Bleb point: mimicker of pneumothorax in bullous lung disease.
In patients presenting with severe dyspnea, several diagnostic challenges arise in distinguishing the diagnosis of pneumothorax versus several other pulmonary etiologies like bullous lung disease, pneumonia, interstitial lung disease, and acute respiratory distress syndrome. Distinguishing between large pulmonary bullae and pneumothorax is of the utmost importance, as the acute management is very different. While multiple imaging modalities are available, plain radiographs may be inadequate to make the diagnosis and other advanced imaging may be difficult to obtain. Ultrasound has a very high specificity for pneumothorax. We present a case where a large pulmonary bleb mimics the lung point and therefore inaccurately suggests pneumothorax.


Relationship between the characteristics of frozen-thawed ram spermatozoa and in vitro embryo production.
To select rams suitable for ovine in vitro embryo production (IVP), the predictive values of the screening tests used to identify unsuitable rams need to be established. The present study examined some characteristics of frozen-thawed ram spermatozoa that might be evaluated routinely in a commercial breeding programme. These included sperm motility, plasma membrane integrity, morphology, and acrosome and capacitation status of the sperm population. Cryopreserved spermatozoa from four Dorset rams, which had previously satisfied the selection criteria for inclusion in a commercial breeding programme, were used for IVP. The overall contribution of the four rams and the ejaculates within each ram to the variability (R2) in the production of blastocysts was very small (2.1% and 2.5% respectively). The analysis of the sperm characteristics by logistic regression revealed a significant and positive association between total post-thaw sperm motility, viability and longevity with in vitro blastocyst production. However, there was no association between the other surface characteristics of the spermatozoa measured in this study with embryo production. Despite the absence of differences between the rams in the low incidence of polyspermic fertilization, the significant and detrimental effects of polyspermic fertilization on in vitro blastocyst production rates were quantified by logistic regression analysis. A large proportion of the variability within the IVP system was unaccounted for by the analysis of sperm and oocyte characteristics evaluated in this study. Thus, the identification of other factors contributing to the variability in the production of embryos in vitro warrants further investigation. No single sperm characteristic was sufficient to predict the ultimate outcome of blastocyst production. Rather, assessments of multiple characteristics within the IVP system are required to make accurate predictions.


Soft-mode driven polarity reversal in ferroelectrics mapped by ultrafast x-ray diffraction.
Quantum theory has linked microscopic currents and macroscopic polarizations of ferroelectrics, but the interplay of lattice excitations and charge dynamics on atomic length and time scales is an open problem. Upon phonon excitation in the prototypical ferroelectric ammonium sulfate [(NH4)2SO4], we determine transient charge density maps by femtosecond x-ray diffraction. A newly discovered low frequency-mode with a 3 ps period and sub-picometer amplitudes induces periodic charge relocations over some 100 pm, a hallmark of soft-mode behavior. The transient charge density allows for deriving the macroscopic polarization, showing a periodic reversal of polarity.


[Atypical giant hidrocystoma of the eyelid].
Hidrocystoma belongs to benign tumors of sweat glands. It varies in size from a few millimeters to 1,5cm in rare cases. We report an atypical case of giant hidrocystoma of the eyelid. A 27-year-old woman consulted for a gradually progressing tumor of the right upper eyelid, with ptosis. The tumor was excised, and the histopathological exam revealed a giant hidrocystoma. The originality of this case lies in its atypical size and functional complications in a young patient.


[The preliminary study on biomechanical properties of four synthetic implants for reconstructive surgery of pelvic floor dysfunction].
This study aimed to investigate biomechanical properties of synthetic implants for reconstructive surgery of pelvic floor dysfunction. In this dissertation, we chose four synthetic implants, i.e. total pelvic floor repair system (PROLIFT), gynecone TVT obtutator system (TVT-O), intra-vaginal sling placement device (IVS) and acellular dermal matrix (Renov), for tensile test respectively. The biomechanical properties of four synthetic implants were measured and analyzed using a material testing machine (Instron 4302 versatile material testing machine). The biomechanical parameters included ultimate stress strength, modulus of elasticity, maximum load and maximum elongation. The results showed that the maximum load of the four symthetic implants was TVT-O > IVS > PROLIFT > Renov, and the maximum load of TVT-O was significantly higher than PROLIFT and Renov ( P < 0.05). The ultimate stress strength was TVT-O > IVS > PROLIFT > Renov, with no significant differences among them ( P > 0.05). The maximum elongation of the four implants was TVT-O > PROLIFT > IVS > Renov, and the maximum elongation of TVT-O and PROLIFT were both significantly higher than Renov ( P < 0.05). The modulus of elasticity was IVS > Renov > TVT-O > PROLIFT, with no significant differences among them ( P > 0.05). Taken together, the present study demonstrates that the modulus of elasticity of IVS was the highest in the four synthetic implants; TVT-O had the highest mechanical strength; The maximum load, ultimate stress strength and maximum elongation of Renov were all the lowest; The mechanical properties of PROLIFT was the most stable, and its modulus of elasticity was the lowest in the four synthetic implants, which had good extensibility and elasticity. Therefore, it is necessary to pay attention to the biomechanical properties of new pelvic reconstructive materials for the clinical pelvic reconstructive surgery.


The Effect of Hearing Aids and Cochlear Implants on Balance During Gait.
Auditory input in people with hearing impairment will improve balance while walking. Auditory input is increasingly recognized as an additional input for balance. Several studies have found auditory cues to improve static balance measured on a sway platform. The effect of audition on gait, a dynamic task also linked to fall risk, has not been fully examined. If a positive effect were shown between audition and balance, it would further indicate that improving hearing could also improve balance. Inertial sensors quantified gait parameters of 13 bilateral hearing aid users and 12 bilateral cochlear implant (CI) users with their hearing devices on and off. Outcome measures included gait velocity, stride length variability, swing time variability, and double support phase. Group analysis of each of the gait outcomes showed no significant differences between the aided and unaided conditions in both the hearing aid and CI groups. Gait velocity, an outcome most strongly linked to fall risk had 95% confidence interval differences of -2.16 to 1.52 and -1.45 to 4.17 cm/s in hearing aid and CI users, respectively (aided versus unaided condition). There was considerable variation among participants with some individuals improving in all four parameters. The overall findings were not statistically significant, however, a small subset of our population improved clinically across several outcomes. This demonstrates that audition may have a clinically beneficial effect on balance in some patients.


Traumatic posterior sternoclavicular joint dislocation in a child: a case report.
Sternoclavicular joint dislocation is a rare event. It occurs most often in a violent trauma. The authors report the case of a10 years old child, received at emergencies for right shoulder blunt trauma after been punched by another child. He presented with right shoulder pain, right upper limb functional impairment and right sternoclavicular joint depression. Standard chest radiographs were normal. Chest CT scan showed posterior dislocation and allowed us to determine its variety. Twelve hours after the trauma, a closed reduction has been done under general anesthesia. A control CT scan showed a restoration of normal joint anatomy. After 18 months, the shoulder was painless and mobile in all directions. It is an isolated recent posterior sternoclavicular joint dislocation in a child. With this observation the authors emphasizeon the unusual mechanism of such a dislocation occurrence, the primary role of CT scan in the diagnosis and early closed reduction.


Prolonged antimicrobial prophylaxis following cardiac device procedures increases preventable harm: insights from the VA CART program.
The rate of cardiovascular implantable electronic device (CIED) infection is increasing coincident with an increase in the number of device procedures. Preprocedural antimicrobial prophylaxis reduces CIED infections; however, there is no evidence that prolonged postprocedural antimicrobials additionally reduce risk. Thus, we sought to quantify the harms associated with this approach. To measure the association between Clostridium difficile infection (CDI), acute kidney injury (AKI) and receipt of prolonged postprocedural antimicrobials. CIED procedures entered into the VA Clinical Assessment Reporting and Tracking Electrophysiology (CART-EP) database during fiscal years 2008-2016 were included. The primary outcome was 90-day incidence of CDI and the secondary outcome was the 7-day incidence of AKI. The primary exposure measure was duration of postprocedural antimicrobial therapy. Associations were measured using Cox-proportional hazards and binomial regression. Prolonged postprocedural antimicrobial therapy was identified following 3,331 of 6,497 CIED procedures (51.3%), and the median duration of prophylaxis was 5 days. Prolonged postprocedural antimicrobial use was associated with increased risk of CDI (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.54-5.46). Of the 27 patients who developed CDI, 11 subsequently died. Postprocedural antimicrobial use with ≥2 antimicrobials was associated with an increased risk of AKI (OR, 4.16; 95% CI, 2.50-6.90). The impact was particularly significant when one of the dual agents prescribed was vancomycin (adjusted OR, 8.41; 95% CI, 5.53-12.79). Prolonged antimicrobial prophylaxis following CIED procedures increases preventable harm; this practice should be discouraged in procedural settings such as the cardiac electrophysiology laboratory.


