The Current Progress of Tetrahedral DNA Nanostructure for Antibacterial Application and Bone Tissue Regeneration.
Recently, programmable assembly technologies have enabled the application of DNA in the creation of new nanomaterials with unprecedented functionality. One of the most common DNA nanostructures is the tetrahedral DNA nanostructure (TDN), which has attracted great interest worldwide due to its high stability, simple assembly procedure, high predictability, perfect programmability, and excellent biocompatibility. The unique spatial structure of TDN allows it to penetrate cell membranes in abundance and regulate cellular biological properties as a natural genetic material. Previous studies have demonstrated that TDNs can regulate various cellular biological properties, including promoting cells proliferation, migration and differentiation, inhibiting cells apoptosis, as well as possessing anti-inflammation and immunomodulatory capabilities. Furthermore, functional molecules can be easily modified at the vertices of DNA tetrahedron, DNA double helix structure, DNA tetrahedral arms or DNA tetrahedral cage structure, enabling TDN to be used as a nanocarrier for a variety of biological applications, including targeted therapies, molecular diagnosis, biosensing, antibacterial treatment, antitumor strategies, and tissue regeneration. In this review, we mainly focus on the current progress of TDN-based nanomaterials for antimicrobial applications, bone and cartilage tissue repair and regeneration. The synthesis and characterization of TDN, as well as the biological merits are introduced. In addition, the challenges and prospects of TDN-based nanomaterials are also discussed.


[Hepatitis D].
The hepatitis D virus (HDV), also called delta virus, is a small circular RNA virus. The HDV is dependent on the hepatitis B virus (HBV) and can cause infection in normal individuals with hepatitis B or yet, superinfect chronic HBV carriers. Three genotypes have already been cloned and sequenced. Infection with HDV has a worldwide distribution and a high HDV endemicity has been documented in the western Amazon region, in Brazil. It has been estimated that 18 million people are infected with this virus amongst the 350 million carriers of the HBV around the world. The HDV transmission and risk factors for infection are similar to those for HBV infection. The diagnosis is based on the immunohistological identification of HDAg in the liver and detection of IgM and IgG anti-HD in serum using RIA or EIA. The clinical course of hepatitis D is variable. Fulminant disease occurs more commonly in hepatitis B and D than in other forms of acute viral hepatitis. Chronic HDV infection is usually associated with severe histological changes in the liver and with a rapidly progressive course, that can lead to cirrhosis, liver failure and death. Treatment of chronic hepatitis D is currently unsatisfactory and interferon alpha is the only agent found to have some effect on the course of chronic hepatitis. Orthotopic liver transplantation is indicated for terminal cases of cirrhosis. Prophylaxis for HDV infection is possible by vaccination against the hepatitis B virus.


Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin.
1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.


New asthma biomarkers: lessons from murine models of acute and chronic asthma.
Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma.


Annoyance, type and duration of postannoyance activity, and aggression: the "cathartic effect".
A series of experiments was conducted to elucidate the conditions conductive to a decrease in aggression following annoyance. The potential capacity of expression of aggression to bring about a reduction in the amount of subsequent aggression was of particular interest. This empirical concern was supplemented by tests of several influential and competing theoretical concepts dealing with the cathartic aspects of human aggressive behavior. Given the failure of such concepts to account for major portions of the data, an integrative theoretical model was proposed. experiment 1 evaluated the usefulness of the hydraulic, self-arousal, and dissipation of anger concepts in accounting for the earlier demonstrations of the cathartic effect. In a 2 x 3 x 2 design, half of the subjects were annoyed by a confederate, while the other half were treated neutrally. During the next stage (the interpolated period), a third of all subjects gave "shocks" to the confederate, another third simply waited, while the remaining third worked on mathematical problems. Orthogonal to the first two facotrs was the duration of the interpolated period (7 to 13 min). The main dependent measure was the number of shocks administered to the confederate in the final stage of the experiment. It was found that annoyed subjects gave more shocks than nonannoyed ones did, and that only the former were substantially affected by other manipulations. In the case of the annoyed wait and annoyed math subjects, the anger dissipation hypothesis correctly predicted that the mere passage of time would decrease the amount of subsequent aggression, presumably due to the action of homeostatic processes. The self-arousal hypothesis correctly predicted that the annoyed math subjects would give fewer shocks than the annoyed wait ones would. Since the subjects were engaged in an absorbing activity, the likelihood of their arousing themselves by ruminations about the preceding annoying incident was minimized, and the amount of subsequent aggression reduced. Yet, when annoyed subjects had given the confederate a moderate number of shocks in the interpolated period, they subsequently gave him fewer shocks than the 7-min annoyed wait and annoyed math subjects; this was the only outcome predicted correctly by the hydraulic model. In contrast, when a large number of shocks had been administered in the interpolated period, the amount of subsequent aggression was relatively high. The interpretation of the latter result in terms of an "adaption effect" was tested by further experiments.


Heat sterilization of water in a large open vessel.
A safe, convenient, and economical method of preparing and dispensing a large volume of sterile water in a movable container is described. A caster-mounted, rectangular, 100-gal, stainless-steel water tank was fabricated. An audible, solid-state water-level alarm was developed for use with a detachable sensing probe that could be autoclaved. A filter system was constructed to allow the tank to be autoclaved as an open vessel. Thermocouples were mounted within the tank of water to study the time-temperature relationships of the water during the sterilization cycle. In a downward displacement autoclave with a hot jacket, 75 min were required for the water temperature to rise from 140 to 240 F (60 to 116 C). A total of 3 hr for heating and holding includes an adequate safety factor to insure the sterility of the water immediately after autoclaving. The long-term sterility of the water and the safety of the system were verified by using the water to maintain a germ-free animal colony.


Localization of idiotypic antigenic determinants in the Fv region of murine myeloma protein MOPC-315.
Rabbit antisera were prepared against the idiotypic determinants of the mouse IgA myeloma protein-315, its purified heavy and light chains, and the Fv fragment comprising the variable region of both heavy and light chains. Agar diffusion demonstrated a line of identity between protein-315 and its Fv fragment against either homologous antiserum. Protein-315 and Fv fragment were labeled with (125)I and reacted with their anti-idiotypic antisera. Inhibition studies confirmed that the Fv fragment contained all the idiotypic specificities present in the intact protein. Fv was as effective as protein-315 on a weight basis in inhibiting the reaction between anti-idiotypic antiserum and protein-315. Protein-315 has high affinity for the 2,4-dinitrophenyl group, and such ligands can inhibit the reaction between protein-315 and its anti-idiotypic antibodies. Hapten inhibition was also obtained with the Fv fragment and its anti-idiotypic antiserum, implying that Fv contains an intact combining site. In this system with protein-315 the antigenic determinants expressed as idiotypic specificities are entirely within the variable region and are not influenced in their expression by the constant region. We therefore suggest that, in general, idiotypic determinants are antigenic determinants of the Fv protions of immunoglobulins.


Ocular complications in children within 1 year after hematopoietic stem cell transplantation.
It is essential to have insights into the risk of ocular involvement after hematopoietic stem cell transplantation (HSCT) in the pediatric population because young and severely ill children are unaware of their ocular problems. To study the development of ocular complications in children within 1 year after HSCT. This prospective study includes all consecutive patients who had undergone an HSCT at the Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands, in 2009 and 2010. Forty-nine consecutive patients underwent systematic ophthalmologic evaluations before HSCT, before leaving the HSCT unit after HSCT, and 3, 6, and 12 months after HSCT. Additional examinations were performed during systemic viral reactivations. Development of ocular complications, including uveitis, hemorrhagic complications, optic disc edema, and dry eye syndrome. Thirteen patients (27%) developed an ocular complication after HSCT. These complications included DES (n = 7 [14%]), (sub)retinal hemorrhage (n = 6 [12%]), optic disc edema (n = 3 [6%]), chorioretinal lesions (n = 2 [4%]), vitritis (n = 1 [2%]), and increased intraocular pressure (n = 1 [2%]). Median time to the development of dry eye syndrome was 5 months after HSCT, whereas all other ocular complications were detected within the first 3 months after HSCT. In most cases, the symptoms were mild and self-limiting. Children with malignant disease had a higher risk of the development of ocular complications compared with children with nonmalignant disease. Ocular complications in pediatric HSCT patients are common, although mostly mild. The risk of viral uveitis development during systemic viral reactivations is low; however, the potential risk of vision-threatening complications in this population cannot be ruled out.


[Inappropriateness of hospital use in two acute geriatrics department: description of the phenomenon and analysis of risk factors].
Inappropriateness of hospital use occurs when a gap between the patient's needs and the level of care delivered exists. Taking into account the improvement of number of acute geriatric care, it appears relevant to study the rate and causes of inappropriate hospital use in this context. All patients in two services of acute geriatrics were included: medical and socioeconomic data were collected, the appropriateness of each day of their hospitalization was evaluated using the French version of the Appropriateness Evaluation Protocol and the inappropriate days' Causes Analysis Protocol. Risk factors of having at least one inappropriate day occurring during the stay were searched using relevant statistical tests. A logistic regression model assessed influence of independent variables on the risk of inappropriateness. Only the existence of cognitive impairment and the department where the hospitalization takes place were found to be risk factors of inappropriateness. The ranking of inappropriateness according to the causes is the same in the two services, yet with statistically different rates, in particular for causes related to waiting for admission in subacute or long-term care institutional network and for a service provided outside the hospital where the patient was admitted. In the two departments, over 25% of the inappropriate days were related to a patient's or his family's choice. Access to subacute or long-term care institution is the first cause of inappropriate hospital use in the two departments. The importance of the rate of inappropriate days related to a choice of the patient or his family was probably a Geriatric specificity. Furthermore, in view of reducing the inappropriate hospital use, attention should be particularly paid on patients with cognitive impairment.


