Transformation of (1,2-3H)aldosterone in the foetal and placental compartments of the guinea pig.
In vivo and in vitro transformation of labelled d-aldosterone (11beta, 21-dihydroxy-3,20-dioxo-4-pregnen-18-al) was studied in the foetal tissues and placenta of guinea pig (35-45 days of gestation). The principal metabolite found in all of these tissues was tetrahydroaldosterone (3alpha, 18,21-trihydroxy-20-oxo-5beta-pregnan-18-al). A large transformation into this metabolite was found in foetal liver (67-68%) and in the placenta (69-82%). Incubation of [3H]- or [14C]aldosterone with the isolated placenta also showed a large conversion to the tetrahydroderivative suggesting that the reductase(s) of ring A of aldosterone is present in this tissue. Most of the unmetabolized aldosterone and tetrahydroaldosterone was found in the unconjugated fraction. Very little of the radioactive material was present in the polar steroids extracted with n-butanol. Aldosterone and tetrahydroaldosterone were liberated from this fraction after enzymatic hydrolysis (beta-glucuronidase and sulphatase) or by solvolysis, suggesting that part of these conjugates is present in the foetal compartment as sulphate esters and glucuronides. Moreover, in this fraction a polar, unconjugated aldosterone metabolite with the characteristics of an acidic compound was detected.


Spinal cord pilocytic astrocytoma with leptomeningeal dissemination to the brain. Case report and review of the literature.
Leptomeningeal dissemination of low-grade spinal cord gliomas is an uncommon event. The authors report a unique case of leptomeningeal dissemination of a spinal cord pilocytic astrocytoma (PCA) to the intracranial cerebral subarachnoid spaces in a child. A 2-year-old boy presented with a loss of balance and the inability to walk or stand. An intradural intramedullary spinal cord tumor was identified, and the lesion was subtotally resected and diagnosed by the pathology department to be a PCA. Subsequently, the patient had recurrences of the intradural intramedullary tumor at 6 months and 2 years after his original presentation. He underwent a repeated resection of the recurrent tumor and fenestration of an associated syrinx on both occasions. The pathological characteristics of the reresected tumor remained consistent with those of a PCA. Postoperative imaging after his last surgery revealed diffuse intracranial leptomeningeal dissemination into the cisternal space surrounding the midbrain, the suprasellar region, and the internal auditory canal, as well as nodular subarachnoid disease in the upper cervical region. The patient then underwent chemotherapy, and total spine magnetic resonance (MR) imaging 2 months later demonstrated stability in the size of the spinal cord tumor and a decrease in the associated syrinx. However, an MR image of the head demonstrated two new areas of supratentorial subarachnoid leptomeningeal spread of the primary spinal cord tumor at the 2-month follow-up examination. At the 6-month follow-up examination, MR imaging of the head and spine demonstrated stable metastatic disease. This case illustrates a unique instance of supratentorial leptomeningeal dissemination of an intramedullary spinal cord PCA in a child.


Nucleolus precursor body (NPB): a distinct structure in mammalian oocytes and zygotes.
Nucleoli in mammalian oocytes and zygotes, sometimes referred to as nucleolus precursor bodies (NPBs), are compact and morphologically different from nucleoli in somatic cells. We applied a unique NPB analyzing method "enucleolation" technique to zygotes to remove the NPBs. It has been reported that oocyte NPBs are essential for embryonic development; in their absence, the oocytes complete maturation and can be fertilized, but no nucleoli are formed in the zygotes and embryos, leading to developmental failure. However, we found that when NPBs were removed from zygotes, the zygotes developed successfully to live-born pups. These results indicated that oocyte NPBs are essential for embryonic development, but zygote NPBs are not. In addition, the enucleolated zygotes formed somatic-type nucleoli during early embryonic development, demonstrating that somatic-type nucleoli do not originate from zygote NPBs. We summarize our recent investigation on NPBs, and provide additional comments and findings.


Lyme Borreliosis--the Utility of Improved Real-Time PCR Assay in the Detection of Borrelia burgdorferi Infections.
Infections of Borrelia burgdorferi sensu lato reveal clinical manifestations affecting numerous organs and tissues. The standard diagnostic procedure of these infections is quite simple if a positive history of tick exposure or typical erythema migrans appears. Lack of unequivocal clinical symptoms creates the necessity for further evaluation with laboratory tests. This study discusses the utility of a novel, improved, well-optimized, sensitive and highly specific quantitative real-time PCR assay for the diagnostics of infections caused by Borrelia burgdorferi sensu lato. We designed an improved, specific, highly sensitive real-time quantitative polymerase chain reaction (RQ-PCR) assay for the detection and quantification of all Borrelia burgdorferi genotypes. A wide validation effort was undertaken to ensure confidence in the highly sensitive and specific detection of B. burgdorferi. Due to high sensitivity and great specificity, as low as 1.6×10² copies of Borrelia per mL of whole blood could be detected. As much as 12 (3%) negative ELISA IgM results, 14 (2.8%) negative results of Line blot IgM, 11 (3.1%) and 7 (2.7%) of negative ELISA IgG and Line blot IgG results, respectively, were positive in real-time PCR. The data in this study confirms the high positive predictive value of real-time PCR test in the detection of Borrelia infections.


Effect of Zingiber officinale Roscoe rhizome (ginger) capsule on postpartum pain: Double-blind randomized clinical trial.
Postpartum pain contributes to increased irritability and excessive stress in the mother and consequently may inhibit successful breastfeeding, reduce a mother's ability to take care of her baby, and cause an imperfect mother-baby interaction. Evidence suggests the positive effect of ginger on reduction in uterus-associated pain. The objective of this study is to investigate the effect of ginger capsules on postpartum pain. The present double-blinded, randomized, placebo-controlled trial was conducted in Mahdiyeh Educational Hospital, Tehran. One hundred and twenty-eight mothers having moderate-to-severe pain following vaginal delivery were included. The participants were divided into two groups (A and B). Interventions were performed every 8 h in 24 h. In the first intervention (2 h after the delivery), Group A received 500 mg of placebo capsules (containing chickpea flour) and Group B received 500 mg of Zintoma (ginger rhizome) capsules. In the second and third interventions, Group A received 250 mg placebo capsules and Group B received 250 mg Zintoma capsules. All participants received 250 mg capsules of mefenamic acid in each intervention in addition to ginger or placebo capsules. The pain severity was measured before and half an hour, an hour, and 2 h after each intervention. Statistical analysis was performed using the SPSS software version. 22. The Chi-square, Fisher's, and t tests and the GEE model were applied to assess the pain severity. The average pain severity was not statistically significant between the groups in the beginning of the intervention (P = 0.623). The mean score of pain significantly decreased within the duration of intervention in both groups (P < 0.001); however, the pain severity was significantly lower in the intervention group as compared to the control group at any point after the intervention (P = 0.006). Ginger can be used as an effective remedy for postpartum pain relief.


Limitless Possibilities With Full-Arch Zirconia Monolithic Hybrid Restorations.
Although technology continues to profoundly change dentistry, the human touch and human intelligence remain the defining forces in the final outcome to create beautiful teeth. Dental professionals ask patients to rely on their expertise, making it incumbent on the dental team to understand the materials in use. The author explores how to leverage the technological advancements with the uniqueness of the dental professional's personal touch to create implant-supported solid zirconia hybrid restorations. The tips and strategies shared in this article will enhance both efficiency and predictability.


Using Kinetic eGFR for Drug Dosing in AKI: Concordance between Kinetic eGFR, Cockroft-Gault Estimated Creatinine Clearance, and MDRD eGFR for Drug Dosing Categories in a Pilot Study Cohort.
Drug dosing in patients with acute kidney injury (AKI) is based on the Cockroft-Gault (CG) equation-derived estimated Creatinine clearance (CGeCrCl) for historical reasons due to the lack of a validated method for estimating glomerular filtration rate (GFR) when Cr is rapidly changing. The kinetic equation (kinetic estimated GFR [KeGFR]) estimates GFR for the nonsteady-state Cr level. It is being validated in patient cohorts and could potentially be used for drug dosing when the Cr level is in the nonsteady state. The aim of the study was to measure the concordance and the degree of agreement between KeGFR-, CGeCrCl, and MDRD eGFR-based drug dosing categories in patients with nonsteady Cr levels. In the pilot study published previously, 80 adult patients with a significant change in Cr level after admission to the acute medical ward were classified as per the Acute Kidney Injury Network (AKIN) criteria and compared to a KeGFR-based criterion. The CG equation and the MDRD equation were applied retrospectively to the same dataset, and the concordance of the eGFR categories between the 3 methods was studied. The 3 eGFR categories (<30, 30-49, and >50 mL/min) were chosen to reflect the frequently used drug dosing categories in patients with renal impairment. The concordance between CGeCRCL and KeGFR for drug dosing categories was only 62%, with 27 (90%) of the 30 discordant subjects falling into a higher eGFR category when KeGFR was used. The agreement between KeGFR and CGeCrCl was also unsatisfactory. There was better concordance (75%), but the agreement was also not satisfactory between MDRD eGFR and KeGFR for the drug dosing categories. In AKI, compared to CGeCrCL, using KeGFR may affect drug dosing significantly by changing the eGFR category. Further studies of KeGFR for drug dosing will need therapeutic drug monitoring and pharmacokinetic studies for validation.


Backbone NMR resonance assignments for the C terminal domain of the Streptococcus mutans adhesin P1.
Adhesin P1 (aka AgI/II) plays a pivotal role in mediating Streptococcus mutans attachment in the oral cavity, as well as in regulating biofilm development and maturation. P1's naturally occurring truncation product, Antigen II (AgII), adopts both soluble, monomeric and insoluble, amyloidogenic forms within the bacterial life cycle. Monomers are involved in important quaternary interactions that promote cell adhesion and the functional amyloid form promotes detachment of mature biofilms. The heterologous, 51-kD C123 construct comprises most of AgII and was previously characterized by X-ray crystallography. C123 contains three structurally homologous domains, C1, C2, and C3. NMR samples made using the original C123 construct, or its C3 domain, yielded moderately resolved NMR spectra. Using Alphafold, we re-analyzed the P1 sequence to better identify domain boundaries for C123, and in particular the C3 domain. We then generated a more tractable construct for NMR studies of the monomeric form, including quaternary interactions with other proteins. The addition of seven amino acids at the C-terminus greatly improved the spectral dispersion for C3 relative to the prior construct. Here we report the backbone NMR resonance assignments for the new construct and characterize some of its quaternary interactions. These data are in good agreement with the structure predicted by Alphafold, which contains additional β-sheet secondary structure compared to the C3 domain in the C123 crystal structure for a construct lacking the seven C-terminal amino acids. Its quaternary interactions with known protein partners are in good agreement with prior competitive binding assays. This construct can be used for further NMR studies, including protein-protein interaction studies and assessing the impact of environmental conditions on C3 structure and dynamics within C123 as it transitions from monomer to amyloid form.


