Quality of Life Achieved by Carboplatin Plus Etoposide as Third-Line Chemotherapy Compared with Best Supportive Care in Non-Small Cell Lung Cancer Stage IIIB/IV.
Advanced stage (IIIB/IV) non-small cell lung cancers (NSCLC) are mostly treated with paclitaxel or gemcitabine combination chemotherapy as first-line treatment and docetaxel as second-line therapy under the national reimbursement program, but there is no treatment specified for use after disease progression. New third-line chemotherapy drugs including new targeted therapies are expensive and bring about only slightly prolonged progression-free survival and minimally better response in healthy patients. Carboplatin plus etoposide chemotherapy, which was formerly used as a low-cost first-line treatment, was used as third-line therapy for advanced NSCLC in order to compare its results with those of best supportive care as a treatment for improved quality of life (QoL) and progression-free survival. This prospective study of advanced NSCLC stage IIIB/IV enrolled 47 patients receiving either third-line chemotherapy with carboplatin plus etoposide or best supportive care in the Oncology Unit, Medicine Department, Rajavithi Hospital from 1 January 2005 to 31 December 2012. Results of treatment and quality of life of the two groups (QoL) were evaluated using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L). The 47 advanced NSCLC patients were given either carboplatin plus etoposide chemotherapy (27 cases) or best supportive care (20 cases). No statistically significant differences were found in baseline characteristics and quality of life in the two groups. The median progression-free survival after two months was significantly higher (88.9% vs. 75.0%, p-value < 0.001) in the chemotherapy group than in the best supportive care group, but no there were no statistically significant differences between QoL of patients in the two groups. Carboplatin plus etoposide as third-line chemotherapy regimen demonstrated higher median progression-free survival in advanced NSCLC patients and did not adversely affect QoL.


Possibilities for extremophilic microorganisms in microbial electrochemical systems.
Microbial electrochemical systems exploit the metabolism of microorganisms to generate electrical energy or a useful product. In the past couple of decades, the application of microbial electrochemical systems has increased from the use of wastewaters to produce electricity to a versatile technology that can use numerous sources for the extraction of electrons on the one hand, while on the other hand these electrons can be used to serve an ever increasing number of functions. Extremophilic microorganisms grow in environments that are hostile to most forms of life and their utilization in microbial electrochemical systems has opened new possibilities to oxidize substrates in the anode and produce novel products in the cathode. For example, extremophiles can be used to oxidize sulfur compounds in acidic pH to remediate wastewaters, generate electrical energy from marine sediment microbial fuel cells at low temperatures, desalinate wastewaters and act as biosensors of low amounts of organic carbon. In this review, we will discuss the recent advances that have been made in using microbial catalysts under extreme conditions and show possible new routes that extremophilic microorganisms open for microbial electrochemical systems.


Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy.
In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1β/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.


The Association of Surgical Timing and Injury Severity With Systemic Complications in Severely Injured Patients With Pelvic Ring Injuries.
To evaluate the relationship between timing of definitive fixation, injury severity, and the development of systemic complications in severely injured patients with pelvic ring injuries. Retrospective review. Level 1 trauma center. One hundred eighteen severely injured [Injury Severity Score (ISS) ≥ 16] adult patients with pelvic ring injuries undergoing definitive fixation, excluding patients treated with external fixation for hemodynamic instability. Early fixation (≤36 hours) in 37 patients and delayed fixation (>36 hours) in 81 patients. Systemic complications (acute respiratory distress syndrome, pulmonary embolism, deep venous thrombosis, sepsis, multi-organ failure, and death). The delayed fixation group had a higher ISS and had more patients with chest injuries. There was no detectable difference in the number of patients with systemic complications between early versus delayed fixation groups [8 (22%) vs. 29 (35%), P = 0.1]. The only difference detected in specific complications was a higher incidence of pneumonia with delayed fixation [16 (20%) vs. 0 (0%), P = 0.004] with 11 of the 16 cases being associated with chest injury. Univariate analysis showed an association between complication and time to fixation, ISS, Glasgow Coma Scale, pH, base excess, and injuries to the head, chest, and abdomen. On multivariate analysis, only ISS remained significantly associated with the development of complications [Odds ratio 2.6 per 10 point increase, 95% confidence interval (CI), 1.4-4.4]. These data suggest that the severity of injury is most highly associated with systemic complications after definitive fixation of pelvic ring injuries. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Distinguishing androgenetic alopecia from chronic telogen effluvium when associated in the same patient: a simple noninvasive method.
Distinguishing chronic telogen effluvium (CTE) from androgenetic alopecia (AGA) may be difficult especially when associated in the same patient. One hundred consecutive patients with hair loss who were clinically diagnosed as having CTE, AGA, AGA + CTE, or remitting CTE. Patients washed their hair in the sink in a standardized way. All shed hairs were counted and divided "blindly" into 5 cm or longer, intermediate length (>3 to <5 cm), and 3 cm or shorter. The latter were considered telogen vellus hairs, and patients having at least 10% of them were classified as having AGA. We assumed that patients shedding 200 hairs or more had CTE. The kappa statistic revealed, however, that the best concordance between clinical and numerical diagnosis (kappa = 0.527) was obtained by setting the cutoff shedding value at 100 hairs or more. Of the 100 patients, 18 with 10% or more of hairs that were 3 cm or shorter and who shed fewer than 100 hairs were diagnosed as having AGA; 34 with fewer than 10% of hairs that were 3 cm or shorter and who shed at least 100 hairs were diagnosed as having CTE; 34 with 10% or more of hairs that were 3 cm or shorter and who shed at least 100 hairs were diagnosed as having AGA + CTE; and 14 with fewer than 10% of hairs that were 3 cm or shorter and who shed fewer than 100 hairs were diagnosed as having CTE in remission. This method is simple, noninvasive, and suitable for office evaluation.


Clinical use of percutaneous mechanical circulatory assistance in a patient with end-stage right-sided heart failure and massive tricuspid insufficiency due to congenital heart disease: first-in-the-world case report.
Due to improvement in the management of patients with congenital heart disease (CHD), the likelihood of their survival to adulthood is increasing. A relevant population suffers end-stage right ventricular failure (RVF) in their 3rd-4th decade of life. Hence, heart transplantation is still gold standard of treatment of end-stage heart failure, mechanical circulatory assistance has become a valuable tool in the bridging to heart transplant or definitive therapy. Use of implantable short-term or long-term devices is reported by others. However, within this clinical context, presence of significant tricuspid regurgitation (TR) or CHD is used as exclusion criteria for insertion of a percutaneous right ventricular circulatory support. We described a 36-year-old patient diagnosed with Ebstein's anomaly and severe TR who is admitted to hospital due to RVF refractory to standard medical treatment. After case presentation to the heart team, an Impella RP device insertion was scheduled, in spite of the presence of TR or CHD after evaluation of pulmonary valve competency and 3D reconstruction with virtual device implantation. During support, the patient improved clinically and haemodynamically. Due to device displacement to the right ventricle, it was bedside explanted after 30 days of support. After mechanical unloading during 30 days patients' right ventricle recovered partially, permitting patient to improve his functional class. Although TR and CHD are exclusion criteria for the implantation of the Impella RP device, we report clinical experience in patient with Ebstein's anomaly and severe TR supported with percutaneous device as bridge to heart transplantation during 30 days.


Effects of female sex steroids on Parkinson's disease in postmenopausal women.
There are conflicting reports about estrogen modulating the activity of nigrostriatal dopaminergic neurons. Furthermore, modulation may be influenced by progesterone levels. Therefore, the clinical effects of sex steroids on parkinsonian symptoms in postmenopausal women with Parkinson's disease (PD) were analyzed in the present study. Patients (n = 12) were under the age of 80, able to perform the motor function tests, and showed no contraindications for estrogen suppletion. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and a patient interview on subjective changes. In a placebo-controlled, randomized, double-blind trial lasting 8 weeks, no significant dopaminergic effect of estradiol (E2) could be demonstrated, whereas in an open trial phase lasting 2 weeks, progesterone seemed to have an antidopaminergic effect. Several mechanisms are discussed that can account for the fact that we found no effect of E2 on motor functioning in our patients with PD.


Mandarin tone perception in multiple-talker babbles and speech-shaped noise.
Lexical tone recognition in multiple-talker babbles (N = 1, 2, 4, 8, 10, or 12) and in speech-shaped noise at different signal-to-noise ratios (SNRs = -18 to -6 dB) were tested in 30 normal-hearing native Mandarin-speaking listeners. Results showed that tone perception was robust to noise. The performance curve as a function of N was non-monotonic. The breakpoint at which the performance plateaued was N = 8 for all SNRs tested with a slight improvement at N > 8 at -6 and -9 dB SNR.


Genetic therapy, identity and the person-regarding reasons.
It has been argued that there can be no person-regarding reasons for practising genetic therapy, since it affects identity and causes to exist an individual who would not otherwise have existed. And there can be no such reasons for causing somebody to exist because existing cannot be better for an individual than never existing. In the present paper, both of these claims are denied. It is contended, first, that in practically all significant cases genetic therapy will not affect the identity of beings of our kind. This is so irrespective of whether, essentially, we are beings with minds or beings of a certain biological species, the human one. Second, it is contended that, even if genetic therapy were to affect our identity, there could be person-regarding reasons for conducting it, for existence can be better than non-existence for the individual.


