Possible association between mandibular repositioning device for sleep apnea and osseous lytic lesion with fracture of the coronoid process of the mandible: A case report.
Mandibular repositioning devices (MRDs) increase the patency of the upper airway by repositioning the mandible forward, resulting in displacement of the oropharyngeal tissues preventing upper airway collapsibility. Mandibular anterior repositioning is counteracted by muscle force from the temporalis muscle. A 39-year-old man had an osteolytic lesion with fracture of the coronoid process of the mandible secondary to wearing a MRD for sleep apnea. Continuous stress generated on the coronoid process temporalis muscle resulted in osteolysis and fracture of the coronoid process on the patient's right side, resulting in swelling and limited ability to open his mouth. The patient was managed with intravenous antibiotics to control the osteomyelitis and surgical debridement, with removal of the coronoid process of the mandible. It is unclear why the fracture only occurred on the right side. Pathologic fracture of the coronoid process due to chronic stress and secondary osteomyelitis is a rare severe complication of treatment for obstructive sleep apnea syndrome with a MRD.


Urodynamic assessment of stress incontinence and its therapeutic implications.
Urethral fibrosis and sphincter incompetence commonly are associated in the genesis of stress incontinence. Other factors are often associated, such as bladder hyperactivity and increased demand on the sphincter mechanism created by contracted or large atonic bladder or polyuria. The frequent association of several factors and the limited information given by the classical methods suggest a need for the routine use of objective urodynamic studies in the assessment of stress incontinence. A more conservative, better oriented, therapeutic approach may result from this concept.


The Cpx envelope stress response modifies peptidoglycan cross-linking via the L,D-transpeptidase LdtD and the novel protein YgaU.
The Cpx envelope stress response mediates a complex adaptation to conditions that cause protein misfolding in the periplasm. A recent microarray study demonstrated that Cpx response activation led to changes in the expression of genes known, or predicted, to be involved in cell wall remodeling. We sought to characterize the changes that the cell wall undergoes during activation of the Cpx pathway in Escherichia coli. Luminescent reporters of gene expression confirmed that LdtD, a putative l,d-transpeptidase; YgaU, a protein of unknown function; and Slt, a lytic transglycosylase, are upregulated in response to Cpx-inducing conditions. Phosphorylated CpxR binds to the upstream regions of these genes, which contain putative CpxR binding sites, suggesting that regulation is direct. We show that the activation of the Cpx response causes an increase in the abundance of diaminopimelic acid (DAP)-DAP cross-links that involves LdtD and YgaU. Altogether, our data indicate that changes in peptidoglycan structure are part of the Cpx-mediated adaptation to envelope stress and indicate a role for the uncharacterized gene ygaU in regulating cross-linking.


Evolution of nectar spur length in a clade of Linaria reflects changes in cell division rather than in cell expansion.
Nectar spurs (tubular outgrowths of a floral organ which contain, or give the appearance of containing, nectar) are hypothesized to be a 'key innovation' which can lead to rapid speciation within a lineage, because they are involved in pollinator specificity. Despite the ecological importance of nectar spurs, relatively little is known about their development. We used a comparative approach to investigate variation in nectar spur length in a clade of eight Iberian toadflaxes. Spur growth was measured at the macroscopic level over time in all eight species, and growth rate and growth duration compared. Evolution of growth rate was reconstructed across the phylogeny. Within the clade we then focused on Linaria becerrae and Linaria clementei, a pair of sister species which have extremely long and short spurs, respectively. Characterization at a micromorphological level was performed across a range of key developmental stages to determine whether the difference in spur length is due to differential cell expansion or cell division. We detected a significant difference in the evolved growth rates, while developmental timing of both the initiation and the end of spur growth remained similar. Cell number is three times higher in the long spurred L. becerrae compared with L. clementei, whereas cell length is only 1.3 times greater. In addition, overall anisotropy of mature cells is not significantly different between the two species. We found that changes in cell number and therefore in cell division largely explain evolution of spur length. This contrasts with previous studies in Aquilegia which have found that variation in nectar spur length is due to directed cell expansion (anisotropy) over variable time frames. Our study adds to knowledge about nectar spur development in a comparative context and indicates that different systems may have evolved nectar spurs using disparate mechanisms.


Defective Metal-Organic Frameworks.
The targeted incorporation of defects into crystalline matter allows for the manipulation of many properties and has led to relevant discoveries for optimized and even novel technological applications of materials. It is therefore exciting to see that defects are now recognized to be similarly useful in tailoring properties of metal-organic frameworks (MOFs). For instance, heterogeneous catalysis crucially depends on the number of active catalytic sites as well as on diffusion limitations. By the incorporation of missing linker and missing node defects into MOFs, both parameters can be accessed, improving the catalytic properties. Furthermore, the creation of defects allows for adding properties such as electronic conductivity, which are inherently absent in the parent MOFs. Herein, progress of the rapidly evolving field of the past two years is overviewed, putting a focus on properties that are altered by the incorporation and even tailoring of defects in MOFs. A brief account is also given on the emerging quantitative understanding of defects and heterogeneity in MOFs based on scale-bridging computational modeling and simulations.


Primary Dural Lymphoma: Clinical Cases and Literature Review.
Primary dural lymphoma (PDL) is an extranodal non-Hodgkin lymphoma that accounts for less than 1% of all central nervous system lymphomas. Primary dural lymphoma grows from the dura mater, and it is often diagnosed as meningioma or acute subdural hematoma due to its radiological characteristics. Surgery is the gold standard of therapy; in many patients, PDL is relatively benign with good outcome. Authors report their experience in three patients affected by extranodal non-Hodgkin lymphoma (PDL) mimicking a meningioma.


Validity and reliability of a high school drug use questionnaire among Mexican students.
This study was carried out to ascertain the validity and reliability of data generated through an internationally developed self-administered questionnaire. Data were collected from two student populations in which prevalence of drug use was known (high and low prevalence rates) and information obtained from the questionnaire checked through personal interview. The questionnaire covered both demographic characteristics and drug use items. A total of 474 students were tested and 335 students (70.7 per cent) retested. Although percentages of missing data and inconsistent responses were high, the questionnaire appeared valid and reliable when analysed on a group basis. It was less reliable on an individual basis. In conclusion, it is considered that with minor modifications the questionnaire can be used in the populations studied with enough confidence in validity and reliability to allow comparisons.


[Concurrent renal cell carcinoma and urothelial carcinoma: long-term follow-up study of 24 cases].
Objective: To investigate the clinical manifestation, diagnosis, treatment and outcome of simultaneous occurrence of renal cell carcinoma and urothelial carcinoma. Methods: Twenty-four consecutive patients with synchronous renal cell carcinoma and urothelial carcinoma treated in our center from March 2005 to December 2015 were retrospectively reviewed. Their clinical, pathological and prognostic features were evaluated. Kaplan-Meier curves were used to estimate overall survival. Results: Patient' age was range from 48 to 79 yrs (median 69.5). Fourteen patients presented with macroscopic hematuria, and 10 patients were asymptomatic. B-ultrasound, computed tomography (CT) and cystoscopy initially indicated renal cell carcinoma concurrent with ipsilateral upper urinary tract urothelial carcinoma (UTUC) in 4 cases, renal cell carcinoma concurrent with bladder tumor in 16 cases, renal cell carcinoma concurrent with both ipsilateral UTUC and bladder tumor in 1 case, renal cell carcinoma in 2 cases and ureter carcinoma in 1 case. Different treatments were performed. The median follow-up time after surgery was 22.5 months. For patients with synchronous renal cell carcinoma and bladder tumor, there was no significant survival difference between patients treated with partial nephrectomy or radical nephrectomy. During follow up, 3 patients died of renal cell carcinoma, 3 patients died of non-oncological disease and 1 patient died of ureter carcinoma. The 3-year overall survival rate was 82.7%. For patients with synchronous renal cell carcinoma and bladder tumor, there was no significant survival difference between patients treated with partial nephrectomy or radical nephrectomy (P=0.874). Conclusions: Concurrence of renal cell carcinoma and urothelial carcinoma is clinically rare. Treatments should be individualized. The prognosis for a patient with synchronous renal cell carcinoma and urothelial carcinoma is associated with the more aggressive one.


Monocyte enhancers are highly altered in systemic lupus erythematosus.
Histone modifications set transcriptional competency and can perpetuate pathologic expression patterns. We defined systemic lupus erythematosus (SLE)-specific changes in H3K4me3 and K3K27me3, histone marks of gene activation and repression, respectively. We used ChIP-seq to define histone modifications in monocytes from SLE patients and controls. Both promoters and enhancers exhibited significant changes in histone methylation in SLE. Regions with differential H3K4me3 in SLE were significantly enriched in potential interferon-related transcription factor binding sites and pioneer transcription factor sites. Enhancer activation defines the character of the cell and our data support extensive disease effects in monocytes, a particularly plastic lineage. Type I interferons not only drive altered gene expression but may also alter the character of the cell through chromatin modifications.


[Association of body mass index and male primary osteoporosis].
To explore the association between body mass index (BMI) and male primary osteoporosis (OP) in a Chinese Han population. The association of BMI with OP was assessed in 276 Chinese healthy aged males for physical examination. They were classified into OP, osteopenia and normal groups according to the World Health Organization (WHO) criteria, i.e. OP was defined arbitrarily when any T-score was -2.5 standard deviations or less at femoral neck, total hip or lumbar spine (L1-4) site. We also classified the subjects as different BMI groups of low weight, normal weight, overweight and obesity. The prevalence of OP was compared among different BMI groups. We determined the sensitivity, specificity and area under the curve of receiver operating characteristic (ROC) for validating the valuation of BMI to predict male primary OP. Among them, 6/12 had OP in the low weight group, 17.36% (21/121) in the normal group and 12.59% (18/143) in the overweight and obesity group. And the difference was significant. The analysis of ROC curve showed that BMI was of limited value in predicting OP (P > 0.05). BMI has a positive correlation with male OP. The value of BMI is limited for predicting OP in males. And the relevant factors associated with male OP should to be further studied.