[Stabilization of 150 unstable spinal injuries with the Cotrel-Dubousset instrument--analysis of results].
The present study is a retrospective analysis of spinal fracture treatment with the Cotrel-Dubousset instrumentation technique. 150 unstable injuries of the spine were treated with the CD implant at the University of Louisville--Level I Trauma Center--between February 1985 and March 1989. There were 67 burst fractures, 48 compression fractures and 21 fracture dislocations, 8 flexion distraction fractures and 6 flexion rotation injuries. Ninety-three patients underwent anterior cord decompression and strut grafting followed by posterior CD instrumentation and posterolateral fusion. Fifty-seven patients had posterior CD instrumentation and fusion alone. No neurological deterioration after the procedure was observed, 33 patients improved neurologically. Hospital stay ranged between 7 and 60 days (mean 20 days). 114 patients had a minimum follow up of 6 months (range 6-52 months). The mean follow up was 17.7 months. At final follow up 77.8% of the patients had returned to work and 84.2% of the patients were almost painfree. The mean loss of correction in the sagittal plane was 6.2 degrees (range: 0 and 42 degrees) at final follow up. As technical complications there were four hook cut outs (2.6%) of which two underwent reosteosynthesis and two did not effect the clinical or radiographic result. The high stability of the device provides a decreased risk of neurological deterioration, a decreased risk of posttraumatic kyphosis and early rehabilitation.


Crime and Violence among MDMA Users in the United States.
The question of whether MDMA use is associated with increased crime and violence has not been adequately explored especially in nationally representative samples. This study used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to assess the association between MDMA use and violent and non-violent antisocial behavior while controlling for sociodemographic variables, lifetime psychiatric, alcohol and drug use disorders, and family history of antisocial behavior. MDMA users, both male and female, were involved in a number of crimes in acts of violence including drunk driving, shoplifting, theft, intimate partner violence, and fighting. Notably, female MDMA users were more antisocial than male non-MDMA users. Although adjusting the results for numerous confounds attenuated the relationships, MDMA users were still at significantly greater odds of engaging in violent and nonviolent crime than non-MDMA users. Although MDMA has been considered a facilitator of empathy and closeness, the current study suggests a dark side as MDMA is associated with a broad array of crimes and transgressions. Additional tests of the MDMA-crime link are needed to properly inform policy.


Posterior Semicircular Canal Approach for Inner Ear Gene Delivery in Neonatal Mouse.
Inner ear gene therapy offers great promise as a potential treatment for hearing loss and dizziness. One of the critical determinants of the success of inner ear gene therapy is to find a delivery method which results in consistent transduction efficiency of targeted cell types while minimizing hearing loss. In this study, we describe the posterior semicircular canal approach as a viable method for inner ear gene delivery in neonatal mice. We show that gene delivery through the posterior semicircular canal is able to perfuse the entire inner ear. The easy anatomic identification of the posterior semicircular canal, as well as minimal manipulation of the temporal bone required, make this surgical approach an attractive option for inner ear gene delivery.


Diabetes-induced rat tracheal segment supersensitivity to carbachol.
Contractile responses to carbachol of tracheal segments isolated (i) from rats made diabetic 4 months prior by a single intravenous injection (50 mg/kg) of streptozotocin (group B), and (ii) from diabetic rats that had been treated during the same period with a daily dose (2-4 U/animal) of long-acting insulin (group C) were compared with the contractile responses of trachea isolated from age-matched control animals (group A). Tracheal segments from group B were significantly more responsive to carbachol than those from group A or C at low, but not at high carbachol concentrations. Carbachol pD2 values were higher in group B (6.85 +/- 0.05) than in groups A (6.46 +/- 0.07) or C (6.37 +/- 0.06), but were not significantly different between groups A and C. These data indicate that diabetes induces a supersensitivity to carbachol in airway smooth muscles, possibly related to a diabetes-induced vagal autonomic neuropathy.


Acid-fast bacterium detection and identification from paraffin-embedded tissues using a PCR-pyrosequencing method.
Acid-fast bacterium (AFB) identification from formalin-fixed paraffin-embedded (FFPE) tissues is challenging and may not be readily available to the clinical laboratory. A method to detect and identify AFB from FFPE tissues using PCR and pyrosequencing (PCR-Seq) was developed and evaluated. The method was validated using spiked cell-clotted paraffin blocks before use with patients' specimens. DNA was extracted from tissue sections, and a 16S rRNA gene fragment was amplified and a signature sequence was produced on a PyroMark ID system. Sequences were aligned to established databases for AFB identification. Additional tissue sections were stained and examined for AFB. Both sensitivity and specificity were 100% on spiked cell-clotted blocks without cross-reactivity with non-AFB. Of 302 FFPE tissues from patients, 116 (38%) were AFB-stain positive; 83 (72%) of these had AFB identified. The 21 AFB identified included Mycobacterium tuberculosis complex (14 cases), Mycobacterium leprae (3), Mycobacterium genavense (2), Mycobacterium marinum-ulcerans group (3) and 17 other AFB (61). Thirteen cases were AFB-stain indeterminate and 4 were positive by the PCR-Seq method. Of the AFB stain-negative cases, 167 were negative and 6 were positive by PCR-Seq. The PCR-Seq method provided specific identification of various AFB species or complexes from FFPE tissues.


Unilateral malignant optic glioma following glioblastoma multiforme in the young: a case report and literature review.
Malignant optic gliomas are rare, but they rapidly become lethal visual pathway tumors. We present the clinical course, treatment, and prognosis of a case of unilateral malignant optic glioma in a young man with a history of brain glioblastoma multiforme (GBM). A 21-year-old man, who had GBM 7 years ago complained of a transient shadow in his vision and presented with normal visual acuity but optic disc edema and an enlarged blind spot in the right eye (oculus dexter, OD). Magnetic resonance imaging (MRI) showed a right intraorbital optic nerve tumor without a brain lesion. Chiasm involvement and severe vision deterioration occurred 3 months later. A biopsy of the right optic nerve revealed glioblastoma. Concurrent chemoradiotherapy (CCRT) prevented involvement of the fellow eye 1 year after symptom onset. This report demonstrated that a regular ocular exam should be recommended for several years after GBM. In young healthy patients who are able to undergo chemotherapy and radiotherapy, visual function in the fellow eye can be preserved.


Chronic lymphocytic leukaemia: An updated approach to diagnosis and management in general practice.
Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in Australia. Improvements in the understanding of this disease have led to drastic changes in regards to diagnosis, management and prognosis. The aim of this article is to give an updated approach to the diagnosis, investigation, monitoring and new treatments of CLL. With the advent of new medications and improved investigations to predict outcomes, CLL has now become a chronic disease that requires long-term monitoring by haematologists and general practitioners (GPs).


Ultrastructural analysis of an enterolith composed of deoxycholic acid.
A 67-year-old Japanese man underwent enterotomy because of enterolith ileus. Component analysis by infrared spectroscopy revealed that the enterolith was composed of a high concentration of deoxycholic acid. We further analyzed and compared the ultrastructure of the enterolith and a commercially available powdered form of deoxycholic acid by means of scanning electron microscopy and energy dispersive X-ray spectroscopy. Energy dispersive X-ray spectroscopy analysis revealed that the ratios of carbon and oxygen in the enterolith were equal to those in the deoxycholic acid powder. Scanning electron microscopy analysis showed rectangular prism-shaped particles on the surface of the enterolith. This structure was similar to that of the deoxycholic acid powder. The surgically removed enterolith had a twisted and coiled appearance. Possible mechanisms underlying the formation of this unique form are discussed.


Accuracy of ICD-9-CM coding of cervical spine fractures: implications for research using administrative databases.
ICD-9-CM codes are often used for trauma research due to their ready availability in administrative databases. They are also used to classify injury severity in trauma patients. However, errors in coding may limit the use of these codes. Prior studies have found coding accuracy ranging from 20 to 100%, casting doubt on the reliability of studies utilizing these codes. The goal of this study was to determine the accuracy of ICD-9-CM coding for cervical spine fractures. We used ICD-9-CM codes to identify trauma admissions and cervical spine fractures at a Level I trauma center in 2006. Cervical spine CT or CTA reports were reviewed by two independent observers. Data were compared to ICD-9-CM codes to determine accuracy. Of 1620 trauma admissions, 174 (11%) included a cervical spine fracture defined by ICD-9-CM codes. A cervical spine fracture was the primary diagnosis in 79 admissions and a secondary diagnosis in 63 admissions. Of the 142 cervical spine fractures defined by ICD-9-CM code, there were 133 (94%) cervical fractures by radiology report. Accuracy varied by primary diagnosis (97%) versus secondary diagnosis (89%). By cervical level, there were 230 fractures by CT report. Of these, 7% of ICD-9-CM codes documented a fractured level not noted in the CT report. Conversely, 14% of fractured levels noted by CT report did not have a corresponding ICD-9-CM code. We found an overall 94% accuracy of ICD-9-CM coding compared to radiology reports. Inaccuracy of coding fracture level ranged from 7 to 14%. Researchers using these codes should refer back to the medical record or perform a sensitivity analysis to improve reliability.


Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-β-D-glucuronidase (heparanase).
Mammalian heparanase is an endo-β-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis and inflammation. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size. This in turn causes the release of growth factors, which accelerate tumor growth and metastasis. Heparanase has two glycosaminoglycan-binding domains; however, no three-dimensional structure information is available for human heparanase that can provide insights into how the two domains interact to degrade heparin fragments. We have constructed a new homology model of heparanase that takes into account the most recent structural and bioinformatics data available. Heparin analogs and glycosaminoglycan mimetics were computationally docked into the active site with energetically stable ring conformations and their interaction energies were compared. The resulting docked structures were used to propose a model for substrates and conformer selectivity based on the dimensions of the active site. The docking of substrates and inhibitors indicates the existence of a large binding site extending at least two saccharide units beyond the cleavage site (toward the nonreducing end) and at least three saccharides toward the reducing end (toward heparin-binding site 2). The docking of substrates suggests that heparanase recognizes the N-sulfated and O-sulfated glucosamines at subsite +1 and glucuronic acid at the cleavage site, whereas in the absence of 6-O-sulfation in glucosamine, glucuronic acid is docked at subsite +2. These findings will help us to focus on the rational design of heparanase-inhibiting molecules for anticancer drug development by targeting the two heparin/heparan sulfate recognition domains.


The role of nitric oxide in the apoptosis of neurons in the retina of the human fetal eye.
The locations of NADPH-diaphorase (NADPH-d), inducible NO synthase (iNOS), and TUNEL-immunoreactive neurons in the retina of human fetuses collected during the first to third trimesters of pregnancy were studied. High levels of NADPH-d activity were seen in the inner segments of light-sensitive cells, amacrine cells, and ganglion cells. The population of NADPH-d-positive amacrine cells included three types of neuron. Type 1 neurons were large and had sparse dendritic fields occupying the inner nuclear and outer retinal layers. Small type 2 neurons were located in the inner retinal layer. Ectopic amacrine cells, type 3, were located in the outer part of the ganglion layer. A high density of NADPH-d-positive neurons was seen in the central part of the retina, surrounding the central fovea and optic disk area. NADPH-d activity increased progressively during ontogenesis and correlated with the appearance of immunoreactive iNOS in neurons. iNOS labeled a subpopulation of amacrine and ganglion cells, which appeared at 20-21 weeks of development and reached a peak of immunoreactivity by the end of the third trimester. TUNEL-immunopositive neuron nuclei with signs of apoptotic destruction were seen at 30-31 weeks of pregnancy. The greatest apoptotic index was seen in the ganglion and amacrine cell populations. These data identify NO as a factor mediating apoptosis of neurons during the critical period of differentiation of interneuronal connections in the human retina.


Mediation of gaseous emissions and improving plant productivity by DCD and DMPP nitrification inhibitors: Meta-analysis of last three decades.
Nitrification inhibitors (NIs), especially dicyandiamide (DCD) and 3,4-dimethylpyrazole phosphate (DMPP), have been extensively investigated to mitigate nitrogen (N) losses from the soil and thus improve crop productivity by enhancing N use efficiency. However, to provide crop and soil-specific guidelines about using these NIs, a quantitative assessment of their efficacy in mitigating gaseous emissions, worth for nitrate leaching, and improving crop productivity under different crops and soils is yet required. Therefore, based upon 146 peer-reviewed research studies, we conducted a meta-analysis to quantify the effect of DCD and DMPP on gaseous emissions, nitrate leaching, soil inorganic N, and crop productivity under different variates. The efficacy of the NIs in reducing the emissions of CO2, CH4, NO, and N2O highly depends on the crop, soil, and experiment types. The comparative efficacy of DCD in reducing N2O emission was higher than the DMPP under maize, grasses, and fallow soils in both organic and chemical fertilizer amended soils. The use of DCD was linked to increased NH3 emission in vegetables, rice, and grasses. Depending upon the crop, soil, and fertilizer type, both the NIs decreased nitrate leaching from soils; however, DMPP was more effective. Nevertheless, the effect of DCD on crop productivity indicators, including N uptake, N use efficiency, and biomass/yield was higher than DMPP due to certain factors. Moreover, among soils, crops, and fertilizer types, the response by plant productivity indicators to the application of NIs ranged between 35 and 43%. Overall, the finding of this meta-analysis strongly suggests the use of DCD and DMPP while considering the crop, fertilizer, and soil types.


Pain relief for women undergoing oocyte retrieval for assisted reproduction.
Various methods of conscious sedation and analgesia have been used for pain relief during oocyte recovery in in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) procedures. The choice of agent has also been influenced by the quality of sedation and analgesia as well as by concerns about possible detrimental effects on reproductive outcomes. To assess the effectiveness and safety of different methods of conscious sedation and analgesia on pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval. We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL (from their inception to present); the National Research Register and Current Controlled Trials. We searched reference lists of included studies for relevant studies and contacted authors for information on unpublished and ongoing trials. There was no language restriction. The search was updated in July 2012. Only randomised controlled trials comparing different methods of conscious sedation and analgesia for pain relief during oocyte recovery were included. Quality assessment and data extraction were performed independently by two review authors. Interventions were classified and analysed under broad categories or strategies of sedation and pain relief to compare different methods and administrative protocols of conscious sedation and analgesia. Outcomes were extracted and the data were pooled when appropriate. With this update, nine new studies were identified resulting in a total of 21 trials including 2974 women undergoing oocyte retrieval. These trials compared five different categories of conscious sedation and analgesia: 1) conscious sedation and analgesia versus placebo; 2) conscious sedation and analgesia versus other active interventions such as general and acupuncture anaesthesia; 3) conscious sedation and analgesia plus paracervical block versus other active interventions such as general, spinal and acupuncture anaesthesia; 4) patient-controlled conscious sedation and analgesia versus physician-administered conscious sedation and analgesia; and 5) conscious sedation and analgesia with different agents or dosage. Evidence was generally of low quality, mainly due to poor reporting of methods, small sample sizes and inconsistency between the trials.Conflicting results were shown for women's experience of pain. Compared to conscious sedation alone, more effective pain relief was reported when conscious sedation was combined with electro-acupuncture: intra-operative pain mean difference (MD) on 1 to 10 visual analogue scale (VAS) of 3.00 (95% CI 2.23 to 3.77); post-operative pain MD in VAS units of 2.10 (95% CI 1.40 to 2.80; N = 61, one trial, low quality evidence); or paracervical block (MD not calculable).The pooled data of four trials showed a significantly lower intra-operative pain score with conscious sedation plus paracervical block than with electro-acupuncture plus paracervical block (MD on 10-point VAS of -0.66; 95% CI -0.93 to -0.39; N = 781, 4 trials, low quality evidence) with significant statistical heterogeneity (I(2) = 76%). Patient-controlled sedation and analgesia was associated with more intra-operative pain than physician-administered sedation and analgesia (MD on 10-point VAS of 0.60; 95% CI 0.16 to 1.03; N = 379, 4 trials, low quality evidence) with high statistical heterogeneity (I(2) = 83%). Post-operative pain was reported in only nine studies. As different types and dosages of sedative and analgesic agents, as well as administrative protocols and assessment tools, were used in these trials the data should be interpreted with caution.There was no evidence of a significant difference in pregnancy rate in the 12 studies which assessed this outcome, and pooled data of four trials comparing electro-acupuncture combined with paracervical block with conscious sedation and analgesia plus paracervical block showed an odds ratio (OR) of 0.96 (95% CI 0.72 to 1.29; N = 783, 4 trials) for pregnancy. High levels of women's satisfaction were reported for all modalities of conscious sedation and analgesia as assessed in 12 studies. Meta-analysis of all the studies was not attempted due to considerable heterogeneity.For the rest of the trials a descriptive summary of the outcomes was presented. The evidence from this review of 21 randomised controlled trials did not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte recovery. The simultaneous use of more than one method of sedation and pain relief resulted in better pain relief than one modality alone. The various approaches and techniques reviewed appeared to be acceptable and were associated with a high degree of satisfaction in women. As women vary in their experience of pain and in coping strategies, the optimal method may be individualised depending on the preferences of both the women and the clinicians and resource availability.


Cancer Immunotherapy: Priming the Host Immune Response with Live Attenuated Salmonella enterica.
In recent years, cancer immunotherapy has undergone great advances because of our understanding of the immune response and the mechanisms through which tumor cells evade it. A century after the first immunotherapy attempt based on bacterial products described by William Coley, the use of live attenuated bacterial vectors has become a promising alternative in the fight against cancer. This review describes the role of live attenuated Salmonella enterica as an oncolytic and immunotherapeutic agent, due to its high affinity for tumor tissue and its ability to activate innate and adaptive antitumor immune response. Furthermore, its potential use as delivery system of tumor antigens and immunomodulatory molecules that induce tumor regression is also reviewed.


A new groundwater species of Pseudoniphargus (Amphipoda: Pseudoniphargidae) fromAlgeria.
Intensive sampling performed in the area of Oum El Bouaghi (Northeastern Algeria) yielded a new species of the stygobiont amphipod Pseudoniphargus, P. djemoi, in wells located in the plain of Tamlouka. The new species belongs to a group that shares the display of a uropod 3 exopod extremely elongate and upcurved in the male, whereas its peduncle is only moderately elongate. This cluster of species appears scattered across the southern Iberian Peninsula, Northern Morocco and the Canary Islands. This discovery increases the number of described species of the stygobiont amphipod genus Pseudoniphargus in north Africa to eight. A key to the species of Pseudoniphargus living in Continental Africa and Mediterranean Islands is provided.


[Benzodiazepine withdrawal syndrome].
Benzodiazepines (BDZ) are widely prescribed in clinical practice for many pathological conditions, because of their anxiolytic, sedative, myorelaxant and anticonvulsant properties. The effectiveness, specificity and rapidity of action, the few side effects and the virtual absence of toxicity, have contributed to the widespread use of these compounds. In the last decade, however, the attitude towards BDZ has greatly changed, due to growing awareness and concern about dependence liability, withdrawal phenomena, and long-term side effects. Withdrawal symptoms have been singled out and specified in the contest of a well-defined syndrome with foreseeable onset, duration and remission. Psychic and physical symptoms and disorders of sensory perception can be observed. These manifestations can be suppressed by resuming treatment. The symptomatic and developmental aspects of BDZ withdrawal syndrome are discussed, according to the available literature, with particular reference to clinical features of patients suffering from anxiety and mood disorders.