Upper digestive tract abnormalities in dogs with chronic idiopathic lymphoplasmacytic rhinitis.
Chronic idiopathic lymphoplasmacytic rhinitis (CILPR) is a common inflammatory disorder of unknown etiology affecting the nasal cavity of dogs. The diagnosis is made by exclusion of other causes of nasal disease and specific therapeutic protocols are lacking. In human medicine, a relationship between CILPR and gastrointestinal clinical signs has been postulated, and remission of respiratory signs after clinical trials with medications for gastrointestinal disorders has been observed. To describe history, clinical presentation, endoscopic and histopathologic concurrent respiratory and digestive tract abnormalities, and to evaluate improvement of respiratory signs after treatment for gastrointestinal signs. Twenty-five dogs with CILPR. Prospective study. For inclusion, following information had to be available: respiratory and digestive clinical signs, airway and digestive tract endoscopic abnormalities, histologic evaluation of respiratory and gastrointestinal tract biopsy specimens, and clinical response to different treatment strategies. Twenty-two dogs had endoscopic gastrointestinal lesions, whereas 13 dogs had concurrent gastrointestinal signs. Most esophageal and duodenal endoscopic abnormalities were classified as moderate or severe. Respiratory and gastrointestinal tract histologic evaluation identified mostly chronic inflammation. Remission or marked improvement of respiratory signs was observed in the majority of dogs treated only for gastrointestinal signs up to 12 months after endoscopy. No significant associations between treatments and follow-up information were found. Nasal and upper digestive tract abnormalities coexist in some dogs with CILPR. Lack of standardized therapeutic protocols suggests caution when interpreting improvement in nasal clinical signs. Additional studies are needed to explore the possibility of a cause-effect relationship between the 2 processes.


Semitransparent organic photovoltaic cells with laminated top electrode.
We demonstrate semitransparent small molecular weight organic photovoltaic cells using a laminated silver nanowire mesh as a transparent, conductive cathode layer. The lamination process does not damage the underlying solar cell and results in a transparent electrode with low sheet resistance and high optical transmittance without impacting photocurrent collection. The resulting semitransparent phthalocyanine/fullerene organic solar cell has a power conversion efficiency that is 57% of that of a device with a conventional metal cathode due to differences in optical absorption.


Plasticity of opsin gene expression in cichlids from Lake Malawi.
Sensory systems play crucial roles in survival and reproduction. Therefore, sensory plasticity has important evolutionary implications. In this study, we examined retinal plasticity in five species of cichlid fish from Lake Malawi. We compared the cone opsin expression profiles of wild-caught fish to lab-reared F(1) that had been raised in a UV minus, reduced intensity light environment. All of the opsin genes that were expressed in wild-caught fish were also expressed in lab-reared individuals. However, we found statistically significant differences in relative opsin expression among all five species. The most consistent difference was in the SWS2B (violet) opsin, which was always expressed at higher levels in lab-reared individuals. Estimates of visual pigment quantum catch suggest that this change in expression would increase retinal sensitivity in the light environment of the lab. We also found that the magnitude of plasticity varied across species. These findings have important implications for understanding the genetic regulation of opsin expression and raise many interesting questions about how the cichlid visual system develops. They also suggest that sensory plasticity may have facilitated the ecological diversification of cichlids in Lake Malawi.


21-gene recurrence score testing in the older population with estrogen receptor-positive breast cancer.
The 21-gene recurrence score (RS) (Oncotype Dx, Genomic Health, Redwood City Ca) has not been validated in an older cohort with estrogen receptor (ER)-positive breast cancer. The objective of this study was to evaluate RS validity in a group of older women with ER-positive breast cancer. Utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database with available RS, we evaluated women with ER-positive breast cancer aged 18-69 and those 70 years of age and older from 2004 to 2014. We utilized multivariable logistic regression models to evaluate factors associated with RS testing as well as a high-risk categorization for those who underwent testing. Survival was analyzed using Kaplan Meier curves and Cox proportional hazard models. We identified 363,876 women aged 18-69 years and 147,107 women aged 70 years and older. A smaller proportion of patients in the older group (8%) underwent RS testing than in the younger group (18%). Of the patients who underwent testing, distribution of RS was similar between groups. High-risk categorization independently predicted a higher likelihood of death for older patients (hazard ratio 1.47, 95% confidence interval 1.15-1.90). Among patients with high-risk RS, chemotherapy was associated with a decreased risk of death in the younger group, but not in the older group. Older women are less likely to receive RS testing, but when tested, older patients have a similar distribution of RS as compared to younger patients. While high-risk categorization in the older cohort was prognostic, chemotherapy was not associated with improved survival.


[Study of the stability and the degradation of fluorescence in the immunofluorescence technic (FTA-ABS) using pulsed lasers].
The use of two pulsed lasers as excitation sources in the immunofluorescent technique FTA-ABS (fluorescent treponemal antibody absorption) shows that excitation of specimens by continuous or long-duration pulses of light (in the order of a millisecond) degrades the fluorescence in such a way that it is impossible to quantify exactly the fluorescent signal or repeat the analysis. Stability of fluorescence can be achieved by very short excitation pulses (in the order of a microsecond) and this fast fluorescent signal can be detected only by an electronic detection and recording system. With such a system, high precision is obtained by elimination of errors by the human eye.


Methods for sampling wound fluid from venous leg ulcers for molecular analyses: A scoping review.
Determining the precise role of molecular factors present in venous leg ulcer exudate will expedite the identification of biomarkers that can optimally guide treatment. However, there is now no standardized approach for collecting, processing and storing wound fluid samples for molecular analyses. This scoping review was conducted to integrate and summarize the multiple types of methods being used currently in studies of venous leg ulcers for collecting, processing and storing wound fluid prior to analysis. PubMed, CINAHL, EMBASE and Scopus databases were searched for eligible studies between 2012 and 2022. Nineteen studies were selected for this scoping review. Five primary methodological categories for wound fluid sampling were identified. The most commonly used collection method involved extracting the fluid from various absorbent materials, and the majority of studies centrifuged wound fluid before storing it at ultra-low temperatures. This review found the wound fluid sampling methods among the included studies to be heterogeneous. Moreover, the data revealed no definitive patterns. There is a critical need to develop standardized wound fluid sampling methods in research to facilitate accurate comparisons of biomarker data across studies and a more rapid determination of biomarkers that can most effectively guide delivery of tailored venous leg ulcer treatments.


Mitochondrial factor and cell cytokines associate with TCM syndrome scale in vascular dementia patients.
Mitochondrial factor and cell cytokines play important roles in the incidence of vascular dementia (VD), but their correlations with inflammatory and mitochondrial factors and the role of both in the kidney essence deficiency pattern and phlegm turbidity blocking orifice pattern are not clear. This study was aimed at studying the correlations between the serum mitochondrial factor and cell cytokines with TCM Syndrome Scale in vascular dementia. According to the inclusion criteria we collected 108 vascular dementia patients which were divided into the kidney essence deficiency pattern and phlegm turbidity blocking orifice pattern based on the TCM Syndrome Scale. We measured serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) concentration using an enzyme-linked immunosorbent assay (ELISA) and serum malondialdelyde (MDA) and superoxide dismutase (SOD) was quantified according to instructions of kits from the 108 patients (45 in kidney essence deficiency pattern, 63 in phlegm turbidity blocking orifice pattern). The scale scores were assessed using TCM Syndrome Scale, MMSE, Hachinski, Barthel, BBS, CDR. There was a significant difference on the scores of CDR and the factors of the memory, judgment, social affairs, personal care, family and hobbies among the two groups, The means of kidney essence deficiency group was higher than that of phlegm turbidity blocking orifice pattern group. IL-18 and SOD in the phlegm turbidity blocking orifice group was higher than those in the kidney essence deficiency pattern; IL-6 in phlegm turbidity blocking orifice pattern group was lower than that in the kidney essence deficiency pattern. By logistic regression analysis, we demonstrated that high concentration of IL-6, TNF-α, and MDA were associated with increased TCM syndrome scores in two groups, while IL-6, IL-18, TNF-α, SOD were associated with decreased MMSE, Barthel. Our study support the notion that IL-6 plays a more important role in the integral of kidney essence deficiency pattern, IL-18 is a more important factor in phlegm turbidity blocking orifice pattern. The results can be used as the theoretical basis of traditional Chinese Medicine prescription and pharmacological research in future, through decrease in IL-6 lever and increase in SOD in integral kidney essence deficiency pattern, and IL-18 as the main anti inflammation index in phlegm turbidity blocking orifice pattern.