Hypercholesterolemia causes generalized impairment of endothelium-dependent relaxation to aggregating platelets in porcine arteries.
The role of the endothelium in response to aggregating platelets was examined in porcine coronary and peripheral (carotid, femoral and renal) arteries from normal and hypercholesterolemic pigs. Male Yorkshire pigs were fed either a normal diet or a 2% high cholesterol diet for 10 weeks. Endothelium-dependent responses were examined in vitro. In all arteries from control animals, aggregating platelets caused endothelium-dependent relaxations, which were augmented by ketanserin (a 5-HT2-serotonergic blocker), attenuated by apyrase (an adenosine diphosphatase and triphosphatase) or methiothepin (a combined 5-HT1 and 5-HT2-serotonergic blocker) and were almost abolished by a combination of apyrase and methiothepin. The platelet-induced relaxations were most pronounced in the coronary arteries. Adenosine diphosphate caused endothelium-dependent relaxations, which were significantly attenuated by apyrase. Serotonin also caused endothelium-dependent relaxations, which were significantly attenuated by methiothepin but augmented by ketanserin. The endothelium-dependent relaxations to adenosine diphosphate were most pronounced in coronary arteries and those to serotonin in coronary and renal arteries. In cholesterol-fed animals, the endothelium-dependent relaxations to aggregating platelets, adenosine diphosphate and serotonin were impaired in all four arteries. These experiments indicate that 1) the endothelium exerts inhibitory effects against aggregating platelets in porcine coronary and peripheral arteries; 2) platelet-induced endothelium-dependent relaxations are achieved by purinergic and 5-HT1-serotonergic receptors on the endothelium; and 3) hypercholesterolemia reduces the endothelium-dependent relaxations to aggregating platelets in a generalized manner because it impairs the relaxations to adenosine diphosphate and serotonin released from the platelets.


Fast modal method for subwavelength gratings based on B-spline formulation.
We present a B-spline modal method for analyzing a stack of complex structured layers. Thanks to a B-spline approximation of the field, we solve the Maxwell equations. Diffraction calculation is based on the scattering matrices algorithm. We prove a good convergence of this method. Moreover, B-spline approximation results in very sparse matrices, which are used to hasten the computation of eigenmodes. A method for cleaning the inverted sparse matrix is also presented.


Meta-analyses of four eosinophil related gene variants in coronary heart disease.
The goal of our study is to assess the contribution of four eosinophil related gene variants (rs12619285, rs1420101, rs3184504 and rs4143832) to the risk of coronary heart disease (CHD). We conducted four meta-analyses of studies examining the association between four eosinophil related gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. A case-control study was conducted between 162 CHD cases and 119 non-CHD controls to explore their contribution to CHD. For rs3184504 of SH2B3 gene, the meta-analysis was performed among 19 study stages among 94,555 participants. Significant association between rs3184504 and CHD risk was observed in European and South Asian populations (OR = 1.13, 95% CI = 1.10-1.16, p < 0.0001, fixed-effect method). For the other SNPs (rs12619285, rs1420101, and rs4143832), we combined our case-control data with the previous studies and found no association of them with the risk of CHD. No significant contribution of the four genetic variants to CHD was observed in Han Chinese (p > 0.05). In conclusion, our results supported a significant association between rs3184504 of SH2B3 gene and the risk of CHD in Europeans and South Asians, although we were unable to observe association between the four variants and the risk of CHD in Han Chinese.


p110δ PI3 kinase pathway: emerging roles in cancer.
Class IA PI3Ks consists of three isoforms of the p110 catalytic subunit designated p110α, p110β, and p110δ which are encoded by three separate genes. Gain-of-function mutations on PIK3CA gene encoding for p110α isoform have been detected in a wide variety of human cancers whereas no somatic mutations of genes encoding for p110β or p110δ have been reported. Unlike p110α and p110β which are ubiquitously expressed, p110δ is highly enriched in leukocytes and thus the p110δ PI3K pathway has attracted more attention for its involvement in immune disorders. However, findings have been accumulated showing that the p110δ PI3K plays a seminal role in the development and progression of some hematologic malignancies. A wealth of knowledge has come from studies showing the central role of p110δ PI3K in B-cell functions and B-cell malignancies. Further data have documented that wild-type p110δ becomes oncogenic when overexpressed in cell culture models and that p110δ is the predominant isoform expressed in some human solid tumor cells playing a prominent role in these cells. Genetic inactivation of p110δ in mice models and highly-selective inhibitors of p110δ have demonstrated an important role of this isoform in differentiation, growth, survival, motility, and morphology with the inositol phosphatase PTEN to play a critical role in p110δ signaling. In this review, we summarize our understanding of the p110δ PI3K signaling pathway in hematopoietic cells and malignancies, we highlight the evidence showing the oncogenic potential of p110δ in cells of non-hematopoietic origin and we discuss perspectives for potential novel roles of p110δ PI3K in cancer.


Successful Treatment of Alopecia Areata Barbae with Platelet-rich Plasma.
Alopecia areata (AA) is a frequent autoimmune disorder in which inflammatory cells attack the hair follicles. AA affecting the beard area is well known and is referred to as alopecia areata barbae (AAB) when involvement is limited exclusively to the beard. Currently, no guidelines are established for specific therapeutic approaches for this condition. We present a case of a healthy 30-year-old male suffering from AAB. Three injections of platelet-rich plasma (PRP) with six-week intervals were applied. Stabilization of the condition was noted at the first follow-up (before the second injection), initial minimal hair regrowth was noted at the second follow-up (before the third injection) and robust regrowth at the one-year follow-up. To our knowledge, this case is the first report of a successful treatment of AAB using PRP. PRP represents a new, safe and potentially effective treatment option for AAB. More studies will be necessary to determine the efficacy of this treatment compared to conventional therapy.


Methicillin-Resistant Staphylococcus aureus in Diabetic Foot Infection in India: A Growing Menace.
Diabetic foot infection (DFI) is a serious and common complication of diabetes mellitus. These infections are potentially disastrous and rapidly progress to deeper spaces and tissues. If not treated promptly and appropriately, DFI can be incurable or even lead to septic gangrene, which may require foot amputation. Mostly, these infections are polymicrobial, where Gram-positive pathogens mainly Staphylococcus aureus play a dominant causative role. Methicillin-resistant Staphylococcus aureus (MRSA) is present in 10% to 32% of diabetic infections and is associated with a higher rate of treatment failure, morbidity, and hospitalization cost in patients with DFIs. The increasing resistance of bacteria and the adverse effects pertaining to the safety and tolerability towards currently available anti-MRSA agents have limited the available treatment options for patients with DFI. Infection control, antimicrobial stewardship, and rapid diagnostics based on the microbiological culture and the antimicrobial susceptibility testing results are important components in helping curb this disturbing trend. Emphasis to revisit a vigorous research effort in order to improve the therapeutic options for the increasingly resistant and highly adaptable MRSA is the need of hour. Through this review article, we have made an attempt to explore the ongoing therapeutic trends in the management of DFI and highlighted the challenges in treatment of DFI. We have also given a brief overview of a few novel drugs that are under development to treat MRSA infections.


Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells.
Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. Controlled laboratory study. MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics-(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)-and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 106 ± 3.7 × 105 and 1.6 × 106 ± 4.7 × 105 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin ( P = .025), aggrecan ( P < .0001), and collagen type 2 ( P = .044) gene expression compared with hADSCs, respectively, after culture in differentiation medium. Moreover, both hAECs and hAMSCs produced significantly greater quantities of mineralized ( P < .0001) and cartilaginous ( P = .0004) matrix at earlier time points compared with hADSCs when cultured under identical osteogenic and chondrogenic differentiation conditions, respectively. Amnion-derived MSCs demonstrate a greater differentiation potential toward bone and cartilage compared with hADSCs. Amniotic MSCs may be the source of choice in the regenerative treatment of bone or osteochondral musculoskeletal disease. They show significantly higher yields and better differentiation toward these tissues than MSCs derived from adipose.


Tea polyphenols may attenuate the neurocognitive impairment caused by global cerebral ischemia/reperfusion injury via anti-apoptosis.
Global cerebral ischemia/reperfusion (GCIR) may incur neurocognitive impairment. Tea polyphenols (TP) have strong anti-oxidant capacity. This study planned to investigate the protective effect of TP against the neurocognitive impairment caused by GCIR and its mechanism. One-stage anterior approach for cerebral four-vessel occlusion (4VO) was used to construct the GCIR model. Sprague Dawley rats were randomly classified into Sham group, GCIR group, and TP group (n = 50 per group). Besides receiving the same 4VO, the rats in TP group were treated with TP (6.4%) injection from the tail vein 30 minutes before cerebral ischemia. Morris water-maze test was used to evaluate the changes in space recognition and memory and open field activity test to assess the activity and motor function of rats. The cell apoptotic study in hippocampal CA1 region at specified time points (12, 24, 48, and 72 hours after surgery) was carried out by the flow cytometry, histology (hematoxylin and eosin staining), and immunohistochemical (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining) examinations. One-way analysis of variance and least significant difference t-test were used and statistical significance considered at P < 0.05. Compared with the GCIR group, the TP group was significantly attenuated in the impairment of space recognition and memory caused by GCIR and so was the neuronal apoptosis in the hippocampal CA1 region (P < 0.05). TP may attenuate the impairment of space recognition and memory caused by GCIR via anti-apoptosis.


