Carbonate formation on bioactive glasses.
The system termed 58S is a sol-gel-synthesized bioactive glass composed of SiO2, CaO, and P2O5, used in medicine as bone prosthetic because, when immersed in a physiological fluid, a layer of hydroxycarbonate apatite is formed on its surface. The mechanism of bioactive glass 58S carbonation was studied in the vacuum by means of in-situ FTIR spectroscopy with the use of CO2, H2O, and CD3CN as probe molecules. The study in the vacuum was necessary to identify both the molecules specifically involved in the carbonation process and the type of carbonates formed. Bioactive glass 58S was compared to a Ca-doped silica and to CaO. On CaO, ionic carbonates could form by contact with CO2 alone, whereas on 58S and on Ca-doped silica carbonation occurred only if both CO2 and an excess of H2O were present on the sample. The function of H2O was not only to block surface cationic sites, so that CO2 could not manifest its Lewis base behavior, but also to form a liquid-like (mono)layer that allowed the formation of carbonate ions. The presence of H2O is also supposed to promote Ca2+ migration from the bulk to the surface. Carbonates formed at the surface of CaO and of Ca-bearing silicas (thus including bioactive glasses) are of the same type, but are produced through two different mechanisms. The finding that a water excess is necessary to start heavy carbonation on bioactive glasses seemed to imply that the mechanism leading to in-situ carbonation simulates, in a simplified and easy-to-reproduce system, what happens both in solution, when carbonates are incorporated in the apatite layer, and during sample shelf-aging.


Comparison of functional outcome after anterior cruciate ligament reconstruction resulting in low, normal and increased laxity.
The aim of the study was to analyse and compare the results after arthroscopic anterior cruciate ligament (ACL) reconstruction using patellar tendon autografts in three groups of patients. The groups were determined by knee laxity as measured with the KT-1000 arthrometer at the follow-up two to five years after the reconstruction. Group A (n=15) had an anterior side-to-side laxity difference of <-3 mm (i.e. the reconstructed knee was less lax than the contralateral non-injured knee), Group B (n=376) had a difference of > or = -1, but < or = +2 mm and Group C (n=38) had a difference of > or g=6 mm. All the patients had a normal contralateral knee. In Group A, 7/15 (47%) patients and, in Group B, 82/375 (22%) patients had an extension deficit of > or =5 degrees (P=0.052). The corresponding values in terms of flexion deficit were 8/15 (53%) and 99/375 (26%) respectively (P=0.04) (one missing value in Group B). In Group C, 14/38 (37%) had an extension deficit (P=0.04; Group B vs Group C). Group C displayed worse results than Group B in terms of the Lysholm score and the one-leg-hop test (P=0.001 and P=0.011 respectively). The corresponding comparison between Group A and Group B revealed no significant differences. We conclude that a considerable number of patients showed persisting deficits in range of motion (ROM) after an ACL reconstruction. No major differences were found if they were analysed in subgroups with decreased, near normal or with increased knee laxity. The worst residual functional impairment, as measured with the Lysholm score and one-leg-hop test, was found in the group with increased knee laxity and most ROM deficits in the knees with decreased laxity.


Analysis of Performance Improvement of Real-time Internet of Things Application Data Processing in the Movie Industry Platform.
The goal of this study is to plan and develop complete strategies to improve the performance of film industry. The primary objectives of this study are to investigate a dataset generated by a IoT application and the nature of the data forms obtained, the speed of the data arriving rate, and the required query response time and to list the issues that the current film industry faces when attempting to handle IoT applications in real time. Finally, in film industry platforms, high performance with varied stream circulation levels of real-time IoT application information was realized. In this study, we proposed three alternative methods on top of the Storm platform, nicknamed Re-Storm, to improve the performance of IoT application data. Three different proposed strategies are (1) data stream graph optimization framework, (2) energy-efficient self-scheduling strategy, and (3) real-time data stream computing with memory DVFS. The work proposed a methodology for dealing with heterogeneous traffic-aware incoming rate of data streams Re-Storm at multiple traffic points, resulting in a short response time and great energy efficiency. It is divided into three parts, the first of which is a scientific model for fast response time and great energy efficiency. The distribution of resources is then considered using DVFS approaches, and successful optimum association methods are shown. Third is self-allocation of worker nodes towards optimizing DSG using hot swapping and making the span minimization technique. Furthermore, the testing findings suggest that Re-Storm outperforms Storm by 20-30% for real-time streaming data of IoT applications. This research focuses on high energy efficiency, short reaction time, and managing data stream traffic arrival rate. A model for a specific phase of data coming via IoT and real-time computing devices was built on top of the Storm platform. There is no need to change any software approach or hardware component in this design, but only merely add an energy-efficient and traffic-aware algorithm. The design and development of this algorithm take into account all of the needs of the data produced by IoT applications. It is an open-source platform with less prerequisites for addressing a more sophisticated big data challenge.


Pediatric Primary Care Diagnoses Among Children with Intrauterine Opioid Exposure.
Characterizing common concerns for children with intrauterine opioid exposure (IOE) can inform tailored primary care. Retrospective analysis of primary care data of children with IOE from birth to age two years within one multi-state pediatric health system. Well child care (WCC) and problem-based visit diagnoses were categorized, and descriptive statistics were tabulated. Three hundred and eighty-five (385) children with IOE had 3,622 primary care visits, of which 51.4% were WCC and 48.6% were problem-based. Most frequent visit diagnoses were upper respiratory complaints (14.8% of visits), feeding difficulties (12.2%), and perinatal viral exposure (9.8%). Although visit type (WCC vs. problem-based) varied across diagnostic category, frequent utilization of both visit types were documented for several diagnoses in infancy (e.g., fussiness/colic, feeding difficulties). Well child care visits for children with IOE are key opportunities for anticipatory guidance with an emphasis on problems that may contribute to acute health care utilization, particularly in early infancy.


Properties of the polysaccharide and mucopeptide components of the cell wall of Lactobacillus casei.
1. The polysaccharide and mucopeptide components of the cell wall of Lactobacillus casei have been separated by mild conditions of acid hydrolysis. 2. Removal of the polysaccharide renders the mucopeptide susceptible to lysozyme. 3. The mucopeptide and polysaccharide components have been analysed and the results compared with those obtained previously. 4. The polysaccharides responsible for group specificity have a terminal reducing N-acetylgalactosamine residue substituted on C((3)) by the adjacent sugar; estimation of this component gave an indication of the molecular weight of the polysaccharides. 5. Evidence has been obtained for the presence of rhamnosyl-(1-->3)-N-acetylgalactosamine among the products of acid hydrolysis of the group B polysaccharide.


Primary Ciliary Dyskinesia and Situs Ambiguus: A Rare Association.
Primary ciliary dyskinesia (PCD) is a rare disorder with impaired ciliary function resulting in a spectrum of clinical manifestations of varying severity. PCD affects approximately one in every 20,000 individuals with a reported prevalence between 1:4000 and 1:50,000. Due to its nonspecific clinical features, the condition is usually diagnosed late in its course, unless situs inversus (SI) or organ laterality defects are discovered at imaging. A small subset of patients with PCD display associated organ laterality defects, different from the classical SI totalis. We present here, the clinical and imaging findings in a young female with PCD along with left-sided isomerism, a variant of heterotaxy syndromes.


Pharmacological properties of prejunctional alpha-adrenoceptors in isolated feline middle cerebral arteries; comparison with the postjunctional alpha-adrenoceptors.
In cat middle cerebral arteries (CMCA) preincubated with 3H-noradrenaline (NA), the outflow of tritium evoked by electrical stimulation was reduced to 32% by alpha-adrenoceptor (alpha-receptor) stimulation with oxymetazoline, and increased to 487% by alpha-receptor blockade with HEAT. The relative order of potency for alpha-receptor agonists on prejunctional receptors was: clonidine greater than or equal to oxymetazoline greater than phenylephrine, and the antagonist rauwolscine was more potent than prazosin. This indicates that the prejunctional alpha-receptors are mainly of alpha 2-type. Rauwolscine was more potent than prazosin in inhibiting the contractions induced by NA, indicating a predominance of alpha 2-receptors postjunctionally. Apart from clonidine having higher intrinsic activity pre- than postjunctionally, all drugs examined (oxymetazoline, phenylephrine, rauwolscine, HEAT (BE2254), and prazosin) had similar concentration-effect curves on the pre- and postjunctional receptors. Furthermore, the ratios of EC50-values pre- and postjunctionally of rauwolscine, oxymetazoline, and clonidine were all close to unity. These results indicate that pre- and postjunctional alpha 2-receptors in the CMCA have similar pharmacological characteristics and cannot be influenced separately by the presently used drugs.


