudan black B staining in nodal (adventitious) and primary (seminal) root axes. Suberin lamellae were evident at a distance of 30-50 mm from the tip of roots growing at 20°C and became more prominent with distance from the tip. Both oxygen deficiency and growth at 13°C produced shorter roots in which the hypodermis was suberized closer to the root tip. There were no suberin lamellae in epidermal cells or cortical collenchyma adjacent to the hypodermis. Plasmodesmata were not occluded by the suberin lamellae: there were twice as many of them in the inner tangential hypodermal wall (1,14 μn-2 ) as in the junction between the epidermis and hypodermis (0.54 μm-2 ). Water uptake by seminal axes (measured by micropotometry) was greater at distances more than 100 mm from the root lip than in the apical zone where the hypodermis was unsuberized. In the more mature zones of roots grown at 13°C rates of water uptake were greater than in roots grown at 20°C even though hypodermal suberization was more marked. Sleeves of epidermal/hypodermal cells (plus some accessory collenchyma) were isolated from the basal 60 mm of nodal axes by enzymatic digestion (drisclase). The roots were either kept totally immersed in culture solution or had the basal 50 mm exposed to moist air above the solution surface. In both treatments the permeabilities to tritiated water and 86 Rb were low (circa 10-5 mms-1 ) in sleeves isolated from the extreme base. In roots grown totally immersed, however, the permeability of sleeves increased 10 to 50-fold over a distance of 40 mm. In roots exposed to moist air the permeability remained at a low level until the point where the root entered the culture solution and then increased rapidly (> 50-fold in a distance of 8 mm). Growth of roots in oxygen depleted (5% O2 ) solutions promoted the development of extensive cortical aerenchymas. These developments were not associated with any reduction in permeability of sleeves isolated from the basal 40 mm of the axis. It was concluded that the presence of suberin lamellae in hypodermal walls does not necessarily indicate low permeability of cells or tissues to water or solutes. The properties of the walls (lamellae?) can be greatly changed by exposure to moist air, perhaps due to increased oxygen availability.


Alternative DNA loops regulate the arabinose operon in Escherichia coli.
The araCBAD regulatory region of Escherichia coli contains two divergently oriented promoters and three sites to which AraC, the regulatory protein of the operon, can bind. This paper presents the results of in vivo dimethyl sulfate "footprinting" experiments to monitor occupancy of the three AraC sites and measurements of activity of the two promoters. These measurements were made both in the absence of the inducer arabinose and at various times after arabinose addition to growing cells containing the wild-type ara regulatory region or the regulatory region containing various deletions and point mutations. The data lead to the conclusion that two different DNA loops can form in the ara regulatory region. These loops are generated by AraC protein molecules binding to two different DNA sites and binding to each other. One of these loops predominates in the absence of arabinose and plays a major role in repressing activity of one of the promoters. Upon the addition of arabinose the amount of the first loop type, the repression loop, decreases and the amount of a second loop increases. Formation of this second loop precludes the counterproductive formation of the repression loop.


Association of a blood-based aging biomarker index with death and chronic disease: Cardiovascular Health Study.
A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration. A Biomarker Index (BI) was constructed in the Cardiovascular Health Study (N=3197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up. The hazard ratio (HR, 95% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7% and 22.0% in women and men, respectively. BI was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.


Food Brands: Friend or Foe?
Food brands are household words to many Americans but some are anathema to nutritionists and they would gladly banish them. Here's a look at the pros and cons of some of the old favorites from our nutrition business editor.


Bovine pancreatic lipase. III. Lipolysis of oils and fats and fatty acid specificity.
Purified bovine pancreatic lipase hydrolyzed butteroil, vegetable oils, and synthetic glycerides. The enzyme hydrolyzed triglycerides more rapidly than di- and monoglycerides and tripropionin faster than any other synthetic glyceride. Triacetin was the least hydrolyzed glyceride. Gas-liquid chromatographic analysis of the free fatty acids liberated by the lipase from milk fat indicated that the enzyme selectively liberated butyric acid in higher proportion than the relative amount originally in the fat. The enzyme released saturated as well as unsaturated fatty acids from commericial vegetable oils. With regard to the lipolytic behavior, in general, the bovine pancreatic lipase closely resembled milk lipase.


Explicit Diversity Index (EDI): a novel measure for assessing the diversity of compound databases.
A novel diversity assessment method, the Explicit Diversity Index (EDI), is introduced for druglike molecules. EDI combines structural and synthesis-related dissimilarity values and expresses them as a single number. As an easily interpretable measure, it facilitates the decision making in the design of combinatorial libraries, and it might assist in the comparison of compound sets provided by different manufacturers. Because of its rapid calculation algorithm, EDI enables the diversity assessment of in-house or commercial compound collections.


Delta(9)-tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: involvement of CB(1) receptors.
The effects of the principal psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), on endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons were investigated. Locally applied Delta(9)-THC (0.03, 3, 300, and 1,000 nM) concentration-dependently increased basal extracellular glutamate levels (+18% +/- 11%, +54% +/- 10%, +90% +/- 14%, +149% +/- 33% vs. basal). The facilitatory effects of Delta(9)-THC (3 and 300 nM) on cortical glutamate were fully counteracted in the presence of the selective CB(1) receptor antagonist SR141716A (10 nM) and by replacement of the normal Krebs-Ringer bicarbonate buffer with a low-Ca(2+) (0.2 mM) medium. Delta(9)-THC application also induced an enhancement in K(+)-evoked glutamate levels. These findings suggest that an increase in cortical glutamatergic transmission mediated by local CB(1) receptor activation may underlie some of the psychoactive and behavioral effects of acute marijuana consumption.


Influence of COVID-19 on the poultry production and environment.
Although chickens are not susceptible to SARS-CoV-2, several coronavirus disease outbreaks have been described concerning poultry processing facilities in different countries. The COVID-19 pandemic and the developed strain caused 2nd, 3rd, and recent Indian strain waves of epidemics that have led to unexpected consequences, such as forced reductions in demands for some industries, transportation systems, employment, and businesses due to public confinement. Besides, poultry processing plants' conditions exacerbate the risks due to the proximity on the line, cold, and humidity. Most workers do not have access to paid sick time or adequate health care, and because of the low wages, they have limited reserves to enable them to leave steady employment. In addition, workers in meat and poultry slaughterhouses may be infected through respiratory droplets in the air and/or from touching dirty surfaces or objects such as workstations, break room tables, or tools. Egg prices have increased dramatically during the lockdown as consumers have started to change their behaviors and habits. The COVID pandemic might also substantially impact the international poultry trade over the next several months. This review will focus on the effect of COVID-19 on poultry production, environmental sustainability, and earth systems from different process points of view.


Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients.
In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg 40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin autoantibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.


Lung Infection Affects Access to Treatment and Short-Term Outcome in Patients With Severe Alcohol-Related Hepatitis Treated With Corticosteroids.
Severe alcohol-related hepatitis (AH) is associated with an increased risk of infection, but the impact of pneumonia has not been specifically analyzed in a specific cohort. All patients admitted for severe AH between 2002 and 2020 were prospectively included. Systematic screening for infection was performed at admission and renewed in the case of clinical suspicion. We included 614 patients (60.4% men, mean age 49.9 years, median model for end-stage liver disease [MELD] 25.2, bilirubin 18.1 mg/dL), 202 (32.9%) with infections at admission (73 lung infections). Encephalopathy ( P = 0.006), MELD score ( P = 0.0002), and tobacco exposure (past vs never smokers: P = 0.002 or active vs past smokers: P = 0.005) were associated with lung infection at admission on multivariate analysis. Factors independently associated with death before steroid initiation were encephalopathy ( P = 0.003), MELD score ( P = 0.05), and especially lung infection ( P < 0.0001). Thus, patients with a lung infection had a lower probability of receiving steroids than those with other infections and noninfected patients: 54.8 vs 88.4 vs 98.1% ( P < 0.0001). One hundred forty-six of the 558 patients who received corticosteroids developed infection, including 57 (39.04%) pneumonias. The risk of respiratory and nonrespiratory infection was higher in nonresponders to steroids (Lille score ≥0.45) than in responders: 13% vs 7.6%, P = 0.03 and 27.9% vs 10.6%, P < 0.001, respectively. The variables independently associated with 3-month mortality after steroid initiation were lung infection ( P = 0.004), nonresponse to steroids ( P < 0.0001), MELD score ( P = 0.0003), ascites ( P = 0.003), and encephalopathy ( P = 0.018), whereas nonrespiratory infections were not ( P = 0.91). Lung infection is frequent during severe AH and influences mortality at admission and after steroid initiation. These results emphasize the need for specific management of lung infection during the course of AH.


Short-Chain Polysaccharide Analysis in Ethanol-Water Solutions.
This study demonstrates that short-chain polysaccharides, or oligosaccharides, could be sufficiently separated with hydrophilic interaction LC (HILIC) conditions and quantified by evaporative light-scattering detection (ELSD). The multianalyte calibration approach improved the efficiency of calibrating the nonlinear detector response. The method allowed easy quantification of short-chain carbohydrates. Using the HILIC method, the oligosaccharide solubility and its profile in water/alcohol solutions at room temperature were able to be quantified. The results showed that the polysaccharide solubility in ethanol-water solutions decreased as ethanol content increased. The results also showed oligosaccharides to have minimal solubility in pure ethanol. In a saturated maltodextrin ethanol (80%) solution, oligosaccharide components with a degree of polymerization >12 were practically insoluble and contributed less than 0.2% to the total solute dry weight. The HILIC-ELSD method allows for the identification and quantification of low-MW carbohydrates individually and served as an alternative method to current gel permeation chromatography procedures.