The effects of muscle fatigue on shoulder joint position sense.
Proprioception, or joint position sense, probably plays an important role in shoulder joint function. In this study, we assessed the effect of muscle fatigue on shoulder proprioception in 20 volunteers with no shoulder abnormalities. Shoulder proprioception was measured as the threshold to first detection of humeral rotation with the joint at 90 degrees of abduction and 90 degrees of external rotation. Subjects were tested while rested, exercised on a isokinetic testing machine until fatigued, and then retested in an identical fashion. Both shoulders were tested, and the order of dominant and nondominant shoulder was randomized. Shoulder proprioception was analyzed for its dependence on arm dominance, direction of rotation, and muscle fatigue. Subjects detected external rotation after significantly less movement than they did internal rotation. Overall, before exercise, motion was detected after a mean of 0.92 degrees of rotation. After exercise, this threshold to detection of movement increased to 1.59 degrees, an increase of 73%. This significant increase occurred with both internal and external rotation. The decrease in proprioceptive sense with muscle fatigue may play a role in decreasing athletic performance and in fatigue-related shoulder dysfunction. It remains to be determined if training can lessen this loss in position sense.


[Preoperative treatment impact for ultralow rectal carcinoma sphincter preservation].
Sphincter preservation for low rectal carcinoma must be evaluated with a plurifactoriel approach. Multicentric randomised studies are unable to demonstrate a relationship between complete tumoral response and conservative sphincteric rate. Intersphincteric resection technique is becoming a main factor to transform conservative indication. Complete tumoral response should not be the only purpose of future trials.


Multiple pathways for activation of E2A expression in human KB cells by the 243R E1A protein of adenovirus type 5.
Adenovirus type 5 (Ad5) mutant dl520, which produces only the smaller 243 residue (243R) E1A protein, induced efficient production of the viral E2A 72-kDa DNA binding protein (DBP) in human KB cells, but not in human WI38, 143, or HeLa cells. In transient expression assays, the 243R E1A protein induced transcription from the E2 early promoter in KB but not in HeLa cells; there was no transcription from the E3 promoter in either cell line. In KB cells, truncation of the E2 promoter from -285 to -97 basepairs dramatically reduced transactivation by the 243R E1A product but not by wt E1A, suggesting that the 243R protein acts through factors binding in this region. Multiple deletions in both exon 1 and exon 2 of the 243R E1A protein failed to disrupt its ability to induce DBP expression. The possible redundant pathways for this induction are discussed. The multiplicity of these pathways and the fact that they are all inactivated in the WI38 and 143 lines are surprising.


Neurosarcoidosis and the complexity in its differential diagnoses: a review.
While uncommon, neurosarcoidosis has been reported to present similarly to schizophrenia, with auditory hallucinations and delusions. We review the evaluation and work-up of neurosarcoidosis and discuss the differential diagnoses of these psychotic symptoms.


Fast reactions of hydroxycarbenes: tunneling effect versus bimolecular processes.
Different uni- and bimolecular reactions of hydroxymethylene, an important intermediate in the photochemistry of formaldehyde, as well as its halogenated derivatives (XCOH, X = H, F, Cl, Br), have been considered using high-level CCSD(T)/CBS quantum chemical methods. The Wentzel-Kramers-Brillouin (WKB) and Eckart approximations were applied to estimate the tunneling rate constant of isomerization of trans-HCOH to H(2)CO, and the WKB procedure was found to perform better in this case. In agreement with recent calculations and experimental observations [Schreiner et al., Nature 2008, 453, 906], the half-life of HCOH at the low temperature limit in the absence of bimolecular processes was found to be very long (approximately 2.1 h). The corresponding half-life at room temperature was also noticeable (approximately 35 min). Bimolecular reactions of trans-hydroxymethylene with parent formaldehyde yield primarily more thermodynamically favorable glycolaldehyde via the specific mechanism involving 5-center transition state. The most preferable reaction of cis-hydroxymethylene with formaldehyde yields carbon monoxide and methanol. Due to very low activation barriers, both processes occur with nearly a collision rate. If the concentration of HCOH (and its halogenated analogues XCOH as well) is high enough, the bimolecular reactions of this species with itself become important, and H(2)CO (or X(H)CO) is then formed with a collision rate. The singlet-triplet energy separation of trans-HCOH is confirmed to be approximately -25 kcal/mol.


Molecular analyses of the metallothionein gene family in rice (Oryza sativa L.).
Metallothioneins are a group of low molecular mass and cysteine-rich metal-binding proteins, ubiquitously found in most living organisms. They play an important role in maintaining intracellular metal homeostasis, eliminating metal toxification and protecting against intracellular oxidative damages. Analysis of complete rice genome sequences revealed eleven genes encoding putative metallothionein (OsMT), indicating that OsMTs constitute a small gene family in rice. Expression profiling revealed that each member of the OsMT gene family differs not only in sequence but also in their tissue expression patterns, suggesting that these isoforms may have different functions they perform in specific tissues. On the basis of OsMT structural and phylogenetic analysis, the OsMT family was classified as two classes and class I was subdivided into four types. Additionally, in this paper we also present a complete overview of this family, describing the gene structure, genome localization, upstream regulatory element, and exon/intron organization of each member in order to provide valuable insight into this OsMT gene family.


Prolonged endurance exercise and sleep disruption.
To determine whether exercise duration effects the recovery sleep following exercise, eight fit male endurance athletes, ages 23-42 yr, had their sleep electrophysiologically studied. This was done on four separate occasions: after a day on which no specific exercise was performed; after a day of a 15-km run; after a 42.2-km run day; after a day in which the athletes participated in a strenuous ultra-triathlon. Sleep patterns following the no exercise day and the 15-km and the 42.2-km run days were similar. The sleep pattern of the ultra-triathlon day when compared with the other three days showed significantly increased wakefulness and delayed and decreased rapid eye movement (REM) sleep. The duration of slow wave sleep (SWS) in the first 6 h after lights out, however, was no different. The increased wakefulness and decreased REM clearly indicate increased stress after the ultra-triathlon. REM sleep appears to be a more sensitive index of exercise induced stress than SWS.


Physiological effects of the herbicide glyphosate on the cyanobacterium Microcystis aeruginosa.
Glyphosate has been used extensively for weed control in agriculture in many countries. However, glyphosate can be transported into the aquatic environment and might cause adverse effects on aquatic life. This study investigated the physiological characteristics of cyanobacteria Microcystis aeruginosa (M. aeruginosa) after exposure to glyphosate, and the results showed that changes in cell density production, chlorophyll a and protein content are consistent. In M. aeruginosa, oxidative stress caused by glyphosate indicated that 48h of exposure increased the concentration of malondialdehyde (MDA) and enhanced the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). To further investigate the toxicity of glyphosate on M. aeruginosa, the viability of treated cells was monitored and the toxin release was determined. The results indicated that glyphosate induced apoptosis of and triggered toxin release in M. aeruginosa. These results are helpful for understanding the toxic effects of glyphosate on cyanobacteria, which is important for environmental assessment and protection. These results are also useful for guidance on the application of this type of herbicide in agricultural settings.


Structure of SALO, a leishmaniasis vaccine candidate from the sand fly Lutzomyia longipalpis.
Immunity to the sand fly salivary protein SALO (Salivary Anticomplement of Lutzomyia longipalpis) protected hamsters against Leishmania infantum and L. braziliensis infection and, more recently, a vaccine combination of a genetically modified Leishmania with SALO conferred strong protection against L. donovani infection. Because of the importance of SALO as a potential component of a leishmaniasis vaccine, a plan to produce this recombinant protein for future scale manufacturing as well as knowledge of its structural characteristics are needed to move SALO forward for the clinical path. Recombinant SALO was expressed as a soluble secreted protein using Pichia pastoris, rSALO(P), with yields of 1g/L and >99% purity as assessed by SEC-MALS and SDS-PAGE. Unlike its native counterpart, rSALO(P) does not inhibit the classical pathway of complement; however, antibodies to rSALO(P) inhibit the anti-complement activity of sand fly salivary gland homogenate. Immunization with rSALO(P) produces a delayed type hypersensitivity response in C57BL/6 mice, suggesting rSALO(P) lacked anti-complement activity but retained its immunogenicity. The structure of rSALO(P) was solved by S-SAD at Cu-Kalpha to 1.94 Å and refined to Rfactor 17%. SALO is ~80% helical, has no appreciable structural similarities to any human protein, and has limited structural similarity in the C-terminus to members of insect odorant binding proteins. SALO has three predicted human CD4+ T cell epitopes on surface exposed helices. The results indicate that SALO as expressed and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing. SALO has a novel structure, is not similar to any human proteins, is immunogenic in rodents, and does not have the anti-complement activity observed in the native salivary protein which are all important attributes to move this vaccine candidate forward to the clinical path.


A targeted delivery strategy for the development of potent trypanocides.
A new drug delivery strategy was investigated for the development of potent anti-parasitic compounds against Trypanosoma brucei, the causative agent of African sleeping sickness. Thus, potent in vitro hexokinase inhibitors were rendered cytotoxic by appending a tripeptide peroxosomal targeting sequence that facilitated delivery of the molecular cargo to the appropriate organelle in the parasite.


PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation.
Renal cell carcinoma (RCC) is one of the most aggressive urologic cancers, however, the mechanism on supporting RCC carcinogenesis is still not clear. By using gene expression profile analysis and functional clustering, PDZ domain-containing 1 (PDZK1) was revealed to be downregulated in human clear cell renal cell carcinoma (ccRCC) samples, which was also verified in several independent public ccRCC data sets. Using PDZK1 overexpression and knockdown models in ccRCC cell lines, we demonstrated that PDZK1 inhibited cell proliferation, cell cycle G1/S phase transition, cell migration and invasion, indicating a tumor-suppressor role in the development and progression of ccRCC. Our study further demonstrated that PDZK1 inhibited cell proliferation and migration of ccRCC via targeting SHP-1. PDZK1 was further identified to suppress cell proliferation by blocking SHP-1 phosphorylation at Tyr536 via inhibition of the association between SHP-1 and PLCβ3, and then retarding Akt phosphorylation and promoting STAT5 phosphorylation in ccRCC cells. Moreover, the inhibitive effects of PDZK1 on SHP-1 phosphorylation and the tumor growth were verified in vivo by xenograft tumor studies. Accordingly, PDZK1 expression was negatively correlated with SHP-1 activation and phosphorylation, advanced pathologic stage, tumor weight and size, and prognosis of ccRCC patients. These findings have provided first lines of evidences that PDZK1 expression is negatively correlated with SHP-1 activation and poor clinical outcomes in ccRCC. PDZK1 was identified as a novel tumor suppressor in ccRCC by negating SHP-1 activity.


Juvenile Nasal Angiofibroma on 68Ga-DOTANOC PET/CT: Exploring Theranostic Avenues.
Somatostatin (SST) cell surface receptors (SSTRs) are expressed in many different malignant, benign, and neuroendocrine tumors. SSTRs are also expressed in the endothelium of human vessels during angiogenesis and not in the nonproliferating vessels. We present a case of 19-year-old boy with juvenile nasal angiofibroma (JNA), who underwent 68Ga-DOTANOC PET/CT to explore SSTRs expression and theranostic potential. The scan revealed high uptake in the tumor, and in certain areas, the uptake was similar to that of the pituitary gland. Performance of DOTANOC PET/CT in JNA opens up new frontiers with respect to radiological staging, early recurrence identification, better delineation from postoperative scar tissue, possible preoperative treatment with SST analogs, and perhaps even radiopharmaceutical based-ligand therapy of inoperable/residual/recurrent JNAs in the future.


Clinical hyperthermia trials: design principles and practice.
The initial development of a significant risk device is predicated upon demonstrable medical need and an adequate biophysical rationale. Although microwave and radiofrequency thermotherapy systems strongly meet these requirements, their clinical evaluation has often suffered from inadequate or inappropriate preclinical laboratory experimentation. It is suggested that devices be tested in animals rather than phantoms and that thermal profiles, cooling curves, power vs. temperature studies et al be carried out in the organ or organs of interest. Clinical trials can then be designed in which an attempt is made to replicate laboratory measurements in humans in order to develop physical dose-response relationships and toxicity data (i.e. a phase-I or feasibility study). The experimental paradigm for clinical drug testing can also be applied, with some modifications, to the further evaluation of devices for the determination of therapeutic response rates (phase-II) and for controlled evaluation against available treatments in a homogeneous patient population (phase-III). It is extremely important that early clinical trials not be contaminated by the possible effects of other concurrent therapies and that sophisticated statistical design be employed to protect human subjects from unnecessary exposure to experimental treatments. The ethical issues involved are best dealt with by good scientific design.


A proteomics approach to quantify protein levels following RNA interference: case study with glutathione transferase superfamily from the model metazoan Caenorhabditis elegans.
Loss-of-function phenotypic analysis via interference RNA (RNAi) technology is a revolutionary approach to assigning gene function. While transcript-based methodologies commonly validate RNAi gene suppression investigations, protein-based validation is less developed. This report illustrates the potential for two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-DE) and gel analysis to quantify protein levels following RNAi. This case study involves three glutathione transferase (GST) genes targeted by RNAi from the model organism Caenorhabditis elegans.


Effect of protein cross-linking aldehydes on nerve activity.
The changes in excitability and conduction properties of frog sciatic nerve under the influence of glutaraldehyde (GA), formaldehyde (FA), butyric aldehyde (BA) and crotonic aldehyde (CA) were examined in the concentration domain 0.01-1.00% (w/v) and at 20, 25, 30 and 35 degrees C. All these reagents irreversibly reduce the amplitude of the compound action potential of the nerve and decrease the conduction velocity up to the complete block. These changes occur as approximately exponential time decays. The decreasing order of efficiency is : CA greater than BA greater than FA greater than GA, showing no obvious correlation with the molecular weight of the aldehydes. The rise in temperature activates the decrease of amplitude but has a compensatory affect on the decrease of conduction velocity. The rising phase of the nervogram apparently remains unchanged, while the duration of the falling phase is up to threefold lengthened--more but slower at low temperatures and concentrations. These changes in the electrical response of the nerve are analysed as expressing the diffusion of aldehydes within the tissue, and their specific reactions with the proteins of the ionic channels.


Spatiotemporal Analysis of Cytokinetic Events in Fission Yeast.
Cytokinesis, the final step in cell division is critical for maintaining genome integrity. Proper cytokinesis is important for cell differentiation and development. Cytokinesis involves a series of events that are well coordinated in time and space. Cytokinesis involves the formation of an actomyosin ring at the division site, followed by ring constriction, membrane furrow formation and extra cellular matrix remodeling. The fission yeast, Schizosaccharomyces pombe (S. pombe) is a well-studied model system that has revealed with substantial clarity the initial events in cytokinesis. However, we do not understand clearly how different cytokinetic events are coordinated spatiotemporally. To determine this, one needs to analyze the different cytokinetic events in great details in both time and in space. Here we describe a microscopy approach to examine different cytokinetic events in live cells. With this approach it is possible to time different cytokinetic events and determine the time of recruitment of different proteins during cytokinesis. In addition, we describe protocols to compare protein localization, and distribution at the site of cell division. This is a basic protocol to study cytokinesis in fission yeast and can also be used for other yeasts and fungal systems.


Persistent corneal epithelial defect responding to rebamipide ophthalmic solution in a patient with diabetes.
Rebamipide ophthalmic suspension was developed for the treatment of dry eyes and for other corneal diseases, promoting the secretion of both mucin in tear fluid and membrane-associated mucin, increasing the number of goblet cells, and restoring the barrier function of the corneal epithelium. We report a case of a persistent corneal epithelial defect in a patient with diabetes treated with topical application of rebamipide ophthalmic suspension. A 73-year-old woman had a history of type 2 diabetes for 35 years and nonproliferative diabetic retinopathy for 23 years. She presented to our department with discharge and ophthalmalgia in the left eye. A corneal ulcer was detected, and culture of corneal scrapings was performed, with Staphylococcus aureus and Streptococcus canis being isolated. The infection was treated with levofloxacin eye drops and ofloxacin ophthalmic ointment based on the sensitivity profile of the isolate. However, a corneal epithelial defect persisted for approximately 2 months despite continuing treatment with 0.1% hyaluronic acid ophthalmic suspension and 0.3% ofloxacin eye ointment. Her hemoglobin A1c was 7.3%. The persistent corneal epithelial defect showed improvement at 2 weeks after treatment with rebamipide unit dose 2% ophthalmic suspension, and it did not recur even when vitrectomy was subsequently performed for vitreous hemorrhage due to progression of diabetic retinopathy. This is the first report about efficacy of rebamipide unit dose 2% ophthalmic suspension for presenting persistent corneal epithelial defect in a patient with diabetes. In the present case, the suggested mechanisms are the following: improving the corneal barrier function, stabilization of mucin on the keratoconjunctival epithelium, and improving the wettability and stability of the tear film, which resulted in the promotion of healing of the corneal epithelial defect in a short time period.


Circular RNA hsa_circ_0078602 may have potential as a prognostic biomarker for patients with hepatocellular carcinoma.
Circular RNA (circRNA), a type of endogenous non-coding RNA, is a closed continuous loop of RNA with no poly(A) tail. Previously, studies have identified that circRNAs are closely associated with several cancer types. However, their function in hepatocellular carcinoma (HCC) has rarely been studied. Therefore, the aim of the current study was to screen differential circRNA expression between HCC tissues and adjacent non-cancerous tissues, and test the potential clinical value of individual circRNAs. CircRNA microarray was used to investigate global circRNA expression profiles. Attention was then focused on the top four circRNAs whose expression levels were reduced in HCC tissues as compared with non-cancerous tissues. Additionally, RNA expression was validated in 30 matched tissue samples using reverse transcription-quantitative polymerase chain reaction. The results revealed that the expression levels of hsa_circ_0078602 and hsa_circ_0018764 were consistent with microarray analysis (P<0.05). Between these two circRNAs, hsa_circ_0078602 demonstrated an association with a favorable diagnostic efficiency, with an area under the receiver operating characteristic curve of 0.787 (P<0.001). To further verify the expression level of hsa_circ_0078602, the patient sample size was increased to 79. The results supported the conclusion that circ_0078602 was downregulated in HCC tissue compared with non-cancerous tissue (P=0.015) and exhibited diagnostic potential. Notably, it was identified that a lower hsa_circ_0078602 expression level was associated with a worse prognosis among patients with HCC. In addition, it was revealed that 9.0×10-5 was the most efficient cut-off value of hsa_circ_0078602 expression to assess the outcomes of patients with HCC. The present study revealed that hsa_circ_0078602 may be a novel diagnostic biomarker of HCC and therefore have potential prognostic value.


Knowledge and practice of breast cancer screening among female nurses and lay women in Osogbo, Nigeria.
Breast cancer is the most common cancer among African women. Most researchers have attributed the late presentation to poor knowledge of breast cancer symptoms. This study was designed to evaluate the relationship between knowledge and practice of breast cancer screening in two groups of women with different levels of knowledge of breast carcinoma. A cross-sectional study was conducted using self administered questionnaire to assess the knowledge, attitudes and practice of breast cancer and screening programmes among nurses in a university teaching hospital, and women in non health professionals in south-western Nigeria. The mean knowledge score for the nurses was 10.9%±3.6 whereas the mean score for non-health professionals was 3.5%±4.1 (p value < 0.001). In those above the age of 40 years, comprising 141 subjects, 35 nurses and 106 women in non-health professionals, 22.9% and 15% respectively had had a mammogram (p=0.289,1.123). Good knowledge does not imply better screening rates in south-western Nigeria.


Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p-selectin and other proteins.
A fast and precise affinity capillary electrophoresis (ACE) method has been developed and applied for the investigation of the binding interactions between P-selectin and heparinoids as potential P-selectin inhibitors in the presence and absence of calcium ions. Furthermore, model proteins and vitronectin were used to appraise the binding behavior of P-selectin. The normalized mobility ratios (∆R/Rf ), which provided information about the binding strength and the overall charge of the protein-ligand complex, were used to evaluate the binding affinities. It was found that P-selectin interacts more strongly with heparinoids in the presence of calcium ions. P-selectin was affected by heparinoids at the concentration of 3 mg/L. In addition, the results of the ACE experiments showed that among other investigated proteins, albumins and vitronectin exhibited strong interactions with heparinoids. Especially with P-selectin and vitronectin, the interaction may additionally induce conformational changes. Subsequently, computational models were applied to interpret the ACE experiments. Docking experiments explained that the binding of heparinoids on P-selectin is promoted by calcium ions. These docking models proved to be particularly well suited to investigate the interaction of charged compounds, and are therefore complementary to ACE experiments.


[Most severe consequences of eye contusion injuries--surgical treatment].
One third of all eye injuries are contusion injuries. The most common causes of contusion eye injuries are squash ball, fist fights, sports, and work with blunt objects. The objective of our study was to analyze the surgical treatment methods and materials for managing the most severe consequences of eye contusion injuries. A large number of complications of contusion eye injuries were treated at Department for Vitreoretinal Surgery of the Eye Clinic, Military Medical Academy, Belgrade. This paper analyzed two periods, from 1991-1999, and 2000-2004. During these periods, 461 patients with contusion eye injuries were surgically treated. Pars plana vitrectomy and phacoemulsification with PCL implantation were the most commonly performed operations. During the analyzed period, a total of 334 pars plana vitrectomies, 253 combined operations (PHACO+ VPP) and 214 operations with PCL implantation (PHACO+VPP+PCL) were performed. Scleral fixation was carried out in 14 patients. After pars plana vitrectomy, some form of extended tamponade of vitreal space, in relation to degree of injury and complications, was performed in 194 cases. Eye traumatism is still one of the leading causes of vision loss (from the earliest ages) in our region. Preventive measures that could lead to decrease of eye injuries should be fully supported, not only through expert meetings and publications, but via media as well.


In vivo anti-obesity efficacy of fucoxanthin/HP-β-CD nanofibers in high-fat diet induced obese mice.
Fucoxanthin (Fx) has poor water solubility and bioavailability, which limits its application in the food industry. To improve the physicochemical properties of Fx, hydroxypropyl-β-cyclodextrin (HP-β-CD) encapsulated Fx nanofibers (Fx/HP-β-CD nanofibers) were fabricated via electrospinning without using polymer. Molecular docking analysis showed the Fx/HP-β-CD nanofibers contained Fx and HP-β-CD at 1:2. Morphological analysis revealed the nanofibers were homogeneous without beads, having a diameter around 499 nm. The thermostability of Fx was significantly improved after encapsulationg by HP-β-CD. Animal studies showed that there was a 14% decrease of body weight, 11% white adipose tissue reduction and 9% lower of liver triglyceride for the mice treated with Fx/HP-β-CD nanofibers as compared with that of Fx treated mice. The total cholesterol was reduced by 23% in mice serum after treatment with Fx/HP-β-CD as compared with that of Fx. Interestingly, the Fx/HP-β-CD in this study could attenuate the testicular histopathology in obese mice.


Integrative transcriptomic and proteomic analyses reveal a positive role of BES1 in salt tolerance in Arabidopsis.
Salt stress is a major environmental factor limiting plant growth and development. Previous studies have indicated that the steroidal hormones-brassinosteroids (BRs) are important regulators of plant responses to salt stress. However, the underlying molecular mechanisms have not been fully understood. (1) Phenotypic analysis of bes1-D, BES1-RNAi and their wild-type (Col-0) under salt treatments with different concentrations of NaCl. (2) Transcriptomic and proteomic profiling of BES1-regulated genes and proteins under salt treatment; (3) qRT-PCR validation of selected BES1-regulated genes under salt stress; (4) Transient transcriptional assay of BES1 regulation on its putative target genes in Arabidopsis protoplasts; (5) Electrophoresis Mobility Shift Assay (EMSA) of BES1 binding with its potential target genes. Phenotypic analysis indicated that bes1-D, a gain-of-function mutant of the BR-regulated transcription factor BES1 in Arabidopsis showed better salt tolerance than the wild-type plant, while a BES1 RNA interference (BES1-RNAi) line was more sensitive to salt stress. Global gene expression profiling and time series clustering analyses identified a total of 1,170 genes whose expression was boosted in bes1-D under salt stress. Further GO enrichment and gene functional network analyses identified several key modules that are regulated by BES1 and most sensitive to salt stress perturbations, including stress response, response to ABA and ROS, flavonoid biosynthesis and transmembrane transport. A comparative proteomic analysis performed under the same stress conditions supported the results from the transcriptome analysis. In addition, transient gene transcription assays in Arabidopsis protoplasts and in vitro DNA binding assays verified that BES1 regulates the expression of some ion transporter genes directly and indirectly. Taken together, our results support a positive role of BES1 in plant salt tolerance.


A Standardized Method of Isolating Adipose-Derived Stem Cells for Clinical Applications.
White adipose tissue is the most abundant and accessible source of stem cells in the adult human body. In this paper, we present a standardised and safe method of isolating and maximizing the number of adipose-derived stem cells (ASCs) from conventional liposuction for clinical applications, which was carried out through both mechanical (centrifuge) and enzymatic (collagenase) means. Isolated cells were characterized through flow cytometry assay. Gathered data showed a greater amount (9.06 × 10(5) ASCs from 100 mL of adipose tissue) of isolated ASCs compared to previous protocol, also with high (99%) cell vitality; the procedure we presented is easy and fast (80 minutes), allowing collecting a significative number of mesenchymal stem cells, which can be used for clinical purposes, such as wound healing.


Revisiting the prevalence of nonclassic congenital adrenal hyperplasia in US Ashkenazi Jews and Caucasians.
PurposeNonclassic 21-hydroxylase deficiency, a mild form of congenital adrenal hyperplasia (CAH), is estimated to be the most common autosomal recessive condition, with an especially high prevalence in Ashkenazi Jews (3.7% affected, 30.9% carriers), based on a 1985 HLA-B linkage study of affected families. Affected individuals, especially women, may suffer from hyperandrogenism and infertility. State-of-the-art genetic studies have not been done to confirm these remarkable rates.MethodsCYP21A2 genotyping was performed in 200 unrelated healthy Ashkenazi Jewish subjects and 200 random US Caucasians who did not self-identify as a specific ethnicity using multiplex minisequencing, real-time polymerase chain reaction and junction site analysis.ResultsNonclassic CAH carriership was found similarly in 15% (95% confidence interval (CI): 10.4-20.7) of Ashkenazi Jews and 9.5% (95% CI: 5.8-14.4) of Caucasians (P=0.13). The proportion of Ashkenazi Jewish nonclassic CAH carriers (0.15 versus 0.309, P<0.0001) and disease affected (0.005 versus 0.037, P=0.009) was not as high as previously reported. The estimated prevalence of nonclassic CAH in Caucasians was 1 in 200 (0.5%, 95% CI: 0.01-2.8).ConclusionNonclassic CAH is a common condition, regardless of ethnicity, and should be considered with preconception and infertility counseling.


Dialysis membrane-dependent removal of middle molecules during hemodiafiltration: the beta2-microglobulin/albumin relationship.
Current hemodialysis therapy modalities such as online hemodiafiltration (HDF) attempt to enhance solute removal over a wide molecular weight range through a combination of diffusion and convection. While the effects of variations of treatment modalities and conditions have been studied reasonably well, few studies have examined the efficacy of HDF to remove middle molecules in relation to the dialyzer and membrane characteristics. In this investigation, diverse high-flux dialyzers, covering a wide range of membrane permeabilities, were compared under identical in vivo conditions to assess their ability to eliminate larger uremic retention solutes (using beta2-microglobulin as a surrogate of middle molecules) without simultaneously causing excessive leakage of useful proteins such as albumin. In a prospective, crossover study, 3 ESRD patients were treated with 8 different brands of high-flux dialyzers at 4 different ultrafiltration (UF)/substitution flow rates (QS: 0, 30, 60, 90 ml/min) in post-dilution HDF mode. Thus, each patient underwent 32 treatment sessions, with a total of 96 treatment sessions conducted during the entire clinical study. Albumin and beta2-microglobulin levels were measured in both, dialysate and blood. Both, albumin and beta2-microglobulin elimination was dependent upon the permeability of the dialysis membrane as well as on the ultrafiltration/substitution flow rates applied. At the maximum UF rate of 90 ml/min, the total albumin loss (measured in the dialysate) ranged from 300 mg/4 h (for the FLX-15 GWS dialyzers) to 7,000 mg/4 h (for the BS-1.3U dialyzers). Up to 50% reduction of albumin occurred within the first 30 minutes of the dialysis treatment, and the leakage of albumin increased exponentially with increasing UF rates as well as increasing transmembrane pressure (TMP). The various dialyzers could be classified according to their UFR-dependent beta2-m reduction rates (RR), into low (< 50%; FLX-15 GWS, CT 150G), medium (50-70%; Polyflux 14 S, BLS 814SD, H4) and high (> 70%; BS-1.3U, APS 650, FX 60) removers of middle molecules. One dialyzer type (CT 150G) showed extremely low beta2-m RR and relatively high albumin losses. Most membranes, however, showed either low albumin leakage coupled with low beta2-m removal, or high beta2-m RR but at the expense of considerable albumin leakage. Only 2 membrane types approached the desired balance between high to medium beta2-m RR while simultaneously restricting the albumin leakage especially at higher filtration/substitution rates. Our investigations demonstrate that not all dialysis membranes classified as "high-flux" are comparable in their ability to specifically and efficiently remove middle molecules, or curtail the unwanted excessive leakage of essential proteins from the patient's blood. Thus, the selection of appropriate high-flux dialyzers for specific patient requirements should be based more upon clinical evaluations and analyses rather than on product specifications alone.


Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning.
Allogeneic hematopoietic stem cell transplantation was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient immunosuppression for allogeneic engraftment. However, it was observed that allogeneic immunocompetent cells transplanted with the stem cells, or arising from them, mediated therapeutic antitumor effects independent of the action of the high-dose therapy. This was termed a graft-versus-tumor effect. This has prompted the recent development of nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation that have opened the way to include elderly patients and those with comorbid conditions. Recent retrospective studies comparing hematopoietic stem cell transplantation after myeloablative or nonmyeloablative regimens suggested that the use of nonmyeloablative conditioning might be associated with lower transplant-related toxicity, lower nonrelapse mortality, and at least similar intermediate-term progression-free survival. Hematopoietic stem cell transplantation after nonmyeloablative conditioning might become the procedure of choice also for younger patients. Phase 3 studies are needed to determine outcomes for different diseases and age groups.


EPR approaches to ion channel structure and function.
The fundamental processes that underlie ion channel function are permeation/ selectivity and gating. In an effort to understand ion channel gating, we have used an approach that combines reporter-group spectroscopic techniques (spin labelling/ electron paramagnetic resonance, EPR) and electrophysiological methods with classical biochemical and molecular biological procedures. As an ideal test channel, we have focused our attention on the K+ channel from Streptomyces lividans, KcsA. Through site-directed spin labelling, cysteine chemistry was used to introduce nitroxide radicals into specific sites within KcsA with high reactivity and specificity. EPR spectroscopy analysis of the spin labelled mutants yields two types of structural information: (1) mobility and solvent accessibility of the attached nitroxide through collisional relaxation methods and (2) distances between pairs of nitroxides through dipole-dipole interactions. Using this approach, we analysed the correlation between KcsA crystal structure and the EPR data, extend it to derive low-resolution folds of full-length KcsA and apply it in the determination of the molecular rearrangements responsible for pH-dependent gating.


The use of complementary and alternative medicine among pediatric cystic fibrosis patients.
The goal of this paper is to assess the use of complementary and alternative medicine (CAM) use among children with cystic fibrosis (CF) and the communication with the primary care physician. The paper is based on data from surveys mailed to 97 patients recruited from Monmouth Medical CF Center. The questionnaire was anonymous and included 47 questions referring to demographic data (age, sex, number of years since diagnosed, state of residence, use of pancreatic enzymes, overall lung function and general health) as well as questions referring to all types of CAM practices: whole medical systems, manipulative practices, body mind medicine, biologically based practices, and energy medicine. The response rate was 50.5%, with 81% being pediatric patients under 18 years old. The results showed that 77% of patients use some form of CAM when the definition of CAM therapy included prayer specifically for health reasons. When prayer was excluded from the definition, the use of CAM decreased to 65%. The most commonly used CAM therapies were biologically based practices (53%) followed by body-mind medicine (49%), manipulative practices (14.5%), and whole medical systems (8%). Most of the patients interviewed did not consult a natural practitioner but considered that CAM treatments were beneficial. The present survey provides current data describing the use of CAM in patients with CF and adds to the increasing body of evidence about CAM use in the United States. Further research is needed to explore the relationship and effectiveness of specific types of CAM practices and their benefits on symptom relief and overall quality of life of CF patients.


A Wearable Combined Wrist Pulse Measurement System Using Airbags for Pressurization.
The pulse measurement instrument is based on traditional Chinese medicine (TCM) and is used to collect the pulse of patients to assist in diagnosis and treatment. In the existing pulse measurement system, desktop devices have large volumes, complex pressure adjusting operations, and unstable pressurization. Wearable devices tend to have no pressurization function or the function to pressurize three channels separately, which are not consistent with the diagnostic method in TCM. This study constructs a wearable pulse measurement system using airbags for pressurization. This system uses guide plates, guide grooves, and positioning screws to adjust the relative position of the wristband and locate Cun, Guan and Chi regions. The pulse signal measured by the sensor is collected and sent to a computer by microcontroller unit. In experiments, this system successfully obtains the best pulse-taking pressure, its pulse waveform under continuous decompression, and the pulse waveform of three regions under light, medium, and heavy pressure. Compared with the existing technology, the system has the advantages of supporting single-region and three-region pulse acquisition, independent pressure adjustment, and position adjustment. It meets the needs of home, medical, and experimental research, and it is convenient and comfortable to wear and easy to carry.


Affibody-based nanoprobes for HER2-expressing cell and tumor imaging.
This article reports the affibody-based nanoprobes specifically target and image human epidermal growth factor receptor type 2 (HER2)-expressing cells and tumors. The affibody molecules are a promising class of targeting ligands with simple, robust, and precise structure and high affinity. Using near-infrared (NIR) quantum dots (QDs) and iron oxide (IO) nanoparticles as two representative nanomaterials, we designed anti-HER2 affibody molecules with a N-terminus cysteine residue (Cysteine-Z(HER2:342)) and precisely conjugated with maleimide-functionalized nanoparticles to make nanoparticle-affibody conjugates. The in vitro and in vivo study showed the conjugates are highly specific to target and image HER2-expressing cells and tumors. This work indicated the nanoparticle-affibody conjugates may be excellent candidates as targeting probes for molecular imaging and diagnosis.


Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence after withdrawal of testosterone.
Testosterone induces susceptibility to Plasmodium chabaudi malaria by imposing restrictions on those mechanisms which mediate resistance controlled by genes of the H-2 complex and the non-H-2 background in mice. This study investigated whether these restrictions are abolished after withdrawal of testosterone. Female mice of the inbred strain C57BL/10 were treated with 0.9 mg testosterone twice a week for 3 weeks and testosterone was then withdrawn for 12 weeks. The treatment raised plasma testosterone levels from 0.18 ng/ml to 3.79 ng/ml. After the testosterone treatment, these levels progressively dropped and reached 0.21 ng/ml by week 12 after testosterone withdrawal. Surprisingly, however, the testosterone-induced susceptibility still persisted. When mice were challenged on week 12 after testosterone withdrawal, P. chabaudi infections were still fatal in testosterone-treated mice, in contrast to self-healing infections in resistant, i.e. untreated, control mice. In addition, testosterone caused a persistent decrease in the levels of total IgG antibodies, especially IgG1 and IgG2b isotypes. In contrast, testosterone-induced changes in spleen cells, such as the reduction in number by 50%, the relative increase in CD8+ cells and the decrease in Ig+ cells, as well as the acquisition of the susceptible phenotype, were completely reversed on week 10 after testosterone withdrawal at the latest. Testosterone did not affect the production of the TH1-signalling cytokine interferon-gamma and the TH2-signalling cytokines interleukin (IL)-4 and IL-10 in response to P. chabaudi malaria. Together, our data indicated that the gene-controlled host resistance to P. chabaudi malaria is subject to superior hormonal imprinting: when once induced by testosterone, mechanisms which suppress resistance thus causing susceptibility persist independently of testosterone.


Genetically-guided algorithm development and sample size optimization for age-related macular degeneration cases and controls in electronic health records from the VA Million Veteran Program.
Electronic health records (EHRs) linked to extensive biorepositories and supplemented with lifestyle, behavioral, and environmental exposure data, have enormous potential to contribute to genomic discovery, a necessary step in the pathway towards translational or precision medicine. A major bottleneck in incorporating EHRs into genomic studies is the extraction of research-grade variables for analysis, particularly when gold-standard measurements are not available or accessible. Here we develop algorithms for age-related macular degeneration (AMD), a common cause of blindness among the elderly, and controls free of AMD. These computable phenotypes were developed using billing codes (ICD-9-CM and ICD-10-CM) and Current Procedural Terminology (CPT) codes and evaluated in two study sites of the Veterans Affairs Million Veteran Program: Louis Stokes Cleveland VA Medical Center and the Providence VA Medical Center. After establishing a high overall positive and negative predictive values (93% and 95%, respectively) through manual chart review, the candidate algorithm was deployed in the full VA MVP dataset of >500,000 participants. The algorithm was then optimized in a data cube using a variety of approaches including adjusting inclusion age thresholds by examining previously-reported genetic associations for CFH (rs10801555, a proxy for rs1061170) and ARMS2 (rs10490924). The algorithm with the smallest p-values for the known genetic associations was selected for downstream and on-going AMD genomic discovery efforts. This two-phase approach to developing research-grade case/control variables for AMD genomic studies capitalizes on established genetic associations resulting in high precision and optimized sample sizes, an approach that can be applied to other large-scale biobanks linked to EHRs for precision medicine research.


Immunoelectron microscopy of Kell and Cellano antigens on red cell ghosts.
The ultrastructural arrangement of Kell (K1) and Cellano (K2) antigens on red cells was studied using ferritin-conjugated rabbit antihuman IgG to stain ghosts derived from antibody-sensitized intact red cells. Estimates of the number of sites under equilibrium binding were obtained by counting both ferritin grains and ferritin clusters on electron micrographs. Values for Kell sites on heterozygous red cells ranged from 2300 to 5900 and for Cellano sites from 2000 to 5000 with no discernible dosage effects. Both the Kell and Cellano antigens were clustered, which was due to conjugate staining of the ghost membranes and does not reflect the topological arrangement of these antigens on the native membrane. The ferritin grain patterns found with the Kell and Cellano antigens was similar to those observed with the Rh antigens except for the markedly reduced antigen site density.