[Cytokines, immunoglobulins, and IgG subclasses in patients with IgG plasmacytomas].
Cytokines play an essential role in normal and malignant B-cell proliferation and isotype-switching. Therefore we determined serum levels of different B-cell activating cytokines including IFN gamma, IL-4 and IL-10, IgG subclasses, further immunoglobulins and the soluble B-cell activation marker sCD23 in 68 patients with recently diagnosed and previously untreated IgG myelomas in comparison with age- and sex-matched healthy controls. Our results demonstrated that 16% of the myeloma patients had elevated IL-10 levels up to 1000 pg/ml and 8% showed increased IFN gamma serum concentrations. By contrast, only 7% of the controls showed detectable IL-10 levels and 3% had measurable IFN gamma levels. While in men 67% of the paraproteins were of the kappa light chain type, we found an equal occurrence of kappa and lambda light chains in women. In addition, the distribution of IgG subclasses differed in men and women. In comparison with the controls, no alteration of sCD23 was detected in myeloma patients. We found an apparent correlation of elevated IL-10 levels and the IgG1 subclass.


Temperature and oxidation-sensitive dioleoylphosphatidylethanolamine liposome stabilized with poly(ethyleneimine)/(phenylthio)acetic acid ion pair.
Temperature and oxidation-sensitive liposomes were prepared by stabilizing dioleoylphosphatidylethanolamine (DOPE) bilayers with the ion pair of poly(ethyleneimine)/(phenylthio)acetic acid (PEI/PTA). An upper critical solution temperature (UCST) behavior was observed when PEI/PTA ion pair was suspended in an aqueous solution. It was observed that the UCST increased with increasing PTA content. The ion pair was self-assembled into nanospheres owing to its amphiphilic property which was confirmed by transmission electron microscopy. The FT-IR spectroscopic spectrum showed that the ion pair formed a salt bridge between the amino group and the carboxyl group and the PTA content in the ion pair was readily oxidized by H2O2. Further, DOPE liposomal membranes could be stabilized with PEI/PTA ion pair. Due to the amphiphilic property, the ion pair played a role as a stabilizer for the formation of DOPE liposomes. The liposome released its payload in a temperature-responsive manner, possibly because when the temperature is raised, the ion pair loses its amphiphilic property and can be detached from the liposomal membrane. The liposome was also oxidation-responsive in terms of release, possibly because the amphiphilic property of the ion pair disappears when the PTA is oxidized.


Study on utilization status of internet and needs assessment for developing nutrition education programs among elementary school children.
This study was to investigate utilization status of internet, health/nutrition websites among children, and to assess the needs for developing nutrition websites and education programs for children. The survey questionnaire was administered to 5-6th grade students (n=434) at two elementary schools. About 32% used the internet every day while 19.5% used it whenever they needed, showing significant differences in internet usage by gender (p<0.01). Although the subjects used the internet frequently, those who used health/nutrition websites were 23.3%. The purpose of using these sites were mainly 'to obtain health/nutrition information' (55%), 'to get information regarding weight control' (17%). Fifty-six percent of the users were satisfied with the nutrition websites, but only 30% said that they were helpful. The preferred topics in developing nutrition websites were assessment of obesity, exercise methods, weight control methods, nutrition information (e.g., diet for stature growth), dietary assessment and food hygiene. Girls showed more interest in these topics than boys (p<0.05). For school nutrition education, girls showed more interest than boys in topics for cooking snacks (p<0.001) and selecting snacks (p<0.05). In nutrition websites, subjects wanted to have information and game/quiz, as well as getting information using Flash animation. The favorite colors for screen and text were slightly different by gender (p<0.01). In school nutrition education, 89.5% of subjects liked to have activities (e.g., cooking, exercise, game). They also liked materials using computers, video and internet than printed materials. If nutrition education was done at schools, subjects wanted to receive 5.7 times of education per semester on average (mean length: 42.6 min./session). This study suggests that nutrition websites and education programs for children should include the topics such as assessment of obesity or diet, weight control and special information (e.g., diet for growth) as well as general information. In designing nutrition websites and programs, methods including game, quiz, Flash animation and activities (cooking, exercise) could be appropriately used to induce the interest and involvement of children.


Site-Selective Cross-Coupling of Polyhalogenated Arenes and Heteroarenes with Identical Halogen Groups.
Methods to functionalize arenes and heteroarenes in a site-selective manner are highly sought after for rapidly constructing value-added molecules of medicinal, agrochemical, and materials interest. One effective approach is the site-selective cross-coupling of polyhalogenated arenes bearing multiple, but identical, halogen groups. Such cross-coupling reactions have proven to be incredibly effective for site-selective functionalization. However, they also present formidable challenges due to the inherent similarities in the reactivities of the halogen substituents. In this Review, we discuss strategies for site-selective cross-couplings of polyhalogenated arenes and heteroarenes bearing identical halogens, beginning first with an overview of the reaction types that are more traditional in nature, such as electronically, sterically, and directing-group-controlled processes. Following these examples is a description of emerging strategies, which includes ligand- and additive/solvent-controlled reactions as well as photochemically initiated processes.


Scalable Manufactured Self-Healing Strain Sensors Based on Ion-Intercalated Graphene Nanosheets and Interfacial Coordination.
Desirable mechanical strength and self-healing performance are very important to highly sensitive and stretchable sensors to meet their practical applications. However, balancing these two key performance parameters is still a great challenge. Herein, we present a simple, large-scale, and cost-efficient route to fabricate autonomously self-healing strain sensors with satisfactory mechanical properties. Specifically, ion-intercalated mechanical milling was utilized to realize the large-scale preparation of graphene nanosheets (GNs). Then, a well-organized GN-nanostructured network was constructed in a rubber matrix based on interfacial metal-ligand coordination. The resultant nanocomposites show desirable mechanical properties (∼5 times higher than that of control sample without interfacial coordination), excellent self-healing performance (even healable in various harsh conditions, for example, underwater, at subzero temperature or exposed in acidic and alkaline conditions), and ultrahigh sensitivity (gauge factor ≈ 45 573.1). The elaborately designed strain sensors offer a feasible approach for the scalable production of self-healing strain-sensing devices, making it promising for further applications, including artificial skin, smart robotics, and other electrical devices.


Data driven adaptive Gaussian mixture model for solving Fokker-Planck equation.
The Fokker-Planck (FP) equation provides a powerful tool for describing the state transition probability density function of complex dynamical systems governed by stochastic differential equations (SDEs). Unfortunately, the analytical solution of the FP equation can be found in very few special cases. Therefore, it has become an interest to find a numerical approximation method of the FP equation suitable for a wider range of nonlinear systems. In this paper, a machine learning method based on an adaptive Gaussian mixture model (AGMM) is proposed to deal with the general FP equations. Compared with previous numerical discretization methods, the proposed method seamlessly integrates data and mathematical models. The prior knowledge generated by the assumed mathematical model can improve the performance of the learning algorithm. Also, it yields more interpretability for machine learning methods. Numerical examples for one-dimensional and two-dimensional SDEs with one and/or two noises are given. The simulation results show the effectiveness and robustness of the AGMM technique for solving the FP equation. In addition, the computational complexity and the optimization algorithm of the model are also discussed.


Periodontal conditions of teeth autogenously transplanted by a two-stage technique.
Inflammatory reactions of the marginal periodontal tissues and loss of attachment could partly account for the often occurring rejection of autogenously transplanted mature teeth. The periodontal conditions of transplanted teeth were investigated from 1 month up to 5 years postoperatively. The parameters plaque, bleeding on probing to the bottom of the pocket, probing pocket depth (PPD), gingival recession and probing attachment loss were analysed by multiple regression analysis. No significant difference was found between transplanted and control teeth in bleeding on probing the bottom of the pockets up to 5 years postoperatively with the exception of increased bleeding on probing of the transplanted teeth at the 1-month postsurgery examination. No significant difference of the mean probing depth between transplanted teeth and control teeth was found at the mesio- and distobuccal surfaces. The transplanted teeth at the buccal surface showed increase of the mean pocket depth during the observation period. Increased mean probing depth without progression over time was found at the transplanted teeth compared to the controls at the distolingual, lingual and mesiolingual surfaces. A small mean gingival recession at the transplants was observed. Loss of attachment was recorded at 13% of the surfaces. Totally 50% of the transplants showed loss of attachment and 5% were removed because of extensive attachment loss. On 13% of the transplanted teeth with loss of attachment, root resorption was also found.


Use of the Øie-Tozer model in understanding mechanisms and determinants of drug distribution.
Volume of distribution (VD) is a key pharmacokinetic property that together with clearance determines the half-life or residence time of drug in the body. It is commonly expressed as steady-state volume of distribution VD(ss) with a physiological basis for its understanding developed by Øie and Tozer in 1979. The Øie-Tozer equation uses terms for plasma protein binding (f(up)), tissue binding (f(ut)), and the extravascular/intravascular ratio of albumin as well as constants for the volumes of plasma, extracellular fluid, and tissue. We explored this model using a data set of 553 drugs for which VD(ss) and plasma protein binding were available in humans. Eighteen percent of cases (102 compounds) did not obey the Øie-Tozer model, with the rearranged equation giving an aberrant f(ut) value (f(ut) < 0 or f(ut) > 1), in particular for compounds with VD(ss) < 0.6 l/kg and f(up) > 0.1. Further analysis of this group of compounds revealed patterns in physicochemical attributes with a high proportion exemplified by logP less than 0 (i.e., very hydrophilic), polar surface area >150 A(2), and a difference between logP and logD >2.5. In addition there was a high representation of certain drug classes including anti-infectives as well as neuromuscular blockers and contrast agents. The majority of compounds were also found to have literature evidence, implicating active transport processes in their disposition. This analysis provides some important insights for pharmacokinetic optimization in this particular chemical space, as well as in the application of the Øie-Tozer model for predicting volume of distribution in humans.