Pressor responsiveness and cardiovascular reflex activity in spontaneously hypertensive and normotensive rates during vasopressin infusion.
Arginine vasopressin (AVP), phenylephrine, and noradrenaline were infused intravenously into conscious and unrestrained adult spontaneously hypertensive (SH) rats and the changes in arterial pressure and heart rate were compared to those in Wistar--Kyoto (WKY) rats. The curve expressing the relationship of the increase in arterial pressure to the logarithm of the plasma concentration of AVP for SH rats was shifted to the left of that for WKY rats by a factor of four. In contrast, the dose--response (arterial pressure) curves for phenylephrine and noradrenaline in SH rats were displaced slightly to the right. In WKY rats, heart rate fell more for a given elevation of arterial pressure during infusions of AVP than during infusions of phenylephrine and noradrenaline; in SH rats, the heart rate response were less pronounced than in WKY rats, and the responses to vasopressin, phenylephrine, and noradrenaline were similar. The results are consistent with the interpretation that cardiovascular reflex activity is particularly enhanced during infusions of AVP in normotensive rats. The absence of this phenomenon in SH rats appears to contribute to the enhanced pressor activity of AVP in these rats.


Ooplasmic injection of elongating spermatids for the treatment of non-obstructive azoospermia.
We applied the technique of ooplasmic elongating spermatid injection to the treatment of non-obstructive azoospermia. Mature oocytes were injected with elongating spermatids isolated from testicular biopsy material obtained from 13 non-obstructed azoospermic men. Seventy-three oocytes were successfully injected with elongating spermatids and were then cultured for 36 h. At 13 h post-injection 68 oocytes were found to be activated and 52 of them were fertilized. Forty-one 2- to 4-cell stage embryos developed from normally fertilized oocytes were transferred. At least two embryos were transferred to each female partner. Two pregnancies were achieved. Elongating spermatid injection may have a role in the treatment of non-obstructive azoospermia.


Efficient and Stable Mg2+-Doped CsPbCl3 Nanocrystals for Violet LEDs.
It has been a challenge to prepare perovskite violet light-emitting diodes due to the low luminous efficiency and poor stability of the relevant materials. In this work, the defect state density of CsPbCl3 NCs was reduced by Mg2+ doping, so the photoluminescence quantum efficiency (PLQY) was increased by 57 times (from 1.3% to 75.8%) compared with undoped CsPbCl3 NCs. The doped CsPbCl3 NCs had no phase change in the atmosphere over 180 days, and the PLQY was only dropped by 19%. Based on the highly efficient luminescence and high stability of Mg2+-doped CsPbCl3 NCs, violet-light-emitting diodes were fabricated. The maximum brightness of device was 135 cd/m2, and the peak EQE reached 0.1%.


The opening dynamics of the lateral gate regulates the activity of rhomboid proteases.
Rhomboid proteases hydrolyze substrate helices within the lipid bilayer to release soluble domains from the membrane. Here, we investigate the mechanism of activity regulation for this unique but wide-spread protein family. In the model rhomboid GlpG, a lateral gate formed by transmembrane helices TM2 and TM5 was previously proposed to allow access of the hydrophobic substrate to the shielded hydrophilic active site. In our study, we modified the gate region and either immobilized the gate by introducing a maleimide-maleimide (M2M) crosslink or weakened the TM2/TM5 interaction network through mutations. We used solid-state nuclear magnetic resonance (NMR), molecular dynamics (MD) simulations, and molecular docking to investigate the resulting effects on structure and dynamics on the atomic level. We find that variants with increased dynamics at TM5 also exhibit enhanced activity, whereas introduction of a crosslink close to the active site strongly reduces activity. Our study therefore establishes a strong link between the opening dynamics of the lateral gate in rhomboid proteases and their enzymatic activity.


Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a.
Complement component C3a is an anaphylatoxin known to induce plasma exudation and smooth muscle contraction in tissues. The effects on inflammatory effector leukocytes, however, are poorly defined and controversial, being at best weak and occurring at very high C3a concentrations. Here, we examined the effect of C3a upon mediator release from human basophils, with and without pretreatment with interleukin 3 (IL-3), a hematopoietic growth factor recently found to profoundly modify the basophil response to various cell agonists. In the absence of cytokines, C3a, even at a concentration of 1 microM, was ineffective or only weakly stimulatory for basophil mediator release. However, when basophils were pretreated with IL-3 at concentrations of only 0.01-1 unit/ml, they became responsive to C3a, releasing large amounts of histamine and also generating leukotrienes. Surprisingly, almost optimal effects occurred with even very low C3a concentrations (1 nM). Another hematopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), was also found to render basophils capable of responding to C3a, but the effect was weaker than that of IL-3. C3a-induced histamine release and leukotriene generation occurred rapidly in IL-3-primed cells, being complete after 0.5 and 2 min, respectively. The rapid and strong degranulation response, occurring at very low concentrations of C3a, suggests the presence of a high-affinity C3a receptor on basophils, which might be inducible by cytokines. Our results demonstrate that, depending on the presence of IL-3 or GM-CSF, C3a is a potent basophil activator, and such a phenomenon could be of relevance in various inflammatory processes, especially hypersensitivity reactions.


Environmental photochemistry in Solanum trilobatum mediated plasmonic nanoparticles as a probe for the detection of Cd2+ ions in water.
Nowadays world deals with a lot of environmental troubles out of which water pollution is very dangerous. Water gets contaminated by heavy metal ions is a universal problem which needs suitable consideration to keep up the quality of the water. It will be advantageous that an easy device can be detecting the concentration of heavy metal ions in water. Here, a contaminant, cadmium from industrial affluent into water is considered and focused. Gold nanoparticles (AuNPs) have been synthesized by Solanum trilobatum leaf extract and its applications of antifungal and sensing activity was reported here. The influences of different concentration of these reducing agent on the synthesis of AuNPs (G5 and G10) have been evaluated. The structural, optical, vibrational, morphological and compositional properties of the AuNPs were studied through XRD, UV-vis spectra, FTIR, HRTEM and EDAX analysis. The optical studies showed surface plasmon absorbance peak at 526 nm. It shows that the absorbance of the peak becomes narrow with a higher concentration of leaf extract. XRD results showed the average size of the AuNPs was 8 nm. It also confirmed the high crystallinity of nanoparticles. FTIR exposes that amine and carboxyl groups may be involved in the stabilization and reduction mechanism. TEM pictures of both G10 and G5 demonstrate merely spherical nanoparticles. This morphology control is taken place owing to the adsorbed amine and carboxyl groups onto the gold nanoparticles cap the particles and improve the stability. The presence of gold elements in the sample was identified with the help of EDAX. The sensitivity of the system towards various Cd2+ concentrations was measured as 0.058/mM for G5 and 0.095/mM for G10. The prepared nanoparticles produced highest zone of inhibition (ZOI) of 17.5 mm and 19 mm against human being pathogenic fungi Aspergillus Flavus and Candida albicans respectively. Here, small sized spherical nanoparticles showed good antifungal activity.


Evaluation of Cyclosporine A with β-TCP in the Treatment of Human Infra bony Defects - A Randomized Controlled Pilot Study.
Cyclosporine A (CsA), an immunosuppressant, is considered a life saver drug in organ transplant cases. It has also been tested in animal and human studies for periodontal applications as it selectively inhibits T lymphocyte proliferation, Interleukin-2 (IL-2) and other cytokine production, without any effect on T suppressor cells, thereby suppressing the cell mediated immunity and suppressing the inflammation. Inflammatory and immunological responses have been found to be decreased and bone formation is found to be increased in immunosuppressed animals. CsA is also supposed to potentiate osseous regeneration due to increase in the bone alkaline phosphatase levels and a direct activating effect on osteoblasts. The present study was aimed at evaluating locally administered low dose of CsA which is potent immunosuppressant along with β-Tricalcium phosphate (β-TCP) in comparison with β TCP alone, in the treatment of human infrabony defects, over a period of six months. Thirty two systemically healthy chronic periodontitis patients with infrabony defects were included in the randomized, controlled, parallel arm study and were allocated into either Group A (n =16), patients treated with β-TCP + CsA (2 mg) or Group B (n =16), patients treated with β-TCP. Clinical parameters [Relative Attachment Level (RAL), Probing Depth (PD), Gingival Recession (GR)] and radiographic parameters were measured at baseline and six months postoperatively. Statistical analysis was done using SPSS version 16 software. Student's paired and independent t-test were used for intra and inter-group analysis. Both Group A and Group B showed statistically significant improvements in clinical and radiographic parameters from base line to six months post-operatively. The Clinical Attachment Level (CAL) gain, Linear Bone Growth (LBG) and Percentage Bone Fill (% BF) were 2.38±1.12 mm, 1.90±1.48 mm and 49.83±29.23 mm in Group A and 2.57±1.22 mm, 2.03±1.16 mm and 62.84±29.70 mm in Group B respectively, inter group comparison showed no statistically significant difference. Both the groups revealed statistically significant improvement in clinical and radiographic parameters and adjunctive use of CsA did not prove beneficial.