Peer-mediated check-in/check-out for students at-risk for internalizing disorders.
The present study investigated the effectiveness of peer-mediated check-in/check-out (CICO) on the internalizing behaviors of elementary school students. A nonconcurrent multiple-baseline design across participants was utilized to evaluate the intervention's effectiveness for 3 students in 1st and 2nd grade. Two 5th grade students were trained to implement CICO under the supervision of an adult intervention specialist. The peer-mediated CICO procedure was effective for 2 of the 3 participants as evidenced by moderate to large effect sizes; however, all 3 participants were identified as "at-risk" on a universal screener for internalizing problems. The results suggest peer-mediated CICO may be a resource-efficient Tier II strategy to meet the needs of students engaging in internalizing behavior within a multitiered framework of service delivery.


Difficult extubation: calming the sympathetic storm.
Tracheal extubation can evoke an equally strong haemodyamic stress response as tracheal intubation. We present a patient with myocardial infarction who repeatedly failed tracheal extubation. He developed acute pulmonary oedema following each attempt at tracheal extubation due to sympathetic overactivity. A change of approach with extubation under propofol sedation followed by continued sympatholysis with dexmedetomidine infusion allowed successful extubation.


[Causes of pilonidal sinus and pyoderma fistulans sinifica].
Pilonidal sinus is of the same origin as the Pyodermia fistulans sinifica . Both diseases are retention dermatopathies . These sinuses are not of congenital origin. Our observations have made an acquired origin seem more likely. Deep skin folds in the rima ani, the stiffness of the body hairs, the rolling movement of naturally separated hairs push the hair through the skin like a pin. If a hair is rubbed, it moves in the direction of its root with the peripherally directed hair scales. Excision of the sinus area and transplantation of an epithelial flap is the best therapy.


Histopathology of biocompatible hydroxylapatite-polyethylene composite in ossiculoplasty.
The biocompatibility of hydroxylapatite-polyethylene composite implants (HAPEX, Smith and Nephew) was investigated in this study. Eleven middle ear prostheses, removed during revision surgery, have been examined by light microscopy, transmission electron microscopy and scanning electron microscopy. The results show that the middle ear prostheses become overgrown by fibrous tissue inside a thin epithelial layer. In some cases the prosthesis is covered by fibrous tissue without an outer layer of epithelial cells. No arguments have been found for the accumulation of macrophages and foreign body giant cells associated with a foreign body reaction to the material. Therefore, hydroxylapatite-polyethylene composite implants (HAPEX, Smith and Nephew) would seem to be very suitable for reconstructive middle ear surgery.


Transient activation of the MAP kinase signaling pathway by the forward signaling of EphA4 in PC12 cells.
In the present study, we demonstrate that ephrin-A5 is able to induce a transient increase of MAP kinase activity in PC12 cells. However, the effects of ephrin-A5 on the MAP kinase signaling pathway are about three-fold less than that of EGF. In addition, we demonstrate that EphA4 is the only Eph member expressed in PC12 cells, and that tyrosine phosphorylation induced by ephrin-A5 treatment is consistent with the magnitude and longevity of MAP kinase activation. Experiments using the Ras dominant negative mutant N17Ras reveal that Ras plays a pivotal role in ephrin-A5-induced MAP kinase activation in PC12 cells. Importantly, we found that the EphA4 receptor is rapidly internalized by endocytosis upon engagement of ephrin-A5, leading to a subsequent reduction in the MAP kinase activation. Together, these data suggest a novel regulatory mechanism of differential Ras-MAP kinase signaling kinetics exhibited by the forward signaling of EphA4 in PC12 cells.


Challenges for providing health care in traumatized populations: barriers for PTSD treatments and the need for new developments.
There is a growing recognition about the effects of traumatic experiences on mental health worldwide. With ongoing conflicts, natural disasters, interpersonal violence, and other traumatic events it is estimated that approximately 70% of the global population have been exposed to at least one lifetime traumatic experience. Research shows a substantial proportion of survivors, especially in low- and middle-income countries, would have a posttraumatic stress disorder (PTSD). During recent decades effective evidence-based treatments for PTSD have been developed. However, there are significant barriers to mental health services and trauma-informed treatments are not easily available for trauma survivors. From the perspective of social psychotraumatology several core barriers to trauma treatments were identified, including the lack of acknowledgment, and avoidance of disclosure. The need for cultural sensitivity in PTSD treatments, the potential of alternative ways of treatment delivery, and the involvement of non-professional volunteers are proposed as directions for future developments in the field.


Alignment and characterization of remote-refocusing systems.
The technique of remote refocusing is used in optical microscopy to provide rapid axial scanning without mechanically perturbing the sample and in techniques such as oblique plane microscopy that build on remote refocusing to image a tilted plane within the sample. The magnification between the pupils of the primary (O1) and secondary (O2) microscope objectives of the remote-refocusing system has been shown previously by Mohanan and Corbett [J. Microsc.288, 95 (2022)JMICAR0022-272010.1111/jmi.12991] to be crucial in obtaining the broadest possible remote-refocusing range. In this work, we performed an initial alignment of a remote-refocusing system and then studied the effect of axial misalignments of O1 and O2, axial misalignment of the primary tube lens (TL1) relative to the secondary tube lens (TL2), lateral misalignments of TL2, and changes in the focal length of TL2. For each instance of the setup, we measured the mean point spread function F W H M xy of 100 nm fluorescent beads and the normalized bead integrated fluorescence signal, and we calculated the axial and lateral distortion of the system; all of these quantities were mapped over the remote-refocusing range and as a function of lateral image position. This allowed us to estimate the volume over which diffraction-limited performance is achieved and how this changes with the alignment of the system.


[Effect of nitroglycerin in acute myocardial infarction. III. Isosorbide dinitrate in patients with or without left-heart failure (author's transl)].
The oral effectiveness of isosorbide dinitrate (Isoket) was tested in 21 pateints with acute myocardial infarction. Patients were divided into two groups according to thier initial left-ventricular filling pressure (more or less than 20 mm Hg). In both groups there was a highly significant decrease in pulmonary artery pressure. In group I (less than 20 mm Hg) the left-ventricular filling pressure fell from 13.6 +/- 4.0 to 7.1 +/- 2.6 mm Hg, while in group II it fell from 26.9 +/- 4.6 to 19.0 +/- 3.6 mm Hg (P less than 0.001). The cardiac output fell in group I from 5.1 +/- 1.0 to 4.5 +/- 0.9 l/min, while in group II there was a significant rise from a low value (3.5 +/- 0.8 l/min) to 4.1 +/- 0.9 l/min (P less than 0.001). In both groups there was a slight but not significant fall in arterial blood pressure, while heart rate remained constant.


Effects of calmodulin antagonists on hormone release and cyclic AMP levels in GH3 pituitary cells.
In GH3 cells the calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-napthalene sulphonamide hydrochloride (W-7) showed a dose-dependent, biphasic effect on the release of growth hormone (GH) and prolactin (PRL). Hormone release was inhibited with 15-30 microM trifluoperazine and with 30-80 microM W-7, while stimulation was observed with 50-100 microM trifluoperazine and with 150 microM W-7. Trifluoperazine (greater than or equal to 30 microM) and W-7 (greater than or equal to 80 microM) increased the concentration of cellular cyclic AMP. Sulphoxides of trifluoperazine and chlorpromazine (less than or equal to 150 microM were without effect on hormone release and cellular cyclic AMP. Hydrolysis of cyclic AMP by GH3 cytosol was reduced after incubation of intact GH3 cells with trifluoperazine (15-60 microM). When trifluoperazine was incubated with cytosol, both the high and low affinity forms of cyclic AMP phosphodiesterase were inhibited competitively with calculated Ki of 4.5 and 56 microM, respectively. Stimulation of cyclic AMP phosphodiesterase caused by endogenous calmodulin was blocked by trifluoperazine. Particulate bound adenylyl cyclase activity was inhibited by trifluoperazine, and this effect was counteracted by endogenous calmodulin.


Biological cloning of functionally diverse quasispecies of HIV-1.
Twenty putative clones of HIV-1, derived by biological cloning from two different individuals, were characterized in vitro for functional activity and genotypic diversity. Many of the biological clones isolated by this method were genetically distinct, and could be further distinguished by differences in replication kinetics, host cell range, and/or cytopathicity. Our findings indicate that biological cloning by limiting dilution cultures is an effective method for isolating replication-competent, functionally diverse quasispecies of HIV-1.


Copper-Catalyzed Oxyvinylation of Diazo Compounds.
A copper(I)-catalyzed vinylation of diazo compounds with vinylbenziodoxolone reagents (VBX) as partners is reported. The transformation tolerates diverse functionalities on both reagents delivering polyfunctionalized vinylated products. The strategy was successfully extended to a three-component/intermolecular version with alcohols. The obtained products contain synthetically versatile functional groups, such as an aryl iodide, an ester, and an allylic leaving group, enabling further modification.