Olive oil in the prevention and treatment of osteoporosis after artificial menopause.
The goal of this study was to investigate the anti-osteoporosis effect of extra virgin olive oil (EVOO) in vivo, and explore its antioxidant, anti-inflammatory properties in Sprague Dawley rats and its anticancer properties in patients. A total of 120 healthy female Sprague Dawley rats aged 6 months were divided into four groups: 1) sham-operated control (Sham group, n=30); 2) ovariectomized (OVX group, n=30); 3) ovariectomized rats supplemented with EVOO (OVX + Olive, n=30); 4) ovariectomized rats supplemented with estrogen (OVX + E2, n=30). EVOO and estrogen were administered by oral gavage at a dose of 1 mL/100 g weight on a daily basis for 12 consecutive weeks. Twelve weeks later blood samples were obtained to detect the levels of calcium, alkaline phosphatase, phosphorus, interleukin-6 (IL-6), malonyldialdehyde (MDA), and nitrate content. Dual energy X-ray absorptiometer measured bone mineral density (BMD) of ovariectomized Sprague Dawley rats that had been fed olive oil for 3 months. Blood samples from patients, who regularly consumed olive oil over a 1 year period were also used to measure carbohydrate antigen 125, carcino-embryonic antigen, α-fetoprotein, and carbohydrate antigen 19-9 levels. BMD of lumbar spine and left femur was also evaluated by dual energy X-ray absorptiometry. Animal experiments showed that EVOO significantly increased BMD and decreased phosphatase, alkaline phosphatase, IL-6, MDA, and nitrate levels. However, it had no significant effect on the Ca(2+) level. In clinical follow-up, EVOO also improved patient BMD levels on L3, L4, and left femoral neck, and reduced carbohydrate antigen 125, α-fetoprotein, and carcino-embryonic antigen levels. But it had no significant effect on the carbohydrate antigen 19-9 level. EVOO illustrated significant anti-osteoporosis, antioxidant, anti-inflammatory, and anticancer properties in vivo. However, further studies are required to determine the active component(s) responsible for these effects.


Chitinophaga dinghuensis sp. nov., isolated from soil.
A Gram-reaction-negative, aerobic, non-motile bacterial strain, DHOC24T, was isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Strain DHOC24T underwent a shape change during the course of culture from long filamentous cells (10-30 × 0.4-0.5 μm) at 2 days to coccobacilli (0.5-1.0 × 0.7-1.0 μm) at 15 days after inoculation. It grew optimally at 28-33 °C and pH 6.5-7.5. The major quinone of strainDHOC24T was MK-7, the main fatty acids were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH and the DNA G+C content was 43.1 mol%. On the basis of 16S rRNA gene sequence analysis, the strain was found to be affiliated with members of the genus Chitinophaga, but was clearly separated from established species of the genus. Strain DHOC24T was most closely related to Chitinophaga jiangningensis JN53T (98.3 % 16S rRNA gene sequence similarity) and Chitinophaga terrae KP01T (97.9 %). DNA-DNA hybridization study showed relatively low relatedness values (32.1 %) of strain DHOC24T with C. jiangningensis JN53T. The phenotypic, chemotaxonomic and phylogenetic data showed that strain DHOC24T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga dinghuensis sp. nov. is proposed. The type strain is DHOC24T ( = CGMCC 1.12995T = DSM 29821T).


Supersonic Transporter Deformity in Transgender Men following Phalloplasty.
Phalloplasty is often the final stage of gender-affirmation surgery for transgender men. Obtaining penile rigidity is important for sexual function, but may also bring complications, including supersonic transporter deformity, in which the glans becomes ventrally displaced and flaccid. Two cases of supersonic transporter deformity are presented here, one with a hydraulic penile implant and one with an autologous bone transplant. Attempt at surgical correction was performed in both. Careful attention must be paid to the unique anatomy of the neophallus and type of penile prosthesis to prevent or correct supersonic transporter deformity in transgender men. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.


New reaction model for O-O bond formation and O2 evolution catalyzed by dinuclear manganese complex.
A new mechanism of the oxygen evolving reaction catalyzed by [H(2)O(terpy)Mn(μ-O)(2)Mn(terpy)OH(2)](3+) is proposed by using density functional theory. This proton coupled electron transfer (PCET) model shows reasonable barriers. Because in experiments excess oxidants (OCl(-) or HSO(5)(-)) are required to evolve oxygen from water, we considered the Mn(2) complex neutralized by three counterions. Structure optimization made the coordinated OCl(-) withdraw a H(+) from the water ligand and produces the reaction space for H(2)O(2) formation with the deprotonated OH(-) ligand. The reaction barrier for the H(2)O(2) formation from OH(-) and protonated OCl(-) depends significantly on the system charge and is 14.0 kcal/mol when the system is neutralized. The H(2)O(2) decomposes to O(2) during two PCET processes to the Mn(2) complex, both with barriers lower than 12.0 kcal/mol. In both PCET processes the spin moment of transferred electrons prefers to be parallel to that of Mn 3d electrons because of the exchange interaction. This model thus explains how the triplet O(2) molecule is produced.


Visual-spatial neglect in a child following sub-cortical tumor resection.
Although clinical syndromes of visual-spatial neglect have been well described in adults, clinical features of neglect associated with subcortical dysfunction are infrequently reported in children and have not been described in detail. Unilateral visual-spatial neglect in a 7-year-old male following removal of a right subcortical juvenile pilocytic astrocytoma is reported. Preoperative baseline neurocognitive assessment of the patient established intact attentional and intellectual functioning. Postoperatively visual-spatial neglect was observed that was not accounted for by the patient's visual field deficit. Consistent with classic features of attentional neglect, increases in attentional demands led to greater errors in performance. The risk of unilateral neglect following resection of subcortical tumors that abut the thalamus or disrupt thalamo-cortical projections was confirmed in a retrospective analysis of patients referred for neurocognitive testing at our site. It was concluded that the ventral thalamus may play a role in visual-spatial attention early in development.


Lysosomal positioning diseases: beyond substrate storage.
Lysosomal storage diseases (LSDs) comprise a group of inherited monogenic disorders characterized by lysosomal dysfunctions due to undegraded substrate accumulation. They are caused by a deficiency in specific lysosomal hydrolases involved in cellular catabolism, or non-enzymatic proteins essential for normal lysosomal functions. In LSDs, the lack of degradation of the accumulated substrate and its lysosomal storage impairs lysosome functions resulting in the perturbation of cellular homeostasis and, in turn, the damage of multiple organ systems. A substantial number of studies on the pathogenesis of LSDs has highlighted how the accumulation of lysosomal substrates is only the first event of a cascade of processes including the accumulation of secondary metabolites and the impairment of cellular trafficking, cell signalling, autophagic flux, mitochondria functionality and calcium homeostasis, that significantly contribute to the onset and progression of these diseases. Emerging studies on lysosomal biology have described the fundamental roles of these organelles in a variety of physiological functions and pathological conditions beyond their canonical activity in cellular waste clearance. Here, we discuss recent advances in the knowledge of cellular and molecular mechanisms linking lysosomal positioning and trafficking to LSDs.


Identifying lupus patients in electronic health records: Development and validation of machine learning algorithms and application of rule-based algorithms.
To utilize electronic health records (EHRs) to study SLE, algorithms are needed to accurately identify these patients. We used machine learning to generate data-driven SLE EHR algorithms and assessed performance of existing rule-based algorithms. We randomly selected subjects with ≥ 1 SLE ICD-9/10 codes from our EHR and identified gold standard definite and probable SLE cases by chart review, based on 1997 ACR or 2012 SLICC Classification Criteria. From a training set, we extracted coded and narrative concepts using natural language processing and generated algorithms using penalized logistic regression to classify definite or definite/probable SLE. We assessed predictive characteristics in internal and external cohort validations. We also tested performance characteristics of published rule-based algorithms with pre-specified permutations of ICD-9 codes, laboratory tests and medications in our EHR. At a specificity of 97%, our machine learning coded algorithm for definite SLE had 90% positive predictive value (PPV) and 64% sensitivity and for definite/probable SLE, 92% PPV and 47% sensitivity. In the external validation, at 97% specificity, the definite/probable algorithm had 94% PPV and 60% sensitivity. Adding NLP concepts did not improve performance metrics. The PPVs of published rule-based algorithms ranged from 45-79% in our EHR. Our machine learning SLE algorithms performed well in internal and external validation. Rule-based SLE algorithms did not transport as well to our EHR. Unique EHR characteristics, clinical practices and research goals regarding the desired sensitivity and specificity of the case definition must be considered when applying algorithms to identify SLE patients.