[Potassium depletion. Glucose intolerance. Senile diabetes. A study of possible pathogenetic relations. 2].
The effects of intake of potassium salts for 21-28 days on the glucose tolerance of 10 elderly subjects with clear diabetes were examined by means of the Tolbutamide test (TT) and the i.v. glucose tolerance test (IVGTT). Improvement in tolerance, to the extent of a reduction in glycaemic levels and better coefficients, was observed in all values of the two tests and in basal glycaemia values, with constantly significant differences at statistical examination. In a group of 4 cases in which Tolbutamide treatment was suspended for the same period, this improvement in the Tolbutamide Test was not observed. With this second confirmation of the initial hypothesis, the pathogenetic significance and biological relevance of potassium depletion in senile diabetes and generally, in the ageing process, are discussed.


GTP gamma S and forskolin-stimulated adenylyl cyclase activity in post-mortem brain from depressed suicides and controls.
We have measured basal, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and forskolin-stimulated adenylyl cyclase activity in samples of frontal and parietal cortex obtained at post-mortem from suicides, with a firm retrospective diagnosis of depression. The suicides were divided into those free of antidepressants and those receiving antidepressants. Each suicide was individually compared to a gender and age-matched control. Although we found no significant differences in adenylyl cyclase activity between controls and either antidepressant-free or antidepressant-treated suicides, there was a trend for lower stimulated adenylyl cyclase activity in suicides.


Assessment of adherence to eczema treatment in Hong Kong children.
Introduction: Eczema is the most common childhood skin problem in Hong Kong. Treatment adherence is crucial in symptom management and the effectiveness of eczema management. The Problematic Experiences of Therapy Scale (PETS) is used to assess adherence to treatment among children with eczema. Objective: This study examined the psychometric properties of the translated Chinese version of PETS (C-PETS) among parents and caregivers of children with eczema. Methods: PETS was translated into Chinese and data obtained from a convenience sample of 147 Chinese participants from a regional hospital in Hong Kong. Results: The internal consistency of C-PETS with a Cronbach's α of 0.93 and good test-retest reliability with weighted Kappa ranging from 0.74 to 0.89 were obtained. Significant positive correlations were found among the C-PETS, Children's Dermatology Life Quality Index (r = 0.25, p = .002), and Severity Grading of Atopic Dermatitis scores (r = 0.38, p = .001). A significant negative correlation was found between C-PETS and Chinese adaptation of Generic Self-Efficacy scale (r = -0.40, p = .001). Confirmatory factor analysis showed that the data supported the structural validity of C-PETS. Conclusion: This study indicates that C-PETS is a reliable and valid measure to evaluate treatment adherence for Chinese parents and caregivers of children with eczema.


Anterior tibial plateau fracture: An often missed injury.
In most classifications of tibial plateau fractures, including one used most widely-Schatzker classification, fractures are described as a combination of medial and lateral condyle, primarily in the sagittal plane. Coronal component of these fractures, affecting the posterior tibial condyle is now well recognized. What is not described is anterior coronal component of the fracture, what we are calling "anterior tibial condyle fracture". These fractures are often missed on routine antero-posterior and lateral knee X-rays due to an overlap between the fracture and the normal bone. Eight cases of anterior tibial condyle fractures with posterior subluxation of the tibia, six of which were missed by the initial surgeon and two referred to us early, are described. Two of the six late cases and both the early ones were operated. Reconstruction of the anterior condyle and posterior cruciate ligament reconstruction was done. Primary outcome measures such as union of the fracture, residual flexion deformity, range of motion and stability were studied at the end of 6 months. All operated fractures united. There was no posterior sag in any. In those presenting late and were operated, the flexion deformity got corrected in all (average from 15° to 0°) and mean flexion achieved was 100° (range: 80-120°). In those presenting early and were operated, there was no flexion deformity at 6 months and a mean flexion achieved was 115° (range: 100-130°). None of the operated patients had instability. This article attempts to highlight that this injury is often missed. They should be suspected, diagnosed early and treated by reconstruction of anterior condyle, posterior cruciate ligament reconstruction.


Presynaptic inhibitory effect of Met-enkephalin on [14C] acetylcholine release from the myenteric plexus and its interaction with muscarinic negative feedback inhibition.
The effect of Met-enkephalin on the release of radioactivity (14C) from a myenteric plexus-longitudinal muscle preparation loaded with [14C]choline has been investigated under different conditions, when the muscarinic receptor mediated negative feedback inhibition was operative or when it was completely excluded by atropine. Separation of the [14C]acetylcholine (ACh) and [14C] choline components of the released radioactivity revealed that during 45-min incubation periods about 3.2% of the ACh store became labeled and that during stimulation only the release of [14C]ACh increased above resting level. The fractional release at rest measured in the 5-min collection period was 1.07 +/- 0.09 X 10(-2) in the absence and 1.56 +/- 0.07 X 10(-2) in the presence of physostigmine. Met-enkephalin had no effect on the release of ACh evoked by a 2-Hz stimulation when cholinesterase was inhibited by physostigmine. However, in the presence of atropine or in the absence of cholinesterase inhibition, the release by stimulation was significantly higher and subject to inhibition by Met-enkephalin. The present results indicate that Met-enkephalin is able to reduce ACh release only under those conditions in which the negative feedback modulation is negligible and the release is not yet reduced completely. These findings also suggest that in the myenteric plexus there is no independent population of cholinergic neurons exclusively sensitive to either ACh or to Met-enkephalin; cholinergic varicosities are equipped with at least both types of receptors we studied. When the effect of Met-enkephalin on twitch tension and on the release of radioactivity was studied simultaneously, a positive correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS)


Cost-effectiveness analysis of ceftazidime-avibactam as definitive treatment for treatment of carbapenem-resistant Klebsiella pneumoniae bloodstream infection.
Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic that has been confirmed in the United States and China for use in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI). However, the cost-effectiveness of CAZ-AVI is unknown in China. This study aimed to evaluate the cost-effectiveness of CAZ-AVI compared to polymyxin B (PMB) monotherapy or PMB-based therapy for the treatment of CRKP BSI from the Chinese healthcare perspective. A hybrid decision tree and Markov model were constructed for a hypothetical cohort of patients with CRKP BSI. The time horizon of the Markov model was 5 years with an annual discount rate of 5% used in both costs and quality-adjusted life-years (QALYs). The model data was derived from published literature and publicly available database. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the willingness-to-pay (WTP) threshold of $ 11,600 per QALY were considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model analysis. In the base-analysis, CAZ-AVI provided an additional 60 QALYs and reduced the cost by $ 2,218,300, yielding an ICER of $ -36,730.9/QALY, well below the WTP threshold of $ 11,600 per QALY when compared with PMB-based therapy. CAZ-AVI provided an additional 350 QALYs and increased the cost of $ 208,400, producing an ICER of $ 591.7/QALY that was below the WTP threshold compared to PMB monotherapy. At a $ 11,600/QALY threshold, results were sensitive to the cost of PMB-based strategy, the cost of CAZ-AVI strategy, the probability of cure with CAZ-AVI, and the probability of cure with PMB or PMB-based therapy. CAZ-AVI was an optimal regimen in 76.9% and 80.8% of 10,000 Monte Carlo simulations at $ 11,600/QALY and $ 34,800/QALY, respectively. Meanwhile, CAZ-AVI was cost-effective at the WTP thresholds of all 31 Chinese provinces in 61.4% (Gansu) to 83.1% (Beijing) of simulations. Ceftazidime-avibactam is expected to be a cost-effective treatment compared with PMB monotherapy or PMB-based therapy for CRKP BSI from the Chinese healthcare perspective.


[Kartagener's syndrome with aspergilloma].
A 47-year-old man was referred to our hospital because of hemoplysis. He had a history of chronic sinusitis and surgical treatment of a spinal arteriovenous malformation. A chest X-ray film and computed tomographic scan showed dextrocardia, diffuse bronchiectasis, and an aspergilloma in the right upper lung field. The source of the bleeding could not be detected by fiberoptic bronchoscopy. Transbronchial mocosal biopsy was done and examination of a specimen by transmission electron microscopy revealed the lack of inner and outer dynein arms. A chest X-ray film and computed tomographic scan of his nephew, who had a long history of productive cough showed dextrocardia and right lower-lobe bronchiectasis. These findings indicate that hemoptysis in patients with Kartagener's Syndrome can be caused not only by bronchiectasis but also by aspergilloma.


Exploring diagonal gait using a forward dynamic three-dimensional chimpanzee simulation.
Primates are unusual among terrestrial quadrupedal mammals in that at walking speeds they prefer diagonal rather than lateral gaits. A number of reasons have been proposed for this preference in relation to the arboreal ancestry of modern primates: stability, energetic cost, neural control, skeletal loading, and limb interference avoiding. However, this is a difficult question to explore experimentally since most primates only occasionally use anything other than diagonal gaits. An alternative approach is to produce biologically realistic computer simulations of primate gait that enable the constraints of biomechanical loading and the energetics of different modes of locomotion to be explored. In this paper we describe such a model for the chimpanzee Pan troglodytes. The simulation is able to produce spontaneous quadrupedal locomotion, and the footfall sequences generated are split between lateral and diagonal footfall sequences with no obvious energetic benefit associated with either option. However, out of 10 successful simulation runs, 5 were lateral sequence/lateral couplet gaits indicating a preference for a specific lateral footfall sequence with a relatively tightly constrained phase difference between the fore- and hindlimbs. This suggests that the choice of diagonal walking gaits in chimpanzees is not a simple mechanical phenomenon and that diagonal walking gaits in primates are selected for by multiple factors.