Influence of coccidiosis vaccination on nutrient utilization of corn, soybean meal, and distillers dried grains with solubles in broilers.
Two experiments were conducted to determine the impact of coccidiosis vaccination on the apparent ileal digestibility (AID) of nutrients and ileal digestible energy (IDE) in commonly used feed ingredients in broilers. Eight experimental treatments based on a factorial arrangement of coccidiosis vaccination (control with in-feed diclazuril [CTL] or vaccinated [VAC]) and 4 different diets were administered to male Cobb 500 broilers in floor pens containing 12 birds per pen. For the vaccinated group, a 3× dose of a live coccidiosis vaccine was given via oral gavage on the day of hatch. Experimental diets consisted of a basal diet and 3 test diets in which 30% of the basal diet was replaced with either corn, soybean meal (SBM), or distillers dried grains with solubles (DDGS) to allow for calculation of nutrient digestibility of individual ingredients by difference. Broilers were fed a common diet from 0 to 7 D and experimental diets from 7 to 12 D. On day 12, blood and ileal digesta were collected to measure plasma carotenoids and determine AID of nitrogen, ether extract, IDE (experiments 1 and 2), and amino acids (AA) (experiment 2). Vaccination increased (P < 0.05) excreta oocyst counts and decreased (P < 0.05) plasma carotenoids when compared with CTL birds. Interactive effects (P < 0.05) were observed for AID of nitrogen (experiment 1) which was reduced by vaccination in birds fed the corn diet and increased for birds fed DDGS. No differences (P > 0.05) in IDE were observed between VAC and CTL birds in either experiment, whereas vaccination decreased (P < 0.05) AID of ether extract independently of diet. Interactive effects (P < 0.05) were observed for AA digestibility, whereby digestibility of all AA was reduced by VAC in corn diets but generally increased AA digestibility of DDGS diets, with minimal impact on SBM diets. In conclusion, the impact of coccidiosis vaccination on nutrient and energy digestibility varied among ingredients; however, digestibility was minimally impacted or improved with DDGS.


Coherent Random Lasing from Dye Aggregates in Polydimethylsiloxane Thin Films.
The coherent random laser (CRL) from dye-doped polydimethylsiloxane (PDMS) has been investigated in both nanoparticle-doped (NP-doped) thin films and pure dye thin films. Compared with the literature, the pump threshold is only 1.5 mJ/cm2 in the pure dye thin film with a low dye concentration. The spontaneously formed micro-/nanocrystals of Pyrromethene 597 (PM597) dye support both gain and random feedback in the bulk of the PDMS during the sample preparation. When the SiO2 NPs were doped, the pump threshold was reduced to 0.75 mJ/cm2. The threshold increased after the film was peeled off from glass, which indicates that the photon localization effect of the leaky-waveguide structure plays an important role in the reduction of the CRL threshold. By a change in the pump stripe length or the thickness of the film, the peak wavelength red-shifts 6.7 or 5.93 nm, respectively. The PM597 dye molecule solubility changes, and they spontaneously aggregate in the process of toluene volatilization; the PDMS cures, which is the reason for the formation of PM597 micro-/nanocrystals. This thin film random laser with a low dye concentration can be used in integrated optoelectronics and display imaging.


Proteomics of Culture Filtrate of Prevalent Mycobacterium tuberculosis Strains: 2D-PAGE Map and MALDI-TOF/MS Analysis.
Although diverse efforts have been done to identify biomarkers for control of tuberculosis using laboratory strain Mycobacterium tuberculosis H37Rv, the disease still poses a threat to mankind. There are many emerging M. tuberculosis strains, and proteomic profiling of these strains might be important to find out potential targets for diagnosis and/or prevention of tuberculosis. We evaluated the comparative proteomic profiling of culture filtrate (CF) proteins from prevalent M. tuberculosis strains (Central Asian or Delhi type; CAS1_Del, East African-Indian; EAI-3 and Beijing family) by 2D polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. As a result, we could identify 12 CF proteins (Rv0066c, Rv1310, Rv3375, Rv1415, Rv0567, Rv1886c, Rv3803c, Rv3804c, Rv2031c, Rv1038c, Rv2809, and Rv1911c), which were consistently increased in all prevalent M. tuberculosis strains, and interestingly, two CF proteins (Rv2809, Rv1911c) were identified with unknown functions. Consistent increased intensity of these proteins suggests their critical role for survival of prevalent M. tuberculosis isolates, and some of these proteins may also have potential as diagnostic and vaccine candidates for tuberculosis, which needs to be further explored by immunological analysis.


Polymeric Micelle of A₃B-Type Lactosome as a Vehicle for Targeting Meningeal Dissemination.
Polymeric micelle of the A₃B-type lactosome comprising (poly(sarcosine))₃-b-poly(l-lactic acid) was labeled with 111In. The 111In-labeled A₃B-type lactosome was administered to the model mice bearing meningeal dissemination and bone metastasis at mandible. With single-photon emission computed tomography (SPECT) imaging, the meningeal dissemination was identified successfully by 111In-labeled A₃B-type lactosome, which was superior to 201TlCl in regard of the imaging contrast. The 111In-labeled A₃B-type lactosome was also potential in imaging selectively of bone metastasis at mandible, whilst a nonspecific imaging of the whole bone was obtained by the SPECT imaging using 99mTc-HMDP. The polymeric micelle of the A₃B-type lactosome was therefore found to be effective as a vehicle of 111In to be targeted to meningeal dissemination and bone metastasis.


Testing of microsatellite multiplexes for individual identification of Cape Parrots (Poicephalus robustus): paternity testing and monitoring trade.
Illegal trade in rare wildlife species is a major threat to many parrot species around the world. Wildlife forensics plays an important role in the preservation of endangered or threatened wildlife species. Identification of illegally harvested or traded animals through DNA techniques is one of the many methods used during forensic investigations. Natural populations of the South African endemic Cape Parrot (Poicephalus robustus) are negatively affected by the removal of eggs and chicks for the pet trade. In this study, 16 microsatellite markers specifically designed for the South African endemic Cape Parrot (P. robustus) are assessed for their utility in forensic casework. Using these 16 loci, the genetic diversity of a subset of the captive Cape Parrot population was also assessed and compared to three wild Cape Parrot populations. It was determined that the full 16 locus panel has sufficient discriminatory power to be used in parentage analyses and can be used to determine if a bird has been bred in captivity and so can be legally traded or if it has been illegally removed from the wild. In cases where birds have been removed from the wild, this study suggests that a reduced 12 locus microsatellite panel has sufficient power to assign confiscated birds to geographic population of origin. The level of genetic diversity observed within the captive Cape Parrot population was similar to that observed in the wild populations, which suggests that the captive population is not suffering from decreased levels of genetic diversity. The captive Cape Parrots did however have double the number of private alleles compared to that observed in the most genetically diverse wild population. This is probably due to the presence of rare alleles present in the founder population, which has not been lost due to genetic drift, as many of the individuals tested in this study are F1-F3 wild descendants. The results from this study provide a suit of markers that can be used to aid conservation and law enforcement authorities to better control legal and illegal trade of this South African endemic.


[Recombinational cloning of large DNA fragments of bacterial chromosome by plasmid rescue].
To develop a new method to cline large DNA fragment by combining whole genome sequence information and the principle of plasmid rescue. First, we amplified a fragment downstream the region to be cloned and cloned the fragment into a suicide plasmid to construct targeting plasmid, which was then targeted into chromosome by homologous recombination. Then, genomic DNA was isolated, digested with appropriate enzyme, re-ligated and transformed into host bacteria to rescue the plasmid and the large DNA fragment. The rescued DNA fragment was sub-cloned into new plasmids for special purposes. Using this method, we successfully cloned the 11kb virB operon of Brucella and constructed complementary plasmid. The transcription of the disrupted virB operon was restored with the complementary plasmid, validating the feasibility of the strategy. This recombinational cloning strategy provides us a new method to modify large DNA fragment of bacteria.


What Mindfulness can learn about Dissociation and what Dissociation can learn from Mindfulness.
Mindfulness based psychotherapeutic interventions have shown to be an effective intervention for quite some time now. These intervention, however, have not been that successful with individuals who experience dissociative disorders. There is a very clear disconnect between these two fields. In an attempt to close the gap, reviewing what mindfulness might be from an attachment and human developed lens, one can learn that there is a lot more occurring in a mindful state other than relaxation. There is a level of human development achievement that comes from a regular mindfulness practice that seems to play a role in raising our young and being part of a complex social group. Evidence suggests that the end product of mindfulness is likely deeply connected human relationships and balanced care-giving abilities. In knowing the benefits from a relational perspective of mindfulness those in the dissociative world can utilize adaptations of mindfulness so that their clients can eventually learn to developed mindfulness and, in turn, have the same deeply connected relationship that they often missed. Conversely those in the mindfulness based therapeutic world can learn a lot about dissociation and harmed people by understanding the real difficulties that individuals with dissociative disorders have in experiencing a mindful state. They can learn to understand the need to adapt mindfulness based practices to accommodate individuals who have a system that is phobic of awareness, terrified of being calm and who have no concept of what non-judgement means. Both fields would benefit greatly by knowing more about the other.


Outcomes of discharge from hospital for elderly people.
The numbers of elderly people going home from hospital in the United Kingdom are likely to increase over the next decade. Previous research suggests that this group of people are liable to experience some difficulties on returning home. This paper reports the findings of a study of the outcomes of discharge for 32 elderly people admitted to geriatric wards. A lower level of independence in daily living activities, and an increase in the amount of help needed after hospitalization were found. An increase in the rate of discharge of elderly people will have implications for both formal and informal carers.


