Noninvasive ultrasound evaluation of the vertebral artery in hypertension.
Surgical decompression of the vascular loop of the vertebral artery (VA) at the left lateral medulla can reduce blood pressure (BP) in hypertension, and a larger diameter of the left VA has been found in hypertensive patients. Noninvasive evaluation of the VA in hypertension may assist selecting patients for more appropriate diagnosis and treatment. Duplex ultrasonography is used to study the relationship between VA diameter and BP. A retrospective review of VA duplex ultrasonography was performed in 112 consecutive patients who were sent to the neurovascular laboratory at the Wake Forest University School of Medicine during a 2-month period. All measurements (BP, pulse rate, peak systolic velocity [PSV], end diastolic velocity [EDV], and diameters of both VAs) were determined according to standardized protocols. Left-right comparisons of VA diameters, PSV, and EDV between hypertensives and normotensives were performed by the matched-pairs analysis techniques. Fifty-five women and 57 men with a mean age of 64.8 years were studied. Hypertension was present in 65.2% of all patients. The age-adjusted mean left VA diameter was significantly higher than that of the right VA with an age-adjusted average differences of 0.2 mm (P = .03) for hypertensives compared to 0.04 mm (P = .75) for normotensives. No significant differences were observed in either PSV or EDV. Differences in left-right VA diameter in hypertensive subjects may be a previously unrecognized component of the vascular disturbances associated with the disease and represent an additional criterion for identifying those who may benefit from surgical and medical management.


Impact of Intermediate Susceptibility to Penicillin on Antimicrobial Treatment and Outcomes of Endocarditis Caused by Viridans and Gallolyticus Group Streptococci.
Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.37-26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17-44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24-81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26-3.96; P = .982). Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.


Characterization of bacterial and microbial eukaryotic communities associated with an ephemeral hypoxia event in Taihu Lake, a shallow eutrophic Chinese lake.
While the important roles of microbial communities in oceanic hypoxic zones were beginning to be understood, little is known about microbial community associated with this phenomenon in shallow lakes. To address this deficit, both the bacterial and microbial eukaryotic communities of an ephemeral hypoxic area of Taihu Lake were characterized. The hypoxia provided nutritional niches for various bacteria, which results in high abundance and diversity. Specific bacterial groups, such as vadinBC27 subgroup of Bacteroidetes, Burkholderiales, Rhodocyclales, Pseudomonas, and Parcubacteria, were dominated in hypoxic sites and relevant to the fermentation, denitrification, nitrification, and sulfur metabolism. Conversely, most of microbial eukaryotes disappeared along with the decline of DO. An unexpected dominance of fungi was observed during hypoxia, which partly explained by the accumulation of toxic algae. Mucor was the single dominant genus in the hypoxic zone. We proposed that this group might cooperate with bacterial communities in the anaerobic degradation of algal biomass and woody materials. Generally, the hypoxic microbiome in shallow lakes is mainly involved in fermentative metabolism depending on phytodetritus and is potentially influenced by terrestrial sources. This study provided new insights into the unique microbiome in short-term hypoxia in shallow lakes and lays the foundation for studies that will enhance our understanding of the microbial players associated with hypoxia and their adaption strategy on the global scale.