[The establishing of a state sanitary-epidemiological supervision in occupational health: its goals and prospects].
The requirements are: improved legal basis for work safety and health care of workers; establishment of state sanitary and epidemiologic supervision, system for disclosure and account of occupational diseases in the country and regions; higher role of Research Centers and colleges in specifying scientific and medical documents to help practical medicine. The authors present parameters of occupational morbidity over 10 years (1991-2000) and stress that work conditions and workers' health state did not improve during the period, demonstrate high occurrence of accidents. The authors necessitate more attention to small business enterprises, sketch achievements of Research Centers with RAMSc and Health Ministry in specifying methods and principles to evaluate health risk under exposure to environmental and occupational factors, to set hygienic regulations (including those for complex exposure). The authors formulated main directions of State Sanitary and Epidemiologic Supervision activities: improvement of sanitary laws, scientific basis for sanitary and epidemiologic supervision, skill formation, management measures).


Collaborative care for depression in general practice: study protocol for a randomised controlled trial.
Depression is a common illness with great human costs and a significant burden on the public economy. Previous studies have indicated that collaborative care (CC) has a positive effect on symptoms when provided to people with depression, but CC has not yet been applied in a Danish context. We therefore developed a model for CC (the Collabri model) to treat people with depression in general practice in Denmark. Since systematic identification of patients is an "active ingredient" in CC and some literature suggests case finding as the best alternative to standard detection, the two detection methods are examined as part of the study. The aim is to investigate if treatment according to the Collabri model has an effect on depression symptoms when provided to people with depression in general practice in Denmark, and to examine if case finding is a better method to detect depression in general practice than standard detection. The trial is a cluster-randomised, clinical superiority trial investigating the effect of treatment according to the Collabri model for CC, compared to treatment as usual for 480 participants diagnosed with depression in general practice in the Capital Region of Denmark. The primary outcome is depression symptoms (Beck's Depression Inventory (BDI-II)) after 6 months. Secondary outcomes include depression symptoms (BDI-II) after 15 months, anxiety symptoms (Beck's Anxiety Inventory (BAI)), level of functioning (Global Assessment of Function (GAF)) and psychological stress (Symptom Checklist-90-Revised (SCL-90-R)). In addition, case finding (with the recommended screening tool Major Depression Inventory (MDI)) and standard detection of depression is examined in a cluster-randomized controlled design. Here, the primary outcome is the positive predictive value of referral diagnosis. If the Collabri model is shown to be superior to treatment as usual, the study will contribute with important knowledge on how to improve treatment of depression in general practice, with major benefit to patients and society. If case finding is shown to be superior to standard detection, it will be recommended as the detection method in future treatment according to the Collabri model. ClinicalTrials.gov. NCT02678845 . Retrospectively registered on 7 February 2016.


Deep learning-assisted diagnosis of femoral trochlear dysplasia based on magnetic resonance imaging measurements.
Femoral trochlear dysplasia (FTD) is an important risk factor for patellar instability. Dejour classification is widely used at present and relies on standard lateral X-rays, which are not common in clinical work. Therefore, magnetic resonance imaging (MRI) has become the first choice for the diagnosis of FTD. However, manually measuring is tedious, time-consuming, and easily produces great variability. To use artificial intelligence (AI) to assist diagnosing FTD on MRI images and to evaluate its reliability. We searched 464 knee MRI cases between January 2019 and December 2020, including FTD (n = 202) and normal trochlea (n = 252). This paper adopts the heatmap regression method to detect the key points network. For the final evaluation, several metrics (accuracy, sensitivity, specificity, etc.) were calculated. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the AI model ranged from 0.74-0.96. All values were superior to junior doctors and intermediate doctors, similar to senior doctors. However, diagnostic time was much lower than that of junior doctors and intermediate doctors. The diagnosis of FTD on knee MRI can be aided by AI and can be achieved with a high level of accuracy.


Craniofacial analysis of the Tweed Foundation in Angle Class II, division 1 malocclusion.
This study has defined the cephalometric values of the Craniofacial Analysis of the Tweed Foundation for a sample of Brazilian subjects. The sample consisted of 211 cephalometric radiographs from subjects aged 12-15, which were divided into two groups: Class II group, with 168 lateral teleradiographs (cephalograms) of white Brazilian subjects, with Angle Class II, division 1 malocclusion, of both genders (82 males and 86 females); and the Control Group, with 43 lateral teleradiographs (cephalograms) of subjects whose occlusion was clinically excellent, and also of both genders (21 males and 22 females). The teleradiographs were selected from the files of the Department of Orthodontics, School of Dentistry of Piracicaba, State University of Campinas, previously to the orthodontic treatment. The results demonstrated no sexual dimorphism for each group, as attested by the Student's t-test. The exploratory analysis (+/- 0.5 standard deviation) enabled the tolerance limits to be determined and a Craniofacial Analysis Table to be constructed using the respective cephalometric intervals. In addition, the difference between the two groups was not statistically significant according to the maxilla position. The maxilla was in a good position in relation to the cranial base. On the other hand, the mandible was retruded in relation to the cranial base in the Class II cases. The skeletal pattern was not defined because only the Facial Height Index (FHI) showed a vertical pattern in Class II subjects, while the Y Axis, SN.PlO, SN.GoMe and FMA values did not show any statistically significant difference between the groups. The Class II division 1 subjects showed lower incisors more labially tipped and a convex facial profile.


Acceptance of angulation in the non-operative treatment of paediatric forearm fractures.
Forearm fractures are the most common injury in paediatric traumatology. The unique properties of the juvenile skeleton make it possible to cope well with traumatic deformities such as angulation, apposition and displacement. While we make use of these properties, the exact mechanism and degree of healing remains obscure. Different types of forearm fractures require specific treatment options, each with its limitations. A meta-analysis of recent literature was carried out, and together with the opinions of 18 international experts an effort was made to provide insight into the limits of acceptance of angular deformation in the non-operative treatment of paediatric forearm fractures. With this information we constructed graphs (age versus angulation) for each of the eight types of paediatric forearm fractures. In the absence of proper trials, it is our opinion that the presented Isala graphs can provide useful support in the decision-making process of acceptance of angular deformities in paediatric forearm fractures.


Hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis: 72 cases (1980-2010).
To evaluate differences in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis. etrospective case-control study. Liver tissue specimens from 36 Labrador Retrievers with chronic hepatitis and 36 age- and sex-matched Labrador Retrievers without chronic hepatitis (control dogs). Liver tissue specimens were obtained during 2 study periods (1980 to 1997 and 1998 to 2010). For each tissue specimen, a histologic score was assigned independently by each of 2 interpreters, and the hepatic copper concentration was qualitatively determined via rhodanine staining and quantitatively determined via atomic absorption spectroscopy. Mean hepatic copper concentration was significantly higher in dogs with chronic hepatitis (614 μg/g of dry weight [range, 104 to 4,234 μg/g of dry weight]), compared with that in control dogs (299 μg/g of dry weight [range, 93 to 3,810 μg/g of dry weight]), and increased significantly over time. A higher proportion of liver tissue specimens collected during the 1998-2010 study period had hepatic copper concentrations > 400 μg/g of dry weight (the upper limit of the reference range), compared with the proportion of liver tissue specimens collected during the 1980-1997 study period. The qualitative copper score did not accurately predict quantitative hepatic copper concentration in 33% of study dogs. Results suggested that the increase in hepatic copper concentrations in Labrador Retrievers with and without chronic hepatitis over time may be the result of increased exposure of dogs to environmental copper, most likely via the diet.


Measurements of vaccinia virus dissemination using whole body imaging: approaches for predicting of lethality in challenge models and testing of vaccines and antiviral treatments.
Preclinical evaluation of novel anti-smallpox vaccines and antiviral treatments often rely on mouse -challenge models using pathogenic vaccinia virus, such as Western Reserve (WR) strain or other orthopoxviruses. Traditionally, efficacy of treatment is evaluated using various readouts, such as lethality (rare), measurements of body weight loss, pox lesion scoring, and determination of viral loads in internal organs by enumerating plaques in sensitive cell lines. These methodologies provide valuable information about the contribution of the treatment to protection from infection, yet all have similar limitations: they do not evaluate dissemination of the virus within the same animal and require large numbers of animals. These two problems prompted us to turn to a recently developed whole body imaging technology, where replication of recombinant vaccinia virus expressing luciferase enzyme (WRvFire) is sensed by detecting light emitted by the enzyme in the presence of D: -luciferin substrate administered to infected animal. Bioluminescence signals from infected organs in live animals are registered by the charge-coupled device camera in IVIS instrument developed by Caliper, and are converted into numerical values. This chapter describes whole body bioimaging methodology used to determine viral loads in normal live BALB/c mice infected with recombinant WRvFire vaccinia virus. Using Dryvax vaccination as a model, we show how bioluminescence data can be used to determine efficacy of treatment. In addition, we illustrate how bioluminescence and survival outcome can be combined in Receiver Operating Characteristic curve -analysis to develop predictive models of lethality that can be applied for testing of new therapeutics and second-generation vaccines.


Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.
Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs) combined with vancomycin. We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA) biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria. NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs combined with vancomycin contributed to significantly decreasing the metabolic activity of bacteria in MRSA biofilms (P<0.05). Phase-shift acoustic NDs could exert a significant bactericidal effect against MRSA biofilms through a new stimulation mode. Acoustic NDs present advantages over microbubbles for biofilm damage. This anti-biofilm strategy could be used either alone or as an enhancer of traditional antibiotics in the control of prosthetic joint infections.