Ion channels and early development of neural cells.
In this review we underscore the merits of using voltage-dependent ion channels as markers for neuronal differentiation from the early stages of uncommitted embryonic blastomeres. Furthermore, a fairly large part of the review is devoted to the descriptions of the establishment of a simple model system for neural induction derived from the cleavage-arrested eight-cell ascidian embryo by pairing a single ectodermal with a single vegetal blastomere as a competent and an inducer cell, respectively. The descriptions are focused particularly on the early developmental processes of various ion channels in neuronal and other excitable membranes observed in this extraordinarily simple system, and we compare these results with those in other significant and definable systems for neural differentiation. It is stressed that this simple system, for which most of the electronic and optical methods and various injection experiments are applicable, may be useful for future molecular physiological studies on the intracellular process of differentiation of the early embryonic cells. We have also highlighted the importance of suppressive mechanisms for cellular differentiation from the experimental results, such as epidermal commitment of the cleavage-arrested one-cell Halocynthia embryos or suppression of epidermal-specific transcription of inward rectifier channels by neural induction signals. It was suggested that reciprocal suppressive mechanisms at the transcriptional level may be one of the key processes for cellular differentiation, by which exclusivity of cell types is maintained.


Impact of SiO2 nanoparticles on the structure and property of type I collagen in three different forms.
Silica-based nanoparticles have found application in the development of biocomposites involving reconstituted collagen in tissue engineering and wound healing, and leather modification, specifically targeting collagen fibers. However, a comprehensive investigation into the interaction between collagen-silica nanoparticles and different forms of collagen using biophysical methods remains unexplored. In this study, we examined the interaction between silica (SiO2) nanoparticles and collagen in its fiber, microfibril, and monomer forms through high-resolution scanning electron microscopy, circular dichroism, Fourier-transform infrared spectroscopy, fluorescence analysis, zeta potential measurements, and turbidity assays. Our results reveal that SiO2 nanoparticles exhibited a non-specific attraction towards collagen fibers without disrupting their structural integrity. Interestingly, SiO2 nanoparticles influenced the process of microfibrillation, resulting in heterogeneous fibril diameters while maintaining the natural D-periodicity. This finding is significant, as fibril size variations can impact the properties of collagen composites. Notably, the triple helical structure of collagen in its monomer form remained unaffected in the presence of SiO2 nanoparticles, indicating that the nanoparticles did not disrupt the electrostatic interactions that stabilize the triple helix. Additionally, the increased stability of SiO2 nanoparticles in the presence of collagen confirmed their interaction. These findings provide a promising avenue for the development of SiO2-based nanoparticles to enhance the stability of collagen fibers and control fiber sizes for biomaterial preparation. Moreover, this study advances the potential application of SiO2-based nanoparticles in leather tanning, an emerging field where nanoparticles can play a crucial role.


Oxidases as Oxygen Scavengers in Hypoxic Conditions: A Kinetic Model.
A simple kinetic model allowed for the description of the observed decay of the oxygen content in hypoxic aqueous samples with and without headspace, in the presence of glucose oxidase (Glucox) or laccase and their substrates (glucose for Glucox and ABTS for Laccase). The experimental tests involved both the direct measurement of the oxygen content with a fluorescence-based probe and the indirect stopped-flow spectroscopic detection of colored compounds generated from suitable chromogenic reagents. The complete depletion of dissolved oxygen occurred in the no-headspace samples, whereas some residual oxygen remained in a steady state in the samples with headspace. Simple pseudo-first-order kinetics was adequate to describe the behavior of the system, as long as oxygen was the rate-limiting compound, i.e., in the presence of excess substrates. The values of the kinetic constants drawn from best-fit routines of the data from both experimental approaches were quite comparable. The oxygen residues in the samples with headspace seemed related to the low solubility of O2 in the aqueous phase, especially if compared with the large amount of oxygen in the headspace. The extent of such residue decreased by increasing the concentration of the enzyme. The kinetic model proposed in this paper can be of help in assembling suitable sensors to be used for food safety and quality control.


The Impact of Deep Sternal Wound Infection on Mortality and Resource Utilization: A Population-based Study.
Recent national infection control efforts have been directed at reducing postsurgical infection rates, related morbidity, and cost. We sought to evaluate population-level rates of deep sternal wound infection (DSWI) after cardiac surgery, associated mortality, and resource use compared to patients undergoing cardiac surgery without postoperative DSWI relative to historical trends. We analyzed the MarketScan ® Commercial Claims Databases from 2009 to 2013 to identify adult patients who developed DSWI after open cardiac surgery. Patients with and without DSWI were compared. The outcomes of interest included 30-day, 90-day, and 1-year in-hospital mortality. Utilization outcomes, including total hospital days and inpatient costs, were calculated in the time period from the index cardiac surgery through 90 days after DSWI diagnosis. In this cohort, 176,537 patients underwent one or more cardiac surgery procedures. DSWI occurred in 2835 (1.6 %) patients. One-year mortality for patients with DSWI was 10.7 versus 2.5 % (P < 0.001) in patients without DSWI. Mean hospital days in patients with DSWI were 33 versus 9 days for patients without DSWI (P < 0.001). Mean cost for patients with DSWI was greater than 2.5 times that of patients without DSWI ($211,478 vs $82,089, P < 0.001). Treatment of DSWI results in substantial morbidity, mortality, and excess cost for treating facilities. The rates of DSWI have not decreased dramatically over the last 10-20 years. Thus, more attention needs to be focused toward understanding treatment variation that exists in patients diagnosed with DSWI.


Pyoderma gangrenosum in childhood.
A review of our records disclosed eight children with pyoderma gangrenosum. All had associated inflammatory bowel disease, and four had arthritis. In three patients the bowel disease was severe and required resection of portions of the affected bowel. The cutaneous lesions had a chronic course (average duration, 2 1/2 years), and systemic therapy was required in seven cases. Previously reported cases of pyoderma gangrenosum in children are reviewed, and the management of this skin disorder in childhood is discussed.


Dose-response pharmacology of intrathecal morphine in human volunteers.
Intrathecal morphine sulfate (ITMS) administration was introduced into clinical practice in 1979. Inadequate information exists delineating ITMS respiratory effects in the dosage range most frequently employed today. This study evaluated 0.2, 0.4, and 0.6 mg ITMS in male volunteers. Twenty healthy, young, adult male volunteers received 0.0, 0.2, 0.4, or 0.6 mg preservative-free ITMS in an isobaric solution administered at the L3-L4 interspace in a double-blind randomized fashion. Respiratory function was assessed by finger pulse oximetry (SpO2), respiratory rate, and arterial blood gas analysis via an indwelling arterial catheter and the slope of the ventilatory response to carbon dioxide (VE/CO2). Analgesia was assessed by the effect of ITMS on moderate pain produced by pressure algometry at the tibia. The need for supplemental oxygen, 2 L/min via nasal cannulae, was determined by the failure of verbal and tactile prompts to maintain subjects' SpO2 > or = 85% on more than two occasions. Heart rate, arterial blood pressure, sedation level, pupil size, and the incidence of adverse effects also were documented. All the above measurements were made before and 30 min after ITMS, hourly for 11 h, and then every 2 h for 12 more h. ITMS produced significant dose-related decreases in SpO2. Mild desaturations (SpO2 > or = 85 and < 90%) occurred in 2 of 5, 3 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. Moderate to severe desaturations (SpO2 < 85%) occurred in 0 of 5, 2 of 5, and 4 of 5 subjects receiving 0.2, 0.4, and 0.6 mg ITMS, respectively. The need for supplemental oxygen also was significantly related to ITMS dose, with 0 of 5, 1 of 5, and 4 of 5 subjects requiring oxygen after 0.2, 0.4, and 0.6 mg ITMS, respectively. Nasal oxygen administration consistently alleviated hypoxemia. Increases in arterial carbon dioxide tension (PaCO2) and decreases in pH were significantly related to ITMS dose. Peak mean PaCO2s were 42.4, 44.9, and 50.7 mmHg in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These peaks occurred 6.5-7.5 h after ITMS injection. ITMS produced significant dose-related depression of VE/CO2. Maximum mean depressions of VE/CO2 were to 61%, 63%, and 32% of baseline in the 0.2-, 0.4-, and 0.6-mg groups, respectively. These nadirs occurred 3.5-7.5 h after ITMS injection. Some subjects receiving 0.6 mg ITMS experienced profound (< 20% of baseline) and prolonged (< 50% of baseline for up to 20 h) VE/CO2 depression. Magnitude and duration of analgesia after ITMS were dose-related. Changes in heart rate, systolic blood pressure, and respiratory rate were not significantly related to ITMS dose. Hypoxemia was not related to respiratory rate. Although ITMS produced statistically significant dose-related increases in sedation and decreases in pupil size, these changes were small and did not coincide with hypoxemia. ITMS caused dose-related increases in emesis, but the severity of pruritus and urinary retention was unrelated to dose. ITMS produced dose-related analgesia and respiratory depression in nonsurgical healthy, young, adult male volunteers. Respiratory depression was significant after 0.2 or 0.4 mg and profound and prolonged after 0.6 mg. No clinical signs or symptoms, including respiratory rate, reliably indicated hypoxemia. Pulse oximetry reliably detected hypoxemia after ITMS, and supplemental nasal oxygen (2 L/min) effectively corrected this hypoxemia.


Reducing consequences of child maltreatment during adulthood by public health actions: a Delphi study.
Child maltreatment (CM) is associated with long-lasting poor health outcomes, as well as increased levels of disability and health-services consumption across the life-span. However, less is known about how CM consequences can be reduced during adulthood. We investigated professional opinions on how to mitigate long-term consequences of CM in a public health (PH) perspective. Using the Delphi method in three rounds, we inquired 91 professionals, mostly European researchers and clinicians about potential PH actions to mitigate CM consequences during adulthood. Most experts agreed that PH actions are needed. Increasing community awareness and training emotional regulation in affected adults were prioritized strategies. Enlarging curricular knowledge about CM for professionals and developing evidence-based interventions were considered preferred methods. Reducing the barriers for access to interventions for adults, such as those provided by trauma-informed services were also suggested. Participants highlighted the possibility to reduce CM consequences across generations as a significant benefit. PH programmes to reduce the burden of CM can be enhanced by specific actions to facilitate the recognition of difficulties in affected adults and to expand the availability of helpful resources. The application of these programmes could be assisted by the use of modern information-technology.