CREB-mediated transcriptional activation of NRMT1 drives muscle differentiation.
The N-terminal methyltransferase NRMT1 is an important regulator of protein/DNA interactions and plays a role in many cellular processes, including mitosis, cell cycle progression, chromatin organization, DNA damage repair, and transcriptional regulation. Accordingly, loss of NRMT1 results in both developmental pathologies and oncogenic phenotypes. Though NRMT1 plays such important and diverse roles in the cell, little is known about its own regulation. To better understand the mechanisms governing NRMT1 expression, we first identified its predominant transcriptional start site and minimal promoter region with predicted transcription factor motifs. We then used a combination of luciferase and binding assays to confirm CREB1 as the major regulator of NRMT1 transcription. We tested which conditions known to activate CREB1 also activated NRMT1 transcription, and found CREB1-mediated NRMT1 expression was increased during recovery from serum starvation and muscle cell differentiation. To determine how NRMT1 expression affects myoblast differentiation, we used CRISPR/Cas9 technology to knock out NRMT1 expression in immortalized C2C12 mouse myoblasts. C2C12 cells depleted of NRMT1 lacked Pax7 expression and were unable to proceed down the muscle differentiation pathway. Instead, they took on characteristics of C2C12 cells that have transdifferentiated into osteoblasts, including increased alkaline phosphatase and type I collagen expression and decreased proliferation. These data implicate NRMT1 as an important downstream target of CREB1 during muscle cell differentiation.


Comparison of cell proliferation in the centre and advancing fronts of oral squamous cell carcinomas using Ki-67 index.
The cell proliferation status of 60 oral squamous cell carcinomas from Sri Lankan subjects was examined by immunohistochemistry using the Ki-67 index. A comparison was made between the indices derived from the centre of the tumours and those derived from the invasive fronts of the same tumours. There was a positive correlation between the two indices suggesting a clonal expansion of malignant cells, but the mean index derived for the invasive fronts (29.75 11.64) was significantly higher than the mean index for the body of these tumours (25.65 11.64). Thus, at a given time, more peripheral cells at the invasive front are proliferating and this compartment is likely to be more informative in prognostic and other behavioural studies involving the cell cycle. In squamous carcinomas, increased and uncontrolled cell proliferation at the invasive front may be one feature contributory to the invasion.


Ketamine Reduces Inflammation Pathways in the Hypothalamus and Hippocampus Following Transient Hypoxia in the Late-Gestation Fetal Sheep.
The physiological response to hypoxia in the fetus has been extensively studied with regard to redistribution of fetal combined ventricular output and sparing of oxygen delivery to fetal brain and heart. Previously, we have shown that the fetal brain is capable of mounting changes in gene expression that are consistent with tissue inflammation. The present study was designed to use transcriptomics and systems biology modeling to test the hypothesis that ketamine reduces or prevents the upregulation of inflammation-related pathways in hypothalamus and hippocampus after transient hypoxic hypoxia. Chronically catheterized fetal sheep (122 ± 5 days gestation) were subjected to 30 min hypoxia (relative reduction in PaO2∼50%) caused by infusion of nitrogen into the inspired gas of the pregnant ewe. RNA was isolated from fetal hypothalamus and hippocampus collected 24 h after hypoxia, and was analyzed for gene expression using the Agilent 15.5 k ovine microarray. Ketamine, injected 10 min prior to hypoxia, reduced the cerebral immune response activation to the hypoxia in both brain regions. Genes both upregulated by hypoxia and downregulated by ketamine after hypoxia were significantly associated with gene ontology terms and KEGG pathways that are, themselves, associated with the tissue response to exposure to bacteria. We conclude that the results are consistent with interruption of the cellular response to bacteria by ketamine.


Hepatic porphyrias.
The porphyrias are metabolic disorders characterized by abnormal heme biosynthesis with excessive accumulation and excretion of porphyrias or porphyrin precursors. Defects in the enzymes of the heme biosynthetic pathway result in porphyria. Several of the disorders have been classified as hepatic because the major site of the biochemical defect has been localized to the liver. This article describes the enzymes of the heme biosynthetic pathway, the clinical features of the hepatic porphyrias and management of the disorders.


Multiperiodicity of discrete-time delayed neural networks evoked by periodic external inputs.
In this paper, the multiperiodicity of a general class of discrete-time delayed neural networks (DTDNNs) is formulated and studied. Several sufficient conditions are obtained to ensure n-neuron DTDNNs can have 2n periodic orbits and these periodic orbits are locally attractive. In addition, we give the conditions for a periodic orbit to be locally or globally attractive when the periodic orbit locates in a designated region. As two typical representatives, the Hopfield neural network and the cellular neural network are examined in detail. These conditions improve and extend the existing stability results in the literature. Simulations results are also discussed in three illustrative examples.


Effects of Aerobic Training on Cardiopulmonary Function Based on Multiple Linear Regression Analysis.
In order to study the effect of aerobic training exercise on cardiopulmonary function of the human body, in this study, multiple linear regression based on the particle swarm optimization cardiopulmonary function test method of constructing the sports cardiopulmonary function test model is used. The traditional multiple linear regression after 41 iteration achieves convergence, and after the particle swarm optimization, about 25 times, convergence is achieved. Moreover, the convergence error of pSO is less than that of traditional multiple linear regression algorithm, which verifies the effectiveness of PSO. This method can effectively detect cardiopulmonary function of athletes before and after aerobic training, and the modeling accuracy is high, and the detection performance of cardiopulmonary function of aerobic training is better than the traditional relational model algorithm, which provides a new way for cardiopulmonary model detection of the human body.


Massive weight loss following deep brain stimulation of the nucleus accumbens in a depressed woman.
Obese individuals share behavioral characteristics with drug/alcohol addicts as well as obsessive compulsive disease. Deep brain stimulation (DBS) has been used successfully in these disorders, thus warranting an evaluation in obesity. A woman with treatment-resistant depression as well as severe obesity was selected for DBS of the nucleus accumbens (NAcc) bilaterally with depression being the primary and obesity being the secondary target of treatment. Compared to earlier bariatric surgery, the patient showed accelerated weight loss after DBS. Also, depression was significantly reduced. The current case suggests that DBS of the NAcc warrants further evaluation in patients unresponsive to other treatments.


Familial variable expression of dilated cardiomyopathy in Alström syndrome: a report of four sibs.
Alström syndrome is an autosomal recessive disorder comprised of progressive vision loss (nystagmus, photophobia, and pigmentary retinopathy), progressive sensorineural hearing loss, morbid obesity, male hypogonadism, insulin resistant diabetes, renal failure, and dilated cardiomyopathy. We report on four sibs with Alström syndrome with intra-familial variability in onset, severity, and spectrum of manifestations; the most serious manifestation being dilated cardiomyopathy. This report emphasizes the difficulty of recognizing this constellation of symptoms as Alström syndrome at an early age, the seriousness of cardiac involvement, and the intra-familial variability of phenotypic expression.


Autoimmune Encephalitis.
Autoimmune encephalitis is a common and treatable cause of encephalitis in children and adults. Individuals present with a variety of symptoms, including altered mental status, behavioral changes, irritability, insomnia, developmental regression, seizures, dyskinetic movements, and autonomic instability. Evaluation includes electroencephalography, magnetic resonance imaging, and lumbar puncture. Once infectious and other causes are reasonably ruled out, treatment should be started empirically without waiting for antibody confirmation. Early clinical suspicion is key, as the outcome depends on early initiation of immunotherapy, including corticosteroids, intravenous immunoglobulin, and/or plasmapheresis. Severe or refractory cases require other treatments, such as rituximab, cyclophosphamide, or other immunotherapies using novel monoclonal antibodies. Psychiatry should be involved early for the management of behavioral issues. Additional considerations include management of seizures and dyskinesias. ICU admission may be required for management of hypoventilation necessitating mechanical ventilation (either intrinsic or iatrogenic, eg, from sedatives), refractory seizures, and dysautonomia. Anti-N-methyl-d-aspartate receptor and other forms of autoimmune encephalitis are less often associated with neoplasia (such as ovarian teratoma) in children compared with adults, but screening and removal of tumor if present should be performed.


Clinical outcome, and survival between primary percutaneous coronary intervention versus fibrinolysis in patients older than 60 years with acute myocardial infarction.
The aim of the present study was to compare the short-term and 6-month clinical outcome, and survival in patients older than 60 years with ST-elevation myocardial infarction randomized to either primary percutaneous coronary intervention (PPCI) or thrombolysis. 82 patients with STEMI older than 60 years were randomized to either primary PCI or thrombolysis from September 2006 to August 2008. Angiograms were reviewed by two interventionalists not involved in the study. Patients randomized to primary PCI received Aspirin and 600 mg Clopidogrel. Heparin was administered in conjunction with PCI. Patients randomized to thrombolysis received Aspirin followed by streptokinase infusion for one hour. Rescue PCI was considered if there was ongoing pain and ST-segment resolution was <50% at 90 min. after initiation of thrombolysis or chest pain recurred with ST-segment elevation within 24 hours. All patients were followed up for 6 months. End points were reinfarction and cardiac death using competing-risks regression estimation. The mean time from hospital admission to start of streptokinase infusion was 31 ± 15 min and door to balloon time was 70 ± 25 min. There was no significant difference between the groups in the number of deaths and reinfarctions at 6 months. As expected, the fibrinolysis group had a higher rate of revascularization and heart failure. The higher rates of heart failure and need for revascularization in the fibrinolysis group reinforces benefits of PPCI in patients older than 60 years. PPCI in those who are 60 years and above with AMI is safe and cost effective.