Effect of Education on Preventive Behaviors of Osteoporosis in Adolescents: A Systematic Review and Meta-Analysis.
Osteoporosis is one of the diseases that can be prevented by correcting health behaviors during adolescence. This study was conducted to evaluate the effect of education on preventive behaviors of osteoporosis including physical activity, calcium intake and practice (primary outcomes) and knowledge and attitude related to osteoporosis (secondary outcomes) in adolescents. A search was done in Cochrane Library, PubMed, Embase, Web of Sciences, Scopus, Google Scholar, SID and Magiran regardless of the time limit. To evaluate the quality of selected controlled trials, Cochrane collaboration' instrument was used for assessing the risk of bias. RevMan software was used to analysis and report the data. Of 2159 articles retrieved, 20 of them were reviewed and 18 of them entered the mete-analysis. The meta-analysis showed significant differences between the education and control groups in terms of calcium intake (SMD = 0.78, 95%CI = 0.55 to 1.02, P < 0.00001), practice (SMD = 0.54, 95%CI = 0.41 to 0.68, P < 0.0001), knowledge (SMD = 1.76, 95%CI = 1.10 to 2.42, P < 0.00001) and attitude (SMD = 0.96, 95%CI = 0.53 to 1.40, P < 0.0001) mean score in adolescents but education is not effective on average minute/week of physical activity per week (MD = 31.94, 95%CI = -6.53 to 70.40, P = 0.10), mean score of physical activity (MD = 2.66, 95%CI = -0.55 to 5.88, P = 0.10) and percent of students participated in the physical activity (OR = 1.45, 95%CI = 0.30 to 6.91, P = 0.64). Education is effective in improving their knowledge and attitudes toward osteoporosis. It can also improve some health-related behaviors for bone health such as sufficient dairy calcium intake but it has not been effective in establishing a regular exercise program.


Hyperthyroidism. Current treatment guidelines.
Hyperthyroidism is common and affects approximately 2% of women and 0.2% of men. The most common cause of hyperthyroidism is Graves' disease, an autoimmune disorder associated with circulating immunoglobulins that bind to and stimulate the thyrotropin (TSH) receptor, resulting in sustained thyroid overactivity. Toxic nodular goitres cause hyperthyroidism due to autonomous hyperfunctioning of localised areas of the thyroid. There are 3 recognised modalities of treatment for hyperthyroidism: antithyroid drugs, surgery and radioiodine. All are effective but no single method offers an absolute cure. Patients with Graves' disease may be prescribed antithyroid drugs over a period of 12 to 18 months with a view to inducing a long term remission. These drugs are also often given for a short period to render the patient euthyroid before definitive therapy with radioiodine or thyroidectomy. However, antithyroid drugs will not 'cure' hyperthyroidism associated with a toxic nodular goitre. The use of radioiodine as a first-line therapy for hyperthyroidism is growing. It is well tolerated, with the only long term sequelae being the risk of developing radioiodine-induced hypothyroidism. Radioiodine can be used in all age groups other than children, although it should also be avoided in pregnancy and during lactation. Pregnancy should be avoided for 4 months following its administration. Radioiodine may cause a deterioration in Graves' ophthalmopathy and corticosteroid cover may reduce the risk of this complication. The treatment of choice for toxic nodular goitre hyperthyroidism is radioiodine. Surgery, either subtotal or near-total thyroidectomy, has limited but specific roles to play in the treatment of hyperthyroidism: this approach is rarely used in patients with Graves' disease unless radioiodine has been refused or there is a large goitre causing symptoms of compression in the neck. The goal of surgery is to cure the underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism.


Late, but not early, asthmatic reactions induced by toluene-diisocyanate are associated with increased airway responsiveness to methacholine.
We investigated whether airway responsiveness to methacholine differs in subjects with a history of sensitization to TDI who develop immediate, dual, late, or no asthmatic reactions after exposure to TDI, and also the effect of a TDI inhalation challenge in asthmatic subjects with hyperreactive airways with no history of sensitization to TDI. We measured FEV-1 immediately before and after exposure to TDI (0.018 ppm; 5-30 min) and then hourly for 8 h and the provocative dose (mg) of methacholine that caused a decrease in FEV-1 of 20% (PD20 FEV-1). The results of the present study suggest that the bronchoconstrictor effect of isocyanates is specifically linked to exposure to TDI and subsequent sensitization, excluding a nonspecific irritant effect on the airways. Moreover, they suggest that the increase in airway responsiveness to methacholine associated with the late asthmatic reaction is linked to factors that cause the late component of the asthmatic reaction.


CXCL8 induces M2 macrophage polarization and inhibits CD8+ T cell infiltration to generate an immunosuppressive microenvironment in colorectal cancer.
The poor prognosis of immunotherapy in patients with colorectal cancer (CRC) necessitates a comprehensive understanding of the immunosuppressive mechanisms within tumor microenvironment (TME). Undoubtedly, the anti-tumor immune cells play an indispensable role in immune tolerance. Therefore, it is imperative to investigate novel immune-related factors that have the capacity to enhance anti-tumor immunity. Here, we employed bioinformatic analysis using R and Cytoscape to identify the hub gene chemokine (C-X-C motif) ligand 8 (CXCL8), which is overexpressed in CRC, in the malignant progression of CRC. However, its specific role of CXCL8 in CRC immunity remains to be elucidated. For this purpose, we evaluated how tumor-derived CXCL8 promotes M2 macrophage infiltration by in vivo and in vitro, which can be triggered by IL-1β within TME. Mechanistically, CXCL8-induced polarization of M2 macrophages depends on the activation of the STAT3 signaling. Finally, immunohistochemistry and multiplexed immunohistochemistry analysis identified that CXCL8 not only enhances PD-L1+ M2 macrophage infiltration but also attenuates the recruitment of PD-1+ CD8+ T cells in murine CRC models. Together, these findings emphasize the critical role for CXCL8 in promoting M2 macrophage polarization and inhibiting CD8+ T cell infiltration, thereby links CXCL8 to the emergency of immunosuppressive microenvironment facilitating tumor evasion. Overall, these findings may provide novel strategy for CRC immunotherapy.


Childhood myeloid leukaemias.
Childhood myeloid leukaemias are a diverse collection of conditions. Although many are also seen in adults, some are peculiar to childhood. In childhood AML, as in adults, cytogenetic abnormalities are associated with specific clinical features and define prognostic groups. In infants under 1 year with AML, the incidence of 11q23 abnormalities is particularly high. The finding of identical 11q23 breakpoints in infant leukaemia as in therapy-related leukaemias suggests a role for in utero exposure to topoisomerase II inhibitors. There are a number of constitutional disorders that predispose children to develop AML, usually with a preceding myelodysplastic phase. Monosomy (or deletion of the long arm) of chromosome 7 is the most frequent chromosome abnormality in the bone marrow of such patients. Abnormalities of chromosome 7 are also common cytogenetic findings in all morphological subgroups of childhood myelodysplasia, either as a primary abnormality or associated with disease progression.


Safety of FLT3 inhibitors in patients with acute myeloid leukemia.
Introduction: Acute myeloblastic leukemia (AML) is the most frequent type of acute leukemia in adults with an incidence of 4.2 cases per 100,000 inhabitants and poor 5-year survival. Patients with mutations in the FMS-like tyrosine kinase 3 (FLT3) gene have poor survival and higher relapse rates compared with wild-type cases.Areas covered: Several FLT3 inhibitors have been proved in FLT3mut AML patients, with differences in their pharmacokinetics, kinase inhibitory and adverse events profiles. First-generation multi-kinase inhibitors (midostaurin, sorafenib, lestaurtinib) target multiple proteins, whereassecond-generation inhibitors (crenolanib, quizartinib, gilteritinib) are more specific and potent inhibitors of FLT3, so they are associated with less off-target toxic effects. All of these drugs have primary and acquired mechanisms of resistance, and therefore their combinations with other drugs (checkpoint inhibitors, hypomethylating agents, standard chemotherapy) and its application in different clinical settings are under study.Expert opinion: The recent clinical development of various FLT3 inhibitors for the treatment of FLT3mut AML is an effective therapeutic strategy. However, there are unique toxicities and drug-drug interactions that need to be resolved. It is necessary to understand the mechanisms of toxicity in order to recognize and manage them adequately.


Interaction of proton pump inhibitors with cytochromes P450: consequences for drug interactions.
Omeprazole, lansoprazole and pantoprazole are metabolized by several human cytochromes P450, most prominently by CYP2C19 and CYP3A4. Only pantoprazole is also metabolized by a sulfotransferase. Differences in the quantitative contribution of these enzymes and in the relative affinities of the substrates explain some of the observed interactions with carbamazepin, diazepam, phenytoin and theophylline and of the impact of the CYP2C19 (mephenytoin) genetic polymorphism. Of these drugs, pantoprazole has the lowest potential for interactions, both in vitro and in human volunteer studies.


Complementing mutations in core binding factor leukemias: from mouse models to clinical applications.
A great proportion of acute myeloid leukemias (AMLs) display cytogenetic abnormalities including chromosomal aberrations and/or submicroscopic mutations. These abnormalities significantly influence the prognosis of the disease. Hence, a thorough genetic work-up is an essential constituent of standard diagnostic procedures. Core binding factor (CBF) leukemias denote AMLs with chromosomal aberrations disrupting one of the CBF transcription factor genes; the most common examples are translocation t(8;21) and inversion inv(16), which result in the generation of the AML1-ETO and CBFbeta-MYH11 fusion proteins, respectively. However, in murine models, these alterations alone do not suffice to generate full-blown leukemia, but rather, complementary events are required. In fact, a substantial proportion of primary CBF leukemias display additional activating mutations, mostly of the receptor tyrosine kinase (RTK) c-KIT. The awareness of the impact and prognostic relevance of these 'second hits' is increasing with a wider range of mutations tested in clinical trials. Furthermore, novel agents targeting RTKs are emanating rapidly and entering therapeutic regimens. Here, we present a concise review on complementing mutations in CBF leukemias including pathophysiology, mouse models, and clinical implications.