Elaborating a systems methodology for cascading climate change impacts and implications.
New research is drawing attention to the potential for climate change to generate cascading impacts and implications across linked human-environment systems, requiring closer accounting of these interactions to anticipate the emergence of surprises and feedbacks. However, there is little practical guidance for those interested in characterising, identifying or assessing cascades, and few empirical examples. In this paper, we elaborate a systems-based methodology to identify and evaluate cascading climate change impacts and implications. We illustrate its application using the case of a participatory process with urban infrastructure managers, facing the legacy effects of damaging earthquakes and the prospect of future climate change. The results show the proposed approach and visualisation of cascades as causal diagrams provides a robust and flexible analytical framework. The use of systems thinking, visual aids, interactive discussion and expert elicitation generated valuable information about potential cascades, their interactions across domains of interest, and the implications for management. The process can provide a basis for further empirical application and advance methodological and conceptual development. Specifically, the systems methodology:•Identifies interdependencies and interconnections which may serve as transmission pathways for climate-related impacts;•Enhanced stakeholders' understanding of multiple causes and effects of climate change; and•Produced a useful visual aid for stakeholders to explore cascading impacts and implications, and opportunities for intervention.


The Applicability of a Human Immunohistochemical Panel to Mouse Models of Hepatocellular Neoplasia.
Various immunohistochemical panels are used as aids to distinguish between primary hepatocellular malignancies and metastatic tumors and between benign lesions and carcinomas. We compared the immunohistochemical spectrum of hepatocellular lesions in mice with that of human hepatocellular carcinoma (HCC). Specifically, we compared the staining parameters of 128 murine foci of cellular alteration (FCA) and tumors (adenoma and HCC) from archival tissue blocks of 3 transgenic mouse models (LFABP-cyclin D1, Alb1-TGFβ1, and LFABP-cyclin D1 × Alb1-TGFβ1) with those of archival human HCC (n = 5). Antibodies were chosen according to their published performance and characterization in human hepatocellular tumor diagnosis and included: arginase 1 (Arg1), β-catenin, glutamine synthetase (GS), glypican 3, hepatocyte paraffin 1 (HepPar1), and cytokeratin 19 (CK19). GS was the single best immunostain for identifying hepatocellular tumors in mice, with 100% positive staining. Data showed a trend toward loss of normal function (staining) with Arg1, with a higher percentage of positive staining in FCA than in adenomas and HCC. All FCA lacked murine β-catenin nuclear translocation, which was present in 2 of the 7 adenomas and 22 of the 96 HCC tested. HepPar1 staining was lower than anticipated, except in trabecular HCC (16 of 22 samples were positive). Glyp3 stained very lightly, and only scattered CK19-positive cells were noted (4 of 44 cases of mouse trabecular HCC). Thus, GS appears to be the most useful marker for identifying neoplasia in the transgenic mouse models we tested and should be included in immunohistochemistry assessing hepatocellular neoplasia development.


Using the Beers criteria to identify potentially inappropriate medication use by older adult dental patients.
An aging population indicates that increasing numbers of older adults will seek oral health care and have multiple chronic conditions treated with a number of medications. The authors examined the Medicare Current Beneficiary Survey administrative data set to characterize potentially inappropriate medication (PIM) use by older adults visiting the dentist and related adverse experiences that may affect oral health care. The authors used the 2015 Beers criteria to identify PIMs for older adults. The authors examined the Medicare Current Beneficiary Survey administrative data set for community-dwelling older adults with dental care visits and reported national prevalence estimates of Beers criteria medication prescribing. The authors used logistic regression to identify sociodemographic and health-related characteristics associated with potentially inappropriate prescribing. The authors described medication-related adverse experiences affecting dental care. Among older adults with dental care visits, 56.9% received a prescription for at least 1 Beers criteria medication, and 28.3% received a prescription for 2 or more Beers criteria medications. Beers criteria medication use was associated most strongly with the number of comorbid diseases as represented by higher Charlson Index scores (odds ratios, > 1.0). A substantial proportion of community-dwelling older adults visiting dentists had received prescriptions for 1 or more potentially age-inappropriate Beers criteria medications. Many of these medications have adverse effects that could affect patient safety and oral health care. These results support the need for clinicians to be aware of PIM use by older adults, recognize associated medication-related adverse events, and avoid prescribing age-inappropriate medications to this vulnerable patient population.


ZR-75-1 breast cancer cells generate nonconjugated steroids from low density lipoprotein-incorporated lipoidal dehydroepiandrosterone.
Fatty acid esters of dehydroepiandrosterone (DHEA-FA) are present in the circulation, although no physiological function has yet been attributed to these metabolites. They are formed directly in serum and are predominantly localized in association with lipoproteins. The objective of this study was to determine the capacity of these lipoprotein-incorporated DHEA metabolites to generate nonconjugated steroids after incubation with cells in culture. A method for studying DHEA-FA using a radiolabeling technique that marks human low density lipoproteins (LDL) with tritiated DHEA-FA was elaborated. Analysis of the fatty acid composition of tritiated DHEA-FA-labeled LDL ([3H] DHEA-FA-LDL) indicated the prevalence of DHEA-linoleate/palmitoleate and DHEA-oleate. Incubation of [3H]DHEA-FA-LDL with ZR-75-1 breast cancer cells produced a time-dependent increase in labeled nonconjugated steroids in the cell culture medium, whereas the levels of tritiated DHEA-FA decreased. Lipoidal radioactivity in cells increased with time, but nonconjugated radioactivity associated with the cells showed no such increase. HPLC analysis of the culture medium indicated the presence of DHEA and androst-5-ene-3 beta,17 beta-diol. The endogenous levels of lipoidal DHEA were also determined in human plasma and its lipoprotein components to reveal that these metabolites circulate naturally in the range of 6.5 +/- 0.4 nM. Approximately 90% of this concentration was associated with the lipoprotein components, namely among the LDL and high density lipoprotein fractions. These results suggest that lipoidal DHEA may indeed act as a substrate for potent steroid formation after their entry into steroid target cells.


Perinatal adversities in tuberous sclerosis complex: Determinants and neurodevelopmental outcomes.
To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4-254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93-323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann-Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.


Xanthones from the green fruit hulls of Garcinia mangostana.
Three new xanthones, mangostenol (1), mangostenone A (2), and mangostenone B (3), were isolated from the green fruit hulls of Garcinia mangostana, along with the known xanthones, trapezifolixanthone, tovophyllin B (4), alpha- and beta-mangostins, garcinone B, mangostinone, mangostanol, and the flavonoid epicatechin. The structures of the new xanthones were elucidated by analysis of their spectroscopic data.


Radiation-induced lesions of the brachial plexus correlated to the dose-time-fraction schedule.
Radiation induced brachial plexus lesions were correlated to the dose-time-fraction schedule. Ellis' formula was used and the mathematical treatments were made according to KIRK et coll. (1971). It was found that the frequency of lesions increases very rapidly for small increases of CRE over a certain level.


Dynamics of cholesteric structures in an electric field.
Motivated by Lehmann-like rotation phenomena in cholesteric drops we study the transverse drift of two types of cholesteric fingers, which form rotating spirals in thin layers of cholesteric liquid crystal in an ac or dc electric field. We show that electrohydrodynamic effects induced by Carr-Helfrich charge separation or flexoelectric charge generation can describe the drift of cholesteric fingers. We argue that the observed Lehmann-like phenomena can be understood on the same basis.


[The application of a periarterial synthetic tube results in the formation of rhythmic structures in the intima].
Structure of rabbit carotid artery and aorta after their wrapping with synthetic tube was investigated using light and scanning electron microscopy. Periarterial manipulations lead to the development of myointimal thickening covered with endothelium. Surface of the thickening consisted of rhythmically intermitted elevations and pits situated across the long axis of the vessel. Polymorphism of the covering endothelium was observed. Non-random pattern of the subendothelial smooth muscle cells location (connected with hemodynamic changes) was the main cause of formation of rhythmic structures. Structure of intimal thickening in rabbit arteries is similar to that of human aortic intima at early stages of atherogenesis (before lipid accumulation). This model may be used for studying the mechanisms of atherogenesis as well as for pharmacological investigations.


[Incidentaloma--one of the greatest challenges of modern endocrinology].
Technological advance of the recent years has contributed to the development of the situation during which clinically inapparent masses are discovered in endocrine organs by high-resolution radiological imaging procedures that have been performed for other reasons. Most of these lesions, frequently referred to as incidentalomas, are clinically insignificant benign and hormonally inactive adenomas that neither pose a risk to a patient's health nor warrant the risks of further diagnosis and treatment. One of the greatest challenges of modern endocrinology is to distinguish the vast majority of clinically insignificant changes from other masses requiring further management such as hormone-secreting tumours and malignant lesions. Over the years a myriad of the diagnostic and therapeutic approaches has been recommended and presently there are still no uniform guidelines. The purpose of his article is to give an overview on the recent advances in diagnosis and management of pituitary and adrenal incidentalomas. We provide the reader with practical recommendations and underline areas in which further studies are required.