Prostaglandin treatment and subsequent cystic ovarian disease in Holstein cows.
Using computerized herd health data, a prospective cohort study was devised to determine whether cows treated with prostaglandins had a higher incidence of cystic ovarian disease than comparable cows not treated. Of 744 cows selected as having diseases for which prostaglandin administration may be indicated, 240 received prostaglandin. Sixteen cows had cystic ovarian disease following prostaglandin administration. Chi-square analysis showed no association (P greater than 0.10) between cystic ovarian disease and the use of prostaglandin. Incidence of cystic ovarian disease within 150 days of calving in clinically normal cows was compared with that of cows with reproductive disorders. Cows with reproductive disorders had a significantly (P less than 0.01) higher incidence of cystic ovarian disease.


Chylothorax after blunt chest trauma: an unusual case with a long latent period.
We report on a case of closed chest trauma with an unusual latent period of 11 weeks in a woman 26 years old. The patient had a dual thoracic duct with a dual lesion and was evaluated using lymphography and CT. We discuss the pathogenetic mechanism and the unusual radiological appearance with discontinuity of the duct, and an increase in back pressure which promotes dilatation of lymphatic vessels and nodes. The dual duct had two separate traumatic consequences: a chyloma on the right and leakage in the pleura on the left. Pleuroperitoneal shunting was effective after failure of conservative treatment. Two years after discharge the patient is asymptomatic with normal chest X-ray image. She is near term in a normal pregnancy and without signs of silent malignancy.


Craniofacial and extracranial malformations in the Klippel-Feil syndrome.
The Klippel-Feil syndrome is of special interest to those concerned with cleft palate for the following reasons: (1) Cleft palate is a commonly associated finding: (2) malformations of the cervical vertebrae, in the absence of other stigmata of the syndrome, are a common finding in cleft palate; (3) anomalies of the upper cervical column and cranial base can impede velopharyngeal valving; (4) hearing loss is a common finding in the syndrome irrespective of the presence or absence of cleft palate; (5) cervical anomalies may complicate endotracheal intubation or head extension during pharyngeal surgery, and (5) the short neck may be the primary defect that impedes palatal fusion. This report reviews the literature on 339 patients and seven new cases in an effort to catalog the cranial and extracranial malformations associated with the syndrome and to consider the mode of genetic transmission.


Multiphoton photoemission from a copper cathode illuminated by ultrashort laser pulses in an RF photoinjector.
In this Letter we report on the use of ultrashort infrared laser pulses to generate a copious amount of electrons by a copper cathode in an rf photoinjector. The charge yield verifies the generalized Fowler-Dubridge theory for multiphoton photoemission. The emission is verified to be prompt using a two pulse autocorrelation technique. The thermal emittance associated with the excess kinetic energy from the emission process is comparable with the one measured using frequency tripled uv laser pulses. In the high field of the rf gun, up to 50 pC of charge can be extracted from the cathode using a 80 fs long, 2 microJ, 800 nm pulse focused to a 140 mum rms spot size. Taking into account the efficiency of harmonic conversion, illuminating a cathode directly with ir laser pulses can be the most efficient way to employ the available laser power.


4-Aminopyridine restores impaired hypoxic pulmonary vasoconstriction in endotoxemic mice.
Hypoxic pulmonary vasoconstriction (HPV) is impaired during inflammatory lung processes such as pneumonia or the acute respiratory distress syndrome. Voltage-gated potassium channels play a central role in mediating HPV. The aim of this study was to determine whether 4-aminopyridine (4-AP), a known voltage-gated potassium channel inhibitor, may restore HPV in sepsis. The effects of 0.01, 0.1, and 1.0 mm 4-AP on HPV responsiveness were assessed in isolated lungs of untreated mice and of mice 18 h after lipopolysaccharide injection (20 mg/kg intraperitoneal Escherichia coli 0111:B4 lipopolysaccharide). HPV was quantified as the increase in perfusion pressure in response to hypoxic ventilation in percent of baseline perfusion pressure. Intrinsic pulmonary vascular resistance (R0) and pulmonary vascular distensibility (alpha) were determined by nonlinear regression analysis of pulmonary vascular pressure-flow curves generated during normoxic and hypoxic ventilation, respectively. HPV was impaired in lungs isolated from lipopolysaccharide-challenged mice. Addition of 4-AP to the perfusate did not alter HPV responsiveness in untreated mice but dose dependently restored HPV in endotoxemic mice. Analysis of pulmonary vascular pressure-flow curves revealed that 4-AP (1) counteracted the observed lipopolysaccharide-induced changes in alpha and R0 under normoxic conditions and (2) augmented the hypoxia-induced increase in R0 in lungs of endotoxemic mice. This study demonstrates that lipopolysaccharide-induced pulmonary vascular hyporesponsiveness to hypoxia can be restored by 4-AP in murine endotoxemia and, thus, may be a new therapeutic approach to treat patients with hypoxemia due to impaired HPV.


Translation of phage f1 gene VII occurs from an inherently defective initiation site made functional by coupling.
Expression of the filamentous phage f1 gene VII is shown to be translationally coupled to that of the upstream gene V. Fusions of the gene VII initiation site to the lacZ coding region were used to determine that initiation at the VII site is completely dependent on the process of translation having proceeded up to a stop codon immediately upstream from the VII site. Coupled expression from the VII site was found to be inefficient, proportional to the level of upstream translation, and very sensitive to the distance from the functional upstream stop codon. Independent expression from the VII site was not observed, even in a deletion series designed to remove potentially masking RNA structure. On the basis of the VII site's dissimilarity to ribosome binding site sequences and its properties overall, we suggest that it inherently lacks the features required for independent recognition by ribosomes, and acquires the ability to initiate synthesis of gene VII protein by virtue of the coupling process.


Neural adaptation and behavioral measures of temporal processing and speech perception in cochlear implant recipients.
The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.


Health profile of Ethiopian immigrants in Israel: an overview.
The health profile of two groups of Ethiopian immigrants in Israel was evaluated. Trichophytosis and active trachoma were observed in 5%-8.7% of prepubertal children. Among adults 13% had corneal opacities and 10.4% had cataracts. Goiter, spastic bronchitis, valvular heart disease, leprosy and onchocerciasis were prevalent. Malnutrition was common, with average body weights ranging from 72.4% to 85.2% of normal. Anemia was observed in 6.3% of young children and 70% of all immigrants. Fifty percent of children over 12 years and 98% of adults over 40 years of age had been exposed to hepatitis B virus; 9.8%-11.8% were HBsAg carriers. Tuberculin tests were positive in 9.8%-13%; and intestinal parasites were identified in 86%-98%. Hospitalization was required for 15.7% of immigrants arriving during the period 1978-90, and for 3.7% of those arriving in mid-1991 (Operation Solomon).


Sex Differences in In-Hospital Management and Outcomes of Patients With Acute Coronary Syndrome.
Coronary heart disease is a leading cause of mortality among women. Systematic evaluation of the quality of care and outcomes in women hospitalized for acute coronary syndrome (ACS), an acute manifestation of coronary heart disease, remains lacking in China. The CCC-ACS project (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) is an ongoing nationwide registry of the American Heart Association and the Chinese Society of Cardiology. Using data from the CCC-ACS project, we evaluated sex differences in acute management, medical therapies for secondary prevention, and in-hospital mortality in 82 196 patients admitted for ACS at 192 hospitals in China from 2014 to 2018. Women with ACS were older than men (69.0 versus 61.1 years, P<0.001) and had more comorbidities. After multivariable adjustment, eligible women were less likely to receive evidence-based acute treatments for ACS than men, including early dual antiplatelet therapy, heparins during hospitalization, and reperfusion therapy for ST-segment-elevation myocardial infarction. With respect to strategies for secondary prevention, eligible women were less likely to receive dual antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins at discharge, and smoking cessation and cardiac rehabilitation counseling during hospitalization. In-hospital mortality rate was higher in women than in men (2.60% versus 1.50%, P<0.001). The sex difference in in-hospital mortality was no longer observed in patients with ST-segment-elevation myocardial infarction (adjusted odds ratio, 1.18; 95% CI, 1.00 to 1.41; P=0.057) and non-ST-segment elevation ACS (adjusted odds ratio, 0.84; 95% CI, 0.66 to 1.06; P=0.147) after adjustment for clinical characteristics and acute treatments. Women hospitalized for ACS in China received acute treatments and strategies for secondary prevention less frequently than men. The observed sex differences in in-hospital mortality were mainly attributable to worse clinical profiles and fewer evidence-based acute treatments provided to women with ACS. Specially targeted quality improvement programs may be warranted to narrow sex-related disparities in quality of care and outcomes in patients with ACS. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02306616.


Intra-abdominal gossypiboma: a report of two cases and a review of literature.
Post operative foreign body in the abdominal cavily, though rare continues to occur in surgical practice. Symptoms may start early with abdominal pain but usually have a varying course, ofter leading 10 the formation of gossypiboma. This is usually a great source of embarrassment to the surgeon and the centre, and of serious detrimental effect to the patient. A case report of a 27-year-old trader with intra-abdominal foreign body is presented to highlig at the similarity in presentation with abdominal lymphoma and the need to explore carefully masses in the abdominal cavity especially in patients who have had surgery in the past. A high index of suspicious is required on the part of the clinician in addition to appropriate radiological and sonologic assessment. Prompt diagnosis and treatment ameliorates the patients suffering and brings them back to life.