Observation of dipole-quadrupole interaction in an ultracold gas of Rydberg atoms.
We observe the direct excitation of pairs of Cs atoms from the ground state to molecular states correlating asymptotically to nsn'f asymptotes. The molecular resonances are interpreted as originating from the dipole-quadrupole interaction between the nsn'f pair states and close-by npnp asymptotes (22≤n≤32). This interpretation is supported by Stark spectroscopy of the pair states and a detailed modeling of the interaction potentials. The dipole-quadrupole interaction mixes electronic states of opposite parity and, thus, requires a coupling between electronic and nuclear motion to conserve the total parity of the system. This non-Born-Oppenheimer coupling is facilitated by the near-degeneracy of even- and odd-L partial waves in the atom-atom scattering which have opposite parity.


Aquaporin-11 (AQP11) Expression in the Mouse Brain.
Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA) and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB) in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11-deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema.


Commercial intermediate pressure MALDI ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions.
The first examples of highly charged ions observed under intermediate pressure (IP) vacuum conditions are reported using laser ablation of matrix/analyte mixtures. The method and results are similar to those obtained at atmospheric pressure (AP) using laserspray ionization (LSI) and/or matrix assisted inlet ionization (MAII). Electrospray ionization (ESI), LSI, and MAII are methods operating at AP and have been shown, with or without the use of a voltage or a laser, to produce highly charged ions with very similar ion abundance and charge states. A commercial matrix-assisted laser desorption/ionization ion mobility spectrometry (IMS) mass spectrometry (MS) instrument (SYNAPT G2) was used for the IP developments. The necessary conditions for producing highly charged ions of peptides and small proteins at IP appear to be a pressure drop region and the use of suitable matrixes and laser fluence. Ionization to produce these highly charged ions under the low pressure conditions of IP does not require specific heating or a special inlet ion transfer region. However, under the current setup, ubiquitin is the highest molecular weight protein observed. These findings are in accord with the need to provide thermal energy in the pressure drop region, similar to LSI and MAII, to improve sensitivity and extend the types of compounds that produce highly charged ions. The practical utility of IP-LSI in combination with IMS-MS is demonstrated for the analysis of model mixtures composed of a lipid, peptides, and a protein. Further, endogenous multiply charged peptides are observed directly from delipified mouse brain tissue with drift time distributions that are nearly identical in appearance to those obtained from a synthesized neuropeptide standard analyzed by either LSI- or ESI-IMS-MS at AP. Efficient solvent-free gas-phase separation enabled by the IMS dimension separates the multiply charged peptides from lipids that remained on the delipified tissue. Lipid and peptide families are exceptionally well separated because of the ability of IP-LSI to produce multiple charging.


Early rebleeding of intracranial dural arteriovenous fistulas after an intracranial hemorrhage.
The aim of this study was to evaluate the clinical and angiographic characteristics of dural arteriovenous fistulas (DAVF) presenting with intracranial hemorrhage (ICH), with a focus on early rebleeding according to the initial hemorrhage type. The clinical and radiologic features of 21 dAVFs that presented with intracranial hemorrhage were retrospectively reviewed. The hemorrhage type was classified as pure intraparenchymal hemorrhage (pIPH) and subarachnoid or subdural hemorrhage with IPH (non-pIPH). There were 13 patients with pIPH and 8 with non-pIPH. The median follow-up period was 30 months (range, 1-116 months), and the median interval from hemorrhage to treatment was 4 days (range, 0-72 days). Rebleeding occurred in 8 (38.1%) of 21 patients. Four (50%) of eight patients with non-pIPH suffered from early rebleeding within 3 days, while there was no early rebleeding in patients with pIPH. There was a significantly higher rate of early rebleeding in the non-pIPH group (p = 0.012). Angiographically, venous ectasia (p = 0.005) and direct cortical venous drainage (dCVD) (p = 0.008) showed a significantly higher proportion in the non-pIPH group than in the pIPH group. DAVFs with ICH is likely to rebleed after the first hemorrhage. Thus, early treatment can be needed in all DAVFs with ICH. In addition, DAVFs that presenting with non-pIPH and containing venous ectasia or dCVD on initial angiography may have a higher risk of early rebleeding. Therefore, cautious attention and urgent treatment are necessary for these patients.


Scenario-based modelling for urban sustainability focusing on changes in cropland under rapid urbanization: A case study of Hangzhou from 1990 to 2035.
China is undergoing rapid urbanization, which has brought great pressure on croplands throughout the country, especially in fast developing cities, such as Hangzhou. In this study, an attempt was made to monitor and model the cropland dynamics of Hangzhou from 1990 to 2035. The spatial-temporal changes in the cropland were discussed based on the land cover maps along with urban-rural gradient analysis. After understanding the spatial-temporal patterns of cropland changes, the cellular automata-Markov model was employed using the historical land cover maps and other explanatory data to perform a scenario-based simulation. Accordingly, three scenarios, namely spontaneous scenario (SS), protected area ensuring scenario (PAES), and optimal agriculture developing scenario (OADS), were designed for simulating the cropland distribution in 2035. The monitoring results showed that during 1990-2015, the cropland area decreased 1512.46km2 under rapid urbanization. Areas at a distance of 12km from the city center experienced maximum cropland loss. Among all the spatial metrics, aggregation index of the cropland exhibited the highest correlation with the distance to the city center (r=0.77 in 2015), thereby suggesting an obvious trend in aggregation along the urban-rural gradient. The modelling results reported that under PAES and OADS, the study area could gain 81.76km2 and 255.14km2 more cropland, respectively, than that under SS in 2035. Thus, policies applied in PAES and OADS would be effective for cropland protection.


Sodium Octanoate Modulates the Innate Immune Response of Bovine Mammary Epithelial Cells through the TLR2/P38/JNK/ERK1/2 Pathway: Implications during Staphylococcus aureus Internalization.
Bovine mammary epithelial cells (bMECs) contribute to mammary gland defense against invading pathogens, such as Staphylococcus aureus (intracellular facultative), which is recognized by TLR2. In a previous report, we showed that sodium octanoate [NaO, a medium chain fatty acid (C8)] induces (0.25 mM) or inhibits (1 mM) S. aureus internalization into bMECs and differentially regulates the innate immune response (IIR). However, the molecular mechanisms have not been described, which was the aim of this study. The results showed that α5β1 integrin membrane abundance (MA) was increased in 0.25 mM NaO-treated cells, but TLR2 or CD36 MA was not modified. When these receptors were blocked individually, 0.25 mM NaO-increased S. aureus internalization was notably reduced. Interestingly, in this condition, the IIR of the bMECs was impaired because MAPK (p38, JNK, and ERK1/2) phosphorylation and the activation of transcription factors related to these pathways were decreased. In addition, the 1 mM NaO treatment induced TLR2 MA, but neither the integrin nor CD36 MA was modified. The reduction in S. aureus internalization induced by 1 mM NaO was increased further when TLR2 was blocked. In addition, the phosphorylation levels of the MAPKs increased, and 13 transcriptional factors related to the IIR were slightly activated (CBF, CDP, c-Myb, AP-1, Ets-1/Pea-3, FAST-1, GAS/ISRE, AP-2, NFAT-1, OCT-1, RAR/DR-5, RXR/DR-1, and Stat-3). Moreover, the 1 mM NaO treatment up-regulated gene expression of IL-8 and RANTES and secretion of IL-1β. Notably, when 1 mM NaO-treated bMECs were challenged with S. aureus, the gene expression of IL-8 and IL-10 increased, while IL-1β secretion was reduced. In conclusion, our results showed that α5β1 integrin, TLR2 and CD36 are involved in 0.25 mM NaO-increased S. aureus internalization in bMECs. In addition, 1 mM NaO activates bMECs via the TLR2 signaling pathways (p38, JNK, and ERK1/2), which improves IIR before S. aureus invasion. Additionally, NaO (1 mM) might exert anti-inflammatory effects after bacterial internalization.


Melodic Intonation Therapy for Post-stroke Non-fluent Aphasia: Systematic Review and Meta-Analysis.
Introduction: Melodic intonation therapy (MIT) is one of the most studied speech and language therapy (SLT) approaches for patients with non-fluent aphasia, although the methodological quality of the studies has been rated as low in previous reviews. The aim of this study is to update current evidence on the possible efficacy of MIT for the treatment of non-fluent post-stroke aphasia. Methods: A systematic review and meta-analysis. We selected randomized clinical trials (RCT) that included adult patients over 18 years of age with non-fluent post-stroke aphasia, whose intervention was MIT vs. no therapy or other therapy. We excluded non-RCT studies, mixed populations including patients with aphasia of non-stroke etiology, studies with no availability of post-stroke aphasia-specific data, and incomplete studies. Three sections of communicative ability were analyzed as outcomes: functional communication, expressive language (naming and repetition), and comprehension. Results: We identified a total of four eligible RCTs involving 94 patients. Despite the heterogeneity in the psychometric tests employed among the trials, a significant effect of MIT on functional communication (evaluated by the Communication Activity Log) was found (SMD 1.47; 95% CI 0.39-2.56). In addition, a positive effect of MIT on expressive language (repetition) was found (SMD 0.45; 95% CI 0.01-0.90). No significant effects on comprehension measurements were found, despite a lack of significant statistical heterogeneity. Conclusion: This systematic review and meta-analysis shows a significant effect of MIT on improving functional communication and on repetition tasks. Future larger RCT specifically addressing those outcomes should provide the definite evidence on the efficacy of MIT on post-stroke aphasia recovery. Systematic Review Registration:PROSPERO-URL https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020144604.