[Disease sequelae on function in persons 70 years and older and the acceptance of a new supporting network, the NetzWerk GesundAktiv (NWGA)].
The growing need of nursing care as life expectancy increases is a problem. The Netzwerk AktivGesund (NWGA) tries to change this development in a positive way. In a pilot region of the city of Hamburg, persons 70 years and older were invited by their health insurance companies to participate in the NWGA supportive network. Results of the acceptance analysis are described here. In order to focus on persons at risk of need for help functional competence was assessed by using the LUCAS functional ability index (selfreport questionnaire). In an explorative way, participants, refusers, persons interested (excluded due to high functional competence), and non-responders were compared in a retrospective observational study. Sociodemographic and routine data were used as ICD diagnoses from hospitalisations, number of contacts to physicians and level of need of nursing care during the 12 months before recruitment. There were 962 participants (7.4 %), 948 refusers (7.2 %), 2437 persons with interest (18.6 %) and 8753 non-responders (66.8 %) from the 13 100 persons contacted by mail. The sociodemographic factors differed between these groups. ICDs typical of older patients and ICD codes of functional impairment from the 5422 hospital stays showed different frequencies. Persons with interest had nearly no need of nursing care and the lowest level of morbidity. The results show that impairments of motoric and cognitive functions, in particular, and sociodemographic factors have impact on the acceptance of the NWGA. The recruitment for participation should be improved using approaches that are differentiated, respectively. Awareness of functional impairment as disease sequelae and pacemaker of need of nursing care, in general, might facilitate health promotion and prevention in older persons. An interest in preventative activities was remarkably frequent among the persons 70 years and older.


Women's and midwives' views on the optimum process for informed consent for research in a feasibility study involving an intrapartum intervention: a qualitative study.
Recruitment to intrapartum research is complex. Women are expected to understand unfamiliar terminology and assess potential harm versus benefit to their baby and themselves, often when an urgent intervention is required. Time pressures of intrapartum interventions are a major challenge for recruitment discussions taking place during labour, with research midwives expected to present, discuss and answer questions whilst maintaining equipoise. However, little is known about these interactions. An integrated qualitative study (IQS) was used to investigate information provision for women invited to participate in the Assist II feasibility study investigating the OdonAssist™-a novel device for use in assisted vaginal birth with an aim to generate a framework of good practice for information provision. Transcripts of in-depth interviews with women participants (n = 25), with recruiting midwives (n = 6) and recruitment discussions between midwives and women (n = 21), accepting or declining participation, were coded and interpreted using thematic analysis and content analysis to investigate what was helpful to women and what could be improved. Recruiting women to intrapartum research is complicated by factors that impact on women's understanding and decision-making. Three key themes were derived from the data: (i) a woman-centred recruitment process, (ii) optimising the recruitment discussion and (iii) making a decision for two. Despite evidence from the literature that women would like information provision and the research discussion to take place in the antenatal period, intrapartum studies still vary in the recruitment processes they offer women. Particularly concerning is that some women are given information for the first time whilst in labour, when they are known to feel particularly vulnerable, and contextual factors may influence decision-making; therefore, we propose a framework for good practice for information provision for research involving interventions initiated in the intrapartum period as a woman centred, and acceptable model of recruitment, which addresses the concerns of women and midwives and facilitates fair inclusion into intrapartum trials. ISRCTN. This qualitative research was undertaken as part of the ASSIST II Trial (trial registration number: ISRCTN38829082. Prospectively registered on 26/06/2019).


Giant-cell tumor of the tendon sheath arising from the posterior cruciate ligament of the knee: a case report and review of the literature.
The localized form of a giant-cell tumor of the tendon sheath is uncommon and rarely intraarticular. While the sonographic findings are nonspecific, the magnetic resonance (MR) findings can be diagnostic. Relatively homogeneous iso- or marginal hyperintensity on T2-weighted sequences, lack of susceptibility effects due to hemosiderin, the demonstration of a fibrous capsule and the absence of adjacent joint involvement may help to differentiate localized and diffuse forms of giant-cell tumors of tendon sheaths and pigmented villonodular synovitis.


[Progressive paralysis: prognostic indications by modern imaging procedures. A case report].
The case of a patient with early diagnosed neurosyphilis (general paresis) is presented. Modern neuroimaging techniques such as single photon emission computed tomography (SPECT) may give clues to the treatment outcome as early as 1 month after antibiotic treatment. Improvement of cognitive functions was accompanied by normalization of the initially altered P300-topography.