A 60:40 split: Differential mass support in dogs.
Dogs have been bred for different sizes and functions, which can affect their locomotor biomechanics. As quadrupeds, dogs must distribute their mass between fore and hind legs when standing. The mass distribution in dogs was studied to determine if the proportion of supported mass on each limb couplet is dependent on body size. A total of 552 dogs from 123 breeds ranging in size from Chihuahua to Mastiff were examined. Each dog was weighed on a digital scale while standing, alternating foreleg, and hind leg support. The overall "grand" mean proportion of mass on the forelegs to the total mass was 60.4% (range: 47.6-74.4%). The data set indicated no significant change in the ratio with total mass but there was a significant difference by sex. When separated into American Kennel Club categories, no group was notably different from the grand mean or from each other, but when sex was also considered, there was a significant difference that was not specifically discerned by post hoc analysis. The mean for female Hounds was notably below the grand mean. For clades based on genetics, the mean for European origin mastiffs was notably greater than the grand mean and significantly different from UK origin herders and coursers. The mass of the head, chest, and musculature for propulsion could explain the mass support differential. Mass distribution and terrestrial locomotion in dogs shows substantial variation among breeds.


Use of the ICECI and ICD-10 E-Coding structures to evaluate causes of head injury and concussion from sport and recreation participation in a school population.
The purpose of this study was to identify the most common causes of head injury and associated symptoms of concussion in a population of school children (n=1,372,979). Using standardized injury report forms, we identified the mechanisms of head injury associated with various sports/recreation activities and assessed each injury for the presence of concussion symptoms. Head injury reports (n=7,765) were coded using the WHO's ICECI and ICD-10 E-codes. 1,338 Cases reported symptoms of concussion. The majority of head injuries occurred during School Free-Play/Recess (59.8%). Combative Sports and Wheeled Non-Motored Sports were the activities most often associated with concussion symptoms (rate of concussion (RC): 48.3% and 44.4%, respectively, p<0.001). School Free-Play/Recess and Physical Education Classes were significantly less likely to have head injuries associated with concussion (RC: 16.0%, p<0.001, and 12.4%, p=0.034, respectively). The most common causes of head injury were (1) Struck by an Object (24.9%) and (2) Falling on the Same Level (22.8%). Falling from a Transport was the only etiological code significantly associated with concussion symptoms after head injury (RC: 28.7%, p<.001). Results were similar when using the two coding structures in combination. Prevention efforts should focus on activities where children are moving at high speeds since these are more likely to cause a concussion when a head injury occurs.


Combined ovulation triggering with GnRH agonist and hCG in IVF patients.
The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation.


Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.
Numerous drug interactions with methotrexate have been identified, which can lead to serious life-threatening effects. Up to 90% of methotrexate is excreted unchanged in the urine with primary excretion dependent on organic anion transport in the renal proximal tubule. The two pathways responsible for methotrexate secretion are organic anion transport 1 and primarily organic anion transport 3. Penicillins undergo tubular secretion via organic anion transport, and cephalosporins are believed to also possess a similar risk when administered with methotrexate; however, there are no human studies observing this interaction with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and has low affinity for the same organic anion transports as methotrexate; therefore, ceftriaxone has a low potential to interact with methotrexate. Cefepime is primarily secreted by organic cation transport N2, and also has a low potential to interact with methotrexate. This case report describes the pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving high-dose methotrexate.


Isokinetic muscle torque during glenohumeral rotation in dominant and nondominant limbs.
The purpose of this study was to evaluate the side-to-side differences of isokinetic muscle torque during shoulder rotation in healthy nonathletic subjects. The strength was examined at two angles of glenohumeral abduction in the scapular plane (45 degrees and 90 degrees, respectively) and at three velocities (180 degrees/s, 120 degrees/s, 60 degrees/s) using Biodex System 3Pro dynamometer. The maximal torques were achieved on dominant side in 45-degree abduction at 60 degrees/s velocity, both for external and internal rotation. A general pattern was observed: abduction angle and velocity increase provoked a decrease in torque values, but each antagonistic muscle group was sensitive to a different factor. Significant differences between dominant and non-dominant limb were not observed in nonathletic male.


Serum immunoglobin G4 (IgG4): an important marker in autoimmune pancreatitis?
A unique form of chronic pancreatitis has recently become widely recognised as an important clinical entity in the spectrum of pancreatic diseases under the term autoimmune pancreatitis (AIP). This entity is characterised by irregular narrowing of the pancreatic duct, swelling of parenchyma, lymphoplasmacytic infiltration and fibrosis as well as favourable response to corticosteroid treatment. In addition, increased concentration of serum immunoglobulin G4 (IgG4) is a notable characteristic marker. Some patients undergoing pancreaticoduodenectomy for presumed pancreatic ductal adenocarcinoma have instead been found to have AIP. Early recognition of AIP can prevent pancreaticoduodenectomy in these patients and effective treatment with steroids can be introduced. Based on an interesting case, we discuss the entity of AIP with the rare combination of sclerosing cholangitis and we focus on the relevance of serum IgG4 as a factor in diagnosis and monitoring therapy of AIP.


Secular trends in body height in Balkan populations from 1945 to 1995.
The aim of this study was to look for any secular trend in the stature of Balkan populations from the time of World War II (1939-1945) to the Balkans War (1991-1995). The research was based on the examination of exhumed skeletons of 202 men killed in World War II in the area of the Republic of Slovenia, and 243 men killed in the Bosnian War in Bosnia and Herzegovina. The length measurements of the right and left humerus, femur, tibia and fibula were taken. Since the results revealed no significant differences and the left-sided bones were more complete and recurrent in the sample, the bones of the left side were used in the analysis. Since the increase in height depends mostly on the increase in length of the long bones, with an average absolute change of about 0.28 cm for humerus, 0.55 cm for femur, 0.49 cm for tibia and 0.20 cm for fibula per decade in our case, these results suggest a significant increase of the height of the Balkans population. The difference of the sum of the average femur and tibia length for the study period was 4.13 cm. Recalculated average length increase of the sum length of femur and tibia per decade was 0.88 cm for the left side. Our study revealed that there was a trend towards increased long bone lengths, at least in the male population analyzed.


[Clinical nursing practice, some elements of clarification in the French context].
In France, certified nurse clinicians have been working in various fields of activity for a number of years. Recent political decisions aim to create the role of nurse clinician specialised in oncology as well as advanced nursing practice. In this context, an explanation of the terminology and the history of this domain is necessary in order to shed light on the ongoing discussion process.


Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.
Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.


Changes in Sleep Duration, Quality, and Medication Use Are Prospectively Associated With Health and Well-being: Analysis of the UK Household Longitudinal Study.
Sleep is a plausible target for public health promotion. We examined the association of changes in sleep with subsequent health and well-being in the general population. We analyzed data from the UK Household Longitudinal Survey, involving 30594 people (aged > 16) who provided data on sleep and health and well-being at both Wave 1 (2009-2011) and Wave 4 (2012-2014) assessments. Predicting variables were changes in sleep quantity, sleep quality, and sleep medication use over the 4-year period. Outcome variables were the General Health Questionnaire (GHQ-12) and the 12-Item Short-Form Health Survey (SF-12) mental (MCS) and physical (PCS) component scores at Wave 4. Linear regression on each outcome was fully adjusted for potential confounders and baseline values of the relevant predicting and outcome variables. Better outcomes were associated with an increase in sleep duration (GHQ: β = 1.031 [95% confidence interval {CI}: -1.328, -0.734]; MCS: 1.531 [1.006, 2.055]; PCS: -0.071 [-0.419, 0.56]), sleep quality (GHQ: β = -2.031 [95% CI: -2.218, -1.844]; MCS: 3.027 [2.692, 3.361]; PCS: 0.924 [0.604, 1.245]), and a reduction in sleep medication use (GHQ: β = -1.929 [95% CI: -2.400, -1.459]; MCS: 3.106 [2.279, 3.933]; PCS: 2.633 [1.860, 3.406]). Poorer outcomes were on the other hand associated with a reduction in sleep duration, a decrease in sleep quality, and an increase in sleep medication use. Changes in sleep quality yielded the largest effects on the health and well-being outcomes. Changes in sleep were temporally associated with subsequent health and well-being. Initiatives that aim to protect a critical amount of sleep, promote sleep quality, and reduce sleep medication use may have public health values.


Imaging reactive oxygen species in asthma.
Inflammatory processes in asthma are characterized by an infiltration of inflammatory cells including mononuclear phagocytes. It has been observed that mononuclear phagocytes, alveolar macrophages and blood monocytes, release higher quantities of reactive oxygen species in asthmatic patients than in healthy subjects. Chemiluminescence assays were developed to measure the superoxide anion and the other reactive oxygen species. The chemiluminescence response was first analysed with a luminometer, which made it possible to study cells in suspension before and after PMA-stimulation. Secondly a video-imaging camera was used in experiments on adherent cells before and after stimulation with PMA and/or specific stimulus IgE/anti-IgE. Both techniques showed that human alveolar macrophages, blood monocytes, PMN and lymphocytes were spontaneously primed in vivo and were more easily stimulated in asthma. Analysis of adherent cells in vitro may provide give information on the physiological condition of adherent cells in vivo.