In situ detection of basic fibroblast growth factor by highly specific antibodies.
Basic fibroblast growth factor (bFGF) is thought to be of major importance for fibrosis and angiogenesis. Despite intensive studies dealing with the biochemistry and multiple biologic effects of bFGF, the cellular distribution is virtually unknown. Therefore, using the indirect immunoperoxidase technique, we examined the effect of bFGF on a large pattern of normal, inflammatory, and tumorous human tissues. Staining was performed on cryostat sections with a highly specific affinity-purified antiserum. In normal tissues, especially those of the thymus and placenta, mainly dendritic cells contained the growth factor. High levels of bFGF were also detected in basal cells and gland epithelial cells of skin biopsies. A conspicuous expression was observed in chronic inflammatory tissues corresponding to a generally pronounced proliferation of fibroblasts and endothelial cells in these situations. Tumors revealed a very heterogenous staining pattern. In some lesions, bFGF was predominantly present in infiltrating and endothelial cells. In several, neoplasms tumor cells exhibited an intensive staining. In some, especially vascular tumors, bFGF could not be detected. From the staining results it is concluded that angiogenesis is not simply controlled by the presence of bFGF but is mediated by a balance of several angiogenic inducers and inhibitors.


Effectiveness of two fluoroquinolones for the treatment of chronic respiratory disease outbreak in broilers.
1. Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association with Escherichia coli is the disease most frequently encountered in poultry in Mexico. 2. Differences of antimycoplasmal activity, pharmacokinetics and cost among fluoroquinolones were the impetus for this clinical evaluation of efficacy of enrofloxacin and norfloxacin-nicotinate in broilers with CRD. 3. A total of 99,600 broilers, naturally infected with M. synoviae and E. coli, were treated with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20 mg/kg/d for 3 d) (n = 49,800). 4. Based on survivor analysis, there were no significant differences of efficacy of the 2 drugs. Survivor probabilities were above 0.99. 5. These results indicate that enrofloxacin and norfloxacin-nicotinate are efficacious for treatment of CRD. Questions remaining to be answered by other studies include: public health concern about the use of fluoroquinolones for the treatment of CRD; clinical superiority of one of these drugs on the basis of an attribute other than antimicrobial activity, such as cost:benefit ratio or ability to prevent bacterial resistance. 6. Clinical efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate or enrofloxacin should be used for the treatment of CRD associated with E. coli in broilers.


THE EVOLUTION OF ASYMMETRY IN SEXUAL ISOLATION: A MODEL AND A TEST CASE.
We constructed a model for the evolution of sexual isolation by extending Lande's (1981) model of sexual selection. The model predicts that asymmetric sexual isolation is a transient phenomenon, characteristic of intermediate stages of divergence in sexually selected traits. Unlike the Kaneshiro (1976, 1980) proposal, our model does not depend upon drift and the loss of courtship elements to produce asymmetries in sexual isolation. According to our model, the direction of evolution cannot be predicted from asymmetry in sexual isolation. We tested some features of the model using data from an experimental study of sexual isolation in the salamander Desmognathus ochrophaeus. We tested for sexual isolation between 12 allopatric populations and found significant asymmetry in sexual isolation in about a quarter of the test cases. The highest degrees of asymmetry were associated with intermediate levels of divergence. A curvilinear relationship between isolation asymmetry and divergence was predicted by our model and was supported by statistical analysis of the salamander data.


Sublingual immunotherapy tablet: a cost-minimizing alternative in the treatment of tree pollen-induced seasonal allergic rhinitis in Canada.
A cost-minimization analysis (CMA) was performed to evaluate the economic implications of introducing the SQ Tree sublingual immunotherapy (SLIT)-tablets marketed as ITULATEK® (Health Canada regulatory approval in April 2020) for the treatment of pollen-induced (birch, alder and/or hazel) seasonal allergic rhinitis in Canada (Ontario and Quebec), where Tree Pollen subcutaneous immunotherapy (SCIT) is already an available treatment option. A CMA was deemed appropriate and was based on the assumption that the SQ Tree SLIT-tablets have comparable efficacy to Tree Pollen SCIT. A societal perspective was adopted in the model, including relevant costs of medications, costs of health care services, and productivity losses. The time horizon in the model was three years, which corresponds to a minimal treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where available, and validated by Canadian specialist clinicians (allergists) in active practice in Ontario and in Quebec, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, scenario analyses were performed by testing alternative assumptions for selected parameters (e.g., Tree Pollen SCIT resource use, discount rates, number of injections, annual SCIT dosing with maintenance injections, and nurse time support), to evaluate their impact on the results of the analysis. The direct costs, including the drug costs, and physician services costs, for three years of treatment, were similar for both SQ Tree SLIT-tablets vs. Tree Pollen SCIT in both Ontario and Quebec ($2799.01 and $2838.70 vs. $2233.76 and $2266.05 respectively). However, when the indirect costs (including patient's travel expenses and lost working hours) are included in the model, total savings for the treatment with SQ Tree SLIT-tablets of $1111.79 for Ontario and $1199.87 for Quebec were observed. Scenario analyses were conducted and showed that changes in assumptions continue to result in the savings of SQ Tree SLIT- tablets over Tree Pollen SCIT. The CMA indicates that SQ Tree SLIT-tablets are a cost-minimizing alternative to Tree Pollen SCIT when considered from a societal perspective in Ontario and Quebec.


Antidepressants and suicidality: the basis of controversies.
Regulatory agencies of different European countries and the United States have been critically examining the possible link between suicidality and antidepressant use in children and adults, which has resulted in an FDA directive to the manufacturers of all antidepressant medications to add a 'black box' warning. 'Black box' warning describes the increased risk of suicidality in persons who take antidepressants. Because the news media's coverage of the antidepressant-suicide controversy has increased dramatically in the last few years, serious concerns need to be performed. In this review, the possible risk-benefit ratio has been estimated according to the use of selective serotonin reuptake inhibitors (SSRIs) antidepressants due to relevant psychobiological, clinical and epidemiologic data.


Social and psychiatric influences on urban-rural differentials in Australian suicide.
The purpose of this study was to investigate urban-rural differentials in Australian suicide rates, and to examine influences that previously have remained largely speculative. Suicide rates for males (all ages and young adults) were significantly higher in rural areas compared to urban areas. Urban-rural suicide rate differences in males were rendered nonsignificant after adjustment for migrant and area socioeconomic status. Adjusting for mental disorder prevalence, in addition to migrant status, reduced the excess suicide risk in rural areas; the excess was reduced further with addition of mental health service utilization. The implications of this study are that socioeconomic circumstances in rural populations contribute to higher male suicide rates compared to urban areas, but these conditions may be partly mediated by mental disorder prevalence and mental health service utilization.


Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes.
It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and beta-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor-alpha (PPAR-alpha), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.


Congenital Heart Disease and Autism: A Case-Control Study.
There has long been an association between congenital heart disease (CHD) and general neurodevelopmental delays. However, the association between CHD and autism spectrum disorders (AuSDs) is less well understood. Using administrative data, we sought to determine the association between CHD and AuSD and identify specific CHD lesions with higher odds of developing AuSD. We performed a 1:3 case-control study of children enrolled in the US Military Health System from 2001 to 2013. Children with International Classification of Disease, Ninth Revision, Clinical Modification codes for AuSD were identified as cases and matched with controls on the basis of date of birth, sex, and enrollment time frame. Each child's records were reviewed for CHD lesions and associated procedures. Conditional logistic regression determined odds ratios (ORs) and 95% confidence intervals (CIs) for comparative associations. There were 8760 cases with AuSD and 26 280 controls included in the study. After adjustment for genetic syndrome, maternal age, gestational diabetes, short gestation, newborn epilepsy, birth asphyxia, and low birth weight, there were increased odds of AuSD in patients with CHD (OR 1.32; 95% CI 1.10-1.59). Specific lesions with significant OR included atrial septal defects (n = 82; OR 1.72; 95% CI 1.07-2.74) and ventricular septal defects (n = 193; OR 1.65; 95% CI 1.21-2.25). Children with CHD have increased odds of developing AuSD. Specific lesions associated with increased risk include atrial septal defects and ventricular septal defects. These findings will be useful for counseling parents of children with CHD.


Withholding feeding during transfusion: Standardization of practice and nutritional outcomes in premature infants.
To evaluate the nutritional impact of a feed-holding guideline during transfusion for infants <32 weeks gestation. A pre-/post-interventional study was conducted after introduction of a guideline to hold feeds during transfusion. Demographic variables in addition to nutritional outcomes were collected on all infants admitted within 48 hours of birth with gestational age <32 weeks. Data was collected during a 6 month period pre-intervention and the 6 month period post-intervention. There were 145 eligible infants. Mean birth weight and gestational age were similar in both periods. In total, 98 infants received transfusions, and 82 of those had an active feeding order prior to at least one transfusion. Total transfusions per infant and transfusions ordered while an infant had active feeding orders were similar in both periods. Time to full feedings was decreased post-intervention (p < 0.001). Weight at 34 weeks, incidence of second IV placement, additional IV fluid use, and hypoglycemia were similar between groups.Of 593 total transfusions, 207 were ordered while an infant had an active order for enteral nutrition. Pre-intervention, 64% of transfusions had feeds held during transfusion. Post-intervention, 87% of transfusions had feeds held during transfusion. Feeds were held more often (p < 0.001) and for a shorter duration (p = 0.005) in the post-intervention group. Implementing a guideline standardizing feeding practices during transfusions in premature infants increases standardization of care and results in decreased variability in practice. Adverse nutritional consequences were not found after the introduction of the routine practice of holding feedings during transfusion in preterm infants.