Simultaneous Sensing of Multiplex Volatile Organic Compounds by Adsorption and Plasmon Dual-Induced Raman Enhancement Technique.
Developing highly efficient gas sensors with excellent performance for rapid and sensitive detection of volatile organic compounds (VOCs) is of critical importance for the protection of human health, ecological environment, and other factors. Here, a robust gas sensor based on Raman technology was constructed by an in situ grown 2D covalent organic framework (COF) on Au nanoparticles' surface in the microchannel. Dual enhancement effects are included for the as-prepared microfluidic sensor. First, acting as a gas confinement chamber, the 2D COF could effectively capture gas molecules with high adsorption capacity and fast adsorption kinetics, resulting in VOCs' preconcentration at a high level in the COF layer. At the same time, after being stacked in the microchannel, abundant hot spots were generated among the nanogaps of Au@COF NPs. The local surface plasmon resonance effect could effectively enhance the Raman intensity. Both factors contribute to the improved detection sensitivity of VOCs. As a demonstration, several representative VOCs with different functional groups were tested. The resultant Raman spectra were subjected to the statistical principal component analysis. Varied VOCs can be successfully detected with a detection limit as low as ppb level and distinguished with 95% confidence interval. The present microfluidic platform provides a simple, sensitive, and fast method for VOCs' sensing and distinguishing, which is expected to hold potential applications in the fields of health, agricultural, and environmental research.


Role of volume in the regulation of vasopressin secretion during pregnancy in the rat.
We previously observed that osmoregulation and the osmotic threshold for antidiuretic hormone secretion were altered during pregnancy in Sprague-Dawley rats and the present study evaluated the influence of volume on arginine vasopressin (AVP) release during gestation in this species. Basal plasma osmolality (Posm) and intravascular volume were 297 +/- 3 mosmol/kg and 16.2 +/- 1.2 ml in virgin animals compared with 290 +/- 2 mosmol/kg and 20.2 +/- 2.3 ml in 14-d pregnant rats and 287 +/- 3 mosmol/kg and 25.2 +/- 2.3 ml in 21-d (near-term) pregnant rats (P less than 0.001, each pregnant group vs. virgin). Isosmotic volume depletion was produced by intraperitoneal polyethylene glycol. Volume decreased from 1 to 26% and blood pressure remained stable during decrements as high as 16%. Plasma AVP (PAVP) did not rise significantly in either group of pregnant animals or virgin controls until blood volume depletion reached 6-7%, after which levels rose in a similar exponential manner in virgin, 14-d, and 21-d pregnant animals. In terms of absolute changes, however, PAVP in gravid rats started to increase when intravascular volume was still considerably greater than basal blood volume in the nonpregnant controls. Other experiments, where Posm was increased by intraperitoneal hypertonic saline, reconfirmed that the osmotic threshold for AVP secretion was reduced congruent to 10 mosmol/kg during pregnancy and that AVP release was stimulated by increments in body tonicity as small as 1-2%. In parallel studies, blood volume contraction and increases in Posm were evoked by intraperitoneal polyethylene glycol dissolved in hypertonic saline and results compared with animals receiving intraperitoneal saline alone. Decrements in volume (congruent to 7%), which alone would increase PAVP minimally, increased the sensitivity of the secretory response to changes in osmolality two- to three-fold, an effect which was similar in virgin and gravid animals. Finally, restricting water intake of pregnant rats to that of virgins on days 16-20 of gestation led to suboptimal volume expansion, hypertonicity, and an exaggerated increase in PAVP. These results demonstrate that despite an intravascular space which at term is nearly twice that of virgin rats, pregnant animals secrete AVP in response to fractional volume depletion in a manner similar to nonpregnant controls; that is, the relationship between total blood volume and AVP secretion is altered during gestation such that the expanded blood volume is recognized as normal.


PON-mt-tRNA: a multifactorial probability-based method for classification of mitochondrial tRNA variations.
Transfer RNAs (tRNAs) are essential for encoding the transcribed genetic information from DNA into proteins. Variations in the human tRNAs are involved in diverse clinical phenotypes. Interestingly, all pathogenic variations in tRNAs are located in mitochondrial tRNAs (mt-tRNAs). Therefore, it is crucial to identify pathogenic variations in mt-tRNAs for disease diagnosis and proper treatment. We collected mt-tRNA variations using a classification based on evidence from several sources and used the data to develop a multifactorial probability-based prediction method, PON-mt-tRNA, for classification of mt-tRNA single nucleotide substitutions. We integrated a machine learning-based predictor and an evidence-based likelihood ratio for pathogenicity using evidence of segregation, biochemistry and histochemistry to predict the posterior probability of pathogenicity of variants. The accuracy and Matthews correlation coefficient (MCC) of PON-mt-tRNA are 1.00 and 0.99, respectively. In the absence of evidence from segregation, biochemistry and histochemistry, PON-mt-tRNA classifies variations based on the machine learning method with an accuracy and MCC of 0.69 and 0.39, respectively. We classified all possible single nucleotide substitutions in all human mt-tRNAs using PON-mt-tRNA. The variations in the loops are more often tolerated compared to the variations in stems. The anticodon loop contains comparatively more predicted pathogenic variations than the other loops. PON-mt-tRNA is available at http://structure.bmc.lu.se/PON-mt-tRNA/.


Demonstration of circulating autoantibodies against the plasma membrane of isolated thyroid cells in Graves' disease.
Antibodies against the plasma membrane of isolated human and porcine thyroid cells were demonstrable by a linear fluorescence pattern in sera from 29 out of 37 patients with Graves' disease. In 3 cases the antibodies reacted only with human thyroid cells. In a group of patients with Hashimoto's thyroiditis, 6 of 8 sera reacted with human thyroid cells in a granular fluorescence pattern. With one exception, sera from patients with non-toxic goiter showed no binding of IgG to thyroid cells. Sera from healthy controls were negative in this test system. There was no correlation between the presence of antibodies against thyroid cells and antibodies against thyroglobulin. Antibodies against thyroid microsomal antigens were found in 80% of patients with circulating thyroid cell membrane antibodies; 5 sera with membrane antibodies were negative for microsomal antibodies. Twenty sera of patients with Graves' disease were tested by passive haemagglutination test against peak I and peak II of the human thyroid fractionation with Sephadex G100. Antibodies against peak I were found in 14 sera and against peak II in all 20 sera. The data indicate that the antibodies in sera from patients with Graves' disease are directed mainly against a species-unspecific antigen of the plasma membrane from thyroid cells with a probable molecular weight between 4-7 S and are unrelated to thyroglobulin.


Asymmetric catalytic synthesis of P-stereogenic phosphines via a nucleophilic ruthenium phosphido complex.
Ruthenium phosphido complexes have been shown to be excellent nucleophiles, reacting via two-electron processes with a variety of electrophiles. A catalytic alkylation reaction was developed using an achiral ruthenium complex, which was then elaborated into a catalytic enantioselective synthesis of P-stereogenic phosphines. These useful and synthetically challenging phosphines can now be accessed in a single step from simple secondary phosphines and alkyl halides. Optimization and scope of the enantioselective alkylation are discussed.


Sociodemographic and Clinical Characteristics of Centenarians in Mexico City.
There is little evidence about the demography and health status of adults aged 100 years and over in Latin America and there are no studies in Mexico. To describe the demographic characteristics and health status of centenarians residing in Mexico City. This is a cross-sectional study using a population base of 393 community-dwelling centenarians in Mexico City. A comprehensive geriatric assessment was performed, including demographic information and health status. The mean age of centenarians was 101.82 ± 2.02 years, of whom 44 (9.1%) were semisupercentenarians (105-109 years old) and 5 (0.2%) were supercentenarians (≥110 years old). The female/male ratio was 3.2 : 1. Twelve (4.5%) reside in nursing homes. Women versus men have unfavorable conditions given their criteria: being without a partner, dependence in 1 or more basic activities, dependence in 1 or more instrumental activities, hypertension, cancer, and Parkinson's disease. Nevertheless, as compared to other populations, Mexican centenarians report having good self-perception of health (78.9%), polypharmacy (17.8%), low rate of pain (11.4%), diabetes (4.8%), and dyslipidemia (1.8%). This is the first study in Latin America that describes the social and clinical characteristics of centenarians in Mexico City. This population has a high percentage of malnutrition and osteoarthrosis, a high self-perception of health, low frequency of diabetes, dyslipidemia, cardiovascular disease, and a high frequency of "escapers" (24%).


[A preliminary study on measurement of muscle activity during mammography positioning].
This study focused on measuring examinees' muscle activities during mammography positioning using surface electromyography. Muscle activities were measured in three women (40-50s) in two-view mammography (MLO: mediolateral oblique, CC: craniocaudal). The muscles measured were the sternocleidomastoid, biceps, trapezius, and gastrocnemius, selected based on the visual analogue scale reported by Sharp et al. We used a multi-purpose portable bio-amplifier (Polymate AP1000) to assess the muscle activities. The results showed that the trapezius in right MLO and sternocleidomastoid in right CC were active in all three subjects. This suggests that the muscles directly related to mammography positioning are highly active. In addition, the gastrocnemius was active throughout the mammography. The biceps and gastrocnemius were also active in at least one of the three women. We believe that quantitative assessment of muscle activities during mammography positioning will contribute to the improvement of pain-reduction programs in mammography.


Pituitary adenomas and normal pituitary tissue: enhancement patterns on gadopentetate-enhanced MR imaging.
A dynamic study of magnetic resonance (MR) imaging was used to obtain successive heavily T1-weighted coronal images (spin-echo [SE] 100/15 [repetition time msec/echo time msec]) of normal pituitary glands and pituitary adenoma immediately after patients were given an intravenous bolus injection of gadopentetate dimeglumine. The images were obtained every minute for 5-8 minutes at 1.5 T. Usual T1-weighted images (SE 600/15) were also obtained before and after the dynamic study was performed. The study group consisted of 18 patients, 10 with normal pituitary glands, and eight with pituitary adenoma. Normal pituitary glands showed maximum enhancement on the first or second image following the administration of gadopentetate dimeglumine, followed by gradual signal reduction through the later images, whereas pituitary adenomas reached a peak of enhancement later and showed slower signal reduction than normal pituitaries. The difference of enhancement patterns between the normal pituitary gland and the pituitary adenoma produced prominent image contrast on the first or second image after administration of gadopentetate dimeglumine, which improved the visualization of one microadenoma and four normal pituitary glands that had been displaced by large adenomas. Dynamic MR imaging is a useful diagnostic procedure not only for detection of microadenomas, but also for visualization of pituitary glands that have been displaced by large pituitary adenomas.