Water-gas-shift reaction on molybdenum carbide surfaces: essential role of the oxycarbide.
Density functional theory (DFT) was employed to investigate the behavior of Mo carbides in the water-gas-shift reaction (WGS, CO + H(2)O --> H(2) +CO(2)). The kinetics of the WGS reaction was studied on the surfaces of Mo-terminated Mo(2)C(001) (Mo-Mo(2)C), C-terminated Mo(2)C(001) (C-Mo(2)C), and Cu(111) as a known active catalyst. Our results show that the WGS activity decreases in a sequence: Cu > C-Mo(2)C > Mo-Mo(2)C. The slow kinetics on C-Mo(2)C and Mo-Mo(2)C is due to the fact that the C or Mo sites bond oxygen too strongly to allow the facile removal of this species. In fact, due to the strong O-Mo and O-C interactions, the carbide surfaces are likely to be covered by O produced from the H(2)O dissociation. It is shown that the O-covered Mo-terminated Mo(2)C(001) (O_Mo-Mo(2)C) surface displays the lowest WGS activity of all. With the Mo oxide in the surface, O_Mo-Mo(2)C is too inert to adsorb CO or to dissociate H(2)O. In contrast, the same amount of O on the C-Mo(2)C surface (O_C-Mo(2)C) does not lead to deactivation, but enhances the rate of the WGS reaction and makes this system even more active than Cu. The good behavior of O_C-Mo(2)C is attributed to the formation of a Mo oxycarbide in the surface. The C atoms destabilize O-poisoning by forming CO species, which shift away from the Mo hollow sites when the surface reacts with other adsorbates. In this way, the Mo sites are able to provide a moderate bond to the reaction intermediates. In addition, both C and O atoms are not spectators and directly participate in the WGS reaction.


Structural characterization of poly-l-lactic acid (P(L)LA) and poly(glycolic acid)(PGA) oligomers.
Structural characterization of poly-l-lactic acid (P(L)LA) and poly(glycolic acid) (PGA) oligomers containing three units was carried out with an atomistic approach. Oligomer structures were first optimized through quantum chemical calculations, using density functional theory (DFT); rotational barriers concerning dihedral angles along the chain were then investigated. Diffusion coefficients of l-lactic acid and glycolic acid in pure water were estimated through molecular dynamic (MD) simulations. Monomer structures were obtained with quantum chemical computation in implicit water using DFT method; atomic charges were fitted with Restrained Electrostatic Potentials (RESP) formalism, starting from electrostatic potentials calculated with quantum chemistry. MD simulations were carried out in explicit water, in order to take into account solvent presence.


NK-1 receptor antagonists as antitumor drugs: a survey of the literature from 2000 to 2011.
After binding to the neurokinin (NK-1) receptor, substance P (SP) induces tumor cell proliferation, the migration of tumor cells (invasion and metastasis) and angiogenesis. By contrast, NK-1 receptor antagonists inhibit tumor cell proliferation (tumor cells die by apoptosis), block the migratory activity of tumor cells and exert antiangiogenic properties. This review offers a 12-year overview of the underlying mechanism of the action of the SP/NK-1 receptor system and NK-1 receptor antagonists in cancer, providing a new approach to the treatment of tumors. Chemically diverse NK-1 receptor antagonists have been identified. The antitumor action of these compounds is independent of their chemical structures and such action is associated with their affinity for the NK-1 receptor and with the dose of the antagonist administered. The NK-1 receptor can be considered as a target in cancer treatment and NK-1 receptor antagonists could be considered as new antitumor drugs. The NK-1 receptor antagonist aprepitant is used in clinical practice and exerts an antitumor action against tumor cells in vitro. In the future, such antitumor action should be tested in human clinical trials.


Predicting the beta-helix fold from protein sequence data.
A method is presented that uses beta-strand interactions to predict the parallel right-handed beta-helix super-secondary structural motif in protein sequences. A program called BetaWrap implements this method and is shown to score known beta-helices above non-beta-helices in the Protein Data Bank in cross-validation. It is demonstrated that BetaWrap learns each of the seven known SCOP beta-helix families, when trained primarily on beta-structures that are not beta-helices, together with structural features of known beta-helices from outside the family. BetaWrap also predicts many bacterial proteins of unknown structure to be beta-helices; in particular, these proteins serve as virulence factors, adhesins, and toxins in bacterial pathogenesis and include cell surface proteins from Chlamydia and the intestinal bacterium Helicobacter pylori. The computational method used here may generalize to other beta-structures for which strand topology and profiles of residue accessibility are well conserved.


[Nonoperative treatment of fractures of the base of the first metacarpal bone--Bennett fracture].
Although described as early as in 1882, the fracture of the metacarpal bone basis is still a therapeutic challenge for first orthopedic surgeons. Several non-operative and operative methods in the treatment of this fracture have been described. The goal of this paper is to analyze nonoperatively treated patients with Bennett's fracture. A group of 50 patients of both sexes, with the fracture of the first metacarpal bone basis fractures and with the average follow-up of 9 (6-13) years, has been analyzed. After an orthopedic reposition, immobilization lasting 5 weeks was applied, followed by a physical therapy in the duration of 4 to 8 weeks. Numerically, according to Steel, both the subjective and objective state of the hand, as well as an x-ray finding, were assessed. The total hand function was excellent and good in 42 patients, satisfactory in 8, and none of the patients had unsatisfactory function of the hand. Regardless of present degenerative changes, the function of the hand was good, especially if reposition with fragment dislocation less than 2 mm was achieved.


Intracranial infantile myofibromatosis.
Infantile myofibromatosis is a proliferative disorder of infancy and early childhood characterized by nodular or diffuse growth of lesions that are comprised of a mixture of mesenchymal elements within the skin, subcutaneous tissues, skeletal muscle, bone, and/or visceral organs. Although these pseudotumors are considered to be the most common fibrous "neoplasm" of infancy, central nervous system involvement is reportedly rare. During the last 7 years, the authors have treated three children with intracranial myofibromas who presented at 6 weeks, 7 months, and 3 3/4 years of age, respectively. Each child had a large calvarial mass that produced significant brain compression despite a paucity of neurological signs. On computerized tomography, these tumors were isodense to brain tissue, enhanced strongly with intravenous contrast material, and showed smoothly marginated bone erosion without surrounding sclerosis. On magnetic resonance imaging, the tumors were hypointense on T1-weighted images, with dense enhancement following the administration of intravenous contrast medium, and hyperintense on T2-weighted images. At operation, the tumors were highly vascular and appeared to arise from within the leaves of the dura, eroding through the overlying bone, but not violating the galeal or arachnoidal layers. Two of the lesions were adherent to major dural venous sinuses. Both of these lesions were completely resected in continuity with the involved dura, and have not recurred 6 years and 1 year, respectively, postoperatively. However, in one patient in whom the involved dura was not resected at the initial procedure, the tumor recurred rapidly. A complete excision of the tumor and involved dura was then performed and the patient is now recurrence-free, 5 1/2 years after the second surgical resection. All patients tolerated resection well, but two have required cranioplasty for persistent calvarial defects. The surgical experience with these lesions is reviewed and the distinctive features of their clinical presentation, radiographic appearance, operative management, and outcome are discussed.


Management of ruptured liver segment IV hepatocellular carcinoma: is transarterial embolization (TAE) superior to chemoembolization (TACE)?-the jury is still out.
HCC rupture is a potentially life-threatening complication owing to underlying vascular dysfunction and coagulopathy. There is still a debate in the literature concerning the best approach in patients presenting in the emergency setting with shock due to spontaneous HCC rupture. In the current report, we describe the case of a 66-year-old female patient with ruptured HCC who was treated successfully by emergency transarterial embolization (TAE) with complete response proved by gradual shrinkage of the tumor. This impressive complete response suggests that TAE followed by elective hepatectomy could be an efficient approach for patients with Child-Pugh class A liver function and adequate liver remnant. More studies are needed in order to construct specific guidelines for the treatment of rHCC that will be based on the disease severity and the patient status.


Epidemiology and diagnostics of primary Sjögren's syndrome.
This review paper contains selected aspects of Sjögren's syndrome. It consists of epidemiology, ultrasound of salivary glands and antimuscarinic antibodies. The first part present studies aimed to determine the prevalence and the incidence of the disease with special emphasize on epidemiological studies performed in Slovenia. This is followed by the demonstration of the role of ultrasound of salivary glands in the diagnosis of Sjögren's syndrome and the value of antimuscarinic antibodies in global assesment of the secretory failure.


High-resolution genotyping of Salmonella strains by AFLP-fingerprinting.
High resolution AFLP fingerprinting, in which subsets of genomic restriction fragments are amplified by means of PCR, was used for the identification of different. Salmonella serotypes to investigate whether this technique is applicable in epidemiological studies. Seventy-eight different Salmonella strains comprising 62 serotypes were genetically identified by AFLP. Primer combination M00 (MseI primer without additional 3' nucleotides) and E11 (EcoRI primer with two additional 3' nucleotides) resulted in reproducible profiles containing approximately 50 bands. All serotypes were characterized by a unique profile. In addition, AFLP fingerprinting enabled phage type identification. Different strains previously identified as identical, using typing methods with lower resolution, could be distinguished, showing that AFLP fingerprinting is well suited for bacterial epidemiology and identification.


Charge transport in graphene with resonant scatterers.
The full counting statistics for the charge transport through an undoped graphene sheet in the presence of strong potential impurities is studied. Treating the scattering off the impurity in the s-wave approximation, we calculate the impurity correction to the cumulant generating function. This correction is universal provided the impurity strength is tuned to a resonant value. In particular, the conductance of the sample acquires a correction of 16e{2}/(pi{2}h) per resonant impurity.