MicroRNA1917 targets CTR4 splice variants to regulate ethylene responses in tomato.
Ethylene perception is regulated by receptors, and the downstream protein CONSTITUTIVE TRIPLE RESPONSE1 is a key suppressor of ethylene signalling. The non-conserved tomato (Solanum lycopersicum) microRNA1917 (Sly-miR1917) mediates degradation of SlCTR4 splice variants (SlCTR4sv) but the molecular details of this pathway remain unknown. Sly-miR1917 and the targeted SlCTR4sv are ubiquitously expressed in all tomato organs. Overexpression of Sly-miR1917 enhances ethylene responses, including the triple response in etiolated seedlings, in the absence of ethylene, as well as epinastic petiole growth, accelerated pedicel abscission, and fruit ripening. Enhanced ethylene signalling in Sly-miR1917-overexpressing plants (1917-OE) is accompanied by up-regulation of ethylene biosynthesis and signalling genes, and increased ethylene emission. These phenotypes were recovered by repressing the positive ethylene regulator EIN2. Moreover, the Sly-miR1917-targeted SlCTR4 splice variant SlCTR4sv3, expressed specifically in the abscission zone, exhibited the opposite expression pattern to Sly-miR1917. Complementation of the Arabidopsis thaliana ctr-1 mutant and yeast two-hybrid and bimolecular fluorescence complementation assays suggested that SlCTR4sv3 functions in ethylene signalling. Co-expression of Sly-miR1917 and SlCTR4sv3 in Nicotiana benthamiana further suggested that Sly-miR1917 cleaves SlCTR4sv3 in vivo. Database homology searching revealed a Solanum tuberosum CTR-like splice variant containing a Sly-miR1917 binding sequence, and a homologue of mature Sly-miR1917 in potato, indicating a conserved function for miR1917 and the regulatory miRNA-mediated ethylene network in solanaceous species.


Systemic lupus erythematosus with cytophagic histiocytic panniculitis successfully treated with high-dose glucocorticoids and cyclosporine A.
A 37-year-old male with systemic lupus erythematosus (SLE) presented with high fever, subcutaneous indurations, anemia, thrombocytopenia, elevated liver enzymes and hyperferritinemia. Skin biopsy revealed hemophagocytic histiocytes in the adipose tissues. The patient was diagnosed with SLE with cytophagic histiocytic panniculitis (CHP). Treatment with high-dose glucocorticoids and cyclosporine A induced remission of SLE and CHP. CHP is generally a systemic disorder affecting subcutaneous adipose tissues with a high mortality rate. However, based on the present and previously reported cases, we believe that intensive immunosuppression can ameliorate CHP that occurs as a skin manifestation of SLE.


Complementary therapies in palliative care: a summary of current evidence.
Complementary therapies are often cited as a possible alternative to the management of symptoms in palliative care, as another element in the armoury for coping with unmanageable problems. But how efficacious are these therapies, and what is the evidence to support their use in symptom management? Patients who are in the terminal stages of illness or require palliative care are in a very vulnerable position, so are they being exploited or are there real benefits from using complementary therapies? This article review some of the evidence currently available.


Intraglandular transport of 125I-glandular kallikrein in the rat submandibular salivary gland.
The transport of radiolabelled rat submandibular gland kallikrein was studied after local administration to the resting and activated rat submandibular gland. The iodinated kallikrein was electrophoretically, immunologically, and biologically indistinguishable from the intact enzyme. After intraductal and intraglandular application the radioactivity in venous effluent was quantitated and characterized. As judged by gel-filtration 125I-kallikrein in venous effluent eluted at a position similar to that seen when the iodinated enzyme was mixed with plasma, but earlier than the elution of 125I-kallikrein in buffer. In plasma, therefore, glandular kallikrein is probably bound to macromolecules. The radioactive fractions in venous effluent did not contain free iodine. Maximum concentration of 125I-kallikrein in venous effluent of resting glands was repeatedly reached about 20 min after intraductal administration. Moreover, the ductal epithelium represented the main permeation barrier since after intraglandular application the maximum venous 125I-kallikrein concentration was reached almost immediately. In activated gland (parasympathetic and sympathetic nerve stimulation), the venous 125I-kallikrein concentration was inversely related to glandular blood flow. We conclude that kallikrein present in the duct lumen or in the interstitium is able to reach the circulation, thereby making possible the local generation of plasma-kinins.


I like my voice better: self-enhancement bias in perceptions of voice attractiveness.
Previous research shows that the human voice can communicate a wealth of nonsemantic information; preferences for voices can predict health, fertility, and genetic quality of the speaker, and people often use voice attractiveness, in particular, to make these assessments of others. But it is not known what we think of the attractiveness of our own voices as others hear them. In this study eighty men and women rated the attractiveness of an array of voice recordings of different individuals and were not told that their own recorded voices were included in the presentation. Results showed that participants rated their own voices as sounding more attractive than others had rated their voices, and participants also rated their own voices as sounding more attractive than they had rated the voices of others. These findings suggest that people may engage in vocal implicit egotism, a form of self-enhancement.


Mapping molecular diffusion in the plasma membrane by Multiple-Target Tracing (MTT).
Our goal is to obtain a comprehensive description of molecular processes occurring at cellular membranes in different biological functions. We aim at characterizing the complex organization and dynamics of the plasma membrane at single-molecule level, by developing analytic tools dedicated to Single-Particle Tracking (SPT) at high density: Multiple-Target Tracing (MTT). Single-molecule videomicroscopy, offering millisecond and nanometric resolution, allows a detailed representation of membrane organization by accurately mapping descriptors such as cell receptors localization, mobility, confinement or interactions. We revisited SPT, both experimentally and algorithmically. Experimental aspects included optimizing setup and cell labeling, with a particular emphasis on reaching the highest possible labeling density, in order to provide a dynamic snapshot of molecular dynamics as it occurs within the membrane. Algorithmic issues concerned each step used for rebuilding trajectories: peaks detection, estimation and reconnection, addressed by specific tools from image analysis. Implementing deflation after detection allows rescuing peaks initially hidden by neighboring, stronger peaks. Of note, improving detection directly impacts reconnection, by reducing gaps within trajectories. Performances have been evaluated using Monte-Carlo simulations for various labeling density and noise values, which typically represent the two major limitations for parallel measurements at high spatiotemporal resolution. The nanometric accuracy obtained for single molecules, using either successive on/off photoswitching or non-linear optics, can deliver exhaustive observations. This is the basis of nanoscopy methods such as STORM, PALM, RESOLFT or STED, which may often require imaging fixed samples. The central task is the detection and estimation of diffraction-limited peaks emanating from single-molecules. Hence, providing adequate assumptions such as handling a constant positional accuracy instead of Brownian motion, MTT is straightforwardly suited for nanoscopic analyses. Furthermore, MTT can fundamentally be used at any scale: not only for molecules, but also for cells or animals, for instance. Hence, MTT is a powerful tracking algorithm that finds applications at molecular and cellular scales.


Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.
Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.


Articulatory-acoustic relations in the production of alveolar and palatal lateral sounds in Brazilian Portuguese.
Lateral approximant speech sounds are notoriously difficult to measure and describe due to their complex articulation and acoustics. This has prevented researchers from reaching a unifying description of the articulatory and acoustic characteristics of laterals. This paper examines articulatory and acoustic properties of Brazilian Portuguese alveolar and palatal lateral approximants (/l/ and /ʎ/) produced by six native speakers. The methodology for obtaining vocal tract area functions was based on three-dimensional/four-dimensional (3D/4D) ultrasound recordings and 3D digitized palatal impressions with simultaneously recorded audio signals. Area functions were used to calculate transfer function spectra, and predicted formant and anti-resonance frequencies were compared with the acoustic recordings. Mean absolute error in formant frequency prediction was 4% with a Pearson correlation of r = 0.987. Findings suggest anti-resonances from the interdental channels are less important than a prominent anti-resonance from the supralingual cavity but can become important in asymmetrical articulations. The use of 3D/4D ultrasound to study articulatory-acoustic relations is promising, but significant limitations remain and future work is needed to make better use of 3D/4D ultrasound data, e.g., by combining it with magnetic resonance imaging.


Autologous hematopoietic stem cell transplantation for multiple sclerosis: A current perspective.
The most effective treatment at halting inflammation in patients with highly active multiple sclerosis (MS) is immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT). Better patient selection and supportive management, as well as advances in conditioning regimens have resulted in improved safety with AHSCT. However, which comorbidities or prior therapies increase the risks associated with AHSCT still need to be determined. In addition, there is still debate as to which AHSCT conditioning regimen offers the best balance of long-term efficacy and safety. New studies comparing AHSCT with highly effective disease-modifying therapies will help to inform on the ideal placement of AHSCT in the treatment algorithm. Currently, many centers are experienced and use AHSCT to treat select patients with MS, contributing to ongoing registries and clinical trials which will help answer these questions.


Postprocessing Algorithm for Driving Conventional Scanning Tunneling Microscope at Fast Scan Rates.
We present an image postprocessing framework for Scanning Tunneling Microscope (STM) to reduce the strong spurious oscillations and scan line noise at fast scan rates and preserve the features, allowing an order of magnitude increase in the scan rate without upgrading the hardware. The proposed method consists of two steps for large scale images and four steps for atomic scale images. For large scale images, we first apply for each line an image registration method to align the forward and backward scans of the same line. In the second step we apply a "rubber band" model which is solved by a novel Constrained Adaptive and Iterative Filtering Algorithm (CIAFA). The numerical results on measurement from copper(111) surface indicate the processed images are comparable in accuracy to data obtained with a slow scan rate, but are free of the scan drift error commonly seen in slow scan data. For atomic scale images, an additional first step to remove line-by-line strong background fluctuations and a fourth step of replacing the postprocessed image by its ranking map as the final atomic resolution image are required. The resulting image restores the lattice image that is nearly undetectable in the original fast scan data.