Recent indications and methods of surgery for inflammatory bowel disease.
Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can require surgical intervention. Surgery represents only one of the treatment options, but prediction of whether UC and CD are likely to progress to serious conditions and determination of when to undertake surgery is essential. Various surgical procedures have been developed over time, and the postoperative results are now generally good. Regarding laparoscopic surgeries, relatively few cases have been accumulated, and addressing the indications and limitations is premature at this point. However, this procedure is likely to fulfill a central role in surgical treatment strategies and represent a major benefit to patients. This paper discusses surgical treatment indications and methods for UC and CD, and explains the practical aspects of laparoscopic surgery, which has made remarkable progress in recent years, for such cases.


Choriocarcinoma of the stomach: pathogenesis and clinical characteristics.
A patient with primary choriocarcinoma of the stomach is reported. Abdominal pain, weight loss, a palpable epigastric mass, and gastrointestinal bleeding are the most common clinical features of this germ cell tumor, making it difficult to distinguish choriocarcinoma from primary adenocarcinoma of the stomach. The unique aspect of this case is the mixed histology of this rare neoplasm, containing both adenomatous and embryonal carcinoma, in addition to the choriocarcinoma. We believe that this unusual tumor probably results from dedifferentiation of primary adenocarcinoma of the stomach. On the average, patients with this disease live less than 2 months from the time of diagnosis, and treatment with combination chemotherapy has not improved the survival.


Photovoltaic Field-Effect Transistors Using a MoS2 and Organic Rubrene van der Waals Hybrid.
A several-layer n-type MoS2 was partially hybridized with an organic crystalline p-type rubrene nanosheet through van der Waals interactions to fabricate a two-dimensional (2-D) lateral-type n-p heterojunction optoelectronic device. The field-effect transistors (FETs) using lateral-type MoS2/rubrene hybrids exhibited both gate-tunable diode and anti-ambipolar transistor characteristics. The FET devices show the coexistence of n-type states, p-type states, and off-states controlled by the gate bias. From the photocurrent mapping experiments, the gate-bias-dependent photovoltaic effect was observed from the heterojunction regions of the MoS2/rubrene FETs. Furthermore, the photovoltaic FETs were successfully operated by light irradiation without applying source-drain bias and controlled using gate bias. These devices represent new solar-energy-driven 2-D multifunctional electronic devices.


The role of pH in symptomatic relief and effective treatment of gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is a condition in which gastroduodenal contents pass into the oesophagus and cause troublesome symptoms and complications. The aetiopathogenesis of gastroesophageal reflux disease is complex and multifactorial. Acid reflux plays an important role in the GERD pathogenesis, both in erosive and non-erosive reflux disease. Reduction of GERD symptoms and mucosal healing correlates with the number of hours that intragastric acid is suppressed to a pH > 4.0. Mucosal healing was achieved in most of patients who received different types of proton pump inhibitors, but only in 50% of those who received H2 blockers. These findings seem to be best accounted for by differences in the duration and degree of acid suppression achieved by different classes of drugs and perhaps between agents within those classes.


Local Hamiltonians for quantitative Green's function embedding methods.
Embedding calculations that find approximate solutions to the Schrödinger equation for large molecules and realistic solids are performed commonly in a three step procedure involving (i) construction of a model system with effective interactions approximating the low energy physics of the initial realistic system, (ii) mapping the model system onto an impurity Hamiltonian, and (iii) solving the impurity problem. We have developed a novel procedure for parametrizing the impurity Hamiltonian that avoids the mathematically uncontrolled step of constructing the low energy model system. Instead, the impurity Hamiltonian is immediately parametrized to recover the self-energy of the realistic system in the limit of high frequencies or short time. The effective interactions parametrizing the fictitious impurity Hamiltonian are local to the embedded regions, and include all the non-local interactions present in the original realistic Hamiltonian in an implicit way. We show that this impurity Hamiltonian can lead to excellent total energies and self-energies that approximate the quantities of the initial realistic system very well. Moreover, we show that as long as the effective impurity Hamiltonian parametrization is designed to recover the self-energy of the initial realistic system for high frequencies, we can expect a good total energy and self-energy. Finally, we propose two practical ways of evaluating effective integrals for parametrizing impurity models.


The relationship between measured moisture conditions and fungal concentrations in water-damaged building materials.
We determined the moisture levels, relative humidity (RH) or moisture content (MC) of materials, and concentrations of culturable fungi, actinomycetes and total spores as well as a composition of fungal flora in 122 building material samples collected from 18 moisture problem buildings. The purpose of this work was to clarify if the is any correlation between the moisture parameters and microbial levels or generic composition depending on the type of materials and the time passed after a water damage. The results showed an agreement between the concentrations of total spores and culturable fungi for the wood, wood-based and gypsum board samples (r > 0.47). The concentrations of total spores and/or culturable fungi correlated with RH of materials particularly among the wood and insulation materials (r > 0.79), but not usually with MC (r < 0.45). For the samples collected from ongoing damage, there was a correlation between RH of materials and the concentrations of total spores and culturable fungi (r > 0.51), while such a relationship could not be observed for the samples taken from dry damage. A wide range of fungal species were found in the samples from ongoing damage, whereas Penicillia and in some cases yeasts dominated the fungal flora in the dry samples. This study indicates that fungal contamination can be evaluated on the basis of moisture measurements of constructions in ongoing damage, but the measurements are not solely adequate for estimation of possible microbial growth in dry damage.


Primary neuroendocrine tumors - an extremely rare cause of obstruction of extrahepatic bile ducts: a case report.
Primary neuroendocrine tumors of the extrahepatic bile ducts are extremely rare - up to date, only 77 cases have been reported in the literature, which represents between 0.2-2% of all gastrointestinal carcinoid tumors. The paper focuses on the case of a woman patient, aged 37 years, admitted to the Clinic with the diagnosis of obstructive jaundice, unaccompanied by pain and where imaging indicates a tumor in the third average of the common bile duct (CBD). The surgery involved the excision of CBD, lymphadenectomy and restoring the biliodigestive continuity of Roux-en-Y hepaticojejunostomy. The histopathological and immunohistochemical examinations revealed the presence of a well-differentiated neuroendocrine tumor of CBD. Based on the case report and literature, we attempted to accurately identify and relate this type of tumor to other varieties encountered in the extrahepatic bile ducts, pointing out elements of a positive diagnosis, differential diagnosis, histopathology and immunohistochemistry, and referring to the therapeutic attitude, evolutionary methods and prognosis.


Precise diagnosis by gene analysis and successful management of delivery in three patients with type IIB von Willebrand disease.
Type IIB is a rare variant of von Willebrand disease (vWD). An affected individual's bleeding tendency and thrombocytopenia are exacerbated with pregnancy, and the proper management of these patients during delivery has not been well established. Since it is important to distinguish this disease from the platelet type vWD in order to administer the appropriate therapy, gene analysis is necessary to make the precise diagnosis. We now report the successful management of delivery in three patients, who were diagnosed as having type IIB vWD by the detection of missense mutations in the von Willebrand factor (vWF) gene (C3916-->T and C3922-->T). These changes cause Arg543-->Trp and Arg545-->Cys substitutions in the A1 domain of vWF. We were able to manage the bleeding tendency of these patients at delivery mainly with vWF concentrates to supply normal vWF.


Outcome of orthograde endodontic retreatment--A two-year follow-up.
Endodontic retreatment is a complex intervention that requires detailed analysis of possible reasons for failure, and flawless practical execution of the procedure. The aim of the study was to assess the outcome of endodontic retreatment based on clinical and radiographic criteria after a two-year observation period. Clinical study included 49 teeth indicated for endodontic retreatment based on periapical index (PAI). All teeth were divided into two groups. Group I comprised teeth without any periapical lesion (PAI score of 1 and 2) while Group II consisted of teeth with visible periapical radiolucency (PAI score of 3, 4, and 5). Endodontic retreatment was completed in two visits with inter-appointment medication of 2% chlorhexidine and calcium hydroxide for two weeks. Outcome of endodontic retreatment was evaluated 12-24 months after final obturation. Endodontic retreatment was successful in 93.3% in Group I after 24 months. In Group II, successful treatment and complete healing was found in 52.9% of teeth, whereas 14.7% of teeth showed only partial healing. However, clinical symptomatology was not present in any of the cases. Considering the absence of clinical signs and subjective symptoms, retreatment was successful in 67.6% of cases where chronic periapical inflammation was present. Endodontic retreatment was successful in high percentage in teeth with and without periapical lesions.


Polymeric Tubular Aromatic Amide Helices.
Conjugated polymers may be induced by intra- and/or intermolecular non-covalent forces to fold into helical conformations. Helices formed by aromatic amide, hydrazide, and urea polymers possess a well-organized cavity and depth, which is defined by their degree of polymerization. Driving forces may be intramolecular hydrogen bonding and/or solvophobicity, or guest induction. The resulting long helices represent a new class of unimacromolecular dynamic tubular architectures that exhibit unique properties or functions in, for example, molecular recognition, chirality transfer, and ion transporting. The recent advances are highlighted here.