Studies on optimum harvest time for hybrid rice seed.
Timely harvest is critical for hybrid rice to achieve maximum seed viability, vigor and yield. However, how to predict the optimum harvest time has been rarely reported so far. The seed vigor of Zhuliangyou 06 (ZLY06) increased and reached the highest level at 20 days after pollination (DAP), when seed moisture content had a lower value, which was maintained until final seed maturation. For Chunyou 84 (CY84), seed vigor, fresh and dry weight had relatively high values at 25 DAP, when seed moisture content reached the lowest value and changed slightly from 25 to 55 DAP. In both hybrid rice varieties, seed glume chlorophyll content declined rapidly from 10 to 30 DAP and remained at a very low level after 35 DAP. Starch content exhibited an increasing trend during seed maturation, while both soluble sugar content and amylase activity decreased significantly at the early stages of seed development. Moreover, correlation analyses showed that seed dry weight, starch content and superoxide dismutase activity were significantly positively correlated with seed vigor. In contrast, chlorophyll content, moisture content, soluble sugar, soluble protein, abscisic acid, gibberellin content, electrical conductivity, catalase and ascorbate peroxidase activities were significantly negatively correlated with seed vigor. Physiological and biochemical parameters were obviously more closely related with seed vigor than with seed germinability during seed development. Seed vigor could be better used as a comprehensive factor to predict the optimum seed harvest time. It is suggested that for ZLY06 seeds could be harvested as early as 20 DAP, whereas for CY84 the earliest optimum harvest time was 25 DAP. © 2016 Society of Chemical Industry.


Circ_0088036 facilitates the proliferation and inflammation and inhibits the apoptosis of fibroblast-like synoviocytes through targeting miR-326/FZD4 axis in rheumatoid arthritis.
The function and pathological significance of circular RNAs (circRNAs) in autoimmune diseases, such as rheumatoid arthritis (RA), are barely known. Here, we explored the role of circ_0088036 in RA progression and its associated mechanism. The synovial lining layer tissues of RA patients and non-RA control patients were collected for clinical study in vivo, and tumour necrosis factor α (TNF-α)-induced RA-fibroblast-like synoviocytes (RA-FLSs) were used for the experiments in vitro. Cell proliferation was assessed by Cell Counting Kit 8 (CCK8) assay and flow cytometry. Cell apoptosis was analyzed by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the release of pro-inflammatory cytokines. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target interaction between microRNA-326 (miR-326) and circ_0088036 or frizzled class receptor 4 (FZD4). Circ_0088036 expression was elevated in the synovial lining layer tissues of RA patients and TNF-α-treated RA-FLSs. Circ_0088036 interference largely reversed TNF-α-induced proliferation and inflammation in RA-FLSs. The interaction between circ_0088036 and miR-326 was verified, and miR-326 silencing largely reversed circ_0088036 knockdown-mediated effects in TNF-α-treated RA-FLSs. MiR-326 bound to the 3' untranslated region (3'UTR) of FZD4 in RA-FLSs. FZD4 overexpression largely diminished miR-326 accumulation-mediated influences in TNF-α-treated RA-FLSs. Circ_0088036 could up-regulate FZD4 by sponging miR-326 in RA-FLSs. Circ_0088036 contributed to TNF-α-induced RA progression partly by targeting miR-326/FZD4 signalling.


Prevalence of Irritable Bowel Syndrome and its Association with Anxiety among Medical Students at King Saud bin Abdulaziz University for Health Sciences in Riyadh.
To quantify the prevalence of Irritable Bowel Syndrome (IBS) among medical students of King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) and to observe the association between anxiety and IBS. This cross-sectional observational study conducted during academic year 2015-2016 has used two self-administered, pre-validated questionnaires: Depression Anxiety Stress Scales-21 (DASS-21) and Rome III criteria. The sample size was 270, and proportional allocation was used to determine distribution of this sample across study population based on percentages of students in each academic year. Convenience sampling was used to select participants. The overall prevalence of IBS was 21% (n=57), with a higher prevalence among females (26%, n=23) than males (19%, n=34). IBS was most and least prevalent among first-year students (14%, n=5) and fifth-year students (29%, n=21) respectively. Anxiety levels were normal, mild, moderate, and severe or extremely severe in 39% (n=105), 7% (n=19), 26% (n=70), and 27%. A significant association was found between gender & IBS and anxiety levels & IBS. The prevalence of IBS in this study was 21% and higher among females than males but were highest among fifth-year students for both genders. More than 50% of students had moderate or high levels of anxiety for both genders. The prevalence of IBS was highest among students of 5th fifth year. The study provides evidence that, as medical students of higher year of their under graduation were having higher level of anxiety which leads to IBS.


Adjuvant radiotherapy does not affect hemostasis.
Cancer is associated with increased risk of venous thromboembolic disease. Venous thromboembolic disease accounts for a substantial addition to morbidity and mortality rates in cancer patients and is the second leading cause of death in cancer patients, exceeded only by the underlying cancer. Only few previous studies have investigated the influence of radiotherapy on hemostasis and whether radiotherapy in itself causes an increased risk of venous thromboembolic disease. The aim was to investigate if adjuvant radiotherapy affects hemostasis after surgery and chemotherapy in patients with breast cancer. Radiotherapy consisted of either 40 Gy/15 fractions or 50 Gy/25 fractions. Blood samples were obtained from 39 consecutive women before and immediately after the first, the intermediate, and the final radiation fraction. Platelet function was measured using impedance aggregometry, and thrombin generation was determined in platelet-poor plasma using calibrated automated thrombogram. Furthermore, P-selectin, international normalized ratio, fibrinogen, activated partial thromboplastin time, coagulation factor VIII, von Willebrand factor, C-reactive protein (CRP), and soluble thrombomodulin were measured before and after radiation treatment. Platelet aggregation was within reference interval before initiation of radiotherapy, and remained unaffected during the radiation course. Neither serum P-selectin, thrombin generation, fibrinogen, coagulation factor VIII, von Willebrand factor, CRP nor thrombomodulin were substantially influenced by radiation treatment. The present study showed that radiotherapy did not affect hemostasis, neither by a single radiation dose nor during the radiation course, in early breast cancer patients receiving adjuvant radiotherapy.


Recording Temperature-induced Neuronal Activity through Monitoring Calcium Changes in the Olfactory Bulb of Xenopus laevis.
The olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. However, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. Premetamorphic Xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. These characteristics make them well suited for studying olfaction, and particularly thermosensitivity. The present article describes the complete procedure for measuring temperature responses in the olfactory bulb of X. laevis larvae. Firstly, the electroporation of olfactory receptor neurons (ORNs) is performed with spectrally distinct dyes loaded into the nasal cavities in order to stain their axon terminals in the bulbar neuropil. The differential staining between left and right receptor neurons serves to identify the γ-glomerulus as the only structure innervated by contralateral presynaptic afferents. Secondly, the electroporation is combined with focal bolus loading in the olfactory bulb in order to stain mitral cells and their dendrites. The 3D brain volume is then scanned under line-illumination microscopy for the acquisition of fast calcium imaging data while small temperature drops are induced at the olfactory epithelium. Lastly, the post-acquisition analysis allows the morphological reconstruction of the thermosensitive network comprising the γ-glomerulus and its innervating mitral cells, based on specific temperature-induced Ca(2+) traces. Using chemical odorants as stimuli in addition to temperature jumps enables the comparison between thermosensitive and chemosensitive networks in the olfactory bulb.


The ACURATE neo™ and neo2™ Valve Systems.
Based on the strength of data from randomized trials and real-world clinical studies, transcatheter aortic valve replacement (TAVR) has become a popular and effective alternative to surgical valve replacement in patients with symptomatic aortic stenosis. The ACURATE neo™ (Boston Scientific, Marlborough, MA, USA) valve system has been commercially available for transfemoral TAVR in Europe since 2014. ACURATE neo2™ is an evolution of the neo design and was declared CE marked by the manufacturer in 2020. The neo and neo2 valves have been studied in high-risk patients, and the currently active randomized trial for neo2 will include over 1,500 patients of all risk categories in the USA. The goal of this review is to help inform the TAVR community about the ACURATE valve.


Direct cytotoxic response of human lymphocytes to porcine PHA-lymphoblasts and lymphocytes.
Transplantation of cells and organs from pigs to human beings offers potential treatment for medical conditions such as diabetes, kidney and heart failure, and Parkinson's disease. When the antibody-mediated hyperacute rejection barrier is overcome, a xenograft may not be treated as an allograft by the human immune system. Without prior culture with porcine cells, human lymphocytes are cytotoxic to some porcine cells. Our aim was to functionally characterize this direct cytotoxic response to porcine PHA-lymphoblasts and lymphocytes. Peripheral blood mononuclear cells from seven of eight human beings were cytotoxic to porcine PHA-lymphoblasts in bulk chromium-release assays, but not to the porcine lymphocytes from which the PHA-lymphoblasts were derived. The NK cell-sensitive cell line K562 only partly blocked the response to the PHA-lymphoblasts. IL-2-expanded clones of human lymphocytes were able to discriminate between PHA-lymphoblasts from two pigs and unable to lyse K562. When using IL-2 to make the anti-porcine cells proliferate under limiting dilution conditions, the proliferation and/or function of these cells did not conform to single-hit kinetics. All the observations from experiments with cells in bulk cultures and as short-term clones suggest that the direct cytotoxic response of human lymphocytes to porcine cells is heterogeneous and composed of a small population of in vivo-activated T cells as well as NK cells.