Protected carotid stenting: safety and efficacy of the MedNova NeuroShield filter.
Neuroprotection during carotid stenting has the potential to reduce procedural atheroembolic sequelae. We report the United Kingdom experience of NeuroShield (MedNova Ltd, Horsham, West Sussex, United Kingdom). We performed a prospective cohort analysis of 50 consecutive patients (50 lesions) in a regional vascular tertiary referral center (catchment area one million) that provides an institutional service for the short term. The subjects were all the patients referred for carotid stenting after preassessment by a multidisciplinary team. All the patients underwent pretreatment with antiplatelet agents. Forty-two patients had atherosclerotic stenosis of the carotid bifurcation between 70% and 95% (with North American Symptomatic Carotid Endarterectomy Trial criteria). Six patients had restenosis after endarterectomy. Two had previous local radiotherapy. Forty-two patients were symptomatic (amaurosis fugax/central retinal artery occlusion in 11 cases, and hemispheric transient ischemic attack/cerebrovascular accident in 31 cases). Eight patients were asymptomatic with bilateral high-grade stenoses, with six cases before coronary artery bypass grafting. The intervention performed was protected primary carotid stenting. Outcome measures were procedural atheroembolic events, including all-stroke and death rates up to 30 days, and analysis of retrieved debris in a subset of 11 cases. The technical success rate was 50/50 (100%) for stenting and 49/50 (98%) for filter placement/retrieval. Technical complications comprised nonsymptomatic spasm at the filter site (flow limiting in two cases and non-flow limiting in five cases). Procedural events were one minor stroke (patient fully recovered within 48 hours) in a complex clinical setting and one ventricular fibrillation arrest in a patient before coronary artery bypass grafting who was resuscitated without neurologic event. At 30 days, the death or major disability from stroke rate was 2/50 (4%). No cases were atheroembolic. The all-stroke/death rate was 3/50 (6%). The two deaths were the result of a fatal hemorrhagic stroke that occurred at 4 days and was thought to be caused by reperfusion and a perforated ventricle caused by a temporary pacing wire. One femoral pseudoaneurysm followed failed closure device deployment and required percutaneous thrombin injection. The mean particle number per patient was 12 (range, 0 to 41). The mean particle diameter was 284.9 microm(range, 31 to 1430 microm). The mean ellipsoid volume load was 0.1602 mm(3) (range, 0.0005 to 0.1968 mm(3)). Carotid stenting protected with NeuroShield is safe. The filter traps embolic debris liberated during the procedure.


Temporal Discounting and the Tendency to Delay Gratification across the Eating Disorder Spectrum.
Bulimia nervosa (BN) and binge eating disorder (BED) have been associated with poorer reward-related inhibitory control, reflected by a reduced tendency to delay gratification. The opposite has been reported in anorexia nervosa (AN), but differences have not been directly compared across eating disorders (EDs). This study investigated self-reported (Delaying Gratification Inventory) and task-based (temporal discounting) inhibitory control in 66 women with an ED and 28 healthy controls (HCs). Poorer task-based inhibitory control was observed in the BN compared with the AN group and poorer self-reported inhibitory control in the BN and in the BED groups compared with the AN and the HC groups, suggesting that reward-related inhibitory control varies across EDs. Symptom severity correlated with poorer self-reported (but not task-based) inhibitory control across the EDs. These data provide some support for transdiagnostic mechanisms and highlight the importance of addressing perceived loss of control in the treatment of EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


Local and global genetic diversity of protozoan parasites: Spatial distribution of Cryptosporidium and Giardia genotypes.
Cryptosporidiosis and giardiasis are recognized as significant enteric diseases due to their long-term health effects in humans and their economic impact in agriculture and medical care. Molecular analysis is essential to identify species and genotypes causing these infectious diseases and provides a potential tool for monitoring. This study uses information on species and genetic variants to gain insights into the geographical distribution and spatial patterns of Cryptosporidium and Giardia parasites. Here, we describe the population heterogeneity of genotypic groups within Cryptosporidium and Giardia present in New Zealand using gp60 and gdh markers to compare the observed variation with other countries around the globe. Four species of Cryptosporidium (C. hominis, C. parvum, C. cuniculus and C. erinacei) and one species of Giardia (G. intestinalis) were identified. These species have been reported worldwide and there are not unique Cryptosporidium gp60 subtype families and Giardia gdh assemblages in New Zealand, most likely due to high gene flow of historical and current human activity (travel and trade) and persistence of large host population sizes. The global analysis revealed that genetic variants of these pathogens are widely distributed. However, genetic variation is underestimated by data biases (e.g. neglected submission of sequences to genetic databases) and low sampling. New genotypes are likely to be discovered as sampling efforts increase according to accumulation prediction analyses, especially for C. parvum. Our study highlights the need for greater sampling and archiving of genotypes globally to allow comparative analyses that help understand the population dynamics of these protozoan parasites. Overall our study represents a comprehensive overview for exploring local and global protozoan genotype diversity and advances our understanding of the importance for surveillance and potential risk associated with these infectious diseases.


[Clinical manifestations of disseminated sclerosis in childhood].
The author studied children from 6-14 years with disseminated sclerosis in the area of a decreased risk to this disease. The early period of the disease in this age group was very difficult to discern. As a rule, disseminated sclerosis in children in detected by a retrospective analysis of the clinical development. In children, as in adults, the clinical course has a remittent development, where there are remissions and exacerbations. More frequently than in adults, the disease acquires a hyperkinetic form, which is considered to be most malignant. Probably the disease occurs not at 12-15 years, as it is being pointed in the literature but much earlier (4-5 years). Exacerbations of disseminated sclerosis in children, unlike exacerbations in adults occur not so much from the influence of cold factors as from warm. In order to avoid a hyperdiagnosis of disseminated sclerosis in children a differential diagnosis should be made between hereditary-degenerative disorders of the nervous system and progressive forms of panencephalitis.


A Novel Rehabilitation Intervention for Older Patients With Acute Decompensated Heart Failure: The REHAB-HF Pilot Study.
This study sought to assess a novel physical rehabilitation intervention in older patients hospitalized for acute decompensated heart failure (ADHF). After ADHF, older patients, who are frequently frail with multiple comorbidities, have prolonged and incomplete recovery of physical function and remain at high risk for poor outcomes. The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) pilot study was a 3-site, randomized, attention-controlled pilot study of a tailored, progressive, multidomain physical rehabilitation intervention beginning in the hospital and continuing for 12 weeks post-discharge in patients ≥60 years hospitalized with ADHF. The primary purpose was to assess the feasibility and reasonableness of the hypothesis that the novel rehabilitation intervention would improve physical function (Short Physical Performance Battery [SPPB]) over 3 months and reduce all-cause rehospitalizations over 6 months. The study enrolled 27 patients with ADHF (ages 60 to 98 years; 59% women; 56% African American; 41% with preserved ejection fraction [≥45%]). At baseline, participants had marked impairments in physical function, multiple comorbidities, and frailty. Study retention (89%) and intervention adherence (93%) were excellent. At 3 months, an intervention effect size was measured for the SPPB score of +1.1 U (7.4 ± 0.5 U vs. 6.3 ± 0.5 U), and at 6 months an effect size was observed for an all-cause rehospitalization rate of -0.48 (1.16 ± 0.35 vs. 1.64 ± 0.39). The change in SPPB score was strongly related to all-cause rehospitalizations, explaining 91% of change. These findings support the feasibility and rationale for a recently launched, National Institutes of Health-funded trial to test the safety and efficacy of this novel multidomain physical rehabilitation intervention to improve physical function and reduce rehospitalizations in older, frail patients with ADHF with multiple comorbidities. (Rehabilitation and Exercise Training After Hospitalization [REHAB-HF]; NCT01508650; A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038).


Efficacy of Carotenoid-Loaded Gelatin Nanoparticles in Reducing Plasma Cytokines and Adipocyte Hypertrophy in Wistar Rats.
The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation.


Stationary cycling and children with cerebral palsy: case reports for two participants.
These case reports describe a stationary cycling intervention and outcomes for two child participants (P1 and P2) with spastic diplegic cerebral palsy. Each child completed a 12-week, 30-session cycling intervention consisting of strengthening and cardiorespiratory fitness phases. P1 exhibited higher training intensities, particularly during the cardiorespiratory phase. Average training heart rates were 59% and 35% of maximum heart rate for P1 and P2, respectively. Lower extremity peak knee flexor and extensor moments, gross motor function (Gross Motor Function Measure (GMFM-66)), preferred walking speed (thirty-second walk test), and walking endurance (600-yard walk-run test) were measured pre- and postintervention. Changes in outcome measurements corresponded with differences in exercise intensity. Greater gains in peak knee extensor moments, GMFM-66 scores (+4.2 versus +0.9), 600-yard walk-run test (-29% versus 0%) occurred for P1 versus P2, respectively. Preferred walking speeds did not increase substantially for P1 and decreased for P2.


Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis.
The effect of consumption of Immulina, a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis, on adaptive immune responses was investigated by evaluation of changes in leukocyte responsiveness to two foreign recall antigens, Candida albicans (CA) and tetanus toxoid (TT), in vitro. Consumption of Immulina by 11 healthy male volunteers caused an immediate, but temporary, increase of CA-induced CD4+ T-helper (Th) cell proliferation (P < .02). TT-induced Th cell proliferation was increased in individuals over 50 years of age (P < .05) and correlated with age (P < .02). Consumption for 8 days enhanced the CA-induced B cell proliferation (P < .02), but after 56 days a diminution was seen (P < .03). The CA-elicited production of the Th1 cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and interferon (IFN)-gamma was increased after Immunlina administration for 3 days (P < .001, < .03, and < .007, respectively), and increased IL-2 production persisted after 56 days (P < .004). The TNF-alpha, IFN-gamma, and IL-6 responses to TT were enhanced after 8 and 14 days (P < .002-.05), while IL-5 responses increased significantly within 3 days (P < .04) and fell below baseline levels after 14 days (P < .008). Conversely, consumption for 3 days inhibited the IL-4 responses to both CA and TT (P < .008 and P < .03, respectively). No effects on IL-10 responses were observed. Upon addition to normal mononuclear cells in vitro, Immulina elicited strong TNF-alpha, IL-1beta, and IL-6 responses, indicating that it acts by inducing a pro-inflammatory state. Taken together, the data suggest that Immulina causes an age-dependent, temporary enhancement of adaptive immune responses.


Energetic aminated-azole assemblies from intramolecular and intermolecular N-HO and N-HN hydrogen bonds.
Compounds with adjacent C-NO2, C-NH2 and N-NH2 groups were designed and synthesized via amination. Their structures were characterized by infrared, and multinuclear NMR spectroscopy, elemental analysis, and X-ray single crystal diffraction. The effect of intramolecular and intermolecular N-HO and N-HN hydrogen bonds is discussed. Detonation properties were calculated by EXPLO 5 software based on calculated HOFs and experimental densities.


Modeling the effects of torsional disorder on the spectra of poly- and oligo-(p-phenyleneethynylenes).
The absorption spectra of phenyleneethynylene oligomers show an unusual change in shape with oligomer length. The unusual aspects of the spectra arise from rotation of the phenylene rings about the long axis of the oligomer. In the ground electronic state, the barrier to this rotation is low and the spectra in room temperature come from an ensemble of different structures. In the excited electronic state, the barrier to rotation is substantially higher, giving rise to strong nonlinear electron-phonon coupling. A multidimensional semiempirical model that includes these effects is developed for the photophysics of phenyleneethynylene oligomers. The ground-state energy is modeled with a molecular mechanics expression, and the excitation energy is modeled with an exciton model. Intermediate Neglect of Differential Overlap/Singles Configuration Interaction (INDO/SCI) calculations verify the exciton model and provide initial estimates of the model parameters. These parameters generate the qualitative features seen in experimental spectra. Inclusion of entropy effects from the multiple torsional coordinates is essential. Refinement of the parameters yields quantitative agreement with experiment. This agreement shows that coupling to torsional motion is a major factor in the spectroscopy and photophysics of these conjugated polymers.


Differentiation of pluripotent stem cells into striatal projection neurons: a pure MSN fate may not be sufficient.
Huntington's disease (HD) is an autosomal dominant inherited disorder leading to the loss inter alia of DARPP-32 positive medium spiny projection neurons ("MSNs") in the striatum. There is no known cure for HD but the relative specificity of cell loss early in the disease has made cell replacement by neural transplantation an attractive therapeutic possibility. Transplantation of human fetal striatal precursor cells has shown "proof-of-principle" in clinical trials; however, the practical and ethical difficulties associated with sourcing fetal tissues have stimulated the need to identify alternative source(s) of donor cells that are more readily available and more suitable for standardization. We now have available the first generation of protocols to generate DARPP-32 positive MSN-like neurons from pluripotent stem cells and these have been successfully grafted into animal models of HD. However, whether these grafts can provide stable functional recovery to the level that can regularly be achieved with primary fetal striatal grafts remains to be demonstrated. Of particular concern, primary fetal striatal grafts are not homogenous; they contain not only the MSN subpopulation of striatal projection neurons but also include all the different cell types that make up the mature striatum, such as the multiple populations of striatal interneurons and striatal glia, and which certainly contribute to normal striatal function. By contrast, present protocols for pluripotent stem cell differentiation are almost entirely targeted at specifying just neurons of an MSN lineage. So far, evidence for the functionality and integration of stem-cell derived grafts is correspondingly limited. Indeed, consideration of the features of full striatal reconstruction that is achieved with primary fetal striatal grafts suggests that optimal success of the next generations of stem cell-derived replacement therapy in HD will require that graft protocols be developed to allow inclusion of multiple striatal cell types, such as interneurons and/or glia. Almost certainly, therefore, more sophisticated differentiation protocols will be necessary, over and above replacement of a specific population of MSNs. A rational solution to this technical challenge requires that we re-address the underlying question-what constitutes a functional striatal graft?


Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia.
To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein (HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipidemia. A randomized, double-blind placebo controlled and parallel group trial was conducted. Patients with CHD and CHD risk equivalents with mixed dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while triglyceride (TG) > or = 200 mg/dL and < 500 mg/dL, was combined with omega-3 fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on HsCRP, total cholesterol (TC), LDL-ch, high-density lipoprotein cholesterol (HDL-ch), TG, lipoprotein (a) [LP (a)], apolipoprotein A1 (apoA1), apolipoprotein B (apoB), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were investigated. Forty patients finished the study with each group consisting of twenty patients. (1) There were significant reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 +/- 2.77 mg/L (38.5%), 94.0 +/- 65.4 mg/dL (31.1%), 13.3 +/- 22.3 mg/dL (6.3%), 0.78 +/- 1.60 respectively in the omega-3 fatty acids group (P < 0.01, < 0.001, < 0.05, < 0.05) compared to the baseline. HsCRP and triglyceride reduction were more significant in omega-3 fatty acids group compared to the placebo group (P = 0.021 and 0.011 respectively). (2) In the omega-3 fatty acids group, the values and percentage of TG reduction had a significantly positive relation with HsCRP reduction (r = 0.51 and 0.45, P = 0.021 and 0.047 respectively). In CHD and CHD risk equivalent patients with mixed dyslipidemia, dyslipidemia's therapeutic effect using simvastatin and omega-3 fatty acids may result from not only the combination of lipid adjustment, but also enhancement of their own nonlipid influences.


Isolation and partial characterisation of the relaxation protein from nuclei of cultured mouse and human cells.
A protein, called relaxation protein because of its ability to remove superhelical turns in closed-circular DNA, has been isolated and partially characterized from the nuclei of LA9 mouse and HeLa cells. The purification was facilitated by an assay method, with PM2 DNA, which used the fluorescence enhancement of the intercalating dye ethidium bromide upon binding to the closed-circular DNA. The amount of dye bound depends upon the degree of the superhelix density of the DNA. The relaxation products were analysed by the buoyant separation method in CsCl containing ethidium bromide and were shown to be completely relaxed. The purification resulted in a single band in a dodecylsulfate gel electrophoresis with an apparent molecular weight of 37000. The pH optimum is 7.0 and the optimal salt concentration is 0.2 M NaCl. The relaxation protein removes negative as well as positive supercoils, the latter generated by the interaction of ethidium bromide with closed-circular DNA. Relaxation of positive supercoils results, after removal of the dye, in the formation of molecules with superhelix densities exceeding that of native PM2 DNA (0.054). The highest negative superhelix density observed was -0.098 +/- 0.001. The corresponding positive superhelix density has been calculated to be + 0.023. A nicking--swivelling--closing mechanism is postulated, but nicked intermediates have so far not been demonstrated. The relaxation protein is not inhibited by known mammalian endonuclease I inhibitors, except for denatured DNA, and does not possess a conventional polynucleotide ligase activity. The relaxation activity was found to be predominantly in the nuclei, with only small amounts present in the cytoplasm and mitochondria. The biological function of transient swivels induced by the relaxation protein is not known. However, transient swivels are considered necessary or useful in the replication of closed-circular DNA or long linear DNA, respectively. Relaxation protein could replace the combined action of an endonuclease and a ligase ahead of the replication fork. Alternatively, transient swivels could be involved in the transcription process.


Hypercalciuria in clinical pediatrics. A review.
Idiopathic hypercalciuria is a cause of a variety of urinary tract complaints in clinical pediatrics. These include gross or microscopic hematuria, enuresis, urinary frequency or urgency, dysuria, sterile pyuria, and proteinuria in addition to renal calculi. A random urine calcium-creatinine concentration ratio can be used to initially screen for hypercalciuria. Patients with indeterminate results should have the test repeated, while those with abnormal values should receive a complete metabolic workup to determine the cause of hypercalciuria. Identifiable causes of hypercalciuria should be treated specifically, and thiazide diuretics are the preferred treatment for uncomplicated renal calculi. Pharmacotherapy in children with idiopathic hypercalciuria and symptomatology other than renal stones is controversial and should be limited to patients with severe clinical manifestations.


Testing Antimicrobial Properties of Human Lactoferrin-Derived Fragments.
Lactoferrin, an iron-binding glycoprotein, plays a significant role in the innate immune system, with antibacterial, antivirial, antifungal, anticancer, antioxidant and immunomodulatory functions reported. It is worth emphasizing that not only the whole protein but also its derived fragments possess antimicrobial peptide (AMP) activity. Using AmpGram, a top-performing AMP classifier, we generated three novel human lactoferrin (hLF) fragments: hLF 397-412, hLF 448-464 and hLF 668-683, predicted with high probability as AMPs. For comparative studies, we included hLF 1-11, previously confirmed to kill some bacteria. With the four peptides, we treated three Gram-negative and three Gram-positive bacterial strains. Our results indicate that none of the three new lactoferrin fragments have antimicrobial properties for the bacteria tested, but hLF 1-11 was lethal against Pseudomonas aeruginosa. The addition of serine protease inhibitors with the hLF fragments did not enhance their activity, except for hLF 1-11 against P. aeruginosa, which MIC dropped from 128 to 64 µg/mL. Furthermore, we investigated the impact of EDTA with/without serine protease inhibitors and the hLF peptides on selected bacteria. We stress the importance of reporting non-AMP sequences for the development of next-generation AMP prediction models, which suffer from the lack of experimentally validated negative dataset for training and benchmarking.