[Ante-partum administration of preventive treatment of Rh-D immunization in rhesus-negative women. Parallel evaluation of transplacental passage of fetal blood cells. Results of a multicenter study carried out in the Paris region].
1,969 non immunized rhesus negative primiparous women were followed up in 23 maternity units in the geographical region of Paris. 1,882 could be retained to study antepartum protection and 1,884 to study transplacental passage of fetal blood cells. Two groups were defined according to whether they were born in even or uneven years, so that: 955 were the "control" group who delivered 590 rhesus D positive infants, and 927 were the "treated" group who delivered 599 rhesus D positive infants. The "control" group were used as controls at the 28th and 34th weeks of pregnancy, while the "treated" group received two injections of anti-D immunoglobulin given on the same dates after taking the necessary tests. Immunological testing at the time of the delivery and after the delivery showed that 7 women had become Rh D immunized in the "control" group whereas only one in the "treated" group. This difference, which is statistically significant, confirms the results of other authors about the efficiency of antepartum rhesus disease prevention. The incidence of immunisation during or immediately after the first pregnancy in women who had no previous story of blood transfusions or of terminations of pregnancy is 1.11%, which is a figure relatively low as compared with studies of series carried out in North America, but close to those carried out in other European centres. When primipara of all categories are lumped together the frequency rises to 1.5%. A study of the passage of fetal red blood cells into the maternal circulation shows that at the 29th week of pregnancy out of 1,884 cases there were 5.5% positive kleihauer tests, without a large volume of blood being detected and at the 34th week of pregnancy when 957 tests were carried out, 7% were positive with one of them being of a massive transfusion of blood from the fetus to the mother, which was life-threatening for the fetus. It may be that the incidence had been under-estimated and that the positive results in the two groups, control and treated, show that there is a statistically significant difference that demonstrates that antepartum treatment in the trial has eliminated a worthwhile percentage of positive kleihauer tests which arose from the transfusion of small quantities of blood.(ABSTRACT TRUNCATED AT 400 WORDS)


Comparison of an immortalized human corneal epithelial cell line and rabbit corneal epithelial cell culture in cytotoxicity testing.
The cytotoxicity of benzalkonium chloride (BAC) and disodium edetate (EDTA) was evaluated in vitro in rabbit corneal epithelial primary cells and in the immortalized human corneal epithelial cell line SV40. Cell injury was assessed by lactate dehydrogenase (LDH) leakage and by reduction of the tetrazolium salt WST-1 to formazan by mitochondrial metabolic activity. Cell cultures were exposed to test compounds both in serum-free and in serum-containing medium. Although WST-1 and LDH tests measured different physiological endpoints, they yielded comparable results. However, the LDH test seemed less reliable due to great variation. The use of serum was found to result in lower toxicity of the compounds in both tests. The rabbit primary cell culture and the human corneal cell line were quite similar in their responses to BAC and EDTA. The human cell line is a promising in vitro alternative in oculotoxicity testing.


The Anti-Arthritic Activity of Diclofenac Lipid-Core Nanocapsules: Stereological Analysis Showing More Protection of Deep Joint Components.
Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is associated with serious adverse effects, even in regular-dose regimens. Drug delivery systems can overcome this issue by reducing adverse effects and optimizing their efficacy. This study evaluated the activity of lipid-core nanocapsules loaded with diclofenac (DIC-LNCs) in an experimental model of adjuvant-induced arthritis. The diclofenac nanoformulation was obtained via self-assembly. A stereological analysis approach was applied for the morphological quantification of the volume, density, and cellular profile count of the metatarsophalangeal joints of rats. Proinflammatory cytokines and biochemical profiles were also obtained. Our results showed that the diclofenac nanocapsule DIC-LNCs were able to reduce arthritis compared with the control group and the DIC group. DIC-LNCs efficiently reduced proinflammatory cytokines, C-reactive protein, and xanthine oxidase levels. Additionally, DIC-LNCs reduced the loss of synoviocytes and chondrocytes compared with the DIC (p < 0.05) and control groups (p < 0.05). These data suggest that DIC-LNCs have anti-arthritic activity and preserve joint components, making them promising for clinical use.


[Directed evolution of lipase of Bacillus pumilus YZ02 by error-prone PCR].
Random mutagenesis on Bacillus pumilus lipase YZ02 gene was conducted by using error-prone PCR strategy. Through two cycles of directed evolution, two optimum mutants BpL1-7 and BpL2-1369 with lipase activity improved 2 folds and 6 folds respectively were screened. The sequence of BpL2-1369 lipase gene showed that four nucleotides substitution, T61C, C147T, A334G and T371A have occurred, and three of them caused amino acid changes. Thus, amine acid Ser21 was changed into Pro21, Arg112 to Gly112, and Leu124 to His124. According to the 3D structure of Bacillus pumilus lipase mimicked by SWISS-MODEL Repository, three mutated amino acids were located at the third amino acid of the first alpha-helix, the turn between the fourth and fifth beta fold, and the first amino acid of the fifth beta fold, respectively. The BpL and BpL2-1369 genes were ligated into pET28a vector, and transferred into E. coli BL21 (DE3). After induced by IPTG the lipases were purified and characterized. The results showed that the specific activity of the evolved lipase was 1.31-fold than that of the wild lipase, and the Km decreased from 8.24 mmol/L to 7.17 mmol/L. The pH stability of the evolved lipase was better than wild lipase when pH>8.0.


Removal of antibiotic resistant microbes by Fe(II)-activated persulfate oxidation.
Sewage in WWTPs is one of main way to spread antibiotic resistant microbes (ARMs), and beach bay water is in direct contact with human skin. It is necessary to pay attention to remove the ARMs in WWTP sewage and bay water. Our results showed that ARMs and total microbes (TMs) can be effectively removed by S2O82-/Fe2+ in the effluent stage of WWTPs and bay water. Quenching experiments using tert-butyl alcohol, dimethyl sulfoxide and Al2O3 as scavengers confirmed that the primary reactive oxidants responsible for microbes removal during the Fe(II)-activated persulfate oxidation process might be SO4•- and Fe(IV), rather than •OH. The bacterial community shifted and the alpha diversity significantly reduced after treatment. In WWTP group, relative abundance of Firmicutes increased to 8.56%, and potential pathogens such as genus Vibrio decreased to 0.03% in bay water after treatment. The ecological toxicity to the environment of S2O82-/Fe2+ further illustrated that the mortality of indicator species Oryzias latipes did not increase after treatment, and the dosage of 60/30 μM can be potentially ideal dosage of S2O82-/Fe2+. This study revealed Fe(II)-activated persulfate oxidation as an eco-friendly and economical method could reduce TMs and ARMs in WWTP sewage and bay water.


Implicit memory for spatial context in depression and schizophrenia.
Deficits in explicit spatial memory, as well as abnormalities of the hippocampus and neighboring medial temporal structures, have been documented in schizophrenia and depression. Recent evidence relying on the contextual cueing paradigm has shown that integrity of these structures is crucial not only for explicit memory but also for implicit spatial memory. Using this paradigm, the authors show that implicit memory for spatial context is severely impaired in clinically depressed patients but reaches a normal level in schizophrenia patients, although in these patients, acquisition is slower than in controls. By contrast, implicit memory for isolated locations and colors is normal in both schizophrenia and depressed patients. These findings suggest an implicit memory impairment specific to spatial context in depression. The implications for research on the differences between schizophrenia and depression in abnormalities of the hippocampal system and for research on the neural correlates of contextual cueing are discussed.


The risk of foot-and-mouth disease becoming endemic in a wildlife host is driven by spatial extent rather than density.
In the past 20 years, free living populations of feral wild boar have re-established in several locations across the UK. One of the largest populations is in the Forest of Dean where numbers have been steadily increasing since monitoring began in 2008, with estimates from 2016 reporting a population of more than 1500. Feral wild boar have significant ecological and environmental impacts and may present a serious epidemiological risk to neighbouring livestock as they are a vector for a number of important livestock diseases. This includes foot-and-mouth disease (FMD) which is currently absent from the UK. We developed an individual-based spatially explicit modelling approach to simulate feral wild boar populations in the Forest of Dean (England, UK) and use it to explore whether current or future populations might be sufficient to produce long-lived outbreaks of FMD in this potential wildlife reservoir. Our findings suggest that if you exclude the spread from feral wild boar to other susceptible species, the current population of boar is insufficient to maintain FMD, with 95% of unmanaged simulations indicating disease burn-out within a year (not involving boar management specifically for disease). However, if boar are allowed to spread beyond their current range into the adjacent landscape, they might maintain a self-sustaining reservoir of infection for the disease.


Bifunctional nanocatalyst of bimetallic nanoparticle/TiO2 with enhanced performance in electrochemical and photoelectrochemical applications.
A novel metal/semiconductor hybrid nanostructure with enhanced catalytic functions has been prepared by a simple self-assembly approach. This new bifunctional nanocatalyst consists of evenly dispersed Au/Pt hybrid nanoparticles (Au/Pt NPs) assembled on NH(2) group functionalized anatase TiO(2) colloid spheres with nanoporous surface (f-TiO(2)). The resulting bimetallic nanoparticles/TiO(2) (noted as f-TiO(2)-Au/Pt NPs) hybrid nanostructure is characterized by various methods and expected as a promising catalyst in electrochemical and photoelectrochemical applications because of its satisfactory or even enhanced catalytic properties from both TiO(2) and Au/Pt NPs. Compared with the f-TiO(2), the electrochemical results indicate that the as-prepared f-TiO(2)-Au/Pt NPs exhibited more prominent electrocatalytic reduction toward hydrogen peroxide at low potential, which was then used as a sensitive sensor with a detection limit of 75 nM. Most importantly, the present hybrid material has the better photocatalytic property, as demonstrated by the photoelectrochemical catalysis of glucose.