Age-related changes in gap junctional intercellular communication in osteoblastic cells.
Aging demonstrates deleterious effects upon the skeleton which can predispose an individual to osteoporosis and related fractures. Despite the well-documented evidence that aging decreases bone formation, there remains little understanding whereby cellular aging alters skeletal homeostasis. We, and others, have previously demonstrated that gap junctions--membrane-spanning channels that allow direct cell-to-cell conductance of small signaling molecules--are critically involved in osteoblast differentiation and skeletal homeostasis. We examined whether the capacity of rat osteoblastic cells to form gap junctions and respond to known modulators of gap junction intercellular communication (GJIC) was dependent on the age of the animal from which they were isolated. We observed no effect of age upon osteoblastic Cx43 mRNA, protein or GJIC. We also examined age-related changes in PTH-stimulated GJIC. PTH demonstrated age-dependent effects upon GJIC: Osteoblastic cells from young rats increased GJIC in response to PTH, whereas there was no change in GJIC in response to PTH in osteoblastic cells from mature or old rats. PTH-stimulated GJIC occurred independently of changes in Cx43 mRNA or protein expression. Cholera toxin significantly increased GJIC in osteoblastic cells from young rats compared to those from mature and old rats. These data demonstrate an age-related impairment in the capacity of osteoblastic cells to generate functional gap junctions in response to PTH, and suggest that an age-related defect in G protein-coupled adenylate cyclase activity at least partially contributes to decreased PTH-stimulated GJIC.


DNA polymerases engineered by directed evolution to incorporate non-standard nucleotides.
DNA polymerases have evolved for billions of years to accept natural nucleoside triphosphate substrates with high fidelity and to exclude closely related structures, such as the analogous ribonucleoside triphosphates. However, polymerases that can accept unnatural nucleoside triphosphates are desired for many applications in biotechnology. The focus of this review is on non-standard nucleotides that expand the genetic "alphabet." This review focuses on experiments that, by directed evolution, have created variants of DNA polymerases that are better able to accept unnatural nucleotides. In many cases, an analysis of past evolution of these polymerases (as inferred by examining multiple sequence alignments) can help explain some of the mutations delivered by directed evolution.


Growth and composition of a transplantable murine Leydig cell tumor.
C57BL/6J mice inoculated sc with 50 mg of a transplantable Leydig cell tumor (M5480) demonstrated a reproducible pattern of slow tumor growth up to day 10 followed by rapid growth at the rate of approximately 0.5 g per day through day 27. The mean survival time of tumor-bearing mice was 33 days, when tumor weight accounted for more than 25% of total body weight. The rapid increase in weight occurring around day 10 resulted largely from a 20-fold increase in the quantity of extravasated blood inside the tumor, which in turn promoted a 50% reduction in host hematocrit. Sustained enlargement of M5480 during the third and fourth weeks of growth was supported by proliferation of tumor cells. Apart from blood-filled cavities, over 90% of the tumor consisted of neoplastic Leydig cells exhibiting generalized cytoplasmic features usually associated with mitotic activity. An activated macrophage was the next most abundant cell type, accounting for 2-3% of the nucleated cell mass. The remaining 3% was occupied by vascular elements, leukocytes, and giant cells. Depending on the age of the tumor, varying proportions of the cell population showed signs of anoxic degeneration. Degenerate cells were minimal at day 14, accounting for less than 4% of the total population, and maximal beyond day 21, when they occupied more than 50% of the cell mass.


Interaction of polymyxin B nonapeptide with anionic phospholipids.
The interaction of polymyxin B nonapeptide (PMBN) and polymyxin B (PMB) with the anionic phospholipids phosphatidylserine (PS), dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidic acid (DPPA), and 1:1 mixtures (w/w) of DPPA and distearoylphosphatidylcholine (DSPC) was studied by calorimetry, electron spin resonance, and fluorescence spectrometry, electron microscopy, and fusion and leakage assays. The phase transition temperatures of DPPA and DPPG were very similar when bound to PMB or PMBN, indicating that the lipids are in a similar state when bound to the cationic peptides. Both PMB and PMBN caused the interdigitation of DPPG bilayers, suggesting that the penetration of hydrophobic side chains from a peptide bound electrostatically on the surface is sufficient to induce this phenomenon. Stopped-flow experiments revealed that PMBN and PMB induced the fusion of small unilamellar PS and large unilamellar DPPA-DSPC vesicles. The aggregation of vesicles was found to be diffusion-controlled process; the subsequent fusion took place with a frequency of 10(2)-(5 X 10(2] s-1 for small vesicles and 1-100 s-1 for large vesicles. The freeze-fracture replicas of the PMB-treated vesicles displayed 12-50-nm depressions on several superimposed bilayers, indicating the formation of stable lipid-PMB domains. Since the incubation with PMBN produced similar depressions only if the specimens were fixed, PMBN-induced domain formation seems to be a reversible rapid process. The differences in the phospholipid-peptide interactions are correlated with the differences in the physiological action of the antibiotic PMB and the nonbactericidal PMBN on the cell envelope of Gram-negative bacteria.


Healthcare utilization and costs in diabetes relative to the clinical spectrum of painful diabetic peripheral neuropathy.
Diabetic peripheral neuropathy (DPN) accompanied by painful symptoms is known as painful DPN (pDPN). This study characterized healthcare resource utilization and costs in patients with DPN, pDPN, and severe pDPN relative to diabetes only. Four adult cohorts were identified from the Humedica database: type 2 diabetes without DPN (n=288,328); DPN (n=35,050); pDPN (DPN subjects with a pain score ≥1 on a 0-10 numeric rating scale; n=3449); and severe pDPN (pain scores 7-10; n=1824). Resource utilization and costs for 12-months post-diagnosis were compared for diabetes relative to the other cohorts. Demographic characteristics were different across cohorts. Relative to diabetes alone, DPN, pDPN, and severe pDPN were characterized by significantly higher proportions of patients with resource utilization for all resource categories (all P<0.0001); the highest resource use generally observed for severe pDPN. Total annual direct medical costs were $6632 for diabetes only, with costs for DPN ($12,492), pDPN ($27,931), and severe pDPN ($30,755) significantly higher (all P<0.0001); outpatient costs were consistently the primary driver of total costs. Patients with DPN, pDPN, and severe pDPN had significantly greater healthcare resource utilization and costs than patients with diabetes only, with the highest burden associated with severe pDPN.


What is the evidence for the use of biologic or biosynthetic meshes in abdominal wall reconstruction?
Although many surgeons have adopted the use of biologic and biosynthetic meshes in complex abdominal wall hernia repair, others have questioned the use of these products. Criticism is addressed in several review articles on the poor standard of studies reporting on the use of biologic meshes for different abdominal wall repairs. The aim of this consensus review is to conduct an evidence-based analysis of the efficacy of biologic and biosynthetic meshes in predefined clinical situations. A European working group, "BioMesh Study Group", composed of invited surgeons with a special interest in surgical meshes, formulated key questions, and forwarded them for processing in subgroups. In January 2016, a workshop was held in Berlin where the findings were presented, discussed, and voted on for consensus. Findings were set out in writing by the subgroups followed by consensus being reached. For the review, 114 studies and background analyses were used. The cumulative data regarding biologic mesh under contaminated conditions do not support the claim that it is better than synthetic mesh. Biologic mesh use should be avoided when bridging is needed. In inguinal hernia repair biologic and biosynthetic meshes do not have a clear advantage over the synthetic meshes. For prevention of incisional or parastomal hernias, there is no evidence to support the use of biologic/biosynthetic meshes. In complex abdominal wall hernia repairs (incarcerated hernia, parastomal hernia, infected mesh, open abdomen, enterocutaneous fistula, and component separation technique), biologic and biosynthetic meshes do not provide a superior alternative to synthetic meshes. The routine use of biologic and biosynthetic meshes cannot be recommended.


Theoretical and experimental studies on circular dichroism of carbo[n]helicenes.
The chiroptical properties of a series of carbo[n]helicenes (n = 4-10) were investigated by the state-of-the-art approximate coupled cluster and density functional theory calculations. The theoretical calculation at the RI-CC2/TZVPP//DFT-D2-B97-D/TZVP level nicely reproduced the experimental CD spectra in both excitation energy and rotational strength without any shift or scaling. These calculations afforded the electric and the magnetic transition dipole moment vectors in [n]helicenes, allowing us to discuss the observed rotational strengths as a function of the number of benzene rings. Although the observed CD intensity was not immediately correlated to any of the calculated parameters, the anisotropy (g) factor of the (1)B(b) band and the specific rotation were found inversely proportional to n and nicely correlated with the helical pitch, but discontinuous at n = 6, where the aromatic rings start to overlap. In contrast, the g factor at the (1)B(a) band was rather insensitive to n. It was also revealed that the excitation energies of the (1)B(b) and (1)B(a) bands are inversely proportional to n over the entire range of n examined. The theoretical predictions also enabled us to rectify the erroneous experimental CD spectra of [5]- and [6]helicenes reported earlier, by using the enantiopure samples resolved by chiral HPLC.


Downregulation of UBC9 promotes apoptosis of activated human LX-2 hepatic stellate cells by suppressing the canonical NF-κB signaling pathway.
UBC9, the only known E2-conjugating enzyme involved in SUMOylation, is a key regulator in fibrosis. However, the roles of UBC9 in liver fibrosis remain unclear. Therefore, in this study, we investigated the roles of UBC9 in HSC apoptosis and liver fibrogenesis. Our results showed that the UBC9 levels in activated LX-2 cells, HepG2 and SMMC-7721 were increased compared with LO2, and the expression of UBC9 in activated LX-2 cells, HepG2 and SMMC-7721 were no significant differences. The expression of UBC9 was effectively down-regulated by the UBC9-shRNA plasmid, and this effect was accompanied by the attenuated expression of the myofibroblast markers smooth muscle actin (α-SMA) and Collagen I. Downregulation of UBC9 also promotes activated HSCs apoptosis by up-regulating cell apoptosis-related proteins. Further, knockdown of UBC9 in activated HSCs inhibited cell viability and caused cell cycle arrest in the G2 phase. Moreover, knockdown of UBC9 suppressed the activation of NF-κB signaling pathways. In conclusion, these results demonstrated that down-regulation of UBC9 expression induced activated LX-2 cell apoptosis and promoted cells to return to a quiescent state by inhibiting the NF-κB signaling pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of UBC9.