Trauma unit attendance: Is there a relationship with weather, sporting events and week/ month-end times? An audit at an urban tertiary trauma unit in Cape Town.
The Groote Schuur Hospital Trauma Unit is a high-volume referral center where patient volumes may be related to temporal and environmental factors. This audit aimed to determine if numbers of patients presenting after motor vehicle collisions (MVCs) and interpersonal violence (IPV) were related to temporal factors, weather variables and important soccer matches. Numbers of patients presenting to the unit per shift over 17 months were obtained from unit logs. Weather data, local soccer match locations and results, and information regarding public holidays and long weekends were obtained for the relevant shifts. Average daily attendances for IPV-related injuries and MVCs were compared across the various external factors described. Poisson regression models were fitted and used to express the relative incidence of attendances. These results are expressed using incidence rate ratios (IRRs). For the study period, 7 350 attendances due to IPV-related injuries, and 3 188 injuries due to MVCs were recorded. Weekdays, long-weekend nights and month-end weekends had increased MVC-related attendance. Precipitation also increased attendances related to MVCs. Public holidays had less MVC-related attendance. IPV-related attendances were increased at night, on long weekends, and on month-end weekends. Weekend shifts were busier than weekday shifts, particularly at month-end. Long weekends showed similar trends to ordinary weekends, and public holidays showed similar trends to ordinary weekdays. Increasing temperatures are associated with increased attendances. Soccer matches and their outcomes have no significant effect on IPV-related attendances. Temporal and weather factors can help predict which trauma unit shifts will be busiest.


Globally-Optimized Local Pseudopotentials for (Orbital-Free) Density Functional Theory Simulations of Liquids and Solids.
The accuracy of local pseudopotentials (LPSs) is one of two major determinants of the fidelity of orbital-free density functional theory (OFDFT) simulations. We present a global optimization strategy for LPSs that enables OFDFT to reproduce solid and liquid properties obtained from Kohn-Sham DFT. Our optimization strategy can fit arbitrary properties from both solid and liquid phases, so the resulting globally optimized local pseudopotentials (goLPSs) can be used in solid and/or liquid-phase simulations depending on the fitting process. We show three test cases proving that we can (1) improve solid properties compared to our previous bulk-derived local pseudopotential generation scheme; (2) refine predicted liquid and solid properties by adding force matching data; and (3) generate a from-scratch, accurate goLPS from the local channel of a non-local pseudopotential. The proposed scheme therefore serves as a full and improved LPS construction protocol.


Peer Phubbing and Social Networking Site Addiction: The Mediating Role of Social Anxiety and the Moderating Role of Family Financial Difficulty.
A growing body of research has pinpointed the consequences as well as mechanisms of phubbing. However, few studies have explored the relationship between peer phubbing and social networking site addiction. Based on the self-determination theory, the exclusion theory of anxiety, the social compensation model, and the reserve capacity model, the present study examined whether peer phubbing was positively related to social networking site addiction among undergraduates, whether social anxiety mediated the relationship, and whether this mediating process was moderated by family financial difficulty. Our theoretical model was tested using the data collected from 1,401 Chinese undergraduates (M age = 18.83 years, standard deviation = 0.93). The participants completed anonymous questionnaires that assessed their peer phubbing, social anxiety, social networking site addiction, and family financial difficulty. The correlation analysis indicated that peer phubbing was positively associated with social networking site addiction. The testing for moderated mediation further revealed that social anxiety partially mediated the association between peer phubbing and social networking site addiction, with family financial difficulty moderating the first stage. To be specific, the indirect association between peer phubbing and social networking site addiction via social anxiety was stronger for undergraduates in high family financial difficulty. The results from this study extend research on the potential consequences of phubbing as well as highlight the significance of uncovering the underlying mechanisms.


[Surgical correction of the upper and lower arm of children].
The causes of post-traumatic deformities of the upper and lower arm shafts as well as the complete elbow are 90% iatrogenic, in the area of the proximal humerus and the distal lower arm they are about 90% the result of chance (premature closure of the growth plate). In general, corrections of deformities are possible at any age, dependent on the patient's symptoms, the expected development, the location of the deformity and its changes during development. The correction technique should allow for the removal of all of the components of the deformity, and to retain the results until healing is complete and the patient's motor stability is ensured. Due to the high percentage of iatrogenic deformities, the optimisation of the primary therapy should receive particular attention rather than increasing the indications for a correction.


Bovine model of chronic ischemic cardiomyopathy: implications for ventricular assist device research.
Ventricular assist devices (VADs) have emerged as a successful treatment option for advanced heart failure. The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves (n = 17, 94 ± 7 kg), 90 μm microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end-organ blood flows were quantified with 15-μm fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test VAD and adjunctive biological therapies.


Unraveling Oxygen Evolution in Li-Rich Oxides: A Unified Modeling of the Intermediate Peroxo/Superoxo-like Dimers.
Peroxo/superoxo is a key intermediate in oxygen evolution/reduction reactions in (electro)catalysis. However, peroxo/superoxo analogues have aroused controversies relevant to the origin of oxygen-anion redox. Specifically, some characteristics such as the magnitude of the O-O bond length in bulk materials have been puzzling during oxygen oxidation, as has the relationship between the peroxo/superoxo intermediate and the release of oxygen. The latter is a major safety concern to the application of oxygen-anion redox in lithium ion batteries. Herein, we present a unified modeling of the full delithiation process for model system Li2MnO3 by using first-principles calculations. We find that the cationic antisite defects and the electron deficiency are two major limiting factors in the anionic oxidation whose state can evolve, as the degree of delithiation increases, from the electron/hole, through peroxo-like O2δ- dimer formation, to the eventual release of gas-phase oxygen molecule. During the delithiation process, the dangling oxygen (i.e., singly coordinated with Mn) pairs play a critical role in intermediate dimer formation. Meanwhile, we identify five generic binding patterns of O2δ- dimers with Mn ions for which the O-O bond length varies from 1.45 Å in the peroxo state to 1.22 Å in the gas-phase oxygen molecule. Moreover, the dominant features of the three molecular orbitals, σc, πa, and πb, are distinguished, with the corresponding energy levels being highly delocalized and mixed as a result of the interplay with the host lattice. This work provides a deep understanding of the intermediate states of the anionic redox and suggests new strategies that mitigate oxygen release for the design of highly efficient and safe Li-rich cathode materials.


Efficient Photoelectrochemical Reduction of Carbon Dioxide to Formic Acid: A Functionalized Ionic Liquid as an Absorbent and Electrolyte.
Photoelectrochemical (PEC) reduction of carbon dioxide (CO2 ) is a potential method for production of fuels and chemicals from a C1 feedstock accumulated in the atmosphere. However, the low solubility of CO2 in water, and complicated processes associated with capture and conversion, render CO2 conversion inefficient. A new concept is proposed in which a PEC system is used to capture and convert CO2 into formic acid. The process is assisted by an ionic liquid (1-aminopropyl-3-methylimidazolium bromide) aqueous solution, which functions as an absorbent and electrolyte at ambient temperature and pressure. Within this PEC reduction strategy, the ionic liquid plays a critical role in promoting the conversion of CO2 to formic acid and suppressing the reduction of H2 O to H2 . At an applied voltage of 1.7 V, the Faradaic efficiency for formic acid production is as high as 94.1 % and the electro-to-chemical efficiency is 86.2 %.


Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists.
The mechanisms by which arginine vasopressin (AVP) exerts its antidiuretic and pressor effects, via activation of V2 and V1a receptors, respectively, are relatively well understood, but the possible associated effects on sodium handling are a matter of controversy. In this study, normal conscious Wistar rats were acutely administered various doses of AVP, dDAVP (V2 agonist), furosemide, or the following selective non-peptide receptor antagonists SR121463A (V2 antagonist) or SR49059 (V1a antagonist). Urine flow and sodium excretion rates in the next 6 h were compared with basal values obtained on the previous day, after vehicle treatment, using each rat as its own control. The rate of sodium excretion decreased with V2 agonism and increased with V2 antagonism in a dose-dependent manner. However,for comparable increases in urine flow rate, the V2 antagonist induced a natriuresis 7-fold smaller than did furosemide. Vasopressin reduced sodium excretion at 1 mug/kg but increased it at doses >5 umg/kg,an effect that was abolished by the V1a antagonist. Combined V2 and V1a effects of endogenous vasopressin can be predicted to vary largely according to the respective levels of vasopressin in plasma,renal medulla (acting on interstitial cells), and urine (acting on V1a luminal receptors). In the usual range of regulation, antidiuretic effects of vasopressin may be associated with variable sodium retention. Although V2 antagonists are predominantly aquaretic, their possible effects on sodium excretion should not be neglected. In view of their proposed use in several human disorders, the respective influence of selective (V2) or mixed (V1a/V2) receptor antagonists on sodium handling in humans needs reevaluation.