Evaluation of a novel tablet application for improvement in colonoscopy training and mentoring (with video).
Endoscopic training can be challenging for the trainee and preceptor. Frustration can result from ineffective communication regarding areas of interest. Our team developed a novel tablet application for real-time mirroring of the colonoscopy examination that allows preceptors to make annotations directly on the viewing monitor. The potential for improvement in team proficiency and satisfaction is unknown. The on-screen endoscopic image is mirrored to an Android tablet and permits real-time annotation directly on the in-room endoscopic image display. Preceptors can also "freeze-frame" an image and provide visual on-screen instruction (telestration). Trainees, precepted by a GI attending, were 1:1 randomized to perform colonoscopy on a training phantom using the application with traditional precepting or traditional precepting alone. Magnetized polyps (size < 5 mm) were placed in 1 of 5 preset location scenarios. Each trainee performed a total of 10 colonoscopies and completed each location scenario twice. During withdrawal, the trainee and the attending identified polyps. Outcome measures included number of polyps missed and participant satisfaction after each trial. Fifteen trainees (6 novice and 9 GI fellows) performed a total of 150 colonoscopies where 330 polyps in total were placed. Fellows missed fewer polyps using the tablet versus traditional precepting alone (4.2% vs 12.5%; P = .04). There was no significant difference in missed polyps for novices (12.5% vs 18.8%; P = .66). Overall, fellows missed fewer polyps when compared with novices regardless of the precepting method (P = .01). The attending and all trainees reported reduced stress with improved communication using the tablet. Fellows missed fewer polyps using the tablet when compared with traditional endoscopy precepting. All trainees reported reduced stress, quicker identification of polyps, and improved educational satisfaction using the tablet. Our application has the potential to improve trainee plus attending team lesion detection and to enhance the endoscopy training experience for both the trainee and attending preceptor.


A variant chromosomal translocation found in a series of 24 patients with Philadelphia positive chronic granulocytic leukaemia.
The bone marrow chromosomes of 24 patients with Philadelphia positive (Ph 1) chronic granulocytic leukaemia (CGL) were studied using banding techniques. In 23 patients, the Ph(1) had been produced by the standard translocation between chromosomes 9 and 22, but in the remaining patient, the Ph(1) chromosome had been formed by a translocation between chromosomes 16 and 22. Clinical and haematological details of this patient are reported.


Cross-Cultural Differences of the Non-Motor Symptoms Studied by the Traditional Chinese Version of the International Parkinson and Movement Disorder Society- Unified Parkinson's Disease Rating Scale.
Given the importance of ethnic differences in the evaluation of various aspects of symptoms in patients with Parkinson's disease (PD), we present the formal procedure for completing the traditional Chinese translation of the International and Parkinson and Movement Disorder Society/UPDRS (MDS-UPDRS) and highlight the discrepancy in nonmotor symptoms (NMS) between patients in Eastern and Western countries. A total of 350 native Chinese-speaking PD patients were recruited from multiple hospitals in Eastern countries; they completed the MDS-UPDRS. The translation process was executed and factor analysis was performed to determine the structure of the scale. Chi-squared and t tests were used to compare frequency and severity of PD symptoms between the Chinese-speaking and English-speaking groups (n = 876). NMS and motor symptoms were more severe in the Western population (Part I: t(1205) = 5.36, P < 0.0001; and Part III: t(1205) = 7.64, P < 0.0001); however, the prevalence of cognitive dysfunction and impairments in activities of daily living were more frequent in the Eastern patients. The comparative fit index was 0.93 or greater, and the exploratory factor analysis revealed compatible results between the translated scale and the original version. The traditional Chinese version of the MDS-UPDRS can be designated as an official translation of the original scale, and it is now available for use. Moreover, NMS in PD constitute a major issue worldwide, and the pattern of NMS among the Chinese population is more marked in terms of cognition-based symptoms and activities of daily living.


Booster vaccination with further live attenuated measles vaccine.
Revaccination with live attenuated measles vaccine was evaluated in a large group of children to determine (1) if protective antibody to measles infection could be augmented and (2) after what interval will the revaccination yield optimal results. The rate of decline in measles hemagglutination-inhibition (HI) antibody was observed to be directly related to the time interval since the previous vaccination, and individuals with declining titers became increasingly responsive to revaccination with a maximal response approximately four to six years after previous vaccination. Six-month follow-up studies demonstrated sustained elevations in measles HI antibody titers. Measles-neutralizing antibody showed less tendency to sustain a titer increase with revaccination. The observations suggest that revaccination with live, further attenuated measles vaccine is safe and may augment immunity.


Marginal analysis of correlated failure time data with informative cluster sizes.
We consider modeling correlated survival data when cluster sizes may be informative to the outcome of interest based on a within-cluster resampling (WCR) approach and a weighted score function (WSF) method. We derive the large sample properties for the WCR estimators under the Cox proportional hazards model. We establish consistency and asymptotic normality of the regression coefficient estimators, and the weak convergence property of the estimated baseline cumulative hazard function. The WSF method is to incorporate the inverse of cluster sizes as weights in the score function. We conduct simulation studies to assess and compare the finite-sample behaviors of the estimators and apply the proposed methods to a dental study as an illustration.


Who participates in support groups for parents of children with autism spectrum disorders? The role of beliefs and coping style.
One hundred forty-nine parents of children with autism spectrum disorders (ASD) completed online questionnaires measuring their beliefs about support groups and ASD, coping style, social support, mood, and use of support groups. Those currently using parent support groups (PSGs) reported using more adaptive coping strategies than both parents who had never used PSGs and parents who had used PSGs in the past. Past PSG users reported that they did not find the groups as beneficial as current users, and parents who had never participated in PSGs reported difficulties with the accessibility of PSGs. Based on the current results, interventions for parents of children with ASD that are focused on meeting the needs identified by participating parents may be most effective.


Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives.
Several new oxalamide and 2-butenediamide derivatives have been designed, synthesized and evaluated as the acetyl- and butyryl-cholinesterase inhibitors for Alzheimer's disease. The enzyme inhibitory activity of the synthesized compounds was measured using Ellman's colorimetric method. It was revealed that compound 1a (N,N'-bis-(4-chloro-benzyl)-N,N'-diphenyl-oxalamide) showed maximum activity against BuChE with a half maximal inhibitory concentration (IC50) = 1.86 µM and compound 2a (but-2-enedioic acid bis-[(4-chloro-benzyl)-phenyl-amide]) exhibited optimum AChE (IC50 = 1.51 µM) inhibition with a high-selectivity index. To better understand the enzyme-inhibitor interaction of the most active compounds towards cholinesterase, molecular modelling studies were carried out. Docking simulations revealed that inhibitors 1a and 2a targeted both the catalytic active site and the peripheral anionic site of 1ACJ and 1P0I.


Prevalence and relevance of the positivity of skin prick testing in patients with chronic urticaria.
Many patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000-2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty-eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One-third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food-induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.


Static gamma-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats.
Ideas about the functions of static gamma-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static gamma-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active gamma-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of gamma-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static gamma-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static gamma-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of gamma-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single gamma-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of gamma-motoneurones on either the primary or the secondary ending, but not on both together. However, gamma-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in alpha-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents.


Severe Ludwig's angina caused by an unknown insect bite.
Hereby, we report a case of a 75-year-old man who presented with a 3-day history of facial swelling and choking sensation. The only history of note was an insect bite on the left parotid gland area 3 days prior. The patient was later diagnosed with insect-bite-induced Ludwig's angina. Enterococcus faecalis was detected on blood cultures and was presumed the source of infection. Intravenous antibiotics and corticosteroids were initiated. The patient was intubated and was subsequently made to undergo a tracheostomy insertion to establish a definitive airway. He was admitted to the intensive care unit and when his condition improved, he was transferred to the ward for full recovery. The patient spent a total of 66 days in hospital before being discharged. This case suggests that Ludwig's angina can be caused by insect bites. However, further similar cases are needed to be documented to explore this theory.


Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial.
Age-related hearing loss is a common chronic condition of elderly persons. Low folate status has been associated with poor hearing. To determine whether folic acid supplementation slows age-related hearing loss. Double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004. The Netherlands. 728 older men and women recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 micromol/L or greater serum and vitamin B12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging. Daily oral folic acid (800 microg) or placebo supplementation for 3 years. 3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies. Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies. The strict criterion for participation on the basis of serum homocysteine concentrations limits extrapolation to the general population. Folic acid fortification of food was prohibited in the Netherlands during the study, so baseline folate levels in participants were about half of those found in the U.S. population. Folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs. Clinicaltrials.gov identifier: NCT00110604.


Improving Cancer Risk Awareness Including Obesity as a Risk Factor for Cancer in a Small U.S. Community.
Obesity is a risk for certain types of cancer; however, awareness of obesity as a risk factor for cancer is low. This study evaluated increases in cancer risk awareness, including obesity as a risk factor for cancer, from a quasi-experimental intervention that provided educational materials and community reinforcement for healthy living. The study uses data on participant's awareness of cancer risk factors along with sociodemographic variables collected from in-person surveys (N = 863) at baseline (June 2011) and post intervention (June 2012). The average awareness that overweight and obesity are risk factors for cancer was low (35 %) compared to chewing tobacco (92 %), using tanning bed (73 %), and sunburn (97 %) at baseline. The intervention significantly increased participants' awareness that overweight and obesity are risk factors for cancer. Based on regression analysis, the unadjusted intervention effect on cancer risk awareness was significant: 0.392 ± 0.165 (p value = 0.020) for matched participants and 0.282 ± 0.125 (p value = 0.024) for community participants. The adjusted intervention effect was significant in the matched participants (0.528 ± 0.189, p value = 0.006). Education, income, gender, and age had a significant impact on cancer risk awareness for the community participants. The results show that community intervention that incorporates community reinforcement can have the desired effect regardless of differences at participant level. Such interventions could be used to prevent cancer risk in communities that are at high risk.