Exposure to polyphenol-rich purple corn pericarp extract restricts fall armyworm (Spodoptera frugiperda) growth.
Bioactive compounds such as polyphenols in plants have been well studied for their potential insecticidal activities. These are considered as safe alternatives against chemical pesticides because of their lower persistence in environment, lower toxicity to humans and other organisms. However, they are present constitutively in lower amounts in plants and have to undergo complicated extraction methods - hampering their commercial exploitation in pest management. Using an inexpensive extraction method developed to recover polyphenol-rich liquid extract from purple corn pericarp, we recently documented that this extract has anti-feeding effects that cascade from larval to adult stages in a model herbivore tobacco hornworm (Manduca sexta). However, M. sexta does not feed on corn or any other major crops other than the species in the nightshade family (Solanaceae). In this study, we explored the same idea but using a generalist and common herbivore on corn, the fall armyworm (Spodoptera frugiperda). We found that purple corn pericarp extract inhibited the larval growth and development as well as negatively affected the pupal stages of S. frugiperda. However, unlike on M. sexta, time to complete larval life cycle was unaffected. Our findings confirm the toxicity of this extract on a generalist, economically important herbivore, but also suggest potential species-specific effects that should be explored further.


Purification and characterization of a ribonuclease from Aspergillus giganteus IFO 5818, the gigantin. Immunological and enzymic comparison with alphasarcin.
A protein has been isolated from a culture medium of Aspergillus giganteus IFO 5818 (gigantin) and purified by ion-exchange chromatography successively on DEAE-cellulose and carboxymethyl-cellulose, and gel-filtration chromatography on Biogel P10. With a high purity, gigantin was found to be a non-glycosylated basic protein with a relative molecular mass of 17000 +/- 200 determined in PAGE/SDS. Gigantin was able to digest the synthetic homopolymers of nucleic acids poly(A), poly(I), poly(C) and poly(U). The catalytic action has an optimal pH around 7.0, an optimal temperature at 45-55 degrees C and can be inhibited by cations. Gigantin activity, analyzed as its capacity to hydrolyze RNA from yeast, was comparable to that of alphasarcin, a similar biochemical protein produced by the strain A. giganteus MDH 18894. A study of the substrate specificity for alphasarcin indicated a preference for poly(A) and poly(I), while gigantin had greater activity on poly(C) and poly(U). The cross reaction of gigantin with a rabbit antiserum to alphasarcin suggests a high sequence similarity between both proteins. However, gigantin is immunologically distinguishable from alphasarcin as alphasarcin antiserum detects epitopes in alphasarcin that are not present in gigantin.


"Longing for individual recognition" - Pregnant women's experiences of midwives' counselling on physical activity during pregnancy.
The aims to explore among pregnant women were their experiences of lifestyle counselling provided by a midwife in antenatal care, addressing health promotion with special focus on physical activity during pregnancy, and factors influencing the trustworthiness of counselling conducted by a midwife. This qualitative study collected data from 14 pregnant, primiparous or multiparous women in gestational week 35-36 using in-depth interviews. The data were collected in Sweden in 2015. Qualitative content analysis was applied. The theme "Longing for fulfilment of individual needs and expectations" emerged during analysis, including four categories; "Being exposed to unsatisfying counselling"; "Appreciating supportive and trustworthy counselling"; "Wrestling with cultures", and "Dealing with physical activity in daily life". The results indicated that some participants experienced limited counselling that was characterized by lack of knowledge, support, and trustworthiness in the midwife. Other participants reported valuable encouragement and support by the midwife. Participants were longing for individual recognition instead of receiving general advice on physical activity that was designed for all pregnant women. Individual counselling on physical activity during pregnancy based on the participant's individual needs was desired. On the contrary, the participants could experience the midwife as having her own agenda, insufficient knowledge and primarily focusing on medical surveillance. There is a need of increased level of knowledge among midwives in antenatal care, regarding lifestyle and lifestyle change during pregnancy. This may enhance promotion of a healthy lifestyle for the pregnant woman during counselling.


Cell shape and cell-wall organization in Gram-negative bacteria.
In bacterial cells, the peptidoglycan cell wall is the stress-bearing structure that dictates cell shape. Although many molecular details of the composition and assembly of cell-wall components are known, how the network of peptidoglycan subunits is organized to give the cell shape during normal growth and how it is reorganized in response to damage or environmental forces have been relatively unexplored. In this work, we introduce a quantitative physical model of the bacterial cell wall that predicts the mechanical response of cell shape to peptidoglycan damage and perturbation in the rod-shaped Gram-negative bacterium Escherichia coli. To test these predictions, we use time-lapse imaging experiments to show that damage often manifests as a bulge on the sidewall, coupled to large-scale bending of the cylindrical cell wall around the bulge. Our physical model also suggests a surprising robustness of cell shape to peptidoglycan defects, helping explain the observed porosity of the cell wall and the ability of cells to grow and maintain their shape even under conditions that limit peptide crosslinking. Finally, we show that many common bacterial cell shapes can be realized within the same model via simple spatial patterning of peptidoglycan defects, suggesting that minor patterning changes could underlie the great diversity of shapes observed in the bacterial kingdom.


Baseball and Softball Pitchers are Distinct Within-Subject Controlled Models for Exploring Proximal Femur Adaptation to Physical Activity.
Within-subject controlled models in individuals who preferentially load one side of the body enable efficient exploration of the skeletal benefits of physical activity. There is no established model of physical activity-induced side-to-side differences (i.e., asymmetry) at the proximal femur. Proximal femur asymmetry was assessed via dual-energy X-ray absorptiometry in male jumping athletes (JMP, n = 16), male baseball pitchers (BB, n = 21), female fast-pitch softball pitchers (SB, n = 22), and controls (CON, n = 42). The jumping leg was the dominant leg in JMP, whereas in BB, SB and CON the dominant leg was contralateral to the dominant/throwing arm. BB and SB had 5.5% (95% CI 3.9-7.0%) and 6.5% (95% CI 4.8-8.2%) dominant-to-nondominant leg differences for total hip areal bone mineral density (aBMD), with the asymmetry being greater than both CON and JMP (p < 0.05). BB and SB also possessed dominant-to-nondominant leg differences in femoral neck and trochanteric aBMD (p < 0.001). SB had 9.7% (95% CI 6.4-13.0%) dominant-to-nondominant leg differences in femoral neck bone mineral content, which was larger than any other group (p ≤ 0.006). At the narrow neck, SB had large (> 8%) dominant-to-nondominant leg differences in cross-sectional area, cross-sectional moment of inertia and section modulus, which were larger than any other group (p ≤ 0.02). Male baseball and female softball pitchers are distinct within-subject controlled models for exploring adaptation of the proximal femur to physical activity. They exhibit adaptation in their dominant/landing leg (i.e., leg contralateral to the throwing arm), but the pattern differs with softball pitchers exhibiting greater femoral neck adaptation.


Assessing Iranians' parental competence: Development and psychometric properties of the Children's Sexual Behavior Questionnaire (CSBQ-IR), Iranian Version.
Background: Parents are the first line mediators in sexuality development of children. However, the majority of parents tend to have close supervision on children sexual behaviors, particularly in the conservative cultures. This article describes the development and psychometric evaluation of an instrument to measure Iranian parents' competence in caring and nurturing their children sexually. Methods: The questionnaire was designed based on the principles in measurement, Waltz'stheory. The Iranian version of Children's Sexual Behavior Questionnaire (CSBQ-IR) was developed and completed by 386 mothers and 101 fathers who participated in a community based sexuality education program in Tehran, capital of Iran. Reliability was assessed by Kuder-Richardson reliability coefficient and Split half. CSBQ-IR was evaluated for its construct, inclusiveness and content validity by principal component analysis. Results: The Kuder-Richardson reliability coefficient and Split half reliability were found 0.425 and 0.457 that was on acceptable range. Meaning, grammar, wording and item allocation of the questionnaire were found to be appropriate with (content validity ratio [CVR]=0.99) and(content validity index [CVI]=0.8) respectively. Conclusion: CSBQ-IR provides a valid assessment of the parents' competency or incompetency in nurturing, communication, and managing their children's sexual behaviors.


Time-Varying Vocal Folds Vibration Detection Using a 24 GHz Portable Auditory Radar.
Time-varying vocal folds vibration information is of crucial importance in speech processing, and the traditional devices to acquire speech signals are easily smeared by the high background noise and voice interference. In this paper, we present a non-acoustic way to capture the human vocal folds vibration using a 24-GHz portable auditory radar. Since the vocal folds vibration only reaches several millimeters, the high operating frequency and the 4 × 4 array antennas are applied to achieve the high sensitivity. The Variational Mode Decomposition (VMD) based algorithm is proposed to decompose the radar-detected auditory signal into a sequence of intrinsic modes firstly, and then, extract the time-varying vocal folds vibration frequency from the corresponding mode. Feasibility demonstration, evaluation, and comparison are conducted with tonal and non-tonal languages, and the low relative errors show a high consistency between the radar-detected auditory time-varying vocal folds vibration and acoustic fundamental frequency, except that the auditory radar significantly improves the frequency-resolving power.


Lectin binding of rat gingival epithelia.
Oral gingival epithelium (OGE), oral sulcular epithelium (OSE) and junctional epithelium (JE) were examined histochemically by using different lectins as markers for epithelial differentiation. The staining pattern of gingival epithelia was compared with that of the buccal and palatal epithelia. Binding of WGA had a uniform distribution in all the epithelia examined. A positive reaction was found in all the basal and spinous layers, but not in the cornified layer of the epithelia. BPA binding was seen in the lower spinous layer of OGE, OSE, buccal and palatal epithelia, and in most of the JE. The basal layer and the cells directly attached to the tooth surface at the apical part of JE were nonreactive with BPA. GS-I reacted with the basal and suprabasal layers of each epithelium and with the cells attached to the tooth at the apical part of JE. UEA-I reacted with the upper spinous layer of OGE, OSE and epithelia of hard palate, but not with any of the cells of the JE. Our results agree with previous data suggesting that OGE and OSE exhibit squamous differentiation similar to that of the masticatory epithelium of hard palate. Furthermore, our results suggested that the JE cells undergo differentiation equivalent to that of the suprabasal and lower spinous cells of OGE. The cells along the tooth surface at the apical part of JE, however, form a distinct population of cells with basal nature.