LiBr. 2H(2)O Crystallization Inhibition in the Presence of Additives.
Experiments have been performed to measure the effect of additives on the crystallization temperature of concentrated LiBr solutions cooled at a rate of 20 degrees C/h. The measured crystallization temperatures correspond not to the temperatures of equilibrium solubility but to the critical temperature for heterogeneous nucleation of the hydrated LiBr salt on the glass wall of the test tube containing the sample solution. Various additives at concentrations from 250 to 1500 ppm have been investigated. Some soluble additives further decreased the experimental crystallization temperature by as much as 13 degrees C, corresponding to 22 degrees C below the equilibrium solubility. Large decreases in the crystallization temperature can be correlated with large values of complexation constants of the additive for either the Li(+) or the Br(-) ion in solution. Solution complexation, however, is not sufficient to explain the magnitude of the decrease in the crystallization temperature. The only phenomenon capable of quantitatively explaining the magnitude of the decrease in the crystallization temperature is the change in the crystal/solution interfacial energy due to adsorption of the additive on the surface of the prenucleation embryos. A quantitative model of the crystal/solution interfacial energy due to adsorption has been developed using both the Langmuir and Gibbs adsorption equations, allowing the quantitative prediction of crystallization temperatures with additive concentration. Copyright 2001 Academic Press.


Racial disparities in minimally invasive esophagectomy and gastrectomy for upper GI malignancies.
Esophageal cancer and gastric cancer are two important causes of upper GI malignancies. Literature has shown that minimally invasive esophagectomies (MIE) and gastrectomies (MIG), have shorter length of stay and fewer complications. However, limited literature exists about the association between race and access to MIE and MIG. This study aims to identify the racial disparities in the different approaches to esophagectomy and gastrectomy. We further evaluate the relationship between the race and postoperative complications. This IRB-approved retrospective study utilized data from the American College of Surgeons National Quality Improvement Program. All recorded cases of MIE, MIG, open gastrectomy, and esophagectomy between 2012 and 2019 were isolated. Propensity score matching and univariate analysis was performed to assess the independent effect of black self-identified race on access and outcomes. p < 0.05 was required to achieve statistical significance. 7891 cases of esophagectomy and 5,132 cases of gastrectomy cases were identified. Using Propensity and logistic regression, we identified that black self-reported race is an independent predictor of open approach to gastrectomy (OR 1.6871943, 95% CI 1.431464-1.989829, p < 0.001). Black self-reported race was not predictive of operative approach among esophagectomy patients (OR 0.7942576, 95% CI 0.5698645-1.124228, p = 0.183). In contrast, black self-reported is an independent predictor of postoperative complications among esophagectomy patients only. Esophagectomy patients of black self-reported race were more likely to experience any complication (OR 1.4373437, 95% CI 1.1129239-1.8557096, p = 0.00537), severe complications (OR 1.3818966, 95% CI 1.0653087-1.7888454, p = 0.0144), and death (OR 2.00779762, 95% CI 1.08034921-3.56117535, p = 0.0211) within 30 days of their surgeries. Our analysis revealed a significant racial disparity in access to MIG and a higher incidence of post-operative complications amongst esophagectomy patients. Minimally invasive techniques are underutilized in racial minorities. The findings herein warrant further investigation to eliminate barriers and disparities.


Pediatric foot surgery.
Muscle balance involves increasing or decreasing the relative strength of a muscle. It also includes redirection of muscle tendons to change their mechanical retrograde pull. Tendoachilles lengthening, gastrocnemius lengthening, anterior tendon teno-suspension, and the Kidner procedure exemplify this method. Muscle balancing is necessary whenever an imbalance exists. However, muscle balancing is usually only able to mildly effect joint position. It is important to eliminate a deforming muscle force and restore the balance of muscle power. Osteotomy to change internal bone shape is effective in pediatric foot surgery since malshape of the osseous structures is a major problem. The osteotomy is becoming a more important part of surgical treatment as a better understanding and recognition of the biomechanics of the foot and leg develops. The arthroerisis procedure for subtalar joint balance using implants is rapidly advancing. The concept that the subtalar joint can be balanced satisfactorily has been demonstrated. However, the lifetime implications are still unexplored. Joint stabilization with some motion still available at the subtalar is a leading concept in treating the foot. Fusion procedures are meant to realign malaligned joints and prevent further motion. They are applicable to pediatric foot surgery only in extreme conditions and in the growing foot at adolescence.


Toxicity Management of Front-Line Pembrolizumab Combined With Axitinib in Clear Cell Metastatic Renal Cell Carcinoma: A Case Study Approach.
Immune checkpoint inhibitors have improved clinical outcomes in many malignancies, including renal cell carcinoma (RCC). Awareness of potential adverse events and effective management of these toxicities is critical to maximizing clinical outcomes. Pembrolizumab plus axitinib is approved as front-line treatment of advanced renal cell carcinoma (aRCC), making it the first checkpoint inhibitor and tyrosine kinase inhibitor combination approved for any malignancy. Given overlapping toxicities with this combination, the toxicity profile of each drug must be considered when assessing and managing toxicities in patients treated with pembrolizumab and axitinib. Use of online resources, including published guidelines from ASCO, the Immuno-Oncology Essentials Web site, and other organizations, can assist oncology and nononcology health care professionals to more effectively manage toxicities, maximize clinical outcomes, and improve quality of life for patients with aRCC. Herein, we describe a case of a patient with aRCC treated with pembrolizumab and axitinib, highlighting a systematic approach to toxicity management.


Knee Extension Loss Secondary to a "Cyclops-Like" Gouty Tophus A Case Report and Literature Review.
While gouty arthritis of the knee is not uncommon, associated mechanical block to extension is a rarely seen complication. This report presents a unique case of extension loss due to a single, isolated intra-articular gouty tophus. Only a few similar reports have been described in the literature involving cases that are often initially suspected to be related to inherent structural knee pathology as opposed to a systemic condition or illness.


The Impact of China's Legal System on Public Health and Quality of Life during the COVID-19 Pandemic: An Empirical Study.
(1) Background: During the COVID-19 pandemic, the methods used to ensure the quality of public health and life changed. This study used empirical research methods to analyze the development of China's legal system during the COVID-19 pandemic and its impact on the quality of public health and life and to clarify its importance in ensuring the quality of public health and life. (2) Materials and Methods: This study analyzed the development of China's rule of law system during the COVID-19 pandemic by using two authoritative databases, the Peking University Magic Key Database and the China Judicial Documents Network, and examined the scope of public health and quality of life under this system. (3) Results: During the COVID-19 pandemic, China's rule of law system, with the main objective of controlling the pandemic, developed rapidly, effectively ensuring the quality of public health and life in different areas. As part of this system, the administrative activities of government departments played a key role. (4) Conclusions: During the period of the COVID-19 pandemic, China's legal system protected the quality of public health and life from the impact of the pandemic in many areas. Meanwhile, along with the important role of government administrative law enforcement activities in the prevention and control of a pandemic, the quality of public health and life should also be protected against illegal administrative acts in the future.


Knowledge of risk factors and the periodontal disease-systemic link in dental students' clinical decisions.
This study evaluated second-, third-, and fourth-year dental students' ability to identify systemic conditions associated with periodontal disease, risk factors most important for referral, and medications with an effect on the periodontium and their ability to apply this knowledge to make clinical decisions regarding treatment and referral of periodontal patients. A twenty-one question survey was administered at one U.S. dental school in the spring semester of 2012 to elicit the students' knowledge and confidence regarding clinical reasoning. The response rate was 86 percent. Periodontal risk factors were accurately selected by at least 50 percent of students in all three classes; these were poorly controlled diabetes, ≥6 mm pockets posteriorly, and lack of response to previous non-surgical therapy. Confidence in knowledge, knowledge of risk factors, and knowledge of medications with an effect on the periodontium improved with training and were predictive of better referral decision making. The greatest impact of training was seen on the students' ability to make correct decisions about referral and treatment for seven clinical scenarios. Although the study found a large increase in the students' abilities from the second through fourth years, the mean of 4.6 (out of 7) for the fourth-year students shows that, on average, those students missed correct treatment or referral on more than two of seven clinical cases. These results suggest that dental curricula should emphasize more critical decision making with respect to referral and treatment criteria in managing the periodontal patient.


Critical stimulus durations for some verbal and nonverbal stimuli.
Durations of stimulus exposures in visual backward masking are determined with reference to critical stimulus durations. These are defined as the minimum, undisrupted, durations of exposure for 100% accuracy for a predetermined number of trials. These durations are shown to vary both within and between classes of stimuli for 10 normal adults with a mean age of 26.40 yr. The verbal stimuli employed (letters of the alphabet) were significantly easier to discern than the nonverbal stimuli (arrows). Although some letters were more readily identified than others, differences were not significant. The results suggest that type of stimuli, nature of response, and the ease with which stimuli can be discerned be considered in the selection of target stimuli for experiments using masking.