Impact of Rater Training on Residents Technical Skill Assessments: A Randomized Trial.
The ACS/APDS Resident Skills Curriculum's Objective Structured Assessment of Technical Skills (OSATS) consists of task-specific checklists and a global rating scale (GRS) completed by raters. Prior work demonstrated a need for rater training. This study evaluates the impact of a rater-training curriculum on scoring discrimination, consistency, and validity for handsewn bowel anastomosis (HBA) and vascular anastomosis (VA). A rater training video model was developed, which included a GRS orientation and anchoring performances representing the range of potential scores. Faculty raters were randomized to rater training or no rater training and were asked to score videos of resident HBA/VA. Consensus scores were assigned to each video using a modified Delphi process (Gold Score). Trained and untrained scores were analyzed for discrimination and score spread and compared to the Gold Score for relative agreement. Eight general and eight vascular surgery faculty were randomized to score 24 HBA/VA videos. Rater training increased rater discrimination and decreased rating scale shrinkage for both VA (mean trained score: 2.83, variance 1.88; mean untrained score: 3.1, variance 1.14, p = 0.007) and HBA (mean trained score: 3.52, variance 1.44; mean untrained score: 3.42, variance 0.96, p = 0.033). On validity analyses, a comparison between each rater group vs Gold Score revealed a moderate training impact for VA, trained κ=0.65 vs untrained κ=0.57 and no impact for HBA, R1 κ = 0.71 vs R2 κ = 0.73. A rater-training curriculum improved raters' ability to differentiate performance levels and use a wider range of the scoring scale. However, despite rater training, there was persistent disagreement between faculty GRS scores with no groups reaching the agreement threshold for formative assessment. If technical skill exams are incorporated into high stakes assessments, consensus ratings via a standard setting process are likely a more valid option than individual faculty ratings.


The dual role of temperature in the regulation of the seasonal changes in dormancy and germination of seeds of Polygonum persicaria L.
The role of temperature in the regulation of seasonal changes in dormancy and germination was studied in seeds of Polygonum persicaria. Seeds were buried in the field and under controlled conditions. Portions of seeds were exhumed at regular intervals and germination was tested over a range of conditions. Seeds of P. persicaria exhibited a seasonal dormancy pattern that clearly showed the typical features of summer annuals, i.e. dormancy was relieved at low winter temperatures, the germination peak occurred in spring and dormancy was re-induced in summer. The expression of the dormancy pattern was influenced by the temperature at which germination was tested. At 30°C exhumed seeds germinated over a much longer period of the year than at 20° or 10°C. Nitrate added during the germination test occasionally stimulated germination. The seasonal changes in dormancy of buried seeds were regulated by the field temperature. Soil moisture and nitrate content did not influence the changes in dormancy. The fact that, on the one hand, field temperature determined the changes in dormancy and, on the other hand, germination itself was influenced by temperature, was used to describe the seasonal germination pattern of P. persicaria with a model. Germination of exhumed seeds in Petri dishes at field temperature was accurately described with this model. Germination in the field was restricted to the period where the range of temperatures over which germination could proceed (computed with the model) and field temperature overlapped.


Development of three-dimensional facial expression models using morphing methods for fabricating facial prostheses.
It is essential to fabricate a best-fit three-dimensional (3D) facial prosthesis model capable of facial expressions. In order for the facial prosthesis to remain in position, especially around marginal areas subject to movement, a new method of making 3D facial expression models using time-series data allowing changes in facial expression by morphing technique was developed. Seven normal subjects and seven patients with nasal defects or nasal deformities participated in this study. Three distinct facial expressions (i.e., a neutral expression, smiled, and open mouthed) were digitally acquired with a facial scanner. Prepared template models were transformed to homologous models, which can represent the form as shape data with the same number of point cloud data of the same topology referring to the scanning data. Finally, 3D facial expression models were completed by generating a morphing image based on two sets of homologous models, and the accuracy of the homologous models of all subjects was evaluated. 3D facial expression models of both normal subjects and patients with nasal defects were successfully generated. No significant differences in shape between the scanned models and homologous models were shown. The high accuracy of this 3D facial expression model in both normal subjects and patients suggests its use for fabricating facial prostheses.