Layer-by-layer-based silica encapsulation of individual yeast with thickness control.
In the area of cell-surface engineering with nanomaterials, the metabolic and functional activities of the encapsulated cells are manipulated and controlled by various parameters of the artificial shells that encase the cells, such as stiffness and elasticity, thickness, and porosity. The mechanical durability and physicochemical stability of inorganic shells prove superior to layer-by-layer-based organic shells with regard to cytoprotection, but it has been difficult to vary the parameters of inorganic shells including their thickness. In this work, we combine the layer-by-layer technique with a process of bioinspired silicification to control the thickness of the silica shells that encapsulate yeast Saccharomyces cerevisiae cells individually, and investigate the thickness-dependent microbial growth.


Large-scale capture of peptides containing reversibly oxidized cysteines by thiol-disulfide exchange applied to the myocardial redox proteome.
Redox regulation is emerging as an important post-translational modification in cell signaling and pathogenesis. Cysteine (Cys) is the most redox active of the commonly coded amino acids and is thus an important target for redox-based modifications. Reactions that oxidize the Cys sulfur atom to low oxidation states (e.g., disulfide) are reversible, while further reactions to higher oxidation states (e.g., sulfonic acid) may be irreversible under biological conditions. Reversible modifications are particularly interesting as they mediate redox signaling and regulation of proteins under physiological conditions and during adaptation to oxidant stress. An enrichment method that relied on rapid and specific alkylation of free Cys, followed by thiol-based reduction and resin capture by thiol-disulfide exchange chemistry was applied to isolate reversibly modified Cys-containing peptides. Chromatographic conditions were optimized to provide increased specificity by removal of noncovalent interactions. The technique was highly efficient, based on near equimolar reactions with the resin, reproducible and linear for peptide elution, as quantified by label-free mass spectrometry. The method was applied to a complex protein lysate generated from rat myocardial tissue and 6559 unique Cys-containing peptides from 2694 proteins were identified. Comparison with the rat database and previous studies showed effective enrichment of proteins modified by S-nitrosylation, disulfide formation, and Cys-sulfenic acid. Analysis of amino acid sequence features indicated a preference for acidic residues and increased hydrophilicity in the regions immediately up- or downstream of the reactive Cys. This technique is ideally suited for the enrichment and profiling of reversible Cys modifications on a proteome-wide scale.


F/Yb-codoped sol-gel silica glasses: toward tailoring the refractive index for the achievement of high-power fiber lasers.
Accurate control of both the doping distribution inside the fiber core and the low refractive index contrast between the fiber core and cladding materials is essential for the development of high-power fiber lasers based on the use of single-mode large-mode-area (LMA) optical fibers. Herein, sol-gel monolithic F/Yb3+-codoped silica glasses were prepared from porous large silica xerogels doped with ytterbium salt solution, which had been subjected to fluorination with hexafluoroethane gas, before subsequent sintering. The fluorine content inside the doped glass has been varied by adjusting the fluorination duration. The space homogeneity of fluorine and ytterbium concentrations in the cylindrical preforms has been checked by chemical analysis and Raman spectroscopy. Moreover, the glass with the lowest fluorine content has been successfully integrated as a core material in a microstructured optical fiber made using the stack-and-draw method. This fiber was tested in an all-fiber cavity laser architecture to evaluate potential lasing performances of the F/Yb3+-codoped silica glass. It presents a maximum efficiency of 70.4%, achieved at 1031 nm from a 1.16 m length fiber. These results confirm the potentialities of the obtained F/Yb3+-codoped glasses for the fabrication of LMA optical fiber lasers.


A comparison between two induction regimes for the interferon treatment of chronic hepatitis C. Response related factors.
Treatment of chronic hepatitis C with alfa interferon for 6 months achieves sustained responses in 15-25% of the patients. The initial induction with higher doses and the prolongation of treatment can improve the results. A randomized, prospective study was carried out to compare the efficacy of a short term induction schedule of interferon alfa-2b (group A) versus a long term one (group B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3 megaunits up to 9 months. The percentage of sustained responses, transient responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8% and 48.1% in group B (NS). The following factors were related to a poor response in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a greater necrosis and fibrosis score. The multivariate analysis revealed that elevated serum iron and ferritin and anti-nuclear antibody positivity had an independent predictive value related to a non response. Our results appear to suggest that an induction with higher doses and the treatment over nine months are more efficient than the classic schedule. The prolongation of the induction period does not provide additional advantages.


Restoring biological width in crown-root fracture: a periodontal concern.
A 10-year-old male child reported to J.S.S. Dental College and Hospital presenting with a vertical crown-root fracture of maxillary central incisor with a history of fall 10 days back. A new treatment protocol was attempted in contrary to various schools of thoughts of coronal fragment removal wherein fractured fragments were approximated and internally reinforced with latest technologies in adhesive dentistry, the goal was to save the tooth, restore its function and esthetics. This case presents the above mentioned philosophy.


Understanding and optimizing health-related quality of life and physical functional capacity in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive pulmonary disease characterized by the insidious onset of shortness of breath due to parenchymal scarring. As IPF progresses, breathlessness worsens, physical functional capacity declines, and health-related quality of life (HRQL) - the impact of health or disease on a person's satisfaction with their overall station in life - deteriorates. These two inextricably linked variables - breathlessness and physical functional capacity - are strong drivers of HRQL. With the emergence of new and prospective therapies for IPF, it is more important than ever to be able to accurately and reliably assess how IPF patients feel and function. Doing so will promote the development of novel interventions to target impairments in these areas and ensure that the field is capable of assessing the effect of therapeutics interventions on these critically important patient-centered outcomes.


Angiogenic Capacity of Dental Pulp Stem Cell Regulated by SDF-1α-CXCR4 Axis.
Previously, the perivascular characteristics of dental pulp stem cells (DPSCs) were reported, which suggested the potential application of DPSCs as perivascular cell source. In this study, we investigated whether DPSCs had angiogenic capacity by coinjection with human umbilical vein endothelial cells (HUVECs) in vivo; in addition, we determined the role of stromal cell-derived factor 1-α (SDF-1α) and C-X-C chemokine receptor type 4 (CXCR4) axis in the mutual interaction between DPSCs and HUVECs. Primarily isolated DPSCs showed mesenchymal stem cell- (MSC-) like characteristics. Moreover, DPSCs expressed perivascular markers such as NG2, α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor β (PDGFRβ), and CD146. In vivo angiogenic capacity of DPSCs was demonstrated by in vivo Matrigel plug assay. We could observe microvessel-like structures in the coinjection of DPSCs and HUVECs at 7 days postinjection. To block SDF-1α and CXCR4 axis between DPSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into Matrigel plug. No significant microvessel-like structures were observed at 7 days postinjection. In conclusion, DPSCs have perivascular characteristics that contribute to in vivo angiogenesis. The findings of this study have potential applications in neovascularization of engineered tissues and vascular diseases.


Structural basis for RNA-silencing suppression by Tomato aspermy virus protein 2b.
The 2b proteins encoded by cucumovirus act as post-transcriptional gene silencing suppressors to counter host defence during infection. Here we report the crystal structure of Tomato aspermy virus 2b (TAV2b) protein bound to a 19 bp small interfering RNA (siRNA) duplex. TAV2b adopts an all alpha-helix structure and forms a homodimer to measure siRNA duplex in a length-preference mode. TAV2b has a pair of hook-like structures to recognize simultaneously two alpha-helical turns of A-form RNA duplex by fitting its alpha-helix backbone into two adjacent major grooves of siRNA duplex. The conserved pi-stackings between tryptophan and the 5'-terminal base of siRNA duplex from both ends enhance the recognition. TAV2b further oligomerizes to form a dimer of dimers through the conserved leucine-zipper-like motif at its amino-terminal alpha-helix. Biochemical experiments suggest that TAV2b might interfere with the post-transcriptional gene silencing pathway by directly binding to siRNA duplex.


Total cellular fatty acid composition of cultured Pneumocystis carinii.
Oleic acid makes up > 50% of the total fatty acids of Pneumocystis carinii grown on WI-38 cells. Oleic acid levels increased in parallel with increasing trophozoites over 7 days in culture. The fatty acid composition of P. carinii resembles that of certain fungi but differs from those of lung surfactant lipid, host cells, and fetal bovine serum.


Reliable surveillance of tick-borne encephalitis in European countries is necessary to improve the quality of vaccine recommendations.
In July-November 2009, 26 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national tick-borne encephalitis (TBE) vaccination recommendations. Information on TBE surveillance, methods used to ascertain endemic areas, vaccination recommendations, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Sixteen countries (57%) reported presence of TBE endemic areas on their territory. Vaccination against TBE was recommended for the general population in 8 (28%) countries, for occupational risk groups - in 13 (46%) countries, and for tourists going abroad - in 22 (78%) countries. Although vaccination recommendations for country residents, and for tourists always referred to endemic areas, there was no uniform, standardized method used to define endemic areas. For this reason, clear recommendations for tourists need to be developed, and standardized surveillance directed to efficient assessment of TBE risk need to be implemented in European countries.


Life cycle of the temporary fish parasite, Gnathia africana (Crustacea: Isopoda: Gnathiidae).
Laboratory work was conducted to elucidate the life cycle of the South African gnathiid isopod, Gnathia africana Barnard, 1914. The natural fish hosts of this temporary parasite, the super klipfish Clinus superciliosus (Linnaeus, 1758), were exposed to gnathiid larvae in the laboratory. It was found that G. africana has three larval stages, consisting of three unfed (zuphea) and three fed (praniza) stages. First-, second- and third-stage zuphea larvae took an average of 2 h 18 min, 2 h 43 min and 10 h 8 min respectively to complete their feeding and the first- and second-stage praniza moulted at 8 and 10 days respectively into the next zuphea stage. Three to six days after its last blood meal, the sex of the third and final praniza stage could be determined by the presence of either a testis or two ovaries in the dorsal pereon. Male larvae moulted into adult males between 8 and 10 days post feeding. Female larvae moulted at approximately 17 days into adult females. Fertilisation of the eggs by the male took place within 24 hours of completion of the female moult. The development of the embryos and subsequent release of the young larvae between 15 and 23 days post fertilisation completed the cycle. This entire cycle took approximately 62 days in water temperatures of 20-25 degrees C.