Competing magnetic phases in La(0.7)Sr(0.3)MnO(3) as deduced from Mn site hyperfine parameters.
Time differential perturbed angular correlation measurements using the (181)Ta probe in La(0.7)Sr(0.3)Mn(0.995)Hf(0.005)O(3) reveal the presence of two distinct hyperfine components, identified with probe atoms occupying Mn sites which are rich and deficient in hole concentration. The Mn(4+) rich zones exhibit ferromagnetic ordering at all temperatures below 360 K, the bulk Curie temperature. In the case of Mn(4+) deficient zones, the paramagnetic order is seen to evolve into a canted antiferromagnetic ordering below 360 K, that becomes ferromagnetic below 250 K. Concomitantly, there is a change in the fractions below 250 K. The implications of these results are discussed in terms of electronic phase separation.


Genetic structure of continental and island populations of the Mediterranean endemic Cyclamen balearicum (Primulaceae).
Cyclamen balearicum is a self-compatible perennial herb endemic to the western Mediterranean Basin. This species occurs in five geographically isolated terrestrial islands in southern France and on four Balearic islands. In this study, we compare genetic variability and differentiation within and among 11 terrestrial island populations and 17 true island populations. Of nine readable enzyme loci, five were polymorphic in both terrestrial and true islands. F statistics showed a significant heterozygote deficiency in all populations, probably due to high levels of autonomous selfing, restricted gene flow, and subsequent genetic drift. Genetic diversity was higher in terrestrial islands than on the Balearic islands, suggesting that the Balearic islands were colonized when they were in contact with the continent. Population differentiation was greater among terrestrial islands (Fst = 0.417 and Gst = 0.344) than among true islands (Fst = 0.112 and Gst = 0.093). Furthermore, differentiation among populations on the Basses Cévennes terrestrial island was greater (Fst = 0.254) than among populations on the true island of Mallorca (Fst = 0.163). The greater genetic differentiation among terrestrial islands could have been caused by genetic bottlenecks associated with changes in climate and human land use that may have reduced population sizes more severely in terrestrial islands in southern France than on the Balearic islands.


Infections with Helicobacter pylori and challenges encountered in Africa.
Helicobacter pylori (H. pylori) is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world's population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for H. pylori acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high H. pylori prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of H. pylori infection and the low incidence of GC has been reported. This phenomenon is the so-called "African Enigma" and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of H. pylori. The aim of this manuscript is to review current literature on H. pylori infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce H. pylori transmission in this continent.


Viability, apoptosis, proliferation, activation, and cytokine secretion of human keratoconus keratocytes after cross-linking.
The purpose of this study was to determine the impact of cross-linking (CXL) on viability, apoptosis, proliferation, activation, and cytokine secretion of human keratoconus (KC) keratocytes, in vitro. Primary KC keratocytes were cultured in DMEM/Ham's F12 medium supplemented with 10% FCS and underwent UVA illumination (370 nm, 2 J/cm(2)) during exposure to 0.1% riboflavin and 20% Dextran in PBS. Twenty-four hours after CXL, viability was assessed using Alamar blue assay; apoptosis using APO-DIRECT Kit; proliferation using ELISA-BrdU kit; and CD34 and alpha-smooth muscle actin (α-SMA) expression using flow cytometry. Five and 24 hours after CXL, FGFb, HGF, TGFβ1, VEGF, KGF, IL-1β, IL-6, and IL-8 secretion was measured using enzyme-linked-immunoabsorbent assay (ELISA). Following CXL, cell viability and proliferation decreased (P < 0.05; P = 0.009), the percentage of apoptotic keratocytes increased (P < 0.05) significantly, and CD34 and α-SMA expression remained unchanged (P > 0.06). Five hours after CXL, FGFb secretion increased significantly (P = 0.037); however no other cytokine secretion differed significantly from controls after 5 or 24 hours (P > 0.12). Cross-linking decreases viability, triggers apoptosis, and inhibits proliferation, without an impact on multipotent hematopoietic stem cell transformation and myofibroblastic transformation of KC keratocytes. CXL triggers FGFb secretion of KC keratocytes transiently (5 hours), normalizing after 24 hours.


Nephrolithiasis: A Red Flag for Cardiovascular Risk.
Epidemiological evidence shows that nephrolithiasis is associated with cardiovascular (CV) morbidities. The association between nephrolithiasis and CV disease is not surprising because both diseases share conditions that facilitate their development. Metabolic conditions, encompassed in the definition of metabolic syndrome (MS), and habits that promote nephrolithiasis by altering urine composition also promote clinical manifestations of CV disease. By inducing oxidative stress, these conditions cause endothelial dysfunction and increased arterial stiffness, which are both well-known predictors of CV disease. Furthermore, the subtle systemic metabolic acidosis observed in stone formers with CV disease may have a pathogenic role by increasing bone turnover and leading to reduced mineral content and osteoporosis/osteopenia. Heart valves and/or coronary artery and aortic calcifications are frequently associated with reduced mineral density. This is known as the 'calcification paradox' in osteoporosis and has also been observed in subjects with calcium nephrolithiasis. Evidence supports the hypothesis that osteoporosis/osteopenia is an independent risk factor for the development of CV calcifications. In the long term, episodes of renal stones may occur from the onset of metabolic derangements/MS to arterial stiffness/atherosclerosis and CV morbidities. These episodes should be considered a warning sign of an ongoing and silent atherosclerotic process. The evaluation of cardiometabolic risk factors and MS components should be routine in the assessment of renal stone formers. This would allow for treatment and prevention of the development of CV complications, which are much more severe for the patient and for public health.


Mycobacterial acyl carrier protein suppresses TFEB activation and upregulates miR-155 to inhibit host defense.
Mycobacterial acyl carrier protein (AcpM; Rv2244), a key protein involved in Mycobacterium tuberculosis (Mtb) mycolic acid production, has been shown to suppress host cell death during mycobacterial infection. This study reports that mycobacterial AcpM works as an effector to subvert host defense and promote bacterial growth by increasing microRNA (miRNA)-155-5p expression. In murine bone marrow-derived macrophages (BMDMs), AcpM protein prevented transcription factor EB (TFEB) from translocating to the nucleus in BMDMs, which likely inhibited transcriptional activation of several autophagy and lysosomal genes. Although AcpM did not suppress autophagic flux in BMDMs, AcpM reduced Mtb and LAMP1 co-localization indicating that AcpM inhibits phagolysosomal fusion during Mtb infection. Mechanistically, AcpM boosted the Akt-mTOR pathway in BMDMs by upregulating miRNA-155-5p, a SHIP1-targeting miRNA. When miRNA-155-5p expression was inhibited in BMDMs, AcpM-induced increased intracellular survival of Mtb was suppressed. In addition, AcpM overexpression significantly reduced mycobacterial clearance in C3HeB/FeJ mice infected with recombinant M. smegmatis strains. Collectively, our findings point to AcpM as a novel mycobacterial effector to regulate antimicrobial host defense and a potential new therapeutic target for Mtb infection.


A case of implantation dermatosis that formed a tumor.
A 51-year-old man visited our hospital complaining of a tumor located above his lip. He had been hit on his upper left lip by a chopstick holder 2 months previously. The lesion turned into a tumor and gradually enlarged. The tumor was well circumscribed, smooth and covered with reddish, partially milk-white skin. During surgery to remove the tumor, a piece of a chopstick was found in the subcutaneous tissue, and a diagnosis of implantation dermatosis (ID) was made. On histology, the tumor appeared as an abscess that had increased fibroblasts, small vessels and a large number of neutrophils. In the Japanese published work, we found 86 cases of ID; three were similar to our case and had been clinically diagnosed as adnexal tumors. There were also six cases that showed abscess formation similar to our case on histology. In a survey of the published work from other countries, there were 44 ID cases. There were no common features found among the cases reported in the published work.


Fractures of the clivus: a contemporary series in the computed tomography era.
We report the morbidity and mortality associated with fractures of the clivus and discuss management approaches specific to this unique diagnostic entity. We performed a boolean search of our electronic medical record database to identify patients with fractures of the clivus that were diagnosed using computed tomography of the head. A retrospective imaging and chart analysis was completed to further characterize the fractures and to analyze outcomes. Between January 1999 and December 2007, 41 patients were identified with fractures of the clivus. We found a 0.21% overall incidence among all head-injured patients presenting to our institution and a 2.3% incidence among those patients with a cranial fracture. Ten of 41 patients (24.4%) died, and neurological and vascular complications associated with central cranial base fractures were observed in 19 of 41 patients (46%). Furthermore, associated cranial fractures remote from the central cranial base and associated intracranial hemorrhages were observed in 40 of 41 (97.6%) and 33 of 41 (80.5%) patients, respectively. In terms of outcomes, 26 of 41 patients (63.5%) had a Glasgow Coma Scale score of 12 or greater at the time of discharge from the hospital. We demonstrate a lower than previously reported mortality rate in patients with clival fractures. Nevertheless, as a result of location, fractures of the clivus were frequently associated with a high rate of complications and neurological sequelae.