[Increased homocysteine levels in polycystic ovary syndrome].
Women with polycystic ovary syndrome (PCOS) exhibit frequently risk factors that predispose to cardiovascular disease. Hyperhomocysteinemia is an independent risk factor for this disease. The aim of this study was to know whether young women with PCOS have increased homocysteine levels. We also analyzed their possible relation with folate and vitamin B12 levels. Thirty nine patients with PCOS were studied; (age: mean [standard deviation] 28.9 [5.8] years), and 39 healthy women similar in age. We evaluated in all of them: smoking, menstrual cycles, hirsutism, body mass index, metabolic syndrome and levels of homocysteine, lipids, glucose, creatinine, folate, vitamin B12, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and androstendione. Menstrual cycles, hirsutism, androstendione, LH levels and LH/FSH were higher, as we expected, in patients with PCOS. Moreover, patients had increased homocysteine (9.1 [2.1] vs 6.4 [1.8] micromol/L; p < 0.001) and glucose levels (99 [13] vs 88 [10] mg/dl; p < 0.001), a higher frequency of abnormal fasting glycemia (> 110 mg/dl) (23% vs 2.5%; p =.01) and lower folate levels (7.6 [3.7] vs 10.2 [3.6] ng/ml; p = 0.02). A multiple linear regression showed a negative association between homocysteine and folate levels (r2 = 0.05; p =.02). Homocysteinemia is increased in women with PCOS, and it is negatively associated with folate levels.


Vascular flow reserve as a link between long-term blood pressure level and physical performance capacity in mammals.
Mean arterial pressure (MAP) is surprisingly similar across different species of mammals, and it is, in general, not known which factors determine the arterial pressure level. Mammals often have a pronounced capacity for sustained physical performance. This capacity depends on the vasculature having a flow reserve that comes into play as tissue metabolism increases. We hypothesize that microvascular properties allowing for a large vascular flow reserve is linked to the level of the arterial pressure.To study the interaction between network properties and network inlet pressure, we developed a generic and parsimonious computational model of a bifurcating microvascular network where diameter and growth of each vessel evolves in response to changes in biomechanical stresses. During a simulation, the network develops well-defined arterial and venous vessel characteristics. A change in endothelial function producing a high precapillary resistance and thus a high vascular flow reserve is associated with an increase in network inlet pressure. Assuming that network properties are independent of body mass, and that inlet pressure of the microvascular network is a proxy for arterial pressure, the study provides a conceptual explanation of why high performing animals tend to have a high MAP.


Psycholegal issues in sibling bone marrow donation.
The only hope of survival for children with a number of life-threatening illnesses is a successful bone marrow transplant (BMT). Unlike the treatment source for most therapies, the raw material for transplant therapy comes from a human being. Although many BMTs are autologous, utilizing the patient's own bone marrow, a large percentage of childhood BMTs rely on bone marrow from children or adolescents who are biological siblings to the sick child. Medical and legal systems are confronted with a dilemma when healthy children are needed to undergo minimally risky, yet somewhat painful, procedures for the benefit of their critically ill siblings. This article reviews legal issues involved in sibling bone marrow donation and psychological research that is relevant to those issues. The article concludes with proposed directions for future psycholegal research and a discussion of ethical issues that are not amenable to empirical investigation.


Understanding medical professionalism using express team-based learning; a qualitative case-based study.
Medical Professionalism (MP) defined as values, behaviours and attitudes that promote professional relationships, public trust and patient safety is a vital competency in health profession education. MP has a distinctive uniqueness due to cultural, contextual, conceptual, and generational variations. There is no standard instructional strategy to probe the understanding of MP in a cohesive, structured, interactive manner. This study aimed to investigate undergraduate medical students' understanding of MP using express team-based learning (e-TBL) at both campuses of Royal College of Surgeons Ireland (RCSI). Using the key principles of a sociocultural theoretical lens in adult learning theory, we designed e-TBL as a context-learning-based educational strategy. We conducted three e-TBL sessions on cross-cultural communication and health disparities, a reflective report on clinical encounters, and professionalism in practice. We collected, collated, and analyzed the student experiences qualitatively using data gathered from team-based case discussions during e-TBL sessions. A dedicated working group developed very short-answer questions for the individual readiness assurance test (IRAT) and MP-based case scenarios for team discussions. In this adapted 4-step e-TBL session, pre-class material was administered, IRAT was undertaken, and team-based discussions were facilitated, followed by facilitator feedback. A qualitative inductive thematic analysis was performed, which generated subthemes and themes illustrated in excerpts. Our thematic analysis of data from 172 students (101 from Bahrain and 71 from Dublin) yielded four unique themes: incoming professional attitudes, transformative experiences, sociological understanding of professionalism, and new professional identity formation. This qualitative study provides a deeper understanding of medical students' perceptions of medical professionalism. The generated themes resonated with divergent and evolving elements of MP in an era of socioeconomic and cultural diversity, transformative experiences, and professional identity formation. The core elements of these themes can be integrated into the teaching of MP to prepare fit-to-practice future doctors.


Comparison of nuclear imaging techniques and volumetric imaging for the prediction of postoperative mortality and liver failure in patients undergoing localized liver-directed treatments: a systematic review.
Although volumetric imaging by computed tomography (CT) is the gold standard for preoperative assessment of the future liver remnant, nuclear imaging studies have shown promising data. This systematic review summarized the results from trials investigating volumetric and nuclear medicine imaging for the prediction of postoperative mortality and liver failure (LF). MEDLINE and Web of Science were searched for papers investigating nuclear imaging methods for the prediction of postoperative clinical outcomes in patients undergoing local, liver-directed treatments. Only papers investigating both preoperative nuclear imaging and CT or magnetic resonance imaging (MR) for the prediction of postoperative mortality and/or LF were included. Twenty-five trials were qualified for this review. All trials but two used technetium-based tracers for the nuclear imaging examination. Four papers used MR imaging and the remaining used CT for the volumetric evaluation. Overall, the studies were heterogeneous both in terms of methodology and imaging technique. Of the thirteen studies reporting on postoperative mortality, most were descriptive without detailed diagnostic data. A few with detailed data found that nuclear imaging had better predictive value than volumetric imaging. Nineteen studies investigated the prediction of postoperative LF of which seven papers investigated the predictive value of both modalities in multivariable regression analysis. Two papers found that only nuclear imaging parameters were predictive of LF, one paper found that the CT parameter was predictive, and four papers found that combined nuclear and CT/MR imaging parameters were predictive of LF. Both methodologies were useful in the preoperative assessment of patients scheduled for liver interventions, especially in combination, but nuclear imaging demonstrated better predictive value for postoperative mortality and LF in a few trials. The overall technical and methodological heterogeneity of the included studies complicates the ability to directly compare the clinical utility of the two imaging techniques.


Characterization of chiral mesoporous materials by transmission electron microscopy.
By using transmission electron microscopy (TEM), the chirality of novel mesoporous materials has been studied. In addition, a computer simulation that uses a simple structural model was employed. The existence of chiral channels inside a tubelike material was confirmed by the observation of fringes along the length of the tubes. The chiral pitch of the channels was measured from the intermittent period, the chirality (right- or left-handed) was determined from the tilt direction of a tube compared with the direction of incident electrons and the curvature direction of the curved intermitted fringes as viewed in the TEM images.


Brain gray matter alterations in Chinese patients with chronic knee osteoarthritis pain based on voxel-based morphometry.
Altered cerebral gray matter volume (GMV) is commonly found in patients with chronic pain. Chronic pain is the prominent characteristic of knee osteoarthritis (KOA), yet little is known about its morphological changes in the brain. Here an MRI study was performed to examine the structural brain abnormalities in 30 KOA patients with knee pain and age-matched healthy subjects. We detected that the patients exhibited significant almost 2-fold age-related decreases of GMV compared to healthy controls. Moreover, KOA patients also had significant loss of regional GMV including in the bilateral orbital frontal cortex (OFC), the right lateral prefrontal cortex (lPFC), and precentral and postcentral cortices. In addition, a high proportion of KOA patients exerted abnormal scores of Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Mini Mental State examination (MMSE), and Montreal Cognitive Assessment (MoCA) compare to controls. Our results imply that chronic pain conditions which preferentially involve PFC might consider as a "cognitive state." And emotion and cognitive function about chronic pain should be highly regarded.


The alpha-conotoxins GI and MI distinguish between the nicotinic acetylcholine receptor agonist sites while SI does not.
The alpha-conotoxins are paralytic peptide toxins from Indo-Pacific cone snails. This paper presents a detailed analysis of how alpha-conotoxins inhibit [125I]-alpha-bungarotoxin (125I-BTX) equilibrium binding to the acetylcholine receptor (AChR) from electric organ of Torpedo californica and Torpedo nobiliana. All three alpha-conotoxins studied, SI, GI, and MI, completely inhibited 125I-BTX binding with the same order of potency in both species (MI approximately GI > SI approximately d-tubocurarine). BTX-concentration curves showed that this inhibition is competitive. However, while SI appeared to bind to a homogeneous population of sites, both GI and MI displayed curare-like heterogeneous binding. Studies using partially-blocked AChR demonstrated that both GI and MI display different affinities toward the two agonist sites, much like small curariform antagonists do. The high-affinity site for these two alpha-conotoxins is also the high-affinity d-tubocurarine site, which is believed to be located at the alpha gamma-subunit interface. The high-affinity binding of MI and GI was of the same order of magnitude as that of d-tubocurarine; however, their affinity for the other agonist site was somewhat greater than that of dTC, resulting in less site selectivity. Despite being homologous to GI and MI, SI did not distinguish between the two sites. A possible molecular basis for this difference is presented.