Effect of chlorin structure on theoretical electronic absorption spectra and on the energy released by porphyrin-based photosensitizers.
In this work eight porphyrins (p) and eight chlorins (c) are theoretically characterized [BLYP/6-31G(d)] in their singlet and triplet states. Nine of them (1p, 1c, 2p, 3p, 4p, 5p, 6c, 7c, and 8c) have already been synthesized and are in trial use in photodynamic therapy (PDT). The seven remaining were built up as chlorins analogous to porphyrins 2p-5p and porphyrins analogous to chlorins 6c-8c. The aim is to investigate the effect of the chlorin structure on the Q-band of electronic spectra at BLYP/6-31G(d) (gas phase, methanol solution) and at BHANDHLYP/6-31+G(d) (methanol solution), and on the triplet --> singlet energy emission, as these two factors determine the quality of a good photosensitizer. It is found that meso substituents lead to greater geometry distortions than beta-substituents in both porphyrins and chlorins and in both singlet and triplet states. In methanol solution, chlorin-like structures with beta substitution present significantly red-shifted Q-bands in comparison with their porphyrin analogues, so they would be better photosensitizers than porphyrins. Concerning to the triplet --> singlet energy emission calculated in methanol solution, three porphyrins (4p, 6p, and 8p) and all the studied substituted chlorins could be useful to generate active (1)O2. 4c would be the best photosensitizer, as it absorbs the largest wavelength in the therapeutic window (approximately 690 nm) and releases the amount of energy closest to the required one (1.22 eV).


Correlation between venous blood gas indices and radiological involvements of COVID-19 patients at first admission to emergency department.
The purpose of this study was to investigate the relation between venous blood gas and chest computerized tomography findings and the clinical conditions of COVID-19 pneumonia. A total of 309 patients admitted to the emergency department and subsequently confirmed COVID-19 cases was examined. Patients with pneumonia symptoms, chest computerized tomography scan, venous blood gas findings, and confirmed COVID-19 on reverse transcription-polymerase chain reaction (PCR) were consecutively enrolled. Multiple linear regression was used to predict computerized tomography and blood gas findings by clinical/laboratory data. The median age of patients was 51 (interquartile range 39-66), and 51.5% were male. The mortality rate at the end of follow-up was 18.8%. With respect to survival status of patients pCO2 and HCO3 levels and total computerized tomography score values were found to be higher in the surviving patients (p<0.001 and p=0.003, respectively), whereas pH and lactate levels were higher in patients who died (p=0.022 and p=0.001, respectively). With logistic regression analysis, total tomography score was found to be significantly effective on mortality (p<0.001). The diffuse and random involvement of the lungs had a significant effect on mortality (p<0.001, 95%CI 3.853-38.769, OR 12.222 and p=0.027; 95%CI 1.155-11.640, OR 3.667, respectively). With linear regression analysis, the effect of pH and lactate results were found to have a positive effect on total tomography score (p=0.003 and p<0.001, respectively), whereas pCO2 was found to have a negative effect (p=0.029). There was correlation between venous blood gas indices and radiologic scores in COVID-19 patients. Venous blood gas taken in emergency department can be a fast, applicable, minor-invasive, and complementary test in terms of diagnosing COVID-19 pneumonia and predicting the prognosis of disease.


5-Hydroxymethylcytosine is a predominantly stable DNA modification.
5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.


Intrarenal dopamine acts at the dopamine-1 receptor to control renal function.
Exogenous dopamine increases renal blood flow and produces diuresis and natriuresis in mammalian species. Dopamine is produced intrarenally and dopamine-1 receptors have been demonstrated within the kidney. However, the role of intrarenal dopamine in the control of renal function is unknown. We studied the renal effects of a specific dopamine-1 antagonist, SCH 23390 (SCH, MW 398, Schering-Plough, Bloomfield, New Jersey, USA) infused into the renal artery of uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 40 mmol/day. The infusion of SCH at 0.01 pmol/kg per min did not change the urinary flow rate or urinary sodium excretion. Significant dose-dependent reductions in urine volume, urinary sodium excretion and fractional excretion of sodium were observed with intrarenal SCH administration at 0.1, 5.0 and 10 pmol/kg per min. Rebound diuresis and natriuresis occurred after cessation of SCH administration. There were no changes in renal haemodynamic function, systemic plasma renin activity (PRA), plasma aldosterone concentration or mean arterial pressure during intrarenal SCH administration. These results demonstrate for the first time that intrarenal dopamine controls renal function physiologically by acting at the renal dopamine-1 receptors.


Identification by High-Throughput Screening of Pseudomonas Acyl-Coenzyme A Synthetase Inhibitors.
Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl-coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl-coenzyme A, while the third one was competitive with fatty acid binding. Although these compounds inhibit the bacterial ACS in cell-free assays, they show modest or no effect on Pseudomonas growth in vitro.


Cationic drug pharmacokinetics in diseased livers determined by fibrosis index, hepatic protein content, microsomal activity, and nature of drug.
The disposition kinetics of six cationic drugs in perfused diseased and normal rat livers were determined by multiple indicator dilution and related to the drug physicochemical properties and liver histopathology. A carbon tetrachloride (CCl(4))-induced acute hepatocellular injury model had a higher fibrosis index (FI), determined by computer-assisted image analysis, than did an alcohol-induced chronic hepatocellular injury model. The alcohol-treated group had the highest hepatic alpha(1)-acid glycoprotein, microsomal protein (MP), and cytochrome P450 (P450) concentrations. Various pharmacokinetic parameters could be related to the octanol-water partition coefficient (log P(app)) of the drug as a surrogate for plasma membrane partition coefficient and affinity for MP or P450, the dependence being lower in the CCl(4)-treated group and higher in the alcohol-treated group relative to controls. Stepwise regression analysis showed that hepatic extraction ratio, permeability-surface area product, tissue-binding constant, intrinsic clearance, partition ratio of influx (k(in)) and efflux rate constant (k(out)), and k(in)/k(out) were related to physicochemical properties of drug (log P(app) or pK(a)) and liver histopathology (FI, MP, or P450). In addition, hepatocyte organelle ion trapping of cationic drugs was evident in all groups. It is concluded that fibrosis-inducing hepatic disease effects on cationic drug disposition in the liver may be predicted from drug properties and liver histopathology.


[Clinical evaluation of the revised International Prognostic Score of Thrombosis for essential thrombocythemia (IPSET-thrombosis) in a cohort of 746 Chinese adult patients].
Objective: To evaluate the role of the revised International Prognostic Score of Thrombosis (IPSET-thrombosis) in predicting the occurrence of thrombotic events in Chinese patients with essential thrombocythemia (ET) and to develop a thrombosis predicting model more applicable to Chinese ET patients. Methods: Medical records of 746 adult patients with an initial diagnosis of ET were retrospectively analyzed. Results: The median age at diagnosis was 52 (18-87) years, with 305 males and 441 females. According to the revised IPSET-thrombosis model, the number of very low-, low-, intermediate-, and high-risk patients were 271 (36.3%) , 223 (29.9%) , 63 (8.4%) and 189 (25.3%) , respectively. The four groups exhibited significantly different thrombosis-free survival (χ(2)=72.301, P<0.001) . Thirty-six patients were reclassified as intermediate-risk according to the revised IPSET-thrombosis instead of low-risk as per the original IPSET-thrombosis. Nineteen intermediate-risk patients as per the original IPSET-thrombosis were upgraded to high-risk according to the revised IPSET-thrombosis. Fifty-one high-risk patients as per the original IPSET-thrombosis were reclassified as low-risk in the revised IPSET-thrombosis. It suggests that the revised IPSET-thrombosis potentially avoids over- or under-treatment. In low-risk patients as per the revised IPSET-thrombosis, the rate of thrombosis in patients with cardiovascular risk factors (CVF) was higher than that in those without (16.3% vs 5.2%, χ(2)=5.264, P=0.022) , and comparable with intermediate-risk patients as per the revised IPSET-thrombosis (16.3% vs 14.3%, χ(2)=0.089, P=0.765) . As a result, a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed in which patients with CVF in the low-risk group as per the revised IPSET-thrombosis were reclassified as intermediate-risk group. Conclusion: For predicting the occurrence of thrombotic events, the revised IPSET-thrombosis model was better than the original IPSET-thrombosis model. The revised IPSET-thrombosis was optimized and a new revised IPSET-thrombosis model more applicable to Chinese ET patients was developed, and the new evidence for risk stratification and treatment of ET in Chinese was provided.


The role of DNA replication in chromosome condensation.
At metaphase, DNA in a human chromosome is estimated to be compacted at least 10,000 fold in length. However, the higher order mechanisms by which the chromosomes are organized in interphase and subsequently further condensed in mitosis have largely remained elusive. One generally overlooked participant in chromosome condensation is DNA replication. Many early studies of eukaryotic chromosome organization and cell fusions have suggested that DNA replication plays a role in chromosome compaction. Recent phenotypic analysis of Drosophila DNA replication mutants has revitalized this old idea. In this review, the role of DNA replication in chromosome condensation will be examined.