Clinical and echocardiographic response of apical vs nonapical right ventricular lead position in CRT: A meta-analysis.
Traditionally the right ventricular (RV) pacing lead is placed in the RV apex in cardiac resynchronization therapy (CRT). It is not clear whether nonapical placement of the RV lead is associated with a better response to CRT. We aimed to perform a meta-analysis of all randomized controlled trials (RCTs) that compared apical and nonapical RV lead placement in CRT. We searched PubMed, EMBASE, Cochrane, Scopus, and relevant references for studies and performed meta-analysis using random effects model. Our main outcome measures were all-cause mortality, composite of death and heart failure hospitalization, improvement in ejection fraction (EF), left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), and adverse events. Seven RCTs with a total population of 1641 patients (1199 apical and 492 nonapical) were included in our meta-analysis. There was no difference in all-cause mortality (5% vs 4.3%, odds ratio (OR) = 0.86; 95% confidence interval (CI) 0.45-1.64; P = .65; I2 = 11%) and a composite of death and heart failure hospitalization (14.2% vs 12.9%, OR = 0.92; 95% CI: 0.61-1.38; P = .68; I2 = 0) between apical and nonapical groups. No difference in improvement in EF (Weighted mean difference (WMD) = 0.37; 95% CI: -2.75-3.48; P = .82; I2 = 68%), change in LVEDV (WMD = 3.67; 95% CI: -4.86-12.20; P = .40; I2 = 89%) and LVESV (WMD = -1.20; 95% CI: -4.32-1.91; P = .45; I2 = 0) were noted between apical and nonapical groups. Proportion of patients achieving >15% improvement in EF was similar in both groups (OR = 0.85; 95% CI: 0.62-1.16; P = .31; I2 = 0). In patients with CRT, nonapical RV pacing is not associated with improved clinical and echocardiographic outcomes compared with RV apical pacing.


Does the VDR gene polymorphism influence the efficacy of denosumab therapy in postmenopausal osteoporosis?
One of the challenges of personalized medicine is a departure from traditional pharmacology toward individualized, genotype-based therapies. Postmenopausal osteoporosis is a prevalent condition requiring intensive treatment, whose effects are measurable only after a long time, and the goal is bone fracture prevention. This study aimed to determine the influence of VDR gene variation on anti-osteoporotic one-year treatment with denosumab in 63 Polish women with postmenopausal osteoporosis. The correlation between bone mineral density (BMD) of the lumbar vertebral column (L1-L4) and femoral neck, and genotype distributions for the ApaI, BsmI, FokI, and TaqI variants of the VDR gene was analyzed. Bone fractures during denosumab therapy were also investigated. In the case of the Bsml polymorphism, female patients with BB and Bb genotypes had statistically significantly higher values of BMD and T-score/Z-score indicators, which persisted after a year of denosumab treatment. Our results indicated that the Bsml polymorphism contributes to better bone status, and, consequently, to more efficient biological therapy. The study did not reveal significant differences between changes (delta) in BMD and genotypes for the analyzed VDR gene loci. In the entire study group, one bone fracture was observed in one patient throughout the yearlong period of denosumab therapy. BB and Bb genotypes of the Bsml polymorphism of the VDR gene determine higher DXA parameter values both before and after one-year denosumab therapy in postmenopausal women with osteoporosis.


Mucinous carcinoma in a male breast.
Male breast cancer is rare as compared to female counterpart. Pure mucinous carcinoma is an extremely rare histological subtype representing less than 1% of male breast cancers. So far very few cases of pure mucinous carcinoma of male breast have been reported in the literature, most of which were diagnosed after surgical resection. Fine-needle aspiration cytology is a well-established procedure for the evaluation of female breast masses but the diagnosis of malignancy in aspirates from male breast masses is rare. We herein present one case of mucinous carcinoma of breast in a 75-year-old male diagnosed by fine-needle aspiration and confirmed by histopathology. After a follow-up of 12 months the patient is free of any recurrence or metastasis.


Degradation of Toluene from Gas Streams by Heterogeneous Fenton Oxidation in a Slurry Bubble Reactor with Activated Carbon-Based Catalysts.
A novel approach for the treatment of volatile organic compounds from gaseous streams was developed. In order to accomplish this, a semi-batch bubble reactor was used, aiming to assess the toluene (selected as model compound) degradation from gaseous streams via heterogeneous Fenton oxidation. Activated carbon-based catalysts-metal-free or iron-impregnated-with different textural and chemical surface properties were used for the first time as catalysts, in order to degrade gaseous toluene using such technology. Complementary characterization techniques, such as nitrogen adsorption at -196 °C, elemental analysis, pH at the point of zero charge (pHPZC), inductively coupled plasma optical emission spectrometry (ICP-OES) and transmission electron microscopy (TEM), were used. The materials' chemical surface properties, particularly the presence of N-surface groups, were herein found to play an important role in toluene adsorption and catalytic performance. The maximum amount of toluene transferred, 6.39 × 10-3 mol, was achieved using melamine-doped activated carbon (N-doped material) that was impregnated with iron (sample herein called ACM-Fe). This iron-based catalyst was found to be quite stable during three reutilization cycles.


Growth of an Ultrathin Zirconia Film on Pt3Zr Examined by High-Resolution X-ray Photoelectron Spectroscopy, Temperature-Programmed Desorption, Scanning Tunneling Microscopy, and Density Functional Theory.
Ultrathin (∼3 Å) zirconium oxide films were grown on a single-crystalline Pt3Zr(0001) substrate by oxidation in 1 × 10-7 mbar of O2 at 673 K, followed by annealing at temperatures up to 1023 K. The ZrO2 films are intended to serve as model supports for reforming catalysts and fuel cell anodes. The atomic and electronic structure and composition of the ZrO2 films were determined by synchrotron-based high-resolution X-ray photoelectron spectroscopy (HR-XPS) (including depth profiling), low-energy electron diffraction (LEED), scanning tunneling microscopy (STM), and density functional theory (DFT) calculations. Oxidation mainly leads to ultrathin trilayer (O-Zr-O) films on the alloy; only a small area fraction (10-15%) is covered by ZrO2 clusters (thickness ∼0.5-10 nm). The amount of clusters decreases with increasing annealing temperature. Temperature-programmed desorption (TPD) of CO was utilized to confirm complete coverage of the Pt3Zr substrate by ZrO2, that is, formation of a closed oxide overlayer. Experiments and DFT calculations show that the core level shifts of Zr in the trilayer ZrO2 films are between those of metallic Zr and thick (bulklike) ZrO2. Therefore, the assignment of such XPS core level shifts to substoichiometric ZrO x is not necessarily correct, because these XPS signals may equally well arise from ultrathin ZrO2 films or metal/ZrO2 interfaces. Furthermore, our results indicate that the common approach of calculating core level shifts by DFT including final-state effects should be taken with care for thicker insulating films, clusters, and bulk insulators.


Detecting spelling errors in compound and pseudocompound words.
Three experiments using a spelling error detection task investigated the extent to which morphemes and pseudomorphemes affect word processing. We compared the processing of transparent compound words (e.g., doorbell), pseudocompound words (e.g., carpet), and matched control words (e.g., tomato). In half of the compound and pseudocompound words, spelling errors were created by transposing adjacent letters and in half of the control words, errors were created by transposing letters at the same location as the matched compound or pseudocompound words. Correctly spelled compound words were more easily processed than matched control words, but this advantage was removed when letter transpositions were introduced at the morpheme boundary. In contrast, misspelled pseudocompound words showed a processing deficit relative to their matched control words when letter transpositions were introduced at the (pseudo)morpheme boundary. The results strongly suggest that morphological processing is attempted obligatorily when the orthography indicates that morphological structure is present. However, the outcomes of the morphological processing attempts are different for compounds and pseudocompounds, as might be expected, given that only the compounds have a morphological structure that matches the structure suggested by the orthography. The findings reflect 2 effects: an orthographic effect that is facilitatory and not sensitive to morphological structure of the whole word, and a morphemic effect that is facilitatory for compounds but inhibitory for pseudocompounds. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Clinical safety profile of sotalol in patients with arrhythmias.
Key safety parameters of sotalol were examined in 1,288 patients entered into recent controlled trials of ventricular (85% of patients) or supraventricular arrhythmias (15%). Most patients were middle-aged male Caucasians with significant heart disease. The most serious adverse event was proarrhythmia, occurring in 56 patients (4.3%). Of these, 27 had hemodynamic compromise due to malignant ventricular arrhythmias. Most had a history of sustained ventricular tachycardia, myocardial infarction, congestive heart failure (CHF) or cardiomyopathy, or a combination of these. The other 29 had nonsevere events; 38% continued taking sotalol. Proarrhythmia was manifested by torsades de pointes in 24 of the 56 patients. No universal causal relation was found with commonly associated factors such as bradycardia, hypokalemia and long QT interval. The mean QT and QTc at baseline within 1 week of a severe proarrhythmic event were greater than those of patients not having proarrhythmia. Nineteen patients (1%) discontinued therapy with sotalol because of drug-related CHF. Predisposing conditions included low initial baseline ejection fraction, history of CHF, cardiomyopathy or cardiomegaly, or both, male gender and age greater than 65 years. Heart failure usually occurred within 7 to 30 days of initiating therapy. The most common reason for premature discontinuation of the drug in patients treated for sustained ventricular tachycardia was ineffectiveness (39%), whereas adverse effects were the most common reasons among patients treated for complex ventricular ectopy (21%). Dyspnea and bradycardia were the most common cardiovascular effects, and fatigue, dizziness and asthenia the most common noncardiac, adverse effects. Although frequently reported, these adverse effects resulted in discontinuation of only 1 to 4% of the patients at risk.(ABSTRACT TRUNCATED AT 250 WORDS)


Total syntheses of seminolipid and its analogues by using 2,6-bis(trifluoromethyl)phenylboronic acid as protective reagent.
A concise total synthesis of seminolipid, a sulfoglycolipid, has been achieved; key features include regioselective, tin-free sulfation of allyl β-d-galactopyranoside using 2,6-bis(trifluoromethyl)phenylboronic acid as protective reagent, stereoselective epoxidation, and site-selective acylation. The utility of this divergent synthetic approach to introduce 2,2,2-trichloroethyl-protected sulfate group at an early stage without toxic and environmentally unfavorable tin reagents was demonstrated by the syntheses of three seminolipid analogues with different side-chains from the common intermediate.