Experimental and modeling study of pure terephthalic acid (PTA) wastewater transport in the vadose zone.
PTA wastewater discharged from a factory was selected as the research object in this project and CODcr was selected as the characteristic pollution factor. Static adsorption and soil column leaching experiments of silty clay and clayey soil were carried out to study the adsorption, bio-degradation and dispersion coefficient of CODcr in PTA wastewater. Hydrus-1D was used to build the convection-diffusion model to demonstrate the migration of PTA wastewater in the vadose zone. The results indicate that silty clay and clayey soil in the vadose zone can adsorb, degrade and impede the contaminants in PTA wastewater; however, the coefficient of adsorption and degradation were very low, they were down to 0.0002 L g(-1), 0.0003 L g(-1) and 0.0097 d(-1), 0.0077 d(-1) for silty clay and clayey soil, respectively. Under the virtual condition that, wastewater in the sewage pool is 5 m deep, CODcr concentration is 4000 mg L(-1), vadose zone is 21 m, PTA wastewater will reach the phreatic surface after 20.87 years. When wastewater in the sewage pool is 7 m with other conditions unchanged, after 17.18 years PTA wastewater will reach groundwater. The results show that there is a higher pollution risk for groundwater if we do not take any anti-seepage measures.


Cardiac damage in athlete's heart: When the "supernormal" heart fails!
Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.


Chemical Composition, Nutritional Value, and Safety of Cooked Female Chaceon Maritae from Namibe (Angola).
Despite being highly appreciated and consumed, the nutritional value of Chaceon maritae from Namibe (Angola) had never been studied. In the present work, edible tissues (muscle, ovaries, and hepatopancreas) of boiled female C. maritae caught off Namibe coast in two distinct seasons were analyzed in terms of proximate chemical composition (fat, ash, protein, and moisture), fatty acid and amino acid profiles, cholesterol, essential minerals (macro and trace) and toxic elements. Results showed that, in both seasons, C. maritae muscle was a valuable source of protein, essential amino acids, polyunsaturated fatty acids, and essential elements, especially zinc, selenium, iodine, and copper. Ovaries and hepatopancreas are also good sources of protein, but were richer in fat, particularly when caught in October. Ovarian fat is rich in polyunsaturated fatty acids and that of hepatopancreas has higher values of monounsaturated and saturated fatty acids. Hepatopancreas and ovaries are also good sources of copper and, especially ovaries, of zinc. Moreover, in both seasons, all the edible tissues of C. maritae analyzed presented very low contents of heavy metals (mercury, cadmium, lead, and arsenic).


Polymerase chain reaction for the identification of Porphyromonas gingivalis collagenase genes.
Porphyromonas gingivalis has been shown to exhibit genetic diversity possibly resulting in variation of virulence. In the present study a potential virulence factor was targeted for the detection of P. gingivalis. A 548 bp fragment of the collagenase gene (prtC) from Porphyromonas gingivalis ATCC 33277 was amplified by polymerase chain reaction (PCR) using oligonucleotides derived from the middle portion of prtC. From 16 of 21 clinical P. gingivalis strains, a PCR product of similar size to the prtC could be obtained. These 16 P. gingivalis strains were confirmed as positive for prtC using DNA hybridization with a digoxigenin-labeled prtC PCR product as a probe. In 12 of the 16 prtC positive strains, the restriction analysis of the PCR products revealed fragment patterns identical to the known sequence. In the other 4 prtC positive strains, 4 distinct patterns were found. Of these strains, nucleotide sequence analysis of a 400 bp PCR product stretch revealed 79.1%, 83.0%, 84.8 and 89.5% homology with the known nucleotide sequence for this specific region. Sequence analysis of the PCR products from the ATCC 33277 strain demonstrated 93.7% homology. The limit of detection for the PCR was about 100 organisms. None of the other 48 tested strains of 16 bacterial species derived from oral and extraoral infections yielded a PCR product. The PCR was also used for the detection of prtC sequences in dental plaque. Our data indicate that not all P. gingivalis strains have prtC. Nucleotide heterogeneity exists among P. gingivalis with prtC.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease.
Chymase is a potent and specific angiotensin II (Ang II)-forming enzyme in vitro. There is also strong evidence to suggest its importance in vivo. Recent clinical studies have suggested that high serum cholesterol levels are associated with increased vascular chymase activity and this may assist in the development of atherosclerosis. This clinical finding has been reproduced in hamster models. Studies with transgenic mice overexpressing the human chymase gene suggest a direct association between vascular chymase upregulation and atherogenesis. There is also increased chymase activity following various cardiac diseases such as myocardial ischaemia, volume overload cardiac failure, cardiomyopathy and viral myocarditis, suggesting that increased cardiac chymase activity appears to be involved in cardiac remodelling.


The effect of sucrose application frequency and basal nutrient conditions on the calcium and phosphate content of experimental dental plaque.
A reduced pool of calcium in dental plaque would be expected to increase the ability of plaque fluid to dissolve the underlying enamel when the pH falls during sugar exposure. We have examined the relationship between frequency of sugar application and Ca and P(i) concentrations in artificial mouth plaque microcosm biofilms. Ten plaques were grown simultaneously from a human saliva inoculum using a continuous flow of simulated saliva, DMM, supplemented with either urea or glucose to modulate the resting pH. In addition the plaques received sucrose applications of varying frequency: 12-, 8-, 6-, or 4-hourly, or not at all. After 15 days the plaques were sampled by taking 4 full-thickness specimens of each, and acid-extractable Ca and P(i), and alkali-soluble protein and carbohydrate were determined. Ca and P(i) concentrations were in a range comparable with those in human plaque, except in the DMM + urea plaque receiving no sucrose, when concentrations were higher. Plaque Ca concentration decreased significantly as sucrose application frequency increased. Increasing sucrose application frequency also reduced the protein, i.e. the cell biomass, content of the plaques and, in the case of DMM + urea plaques, increased the water-insoluble hexose content, presumably extracellular polysaccharide. Reduced biomass was partly due to the bulking of plaque with extracellular polysaccharide, but the marked effect of urea on polysaccharide formation is not understood. This study shows that increasing frequency of sugar application alters dental plaque by reducing its mineral protection capacity.


Gastrointestinal absorption of quaternary ammonium compounds correlated to their binding to small intestinal brush border membrane in rat.
The relationship between absorption of quaternary ammonium compounds (QACs) from rat intestine and their in-vitro binding to isolated brush-border membrane has been examined, using a series of n-alkyltrimethylammoniums. The binding of these QACs gradually increased with each extension of unbranched hydrocarbon chain from octyltrimethylammonium to tetradecyltrimethylammonium. However, hexyltrimethylammonium and heptyltrimethylammonium failed to bind to the membrane. On the other hand, the disappearance of these QACs from rat jejunal loop also increased with the length of hydrocarbon chain over the range of 8.9 to 71.3%. A good correlation was found between binding to the brush-border membrane and disappearance from jejunal loop. From these results, it was suggested that the size of the hydrophobic part of a QAC molecule was a principal determinant of both absorption and membrane binding, and that the absorption of QACs with an appropriate sized hydrophobic part, was closely associated with the degree of binding to the membrane.


United States military fatalities during Operation New Dawn.
Military operations vary by scope, purpose, and intensity, each having unique forces and actions to execute a mission. Evaluation of military operation fatalities guides current and future casualty care. A retrospective study was conducted of all US military fatalities from Operation New Dawn in Iraq, 2010 to 2011. Data were obtained from autopsies and other records. Population characteristics, manner of death, cause of death, and location of death were analyzed. All fatalities were evaluated for concomitant evidence of underlying atherosclerosis. Nonsuicide trauma fatalities were also reviewed for injury severity, mechanism of death, injury survivability, death preventability, and opportunities for improvement. Of 74 US military Operation New Dawn fatalities (median age, 26 years; male, 98.6%; conventional forces, 100%; prehospital, 82.4%) the leading cause of death was injury (86.5%). The manner of death was primarily homicide (55.4%), followed by suicide (17.6%), natural (13.5%), and accident (9.5%). Fatalities were divided near evenly between combatants (52.7%) and support personnel (47.3%), and between battle injury (51.4%) and disease and nonbattle injury (48.6%). Natural and suicide death was higher (p < 0.01, 0.02) among support personnel who were older (p = 0.05) with more reserve/national guard personnel (p = 0.01). Total population prevalence of underlying atherosclerosis was 18.9%, with more among support personnel (64.3%). Of 46 nonsuicide trauma fatalities, most died of blast injury (67.4%) followed by gunshot wound (26.1%) and multiple/blunt force injury (6.5%). The leading mechanism of death was catastrophic tissue destruction (82.6%). Most had nonsurvivable injuries (82.6%) and nonpreventable deaths (93.5%). Operation New Dawn fatalities were exclusively conventional forces divided between combatants and support personnel, the former succumbing more to battle injury and the latter to disease and nonbattle injury including self-inflicted injury. For nonsuicide trauma fatalities, none died from a survivable injury, and 17.4% died from potentially survivable injuries. Opportunities for improvement included providing earlier blood products and surgery. Therapeutic, level V and epidemiological, level IV.