Microinjection of pruritogens in NGF-sensitized human skin.
Single intradermal injections of nerve growth factor (NGF) evoke prolonged but temporally distinct sensitization patterns to somatosensory stimuli. Focal administration of the non-histaminergic pruritogen cowhage but not histamine resulted in elevated itch at day 21 after NGF administration. Here, we injected bovine adrenal medulla peptide 8-22 (BAM8-22), β-alanine (β-ALA) and endothelin-1 (ET-1) into NGF-treated skin of 11 healthy volunteers and investigated the corresponding itch/pain and flare reactions. β-ALA was the weakest pruritogen, while BAM8-22 and ET-1 were equally potent as histamine. NGF did not sensitize itch or flare reactions induced by any compound, but injection and evoked pain were increased at day 21 and 49. The involvement of histamine H1 receptors in itch was explored in eight subjects after oral cetirizine. ET-1-induced itch and flare were significantly reduced. BAM8-22 and β-ALA itch were not affected, but flare responses after BAM8-22 reduced by 50%. The results indicate that a single NGF injection does not sensitize for experimentally induced itch but increases pain upon pruritogen injection. In healthy humans, pruritic and algetic processing appear differentially regulated by NGF. However, in patients suffering chronic itch, prolonged elevation of NGF-levels under inflammatory conditions may contribute to elevated itch.


Adjunct Devices for the Pediatric Difficult Airway: A Case Report.
This is a case report of a pediatric patient with a difficult airway, in which several airway adjuncts were used simultaneously to successfully provide adequate oxygenation and ventilation during cardiac arrest. Difficult airways are low-incidence, high-risk emergencies in children, and airway adjuncts may be used infrequently, let alone in combination. Included in the discussion of this case are a description of each airway adjunct and a discussion of the process needed to incorporate airway adjuncts safely and effectively into patient care.


How are treatment decisions made about artificial nutrition for individuals at risk of lacking capacity? A systematic literature review.
Worldwide, the number of individuals lacking the mental capacity to participate in decisions about their own healthcare is increasing. Due to the ageing global population and advancing medical treatments, there are now many more people living longer with neurological disorders, such as dementia, acquired brain injuries, and intellectual disabilities. Many of these individuals have feeding difficulties and may require artificial nutrition. However, little is known about the decision-making process; the evidence base is uncertain and often ethically complex. Using the exemplar of artificial nutrition, the objective of this review is to examine how treatment decisions are made when patients are at risk of lacking capacity. We undertook a systematic review according to PRISMA guidelines to determine who was involved in decisions, and what factors were considered. We searched PubMed, AMED, CINAHL, EMBASE, PsychINFO, and OpenSigle for quantitative and qualitative studies (1990-2011). Citation, reference, hand searches and expert consultation were also undertaken. Data extraction and quality assessment were undertaken independently and in duplicate. We utilised Thomas and Harden's 'Thematic Synthesis' for analysis. Sixty-six studies met inclusion criteria, comprising data from 40 countries and 34,649 patients, carers and clinicians. Six themes emerged: clinical indications were similar across countries but were insufficient alone for determining outcomes; quality of life was the main decision-making factor but its meaning varied; prolonging life was the second most cited factor; patient's wishes were influential but not determinative; families had some influence but were infrequently involved in final recommendations; clinicians often felt conflicted about their roles. When individuals lack mental capacity, decisions must be made on their behalf. Dynamic interactive factors, such as protecting right to life, not unnecessarily prolonging suffering, and individual preferences, need to be addressed and balanced. These findings provide an outline to aid clinical practice and develop decision-making guidelines.