PaR1 secreted by the type IX secretion system is a protective antigen of Riemerella anatipestifer.
Riemerella anatipestifer mainly infects domestic ducks, geese, turkeys, and other birds, and causes considerable economic losses to the global duck industry. Previous studies have shown that concentrated cell-free culture filtrates of R. anatipestifer induce highly significant protection against homologous challenge. In this study, 12 immunogenic proteins were identified in the culture supernatant of R. anatipestifer strain Yb2 with immunoproteomic analysis. Of these, three immunogenic proteins, AS87_RS06600 (designated "PaR1" in this study), AS87_RS09020, and AS87_RS09965, which appeared in more than three spots on the western-blotted membrane, were expressed in Escherichia coli and purified. Animal experiments showed that the recombinant PaR1 (rPaR1) protein protected 41.67% of immunized ducklings against challenge with virulent Yb2, whereas rAS87_RS09020 or rAS87_RS09965 did not, and that ducklings immunized once with rPaR1 were 20, 40, and 0% protected from challenge with R. anatipestifer strains WJ4 (serotype 1), Yb2 (serotype 2), and HXb2 (serotype 10), respectively. In addition, rPaR1 immunized rabbit serum showed bactericidal activity against strain Yb2 at a titer of 1:8. These results indicate that rPaR1 of strain Yb2 protects against homologous challenge. Amino acid homology analysis show that PaR1 is a non-serotype-specific protein among different R. anatipestifer serotypes. Furthermore, PaR1 is mainly secreted outside the cell through the T9SS. Overall, our results demonstrate that R. anatipestifer PaR1 is a non-serotype-specific protective protein secreted by the T9SS.


Kidney after nonrenal transplantation-the impact of alemtuzumab induction.
Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.


Microbial Baeyer-Villiger oxidation: stereopreference and substrate acceptance of cyclohexanone monooxygenase mutants prepared by directed evolution.
[reaction: see text] An array of random mutants of cyclohexanone monooxygenase (CHMO) from Acinetobacter sp. NCIMB 9871 was screened against a library of structurally diverse ketones for modifications in the substrate acceptance profile and stereopreference of the enzymatic Baeyer-Villiger biooxidation. While the set of mutant biocatalysts was initially evolved for the enantiocomplementary oxidation of 4-hydroxycyclohexanone, improved and/or divergent stereoselectivities were observed for several substrates. In addition, expanded substrate acceptance to facilitate biotransformation of sterically demanding ketones was found.


Novel extraction of German cockroach (Dictyoptera: Blattellidae) fecal pellets enhances efficacy of spray formulation insecticides.
Methanol extracts of German cockroach, Blattella germanica (L.), fecal pellets have limited use as pheromone attractants in the urban environment because of their unpleasant color and odor. To eliminate these characteristics, a novel aqueous extract of German cockroach feces was formulated. Fetal material was extracted with methylene chloride and mixed with water. The aqueous phase of the extract was colorless and relatively odorless compared with methanol fecal extracts. Aqueous extract was bioassayed and compared with methanol extracts for aggregation activity. The efficacy of chlorpyrifos and boric acid formulations was tested with and without the addition of fecal extracts. In tests with chlorpyrifos, the addition of the aqueous extract produced significantly greater mortality in young nymphs than either chlorpyrifos alone or chlorpyrifos + methanol extract. There were no differences in mortality between the 2 extract + boric acid treatments during the test period, and both enhanced mortality.


Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis.
This paper reports the case of an infant presenting with sexual ambiguity at birth. The child presented with labia majora synechia, thready genital tubercle and perineal hypospadias. The karyotype was 46,XY. Low testosterone levels with no response to hCG administration, associated with high LH level for her age, high FSH level, high inhibin B levels and normal AMH indicated a lack of LH receptivity and prompted us to screen the LHCGR gene for mutations. A previously described missense mutation (p.Cys131Arg) was identified at homozygous state in the propositus and at heterozygous state in the mother. This variation, however, was not found in the father. Our attention was drawn by the presence of several single nucleotide polymorphisms (SNPs), identified at homozygous state without any paternal contribution from exon 1 to exon 10 of LHCGR, suggesting a paternal deletion. Array DNA analysis was performed revealing a large deletion extending from 61,493 to 135,344 bp and including the LHCGR gene. Adequate genetic counselling was provided. This paper describes the first application of prenatal diagnosis in LHCGR deficiency for 46,XY disorders of sex development with the subsequent delivery of a normal baby.


High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan.
To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined. Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.


Approaches to genetic studies of asthma.
It is important to remember that any postulated linkage needs to be confirmed and the identification of one major locus does not mean that other major loci are not also present. The failure to replicate a postulated linkage has become a serious problem in studies on the genetics of complex disorders. A major reason for failure to replicate, as discussed by Risch (30) may be the interpretation of a LOD score calculated under an unlikely model. Analysis of a LOD score assumes that the underlying genetic model for the disorder being studied is known. Clear evidence for a specific genetic model for asthma has yet to be delineated. There are several obvious reasons for failure to confirm a postulated linkage. For purposes of replication, it is important to use the same definition of the affected phenotype and the same genetic model that were used in the original study. The presence of genetic heterogeneity is often given as a possible reason for failure to replicate. It seems unlikely that this should be a reason for failure to replicate across relatively homogeneous populations (such as Caucasian families from the U.S.A. and England). However, heterogeneity may be confounded with differing expression of genes because of exposures to different allergens. In addition, if there are several genes that interact in disease expression (oligogenic inheritance), it may be very difficult to replicate a true linkage (31). In different sets of families, different proportions of the genes involved may be present and the linked gene may not be detected in all studies.(ABSTRACT TRUNCATED AT 250 WORDS)


The Na+-K+-ATPase as self-adhesion molecule and hormone receptor.
Thanks to the homeostasis of the internal milieu, metazoan cells can enormously simplify their housekeeping efforts and engage instead in differentiation and multiple forms of organization (tissues, organs, systems) that enable them to produce an astonishing diversity of mammals. The stability of the internal milieu despite drastic variations of the external environment (air, fresh or seawater, gastrointestinal fluids, glomerular filtrate, bile) is due to transporting epithelia that can adjust their specific permeability to H(2)O, H(+), Na(+), K(+), Ca(2+), and Cl(-) over several orders of magnitude and exchange substances with the outer milieu with exquisite precision. This exchange is due to the polarized expression of membrane proteins, among them Na(+)-K(+)-ATPase, an oligomeric enzyme that uses chemical energy from ATP molecules to translocate ions across the plasma membrane of epithelial cells. Na(+)-K(+)-ATPase presents two types of asymmetries: the arrangement of its subunits, and its expression in one pole of the epithelial cell ("polarity"). In most epithelia, polarity consists of the expression of Na(+)-K(+)-ATPase towards the intercellular space and arises in part from the interaction of the extracellular segment of the β-subunit with another β-subunit present in a Na(+)-K(+)-ATPase molecule expressed by a neighboring cell. In addition to enabling the Na(+)-K(+)-ATPase to transport ions and water vectorially, this position exposes its receptors to ouabain and analogous cardiotonic steroids, which are present in the internal milieu because these were secreted by endocrine cells.


Effects of contrast inversion on face perception depend on gaze location: Evidence from the N170 component.
Face recognition is known to be impaired when the contrast polarity of the eyes is inverted. We studied how contrast affects early perceptual face processing by measuring the face-sensitive N170 component to face images when the contrast of the eyes and of the rest of the face was independently manipulated. Fixation was either located on the eye region or on the lower part of a face. Contrast-reversal of the eyes triggered delayed and enhanced N170 components independently of the contrast of other face parts, and regardless of gaze location. Similar N170 modulations were observed when the rest of a face was contrast-inverted, but only when gaze was directed away from the eyes. Results demonstrate that the contrast of the eyes and of other face parts can both affect face perception, but that the contrast polarity of the eye region has a privileged role during early stages of face processing.


[Teen pregnancy in migrants: socioeconomic, gynecobstetric, and neonatal variables].
Identify and correlate characteristics of adolescent mothers in a border city of Mexico with their migratory status. We surveyed post partum adolescent mothers in the discharge rooms of two public hospitals in Tijuana, Mexico. We assessed obstetric, gynecologic, socioeconomic and neonatal variables. Mothers living fewer than 5 years in the area were designated as 'migrant.' 324 adolescent mothers were identified; 86% had healthy babies; 27% had previous pregnancies; age of onset of sexual activity was 15.5 +/- 1.4 years. 115 (36%) were identified as 'migrant,' among whom we found they had interrupted their studies (24% vs. 33%; OR 2.62: CI 95% 1.39-4.94), had a higher incidence of failure to use contraception (74% vs. 62%; OR 1.79: C.I. 95% 1.07-3.01) and a lower incidence of prenatal care (28% vs. 38%; OR 1.8: C.I. 95% 1.04-3.15). A larger percentage of migrant adolescents already lived with their partner (39% vs. 24%; OR 2.00: C.I. 95% 1.21-3.30) and expressed a desire to become pregnant (55% vs. 37%; OR 2.10: C.I. 95% 1.31-3.37). The observed association persisted in multivariate analysis. We did not observe differences between other ob-gyn and neonatal variables. Being a female migrant should be considered a risk factor in the reproductive health of adolescent mothers.