Modulated function of tissue efflux transporters under hyperbilirubinemia in rats.
The effect of hyperbilirubinemia on the function of tissue efflux transporters such as multidrug resistance-associated proteins (Mrps) and organic anion transporting polypeptides (Oatps) was examined by measuring tissue accumulation of 2,4-dinitrophenyl-S-glutathione (DNP-SG) after intravenous administration of 1-chloro-2,4-dinitrobenzene (CDNB), a precursor of DNP-SG, in rats. DNP-SG is known as a substrate of both Mrps and Oatps. Hyperbilirubinemia was induced by a bolus intravenous administration of bilirubin. Treatment with probenecid, an inhibitor for both Mrps and Oatps, significantly increased DNP-SG concentrations in the brain, heart, liver, kidney, jejunum, spleen and skeletal muscle as compared with those in control rats, suggesting the expression of some probenecid-sensitive efflux transporters in these tissues. Rats with more than 70 microM of unconjugated/conjugated bilirubin in plasma exhibited significantly higher DNP-SG concentrations in the brain, liver, jejunum, and skeletal muscle. These results suggested that probenecid-sensitive efflux transporters in tissues were suppressed functionally under hyperbilirubinemia. In conclusion, hyperbilirubinemia accompanied by obstructive jaundice is caused by various disease states, which may increase harmful toxicities of exogenously administered Mrps and/or Oatps substrate drugs at various tissues, by suppressing the efflux transporter's function systemically.


Bioequivalence study of montelukast tablets in healthy Pakistani volunteers.
Montelukast is a leukotrien receptor antagonist used for asthma treatment. Objective of this study was to evaluate the bioequivalence of two montelukast 10mg tablets, Innovator drug (Singulair) as reference and other locally manufactured drug (Montiget) in 12 healthy volunteers. It was randomized, single dose, two-period crossover study with 1 week washout period. Blood samples (4-5 ml) were collected before and after drug administration and plasma was separated for analysis. Concentrations of montelukast at different time intervals were determined by validated UV-HPLC method at 345nm wavelength. Bioequivalence was assessed by using non compartmental approach and also calculated the 90% confidence interval of the least-squared pharmacokinetic parameters (Cmax, AUC0-t and AUC0-OO). On average, Cmax, AUC0-t, AUC0-inf, was 2.35μg/mL, 1.28µg.h./ml, 1.67µg.h./ml, for innovator drug and 2.53μg/mL, 1.53µg.h./ml, 1.96µg.h./ml, for test drug, respectively. Confidence interval (90%) for Cmax, AUC0-t and AUC0-inf was 89-97%, 85-91% and 81-98% respectively. No statistical difference was found between the Cmax and AUC values of test and reference drugs. The confidence intervals for Cmax, AUC0-t and AUC0-OO are fully laid within the acceptable range of FDA (80-125%), thus two formulations are considered to be bioequivalent.


Triazolam in insomniac family practice patients.
Triazolam, 0.5 mg, a benzodiazepine with hypnotic properties, was compared to secobarbital, 100 mg, and placebo in a 1-wk study conducted with 100 insomniac family practice patients. Considerable sensitivity to differential treatment effects was demonstrated for these family practice patients as well as for a research methodology that combines a crossover design, permitting preference ratings, with a between-patient design. In almost all sleep parameters, assessed with a variety of subjective techniques, triazolam and secobarbital were shown to be significantly more effective than placebo. Triazolam was consistently and often significantly indicated to be a more effective hypnotic, particularly for reducing nocturnal awakening, than secobarbital. Analysis of self-report emotional distress data revealed that present insomniac patients were slightly more emotionally symptomatic than other nonpsychiatric populations. Triazolam was followed by the greatest and secobarbital the least relief of emotional symptoms and triazolam emerged as an especially effective hypnotic for initially more depressed insomniac patients. Present findings suggest that type and degree of emotional symptomatology may affect the response of insomniac patients to hypnotics.


The effect of barbiturates on 24-h water intake and renal excretion of sodium and water in dogs.
The effects of barbiturates on 24-h intakes of water and food and urinary excretion of sodium and potassium as well as on plasma concentration of sodium and potassium and osmolality were examined in dogs placed in metabolism cages and fed with a semiliquid diet. Administration of barbiturates stimulated drinking in a Series of 8 dogs having free access to water. Twenty four-h water intake and water balance increased significantly. Food intake, urinary output and urinary excretion of solutes, sodium and water did not change in this Series. A significant decrease in urine output as well as in osmolal clearance and urinary excretion of sodium was observed in a Series of 7 dogs having water restricted for 24 h following administration of barbiturates. Water balance increased in this Series. The same restriction of water in the dogs which had not received barbiturates did not modify renal excretion of water and electrolytes. Plasma osmolality, sodium and potassium concentrations did not change in either Series of experiments. It is concluded that barbiturates induce positive water balance either by stimulation of drinking when water is freely available or by reduction in urine output when water is restricted. The results suggest that expansion of the body fluids following the increased water intake may abolish reduction in urine output and sodium excretion which otherwise occur after administration of barbiturates.


[The EO2-01 automated electrooculography system].
The system EO2-01 is intended for diagnostic electrooculographic examinations of the constant retina potentials in humans and animals. The intensity and the duration of light stimuli are preset. The system performs measuring, processing and recording electrooculograms as well as their amplitude- and time-dependent parameters. The algorithms for data processing built by the conventional method and by the method of the pulse electrooculography are described. A flow chart of the system is presented with the description of its functioning, main specifications are also given. The system permits more objective evaluation and the considerable expansion of diagnostic capabilities during electrooculographic examinations of ocular and general diseases.


Population-based study of long-term outcomes after amniocentesis.
Amniocentesis is now commonly used in many countries; it is important to know whether there are any long-term adverse effects on children born after this procedure, in particular disabilities that may emerge during childhood or adolescence. We studied consecutive liveborn offspring of women who had had amniocentesis and compared them with matched controls whose mothers had not had amniocentesis. The controls were matched for age of mother, residence by geographic health unit, sex, and when the birth occurred. 1296 cases and 3704 controls were studied. With the exception of one disorder, the offspring of women who had had amniocentesis were no more likely than controls to have a registrable disability (such as hearing disabilities, learning difficulties, visual problems, and limb anomalies) during childhood and adolescence. The follow-up period was 7-18 years. Children of women who had amniocentesis had a significantly higher rate of haemolytic disease due to ABO isoimmunisation than matched controls. The results of this study should therefore be reassuring to women having amniocentesis, and be useful to women making decisions about having this procedure.


Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling.
The goal of this study was the development of a method for quantitative expression proteomics on the limited sample amounts obtained through laser capture microdissection (LCM) of tissues, e.g., approximately 10 000 cells, which typically contain roughly 1-4 microg protein. The 16O/18O labeling method was selected as an approach to measure differential expression. A sample preparation protocol including lysis, digestion and 16O/18O labeling was first developed for LCM cell samples. The selected protocol was examined using two LCM caps of 10 000 cells from invasive ductal carcinoma of the breast and shown to be repeatable. A further test of LC-IT-MS/MS in combination with the 16O/18O post-digestion labeling method for studying low level samples was conducted first on a single protein (BSA) and then on a 5-standard protein mixture digest of different protein amounts, each with a total content approximately 1 microg. Next, protein expression was compared between 10 000 cells, each of microdissected normal ductal epithelium and metastatic ductal carcinoma, using the developed method. The proteins from the microdissected cells were extracted, precipitated, digested with trypsin and then 16O/18O labeled. The normal and metastatic cell samples were analyzed using reversed phase LC-ESI-MS/MS on the ion trap mass spectrometer. A total of 76 proteins were identified. Some, such as mitochondrial isocitrate dehydrogenase, actin and 14-3-3 protein xi/delta were found to be significantly up-regulated in the breast tumor cells.


Placental Syphilis: A Comprehensive Review of Routine Histomorphology, HIV Co-infection, Penicillin Treatment, Immunohistochemistry, and Polymerase Chain Reaction.
Introduction: Placental examination is valuable for diagnosing congenital syphilis, but the classic histological triad is not always observed. This study aimed to identify additional morphological clues, evaluate the sensitivity of IHC and qPCR, and investigate the impact of HIV co-infection and penicillin treatment on placental morphology. Materials and methods: Two hundred and fifteen placental specimens with treponemal infection were reviewed. Morphological findings, IHC, and qPCR results were analyzed. Results: Chronic villitis (94%), acute chorioamnionitis (91.6%), and villous immaturity (65.6%) were the most common abnormalities. HIV co-infection and penicillin treatment were associated with reduced frequencies of inflammatory lesions. IHC and qPCR exhibited sensitivities of 74.4 and 25.8%, respectively, confirming the diagnosis in 42 cases with negative or unknown serology. Conclusion: Villitis, chorioamnionitis, and villous immaturity were identified as the predominant placental abnormalities. HIV co-infection and penicillin treatment can impact morphology and hamper the diagnosis. IHC and q-PCR are valuable adjuncts when serology is negative.