Manometric biosensor for on-line measurement of milk urea.
Performance of a prototype sensor for on-line measurement of urea in milk during milking was evaluated. The sensor was based on a manometric assay of the carbon dioxide generated by the enzymatic hydrolysis of urea. Temperature compensation of the sensor was described briefly, and was shown to be effective. The calibration of the sensor was described and resulted in a standard calibration error of about 0.15 mM of urea. The standard error of the sensor in milk was shown to be about 0.25 mM (given a physiological range of about 2-7 mM in cow milk). The sensor was simple, inexpensive, suffered from no interferences in raw milk, and completed a measurement cycle in about 5 min (less than the time to milk a typical cow). A custom made sampling device, whereby milk was passively collected from the milk line under vacuum, was shown to collect an ample volume within 10 s to run a test with the sensor. No measurable bubbles or foam were introduced from the sampling mechanism so that the milk sampled was not diminished in density compared to samples taken by other methods.


Assisted breech delivery, is the art fading?
To review the modes of breech delivery over a 5 year period in Khamis Civil Hospital, Khamis Mushayt, Kingdom of Saudi Arabia, and to evaluate the trend and associated complications. Relevant data was extracted from the delivery room records of all women delivered in Khamis Civil Hospital, Khamis Mushayt, Kingdom of Saudi Arabia, from 1st January 1996 through 31st December 2000. Available data was analyzed. There were 375 breech deliveries, constituting 2.8% of the entire deliveries in the hospital. Eighty-two percent of the breeches were delivered by cesarean section while 18% had assisted vaginal delivery (p=0.0193). Amongst 72 primigravidae breeches, 68 (94.4%) were delivered by cesarean section while 238 (78.5%) out of 303 multigravidae were delivered by cesarean section. There were 2 unexplained neonatal deaths among the vaginal delivery group in multigravidae. Cesarean delivery was associated with less morbidity compared to vaginal delivery. This study has demonstrated a significant increase in delivery of breeches by cesarean section and the resultant drop, in the number available for assisted breech delivery. Less obstetricians will therefore be exposed practically to the art of assisted breech delivery. Most practicing obstetricians seem to be more inclined towards delivering breeches by cesarean section. If this trend continues, the art of assisted breech delivery may fade.


Efficiency of a smooth desorption procedure for the purification of barley beta-amylase using immunoaffinity chromatography.
Immunoaffinity chromatography was used for a one step purification procedure of beta-amylase from the G25 Sephadex gel filtrated fraction of whole barley protein extracts. The immunoglobulin G (IgG) fraction of an anti-barley beta-amylase immune serum was immobilized on Ultrogel. A gentle desorption procedure was used, combining distilled water elution with an interrupted elution. The quality of the purification was assayed by using cross immunoelectrophoresis with a polyspecific anti-barley protein immune serum. The extent of the damaging effect of this procedure was evaluated on the specific activity of the enzyme and on its polymorphism, as displayed by isoelectric focusing. The results underline the efficiency of the purification procedure and its low denaturing effect on the beta-amylase. This opens new possibilities for some aspects of the enzyme study and for the purification of other biologically active proteins.


Validation of a new instrument for evaluating low back pain in the young athlete.
To validate a back-specific instrument for functional assessment in the young athlete for clinical and research purposes, the Micheli Functional Scale (MFS). Prospective cohort study, Diagnostic Level II. Division of Sports Medicine Clinic, Children's Hospital Boston. Male and female patients aged 12 to 22 with and without low back pain. Patients presenting with back pain were compared with a control group of patients presenting with complaints other than back pain. Both groups were given the modified Oswestry Low Back Pain Disability Questionnaire (ODQ) and MFS. Micheli Functional Scale and ODQ score correlations. A total of 94 patients were enrolled (44 patients with low back pain and 50 patients without low back pain). Ages ranged from 12 to 22 for both groups, with no differences in age (P = 0.07) or gender (P = 0.50). Patients with back pain had significantly higher ODQ scores (median, 32 points) and MFS scores (median, 47 points) compared with controls (median, 0 points; P < 0.0001). These results held for male and female patients and younger (12-16.99 years) and older (17-22 years) age groups. The Pearson correlation coefficient showed a high positive correlation between MFS scores and ODQ scores (Pearson r = 0.90, P < 0.0001). Cronbach level indicated excellent item reliability on the MFS (α = 0.904, P < 0.0001). The MFS is a valid instrument for assessing pain and functional levels in the young athlete. This scale considers pain, athletic function, and athletic disability.