Depressed prolactin cell activity in long-term blind-pinealectomized female hamsters is due to loss of estrous cyclicity.
Pinealectomy in the female golden Syrian hamster is not always completely effective in preventing the suppressive effects of long-term light deprivation due to blinding on pituitary prolactin (PRL) cell activity. We examined this curious phenomenon by measuring pituitary PRL mRNA levels, PRL synthesis, and radioimmunoassayable PRL, and correlating these changes with the status of estrous cyclicity. As expected, 12 weeks of light deprivation resulted in loss of estrous cyclicity and a greater than 90% decline in all indices of pituitary PRL cell activity, compared with intact cycling controls. Pinealectomy prevented only 40-50% of this decline. However, if noncycling light-deprived pinealectomized animals were excluded, pinealectomy was completely effective, i.e., cycling intact control animals were no different than cycling blind-pinealectomized. We conclude that the inability of pinealectomy to completely prevent the decline in prolactin cell activity seen after blinding is due to the loss of estrous cyclicity in some blind-pinealectomized females, with the attendant loss of the prolactin-stimulating hormone estrogen.


Sensitivity to spatial and temporal modulations of first-order and second-order motion.
This study characterises the spatiotemporal "window of visibility" for first-order motion (luminance-modulated noise) and three varieties of second-order motion (contrast-modulated, polarity-modulated and spatial length-modulated noise). Direction-identification thresholds (minimum modulation depth producing 79.4% correct) were measured for each motion pattern (acuity permitting) over a five octave range of spatial and temporal frequencies (0.5-16 c/deg and 0.5-16 Hz respectively). Thresholds were converted into modulation sensitivity (1/threshold). For first-order motion patterns, sensitivity functions were generally bandpass. However, for second-order motion patterns, functions were predominantly lowpass in nature. In particular, the functions corresponding to contrast-modulated and polarity-modulated noise were virtually identical in terms of shape and sensitivity. However, sensitivity to modulations of spatial length was extremely poor and more lowpass, suggesting that additional strategies, perhaps a feature-based system, may be required for encoding motion of images of this type.


Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair.
: Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.


A case of hyperreninemic hypertension with unilateral hydronephrosis.
A patient with unilateral ureteral obstruction by urolithiasis at the ureteropelvic junction was accompanied by hypertension. Plasma renin activity (PRA) was high in peripheral veins and was significantly higher in the renal vein drained from the affected kidney than the contralateral. Infusion of angiotensin II antagonist or an oral administration of captopril, an angiotensin converting enzyme (ACE) inhibitor, resulted in a prompt drop of blood pressure. After pyelolithotomy was successfully performed, both the blood pressure and peripheral PRA completely normalized. It is suggested that the renin-angiotensin system might have played a major role in the mechanism of the accompanied hypertension. Hyperreninemia could have been caused by both renal ischemic vasoconstriction, which might be due to uretero-renal reflex, and increased synthesis of prostaglandins resulting from ureteropelvic obstruction.


The mechanism of the tyrosine transporter TyrP supports a proton motive tyrosine decarboxylation pathway in Lactobacillus brevis.
The tyrosine decarboxylase operon of Lactobacillus brevis IOEB9809 contains, adjacent to the tyrosine decarboxylase gene, a gene for TyrP, a putative tyrosine transporter. The two genes potentially form a proton motive tyrosine decarboxylation pathway. The putative tyrosine transporter gene of L. brevis was expressed in Lactococcus lactis and functionally characterized using right-side-out membranes. The transporter very efficiently catalyzes homologous tyrosine-tyrosine exchange and heterologous exchange between tyrosine and its decarboxylation product tyramine. Tyrosine-tyramine exchange was shown to be electrogenic. In addition to the exchange mode, the transporter catalyzes tyrosine uniport but at a much lower rate. Analysis of the substrate specificity of the transporter by use of a set of 19 different tyrosine substrate analogues showed that the main interactions between the protein and the substrates involve the amino group and the phenyl ring with the para hydroxyl group. The carboxylate group that is removed in the decarboxylation reaction does not seem to contribute to the affinity of the protein for the substrates significantly. The properties of the TyrP protein are those typical for precursor-product exchangers that operate in proton motive decarboxylation pathways. It is proposed that tyrosine decarboxylation in L. brevis results in proton motive force generation by an indirect proton pumping mechanism.


Effect of supplemental iron on finishing swine performance, carcass characteristics, and pork quality during retail display.
Crossbred pigs (n = 185) were used to test the effects of dietary Fe supplementation on performance and carcass characteristics of growing-finishing swine. Pigs were blocked by BW, allotted to pens (5 to 6 pigs/pen), and pens (5 pens/block) were allotted randomly to either negative control (NC) corn-soybean meal grower and finisher diets devoid of Fe in the mineral premix, positive control (PC) corn-soybean meal grower and finisher diets with Fe included in the mineral premix, or the PC diets supplemented with 50, 100, or 150 ppm Fe from Availa-Fe (an Fe-AA complex). When the lightest block averaged 118.2 kg, the pigs were slaughtered, and bone-in pork loins were collected during fabrication for pork quality data. During the grower-I phase, there was a tendency for supplemental Fe to reduce ADG linearly (P = 0.10), whereas in the grower-II phase, supplemental Fe tended to increase ADG linearly (P = 0.10). Even though pigs fed NC had greater G:F during the finisher-I phase (P < 0.05) and across the entire trial (P = 0.07), live performance did not (P > or = 0.13) differ among dietary treatments. There were linear increases in 10th-rib fat depth (P = 0.08) and calculated fat-free lean yield (P = 0.06); otherwise, dietary Fe did not (P > 0.19) affect pork carcass muscling or fatness. Moreover, LM concentrations of total, heme, and nonheme Fe were similar (P > 0.23) among treatments. A randomly selected subset of loins from each treatment was further fabricated into 2.5-cm-thick LM chops, placed on styrofoam trays, overwrapped with polyvinyl chloride film, and placed in coffin-chest display cases (2.6 degrees C) under continuous fluorescent lighting (1,600 lx) for 7 d. During display, chops from NC-fed pigs and pigs fed the diets supplemented with 100 ppm Fe tended to have a more vivid (higher chroma value; P = 0.07), redder (higher a* value; P = 0.09) color than LM chops of pigs fed 50 ppm of supplemental Fe. Moreover, greater (P < 0.01) redness:yellowness ratios in chops from pigs supplemented with 100 ppm Fe indicated a more red color than chops from PC-fed pigs or pigs fed diets supplemented with 50 ppm Fe. In conclusion, however, increasing dietary Fe had no appreciable effects on performance, carcass, or LM characteristics, suggesting that current dietary Fe recommendations are sufficient for optimal growth performance, pork carcass composition, and pork quality.


Phase Behavior of Resveratrol Solid Dispersions Upon Addition to Aqueous media.
To investigate the phase behavior of resveratrol amorphous solid dispersions upon addition to aqueous media. Polymers with different crystallization inhibitor properties were used to form amorphous solid dispersions of resveratrol. Resveratrol crystallization in aqueous environments was monitored over time using Raman spectroscopy, and solution concentrations were determined by ultraviolet (UV) spectroscopy. The crystallization behavior varied depending on the type and amount of polymer present in the dispersion. Polyvinylpyrrolidone (PVP) and Eudragit E100 (E100) dispersions did not crystallize for 24 h when slurried in pH 6.8 buffer at 37°C. Even though no crystallization occurred, a supersaturated solution was not achieved, most likely because of resveratrol-polymer complexation. Dispersions formed with cellulose derivatives crystallized rapidly, and the extent of crystallization varied depending on the amount of polymer in the dispersion. The solution concentration achieved in the slurries varied considerably between the various solid dispersions and depended on several factors including the extent of resveratrol crystallization, the nature of the resveratrol-polymer interactions, and the concentration of solid dispersion added to the slurry. It was found that the extent of supersaturation was limited not only by crystallization, but also by soluble and insoluble complex formation between resveratrol and the polymer.


Super-learning of causal judgements.
In three experiments, participants learned which of a variety of foods were capable of causing an allergic reaction in a hypothetical patient during training in which a compound of a treatment and a target food cue was paired with the reaction. In Experiment 1 the causal ratings of the target cue were increased if the treatment cue was pretrained as a preventative cause of the reaction. Experiments 2 and 3 demonstrated that the magnitude of this super-learning is unaffected by the order of compound and treatment cue training. The final study also showed that forward super-learning is not induced solely by simple exposure to the treatment cue prior to compound training but, rather, depends upon training the treatment cue as a preventative cause, whereas retrospective super-learning may be due merely to exposure of the treatment cue. These results are problematic for contingency-based accounts of causal induction but accord with modified and extended associative theories.


Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies?
Studies in gnotobiotic animals have suggested that the intestinal bacterial flora may play an important role in priming the immune system during ontogeny to limit dysfunctional responses, including allergy. Prospective clinical studies have identified a higher incidence of allergy expression in early childhood among children who have low enteric populations of lactic acid bacteria (LAB), such as lactobacilli and bifidobacteria, further supporting a role for gut-colonizing bacteria in regulating immunological atopy. There is some evidence to suggest that supplementing the human diet with probiotic LAB might combat both allergy development and expression of atopy in allergy sufferers; however, definitive information, in the form of controlled intervention trials, remains scant. Recent immunological evidence has indicated that certain strains of LAB can stimulate the production of type I and II interferons and pro-interferon monokines (IL-12 and IL-18), following contact with the immune system; therefore, probiotic forms of immunoregulatory LAB could be used as dietary supplements to modify the gut microflora and provide pro-T helper cell 1 (Th1) STAT-activating signals sufficient to deviate the immune phenotype and correct the Th2-type bias which promotes allergy. This review outlines the clinical and laboratory evidence of a role for LAB in combating allergies, and attempts to explain this phenomenon in terms of our current understanding of immunoregulatory signals produced by gut-colonizing microbes.