CNTF promotes the survival of neonatal rat corticospinal neurons in vitro.
Corticospinal neurons were identified in cell cultures of neonatal rat cortex by immunostaining of cholera toxin B subunit (CTB), retrogradely transported from the cervical part of the spinal cord. The CTB-immunoreactive neurons were larger than the neurons in the overall (unstained) neuronal population and represented a small fraction of it (average of 0.3%) after 6 hours in vitro. The number of both total and CTB-labeled neurons declined progressively with time in culture. The neuronal death was, however, markedly faster in the CTB-labeled neuronal population than in the overall neuronal population. Ciliary neurotrophic factor (CNTF) promoted the survival of CTB-positive corticospinal neurons in a dose-dependent manner; with CNTF, the death rate of the CTB-labeled neurons became identical to that of the overall population.


Prevalence and specificity of immunoglobulin G and immunoglobulin A non-complement-binding anti-HLA alloantibodies in retransplant candidates.
The role of complement-binding donor-directed anti-human leukocyte antigen (HLA) antibodies in graft rejection is well established, whereas the prevalence and relevance of non-complement-binding (NCB) anti-HLA antibodies are less well defined. The aim of our study was to establish a sensitive and reliable test system for the detection and the specification of these NCB anti-HLA antibodies. Sera from 60 patients awaiting retransplantation were analysed for the presence of anti-HLA class I alloantibodies with complement-dependent cytotoxicity (CDC) tests. Immunoglobulin (Ig)G(all) anti-HLA class I and class II alloantibodies were differentiated on generic level by plate-based solid phase enzyme-linked immunosorbent assay. Subsequently, a modified bead-based (Luminex) assay was applied, allowing the investigation of IgG(2/4) NCB isotypes as well as IgA(1/2). The anti-HLA specificities of the NCB alloantibodies were determined and compared with known mismatches from previous transplants. Seventeen of the 60 sera (28%) were positive in the CDC increasing to 26 of 60 (43%) in the class I and 33 of 60 (55%) in the class II plate-based assay. Using the modified bead-based system 24 of 60 sera (40%) contained NCB IgG(2/4), which were mostly donor specific. In addition, a high prevalence of NCB IgA antibodies was detected (26 of 60 sera), which occurred independently of IgG(2/4) NCB, and half of which were donor specific. NCB anti-HLA alloantibodies, including the IgA isotype, can reliably be detected using the modified bead-based test system. These NCB alloantibodies had a high prevalence in retransplant candidates and were mostly donor specific.


Porcine epidemic diarrhea virus reduces feed efficiency in nursery pigs.
Porcine epidemic diarrhea virus (PEDV) infects enterocytes and in nursery pigs, results in diarrhea, anorexia, and reduced performance. Therefore, the objective of this study was to determine how PEDV infection influenced growth performance and repartitioning of amino acids and energy in nursery pigs. A total of 32 barrows and gilts, approximately 1 wk post-wean (BW = 8.46 ± 0.50 kg), and naïve for PEDV were obtained, weighed, and allotted based on sex and BW to one of two treatments: 1) Control, PEDV naïve and 2) PEDV-inoculated (PEDV) with eight pens of two pigs each per treatment. On day post-inoculation (dpi) 0, PEDV pigs were inoculated via intragastric gavage with PEDV isolate (USA/Iowa/18984/2013). Pig and feeder weights were recorded at dpi -7, 0, 5, and 20 in order to calculate ADG, ADFI, and G:F. Eight pigs per treatment were euthanized on dpi 5 and 20, and tissues and blood were collected. At dpi 5, all PEDV pigs were PCR positive for PEDV in feces. Overall, PEDV pigs tended (P < 0.10) to increase ADFI, which resulted in reduced (P < 0.05) feed efficiency. At dpi 5, PEDV pigs had reduced (P < 0.05) villus height and increased (P < 0.05) stem cell proliferation in the jejunum compared with Control pigs. Pigs inoculated with PEDV had increased (P < 0.05) serum haptoglobin and increased insulin-to-glucose ratios compared with Control pigs at dpi 5. Markers of muscle proteolysis were not different (P > 0.05) between treatments within dpi; however, at dpi 5, 20S proteasome activity was increased (P < 0.05) in longissimus dorsi of PEDV pigs compared with Control pigs. Liver and jejunum gluconeogenic enzyme activities were not different (P > 0.05) between treatments within dpi. Overall, PEDV-inoculated pigs did recover the absorptive capacity that was reduced during PEDV infection by increasing proliferation of intestinal stem cells. However, the energy and nutrients needed to recover the epithelium may be originating from available luminal nutrients instead of muscle proteolysis and gluconeogenesis. This study provides insight into the effects of an enteric coronavirus on postabsorptive metabolism in nursery pigs.


A chaperone-activated nonenveloped virus perforates the physiologically relevant endoplasmic reticulum membrane.
The nonenveloped polyomavirus (Py) traffics from the plasma membrane to the endoplasmic reticulum (ER), where it penetrates the ER membrane, allowing the viral genome to reach the nucleus to cause infection. The mechanism of membrane penetration for Py, and for other nonenveloped viruses, remains poorly characterized. We showed previously that the ER chaperone ERp29 alters the conformation of Py coat protein VP1, enabling the virus to interact with membranes. Here, we developed a membrane perforation assay and showed that the ERp29-activated Py perforates the physiologically relevant ER membrane, an event that likely initiates viral penetration. Biochemical analysis revealed that the internal protein VP2 is exposed in the activated viral particle. Accordingly, we demonstrate that VP2 binds to, integrates into, and perforates the ER membrane; the other internal protein, VP3, binds to and integrates into the ER membrane but is not sufficient for perforation. Our data thus link the activity of a cellular factor on a nonenveloped virus to the membrane perforation event and identify a viral component that mediates this process.


Stability of ceftriaxone disodium in Biotrakson and Tartriakson.
The influence of temperature and relative air humidity on the stability of ceftriaxone disodium (CTN) in Biotrakson and Tartriakson was investigated. At RH = 0%, the degradation of ceftriaxone was the first-order reaction, while at RH from 50.9% to 76.4% it was an autocatalytic first-order reaction relative to the substrate concentration. The influence of temperature on the stability of CTN was described by the following equations in the case of Biotrakson: RH =0% ln k = (-23488 +/- 7320) x 1/T+ 45.1; RH = 76.4% ln k = (-9492 +/- 1128) x 1/F + 16.1, and for Tartriakson: RH = 0% ln k = (-23491 +/- 7370) x 1/T + 42.4; RH = 76.4% ln k = (-10397 +/- 3034) x 1/T + 18.8. The influence of humidity on the stability of Biotrakson was described by the following equation: ln k = (0.0823 +/- 0.0272) x RH% -17.0 and for Tartriakson ln k = (0.0895 +/- 0.0246) x RH% -17.6.


Effective lowering of plasma, LDL, and esterified cholesterol in LDL receptor-knockout mice by adenovirus-mediated gene delivery of ApoB mRNA editing enzyme (Apobec1).
Adenovirus-mediated gene delivery of apolipoprotein (apo)B mRNA editing enzyme (AvApobec1) was used to study the effect of apoB mRNA editing on apoB production in homozygous LDL receptor-deficient (LDLR-/-) mice. Intravenous injection of AvApobec1 into these mice resulted in a >80% decrease in plasma apoB-100 with a concomitant increase in plasma apoB-48 level. The plasma apoE level also increased. In all cases, total plasma apoB (apoB-100 + apoB-48) decreased by 60% at day 5 and remained approximately 40% lower in AvApobec1-treated compared with control vector Av1LacZ4-treated animals at day 12. On day 12, total plasma cholesterol decreased by 29% in male mice and 18% in female mice that were transduced with AvApobec1. This was reflected in a reduction in apoB-containing lipoprotein cholesterol, which decreased by 34% and 27% in male and female mice, respectively. Apobec1 gene transfer also decreased the cholesteryl ester contents in the LDL fraction, which were 16%, 22%, and 22% in female and 20%, 20%, and 15% in male animals on days 5, 7, and 12, respectively, compared with Av1LacZ controls with 29%, 32%, and 33%, respectively, in female and 29%, 38%, and 36%, respectively, in male animals. Nondenaturing gradient gel electrophoresis indicated almost complete elimination of LDL particles of 29, 27, and 25 nm at days 7 and 12. We conclude that in the absence of a functioning LDL receptor, hepatic overexpression of Apobec1 is highly efficient in lowering plasma apoB-100 levels, leading to the almost complete elimination of LDL particles and a reduction in LDL cholesterol and cholesteryl ester content.


Young people's proposals for a web-based intervention for sexual health promotion: a French qualitative study.
Promoting sexual health is key to improving the supportive behaviors and well-being of young people. With the advent of the Internet, web-based features for sexual health promotion may be attractive to a diverse range of young people. This study aims to assess young people's proposals regarding a web-based intervention for sexual health promotion. Nineteen French young people aged 15-24 years participated to the study. In a semi-structured interview, they presented their views on a web-based intervention for sexual promotion. Data were coded with N'Vivo and subjected to qualitative thematic analysis to explore their proposals. The majority of participants (n = 18) thought that a web-based intervention for sexual health promotion would be attractive. Young people interviewed made 31 concrete proposals for sexual health promotion on the Internet. Participatory and interactive dimensions on the internet appeared essential, with the need for stimulating activities and interaction with peers, but also with competent professionals and moderation. Face to the risks of the internet, they expressed the need of a secure and confidential space, to generate trust and participation in intervention. For participants, sexual health should be addressed in all its dimensions, taking into account the relational, sexual, and gender dimensions, and by incrementing on the internet valid, credible and personalized content. In sexual health promotion, young people are indispensable stakeholders who can make concrete proposals and can also participate in content creation and research. More broadly, in health promotion, involving target audiences in decisions represents a promising perspective.