[Aldosteroneia in acute kidney failure].
In 19 patients with acute renal insufficiency the plasma renin activity (PRA) and the aldosteronaemia were determined during the phase of anuria and oliguria. Significantly elevated PRA values were found while plasma aldosterone was only moderately elevated in the blood plasma. Apart from this a significantly negative correlation between the aldosterone level and the sodium and bicarbonate concentrations in the blood plasma were found. The lack of a significant positive correlation between PRA and plasma aldosterone levels suggests the participation of factors other than renin in the regulation of the aldosterone secretion in patients with acute renal insufficiency.


Challenges, opportunities, and innovative statistical designs for precision oncology trials.
In the era of precision oncology, improved understanding of tumor heterogeneity, particularly at the molecular level, has caused a shift from traditionally histology based cancer drug development to molecularly targeted drug development. The shift to the molecular view of cancer leads to increasingly small cancer populations for clinical trials which may be underpowered using traditional statistical designs. This paradigm shift lead to the recent developments of innovative clinical trial designs to address the challenges from precision oncology clinical trials. Hence, this paper reviewed and described innovative trial designs for precision oncology. Different strategies were discussed to account patient and treatment effect heterogeneity, including precision dose-finding designs that tailor the optimal dose to different patients at different time points, master protocol designs that match patients' molecular alterations with specific targeted agents, and adaptive enrichment designs that dynamically modify eligibility criteria and enroll patients that are most likely to benefit from the novel agents. Despite their superior performance, better understanding of practical barriers is needed to widen their implementation for precision oncology trials. Therefore, this paper also reviewed the practical challenges regarding the implementation of precision oncology clinical trials, along with the strength and weakness of various approaches of precision oncology clinical trial designs.


Plasma membrane rafts complete cholesterol synthesis by participating in retrograde movement of precursor sterols.
Mammalian cells synthesize significant amounts of precursor sterols, in addition to cholesterol, at the endoplasmic reticulum (ER). The newly synthesized sterols rapidly move to the plasma membrane (PM). The mechanism by which precursor sterols move back to the ER for their enzymatic processing to cholesterol is essentially unknown. Here we performed pulse-chase experiments and showed that the C29/C30 sterols rapidly move from the PM to the ER and are converted to cholesterol. The retrograde precursor sterol transport is largely independent of the Niemann-Pick type C proteins, which play important roles in late endosomal cholesterol transport. In contrast, disrupting lipid rafts significantly retards the conversion of C29/C30 and C28 sterols to cholesterol, causing the accumulation of precursor sterols at the PM. Our results reveal a previously undisclosed function of the PM lipid rafts: they bring cholesterol biosynthesis to completion by participating in the retrograde movement of precursor sterols back to the ER.


tRNA as a positive regulator of transcription antitermination in B. subtilis.
Most Bacillus tRNA synthetase genes are regulated by a common transcription antitermination mechanism but respond individually to limitation for the cognate amino acid. The mRNA leader regions of these genes exhibit extensive structural conservation, with a single codon specific for the appropriate amino acid at the identical position in each structure. Alteration of this sequence in the tyrS gene from UAC (tyrosine) to UUC (phenylalanine) resulted in loss of induction by tyrosine limitation and a switch to induction by phenylalanine limitation. Insertion of an extra base immediately upstream of the codon did not alter regulation, indicating a nontranslational mechanism. A nonsense codon resulted in an uninducible phenotype that was suppressible in a lysyl-tRNA nonsense suppressor mutant, indicating that tRNA acts as an effector.


Cytomegalovirus Retinitis: A Review.
Cytomegalovirus (CMV) is a ubiquitous DNA herpes virus that causes significant morbidity and mortality in immunocompromised individuals. CMV retinitis is a potentially blinding manifestation of CMV infection that was commonly seen in advanced acquired immunodeficiency syndrome (AIDS) in the era before modern combination antiretroviral therapy era, but is also recognized in patients with immune deficiency from multiple causes. The advent of and advances in antiretroviral therapies for human immunodeficiency virus have decreased the incidence of CMV retinitis by over 90% among AIDS patients, and improved visual outcomes in those affected. The diagnosis is generally a clinical one, and treatment modalities include systemic and intravitreal antiviral medications. Retinal detachment and immune recovery uveitis are sight-threatening complications of CMV retinitis that require specific treatments.


[The mechanism of the inhibitory effects of oren-gedoku-to (OGT) on gastric acid secretion in rats].
The effect of oren-gedoku-to (OGT) on gastric acid secretion was examined in the perfused stomach of anesthetized rats. OGT (10-100 mg/kg) given intraperitoneally dose-dependently inhibited the gastric acid secretion stimulated by intracerebroventricular DN-1417, an analogue of TRH, but failed to inhibit the acid secretion stimulated by intracerebroventricular baclofen, an analogue of GABA. The inhibitory effect of OGT on DN-1417-induced acid secretion was antagonized by haloperidol (0.3 and 1.0 mg/kg, i.p.), a dopamine-1/2 antagonist or sulpiride (100 mg/kg, i.p.), a dopamine-2 antagonist; and it was also reversed by yohimbine (0.3 mg/kg, i.p.), an alpha-2 adrenergic antagonist, and prazosin, an alpha-1 antagonist. These results suggest that the ability of OGT to reduce acid secretion is mediated via not only dopamine receptors but also alpha-2 adrenoceptors.


Identification of kakusei, a nuclear non-coding RNA, as an immediate early gene from the honeybee, and its application for neuroethological study.
The honeybee is a social insect that exhibits various social behaviors. To elucidate the neural basis of honeybee behavior, we detected neural activity in freely-moving honeybee workers using an immediate early gene (IEG) that is expressed in a neural activity-dependent manner. In European honeybees (Apis mellifera), we identified a novel nuclear non-coding RNA, termed kakusei, as the first insect IEG, and revealed the neural activity pattern in foragers. In addition, we isolated a homologue of kakusei, termed Acks, from the Japanese honeybee (Apis cerana), and detected active neurons in workers fighting with the giant hornet.


[Anxiety associated with substance abuse].
Substance abuse and anxiety is a common comorbid dyad and an example of so-called dual diagnosis in psychiatry. Comorbidity of anxiety and addictive disorders may be due to interdependence of these states as well as common predisposing factors and pathogenic mechanisms. There are various medicines in the treatment of anxiety associated with substance abuse, including benzodiazepines, calcium channel modulators, non-benzodiazepine anxiolytics, antidepressants and antipsychotics. One of the best approaches to the treatment of chronic anxiety disorders in drug treatment clinic is a long course of treatment with antidepressants, primarily with selective serotonin reuptake inhibitors as first line preparations. Such medications as pregabalin, buspirone, etifoxine and alimemazine are also of interest for the treatment of dual diagnosis patients.


Inositol Improves Cold Tolerance Through Inhibiting CBL1 and Increasing Ca2+ Influx in Rapeseed (Brassica napus L.).
Rapeseed (Brassica napus L.) is an important oilseed crop worldwide. However, its productivity is significantly affected by various abiotic stresses, including cold stress. Among various stresses, cold stress is an important abiotic factor affecting plant growth, yield, and quality. The calcium channels are regarded as key pathways affecting cold tolerance in plants. Thus, improvement in cold tolerance is of great significance for crop improvement. The current study was designed to examine the beneficial role of exogenous inositol in improving cold stress tolerance in rapeseed. From the RNA-seq results, we identified 35 differently expressed genes encoding different inositol enzymes. The results show that inositol (a cyclic polyol) positively regulated cold tolerance by increasing calcium ion (Ca2+) influx in rapeseed. Furthermore, we found that the expression of calcineurin B-like (CBL1) gene was inhibited by inositol. On the other hand, overexpressed plant mediated the Ca2+ flux under cold stress suggesting the key role of inositol-Ca2+ pathway in cold tolerance. Moreover, the overexpression of BnCBL1-2 in Arabidopsis represented that transgenic plants mediated the Ca2+ flux highlighting the vital role of the inositol-Ca2+ pathway in conferring cold stress. Our study provides new insights into rapeseed cold tolerance mechanism and introduces a feasible method to improve the cold tolerance of rapeseed quickly.


Identification of quantitative trait loci that affect endoreduplication in maize endosperm.
Endoreduplication in maize endosperm precedes the onset of starch and storage protein synthesis, and it is generally thought to influence grain filling. We created four backcross populations by reciprocally crossing the F(1) progeny of a cross between Sg18 and Mo17 to the parental inbreds, which differ in endoreduplication by two parameters--mean ploidy and percentage of endoreduplicated nuclei. This four-backcross design allowed us to estimate and test the additive and dominant genetic effects of quantitative trait loci (QTLs) affecting endoreduplication. An analysis of endosperm from the four backcross populations at 16 days after pollination using a modified triploid mapping approach identified three endosperm QTLs influencing mean ploidy and two endosperm QTLs affecting the percentage of endoreduplicated nuclei. Some of these QTLs may manifest their effects on endoreduplication via expression in the embryo. The QTLs detected display strong dominance or over-dominance and interacted epistatically with an embryo-expressed QTL. This helps to explain the genetic basis for transgressive segregation in the backcross progeny. Although the favorable alleles that increase mean ploidy and percentage of endoreduplicated nuclei can be contributed by both parents, the Mo17-derived alleles for endoreduplication were often dominant or over-dominant to the Sg18-derived allele. One QTL on chromosome 7 that may be expressed in both the embryo and endosperm exerted a pleiotropic effect on two different parameters of endoreduplication. The results from this study shed light on the regulation of endoreduplication in maize endosperm and provide a marker-assisted selection strategy for potentially improving grain yield.


Pharmacokinetics and pharmacodynamics of morphine in llamas.
To assess the pharmacokinetics and pharmacodynamics of morphine in llamas. 6 healthy adult llamas. Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis. Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/- 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/- 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score. Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.