[Campylobacter infections].
In recent years the microaerophil organisms of the genus Campylobacter have been cultured with increasing frequency, thanks to more appropriate methods for isolation from fecal cultures. These organisms have been shown to be important causes of acute diarrheal disease, usually with spontaneous recovery. They also are accepted as agents capable of causing serious systemic infection, mainly in patients debilitated by chronic disease. The incidence of Campylobacter enteritis in Switzerland, its epidemiology, the clinical picture of Campylobacter infections and diagnostic and therapeutic problems are briefly reviewed.


In silico polymorphism analysis for the development of simple sequence repeat and transposon markers and construction of linkage map in cultivated peanut.
Peanut (Arachis hypogaea) is an autogamous allotetraploid legume (2n = 4x = 40) that is widely cultivated as a food and oil crop. More than 6,000 DNA markers have been developed in Arachis spp., but high-density linkage maps useful for genetics, genomics, and breeding have not been constructed due to extremely low genetic diversity. Polymorphic marker loci are useful for the construction of such high-density linkage maps. The present study used in silico analysis to develop simple sequence repeat-based and transposon-based markers. The use of in silico analysis increased the efficiency of polymorphic marker development by more than 3-fold. In total, 926 (34.2%) of 2,702 markers showed polymorphisms between parental lines of the mapping population. Linkage analysis of the 926 markers along with 253 polymorphic markers selected from 4,449 published markers generated 21 linkage groups covering 2,166.4 cM with 1,114 loci. Based on the map thus produced, 23 quantitative trait loci (QTLs) for 15 agronomical traits were detected. Another linkage map with 326 loci was also constructed and revealed a relationship between the genotypes of the FAD2 genes and the ratio of oleic/linoleic acid in peanut seed. In silico analysis of polymorphisms increased the efficiency of polymorphic marker development, and contributed to the construction of high-density linkage maps in cultivated peanut. The resultant maps were applicable to QTL analysis. Marker subsets and linkage maps developed in this study should be useful for genetics, genomics, and breeding in Arachis. The data are available at the Kazusa DNA Marker Database (http://marker.kazusa.or.jp).


Determination of ftorafur and 5-fluorouracil levels in plasma and urine.
A gas chromatographic method was developed for ftorafur (Ft) detection in plasma and urine with a sensitivity of 1 mug/ml. Specific determination of its metabolite 5-fluorouracil (FU) with a sensitivity of 1 ng/ml was achieved by column chromatographic separation from Ft and subsequent gas chromatography-mass spectrometry of bis-silyl-FU in the selected ion mode (GC-MS-SIM) using bis-15N-FU as internal standard. Intravenous injections of 2-14C-Ft and 2',5'-14C-Ft were given to rats and rabbits respectively, and plasma and urine were analyzed for Ft, and 14C activity. Unchanged Ft accounted for most of the 14C activity in plasma, while FU concentrations were below 0.15% and 0.4% relative to Ft concentrations in the rabbit and the rat, respectively. 30-60% of the urinary 14C activity was unchanged Ft and less than 0.2% FU. The significance or low FU levels is discussed in view of the hypothesis that Ft acts as a transport form of its metabolite FU.


[Role of magnetic resonance in the diagnosis of cryptorchidism].
The paper reports the authors' personal experience regarding the use of magnetic resonance imaging in the diagnosis of cryptorchidism. The result of the study of 13 patients with non-palpable gonads, who all underwent surgical confirmation (with positive outcome in 66% of cases), encourage the use of this non-invasive method with a high anatomic resolution, which can be used to diagnose both the site, dimensions and possible structural alterations of the gonad.


The element of family medicine in the mega journal of the family medicine specialty: A bibliometric analysis of the journal, Chinese General Practice.
With the evolving specialization of modern medicine, family medicine (FM), also known as general practice, is relatively late in being recognized as a formal specialty in most countries of the world. Because many non-FM specialists were recruited into the new specialty in the early stages of FM specialization, the contents of FM specialty journals might, to an extent, reflect the development of the FM specialization. In this study, the voluminous journal, Chinese General Practice, which is regarded as the most representative specialty journal, was chosen and analyzed to illustrate the current situation of FM in China. A total of 878 articles, relating to the journal, Chinese General Practice in 2018, were retrieved from the publisher's web site and the original articles were categorized into FM- and non-FM- related articles by 3 board-certified FM doctors. Furthermore, the first authors, as well as the institutions and regions where the first authors worked, and their related specialties, were also analyzed. Of the 634 original articles, 252 (39.7%) articles were FM related. Only 41 FM-related articles were written by authors working at FM departments: 3 at community health service centers, 29 at hospitals, and 9 at universities. Of the 382 non-FM related articles, 159 articles dealt with the topic of internal medicine, followed by traditional Chinese medicine (36), obstetrics and gynecology (28), neurology (27), pediatrics (27), and surgery (21). In conclusion, FM publications in China in the study year, as exemplified by Chinese General Practice, were mostly contributed by non-FM authors dealing with non-FM topics. A transition to more FM-oriented development might be anticipated in the near future.


Therapy for recurrent respiratory papillomatosis.
Human papillomaviruses types 6 or 11 are aetiological agents of recurrent respiratory papillomatosis, a disease characterized by benign exophytic tumours usually on the vocal cords. Surgery debulks the tumours, but these growths generally recur at regular intervals. Adjunct medical treatments, aimed at containing the virus and growth of tumours, include indole-3-carbinol or its dimer diindolylmethane, interferon, photodynamic therapy and others. Preventive and therapeutic vaccines hold promise for eliminating the virus.


[Curative effects of cyclosporin A therapy upon myelodysplastic syndrome].
To evaluate the efficacy of cyclosporin A (CsA) in treatment of myelodysplastic syndromes (MDS). Thirty-three patients with MDS, including refractory anemia (RA, n = 24), refractory anemia with ringed sideroblasts (RAS, n = 2), and refractory anemia with excess blasts (RAEB, n = 7), 23 males and 10 females, aged 46 (6 approximately 71), hospitalized in 4 CsA, grade 3 hospitals in Beijing who failed to respond to folic acid and vitamin B12, received CsA 3 approximately 5 mg x kg(-1)x d(-1), 2 times per days, taken orally in 2 separate doses for at least 3 months (2 approximately 27 months). During the course of treatment the dosage was adjusted according to the CsA blood concentration and curative effect. Follow-up was conducted for 14 months on average. The curative effect of those who took CSA for more than 2 months underwent statistical analysis, and for those who took CSA for less than 2 months only the side effects underwent statistical analysis. After 3 months of the treatment, the hematological improvement (HI) was observed in 18 of the 32 evaluative patients (56.3%) by the criteria of the International Working Group (IWG). At the end of the follow-up 4 patients showed alteration of disease progression, including 1 case of complete remission (CR) and 3 cases of partial remission (PR), and 16 patients showed homological improvement, responders numbering 20 totally, with a response rate of 62.5% (20/32). One of the 20 patients respondent to CsA died and 7 of the 12 patients who failed to respond to CsA died. Improving the clinical manifestations and lengthening the survival time, CsA therapy is effective in the patients with RA or RAEB, and both hypoplastic bone marrow and hyperplastic bone marrows respond to the therapy. CsA therapy is potentially the most effective therapy for MDS.


Electroneuromyographic Features in Fabry Disease: A Retrospective Review.
Fabry disease (FD) is an X-linked recessive inherited disorder characterized by lysosomal alpha-galactosidase deficiency. The purpose of our study was to assess and compare the electroneuromyographic (ENMG) findings of 15 patients with Fabry disease and the electroneurographic (ENG) findings of 15 healthy controls. We have not encountered any similar study in the medical literature of our country. Therefore, we believe that our study will contribute to national literature. Fifteen patients with Fabry disease, 13 females and 2 males and 15 healthy controls, 13 females and 2 males, were included in the study. The definite diagnosis of patients with Fabry disease was made based on the enzyme level and genetic mutation. The patients with Fabry disease were examined with ENMG, while the healthy control group was examined with ENG. In the patients with a normal ENMG examination, neuropathic pain was attributed to the small fiber involvement. Patients with Fabry disease had neuropathic pain (LANSS score≥12). While neurological examination was normal in eight patients, glove- and stocking-type hypoesthesia and decreased deep tendon reflexes were observed in five and two patients, respectively. Axonal polyneuropathy was detected in one patient. The ENMG examinations of the other patients were normal. Enzyme replacement therapy could not be initiated in one patient because of pregnancy. The neurological examination of the healthy control group was normal. There was no statistically significant difference between the ENMG features of both groups (p>.05). As in other studies, a routine ENMG examination was normal in our patients with early-stage Fabry disease. Neuropathic pain, seen in patients with Fabry disease in literature, is thought to be due to small fiber involvement. Fabry disease should be considered in the differential diagnosis of patients with neuropathic pain at young ages. It should be kept in mind that ENMG examination can be normal at the early stages. Quantitative sensory test, autonomic tests (R-R interval and sympathetic skin response) and skin biopsy should be performed in such cases. In our country, pediatric physicians work on Fabry disease more than physicians dealing with Fabry disease in adults. Therefore, in this retrospective study, we aimed to draw adult and pediatric neurologists' attention to Fabry disease.


Consequence of social isolation on blood pressure, cardiovascular reactivity and design in spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR), which inherently display exaggerated cardiovascular defence reactions to environmental stimuli (Hallbäck and Folkow 1974), and normotensive control rats (NCR) were kept isolated after they were weaned to reduce such environmental influences which normally induce psychological activation. Mean arterial pressure was followed until 7 months of age, when the cardiovascular defence reactions to acute mental stress were compared and an analysis of cardiovascular design was made. The isolated SHR but no the isolated NCR, had significantly lower pressures than their unisolated controls. Likewise, judged by the relative weight of the left ventricle and the hemodynamically evaluated design of the hindquarter resistance vessels, the structural cardiovascular adaptation was about proportionally less pronounced in isolated than in control SHR. However, their cardiovascular responses to acute "psychological stress" were equally intense, and clearly exaggerated when compared with NCR. Thus, a prolonged reduction of excitatory environmental influences implies a relatively less pronounced development of hypertension in SHR, even though an inherent hyperreactivity concerning neurohormonal pressor responses to alerting stimuli is present. These findings tress the importance of interacting intrinsic-hereditary and extrinsic neurogenic influences for the initiation of primary hypertension.