[Cardiac consequences of adolescent anorexia nervosa].
Cardiac complications are common in adolescent anorexia nervosa and are the cause of a third of deaths. Some workers have reported prolongation of the QT interval and cases of sudden death in these patients. The aim of this study was two-fold: to assess the cardiac complications of anorexic adolescents and to determine the outcome after renutrition in the hospital setting. This was a prospective study of 48 consecutive cases (45 girls) with an average age of 14 +/- 2 years, admitted to the paedopsychiatric unit and fulfilling the DSM-IV criteria of anorexia nervosa. The digitised ECG, Holter ECG and echocardiography were recorded before and after renutrition. Anorexia nervosa was severe with a body mass index < 14 in 2/3 of cases. Over 2/3 of patients had bradycardia with a heart rate < 50/min in half the cases but normal chronotropic function on Holter monitoring. Prolongation of the QTc interval was demonstrated (QTc > 440 ms in 11/44 cases). Echocardiographic abnormalities, in particular left ventricular dysfunction (24/46) and pericardial effusion (12/46) were reversible after renutrition. There were no clinical or biological predictive factors for the occurrence of cardiac complications on admission. The authors confirm that cardiac complications of anorexia nervosa are common, usually benign and always reversible after renutrition in hospital. Therefore, most electrical abnormalities normalise with the heart rate and echocardiographic abnormalities with improvement of conditions of load.


Molecular investigation of 19p13 in standard and variant translocations: the E12 probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia other than pre-B immunophenotype.
The gene E2A has recently been cloned, mapped to 19p13 and shown to be rearranged in cases of pre-B acute lymphoblastic leukemia (ALL) with t(1;19) (q23;p13). Nine cases with a 19p13 breakpoint, four having a phenotype other than pre-B, have been investigated with the E12 probe to the E2A gene. Five cases had t(1;19) (q23;p13) and C-ALL with pre-B phenotype in four out of four cases tested. Two cases had t(1;19) (q21;p13), one with Null cell phenotype, t(4;11), and 'jumping translocations' and the other with acute non-lymphocytic leukemia M5 following bone marrow transplantation for C-ALL. Variant translocations in patients with ALL were t(15;19) (q15;p13) and t(17;19) (q21;p13). Southern blotting with E12 showed rearrangement in the cases with t(1;19) (q23;p13) and t(1;19) (q21;p13), but not in other cases with variant 19p13 breakpoints. Thus rearrangement of the E2A gene is not restricted to cases with pre-B ALL but may also occur in acute leukemias with other immunological phenotypes. Failure to detect rearrangement in 19p13 variants may be due to an E2A breakpoint outside the E12 recognition region. Alternatively, there may be further genes in this location with relevance to leukemogenesis.


The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.
Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.


Draft genome sequence of butanol-acetone-producing Clostridium beijerinckii strain G117.
A recently discovered wild-type strain, Clostridium beijerinckii G117, is unique in producing butanol and acetone but negligible amounts of ethanol, unlike previously identified acetone-butanol-ethanol (ABE)-generating microbes. Here we report the draft genome sequence of strain G117 (5,806,675 bp; GC content, 29.7%) and the novel findings obtained from its genome annotations.


Angiotensin blockade prevents type 2 diabetes by formation of fat cells.
Obesity is the prime risk factor for the development of type 2 diabetes. Recent clinical trials have shown that blockade of the renin-angiotensin system, either by inhibiting the angiotensin-converting enzyme or blocking the angiotensin type 1 receptor, may substantially lower the risk for type 2 diabetes. The mechanism underlying this effect is unknown. Based on our recent observation that angiotensin II markedly inhibits adipogenic differentiation of human adipocytes via the angiotensin type I receptor and that expression of angiotensin II-forming enzymes in adipose tissue is inversely correlated with insulin sensitivity, we propose the hypothesis that blockade of the renin-angiotensin system prevents diabetes by promoting the recruitment and differentiation of adipocytes. Increased formation of adipocytes would counteract the ectopic deposition of lipids in other tissues (muscle, liver, pancreas), thereby improving insulin sensitivity and preventing the development of type 2 diabetes.


Chemical weathering in central iceland: an analog of pre-silurian weathering.
The rate of chemical weathering in central Iceland is two to three times more rapid in areas with plant cover than in barren areas. This relatively small difference in chemical weathering rates suggests that atmospheric CO(2), pressures no greater than five times the present value were needed to sustain present-day rates of chemical weathering before the development of higher land plants in the Silurian.


Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia.
Congenital long-QT syndrome (LQTS) may present during fetal development and can be life-threatening. The molecular mechanism for the unusual early onset of LQTS during fetal development is unknown. We sought to elucidate the molecular basis for severe fetal LQTS presenting at 19 weeks' gestation, the earliest known presentation of this disease. Fetal magnetocardiography was used to demonstrated torsades de pointes and a prolonged rate-corrected QT interval. In vitro electrophysiological studies were performed to determine functional consequences of a novel SCN5A mutation found in the fetus. The fetus presented with episodes of ventricular ectopy progressing to incessant ventricular tachycardia and hydrops fetalis. Genetic analysis disclosed a novel, de novo heterozygous mutation (L409P) and a homozygous common variant (R558 in SCN5A). In vitro electrophysiological studies demonstrated that the mutation in combination with R558 caused significant depolarized shifts in the voltage dependence of inactivation and activation, faster recovery from inactivation, and a 7-fold higher level of persistent current. When the mutation was engineered in a fetal-expressed SCN5A splice isoform, channel dysfunction was markedly potentiated. Also, R558 alone in the fetal splice isoform evoked a large persistent current, and hence both alleles were dysfunctional. We report the earliest confirmed diagnosis of symptomatic LQTS and present evidence that mutant cardiac sodium channel dysfunction is potentiated by a developmentally regulated alternative splicing event in SCN5A. Our findings provide a plausible mechanism for the unusual severity and early onset of cardiac arrhythmia in fetal LQTS.


Acute pancreatitis associated with danazol treatment for endometriosis.
Hypo-oestrogenic and anabolic/androgenic side-effects of danazol are well known by the gynaecologist and some of them are present in > 50% of patients being treated for endometriosis. Additionally, danazol produces hepatocellular damage in approximately 10% of women. The present report describes the first case of acute pancreatitis associated with danazol treatment of endometriosis.


Inhibition of delayed hypersensitivity reactions by colchicine. II. Colchicine inhibits interferon-gamma induced expression of HLA-DR on gut epithelial cell line.
The effects of colchicine and vinblastine on interferon-gamma (IFN-gamma) induced expression of HLA-DR antigens on the HT-29 colonic carcinoma cell line was investigated in vitro. Both drugs prevented the expression of HLA-DR only if applied before or together with IFN-gamma. Methotrexate, an antimitotic drug, failed to inhibit DR expression by these cells. Colchicine and vinblastine, but not methotrexate, act on the cellular microtubules, interfering with the transport of proteins from the protoplasm to the cell surface and thus preventing the appearance of HLA-DR antigens. The reported findings may explain the role of colchicine in preventing delayed hypersensitivity reactions.


A stable prostacyclin analogue (iloprost) in the treatment of Buerger's disease: a prospective analysis of 150 patients.
To assess the efficacy and of iloprost in the treatment of Buerger's disease. In this prospective study, 158 patients with rest pain and/or ischemic ulcers from 17 clinics were administered 1 ng/kg/min intravenous iloprost for 28-days. The primary endpoint was complete healing without pain or major amputation at 24 weeks. The secondary endpoints were pain assessment, reduction in ulcer area, 50% reduction of the ulcer size, shift in the modified SVS/ISCVS clinical status grading scale, global assessment by the investigator and an independent observer at 4 and 24 weeks. The comparisons were carried out with the initial values. The final evaluation was carried out in 150 patients. Complete healing rate was significantly better with iloprost treatment in comparison to the initial values at 24 weeks (<0.001). The secondary endpoints; complete healing rate, pain, the size of the ulcer, 50% reduction of the ulcer size, SVS/ISCVS grading scale, assessment by investigator, assessment by observer parameters were significantly better at 4 and 24 weeks (<0.001). The reduction of the ulcer size was significantly better when comparing 4th and 24th week values (<0.05). The results of this independent study indicate that intravenous iloprost relieves ischemic symptoms efficiently in the acute phase Buerger's disease patients. Considering unsatisfactory results following surgical revascularisation and sympathectomy in Buerger's disease, prostacyclin analogues might be the first line treatment as long as complete abstinence from smoking is achieved.


DNA damage and growth inhibition in cultured human cells by bleomycin congeners.
Bleomycin is hypothesized to cause cell growth inhibition and cell death via DNA cleavage. We have attempted to determine if net DNA cleavage is directly related to growth inhibition by measuring whether both parameters vary in parallel. Of primary importance to these studies was use of several bleomycin congeners. We have shown that these congeners vary in their abilities both to inhibit cell growth and to cause DNA damage. Bleomycin B2, tallysomycin, and phleomycin were the most potent growth inhibitors, and bleomycin B2 caused the most DNA damage. N-Acetylbleomycin A2 was inactive in both assays. The net amount of DNA damage measured at two levels of growth inhibition was compared for each congener and was found to vary widely among the congeners. Similarly, the degree of growth inhibition at a given level of submaximal DNA damage was found to vary widely when individual congeners were compared to each other. Hence, growth inhibition and net DNA damage due to bleomycin are not directly correlated with each other when individual congeners are compared to each other.