Localization of HLA on the short arm of chromosome 6.
A detailed marker gene study in a large Dutch kindred segregating for a reciprocal translocation between the chromosomes 6 and 20, t(6;20) (p21; p13), revealed a close linkage between the HLA genes and the breakpoint on the short arm of 6. During this study an apparent peak lod score of 2.9 was obtained at a recombination value of 0.05 for a linkage between HLA and the breakpoint, indicating that the chromosomal region, carrying the HLA genes, is situated near the breakpoint in band 6p21 close to the transition to 6p22.


Fluorescence and ultrastructural localization of aminergic neurons in the nerve cord of Eisenia foetida (annelida--oligochaeta).
The aminergic nature of the CV neurons present in the genital segments of the nerve cord of Eisenia foetida is demonstrated by fluorescence microscopy and by the chromaffin reaction modified for electron microscopy.


Enriched environments enhance the development of explicit memory in an incidental learning task.
Learning, rendered in an implicit (unconscious) or explicit (conscious) way, is a crucial part of our daily life. Different factors, like attention or motivation, influence the transformation from implicit to explicit memory. Via virtual reality a lively and engaging surrounding can be created, whereby motivational processes are assumed to be a vital part of the transition from implicit to explicit memory. In the present study, we tested the impact of an enriched virtual reality compared to two conventional, non-enriched 2D-computer-screen based tasks on implicit to explicit memory transformation, using an audio-visual sequential association task. We hypothesized, that the immersive nature of the VR surrounding enhances the transfer from implicit to explicit memory. Notably, the overall amount of learned sequence pairs were not significantly different between experimental groups, but the degree of awareness was affected by the different settings. However, we observed an increased level of explicitly remembered pairs within the VR group compared to two screen-based groups. This finding clearly demonstrates that a near-natural experimental setting affects the transformation process from implicit to explicit memory.


A simple highly sensitive and selective aptamer-based colorimetric sensor for environmental toxins microcystin-LR in water samples.
A simple and highly sensitive aptamer-based colorimetric sensor was developed for selective detection of Microcystin-LR (MC-LR). The aptamer (ABA) was employed as recognition element which could bind MC-LR with high-affinity, while gold nanoparticles (AuNPs) worked as sensing materials whose plasma resonance absorption peaks red shifted upon binding of the targets at a high concentration of sodium chloride. With the addition of MC-LR, the random coil aptamer adsorbed on Au NPs altered into regulated structure to form MC-LR-aptamer complexes and broke away from the surface of Au NPs, leading to the aggregation of AuNPs, and the color converted from red to blue due to the interparticle plasmon coupling. Results showed that our aptamer-based colorimetric sensor exhibited rapid and sensitive detection performance for MC-LR with linear range from 0.5 nM to 7.5 μM and the detection limit reached 0.37 nM. Meanwhile, the pollutants usually coexisting with MC-LR in pollutant water samples had not demonstrated disturbance for detecting of MC-LR. The mechanism was also proposed suggesting that high affinity interaction between aptamer and MC-LR significantly enhanced the sensitivity and selectivity for MC-LR detection. Besides, the established method was utilized in analyzing real water samples and splendid sensitivity and selectivity were obtained as well.


Hepatobronchial fistula due to transphrenic migration of hepatic echinococcosis: MR demonstration.
We present an uncommon case of hepatic hydatidosis, complicated by transphrenic migration of the cyst, in which the use of magnetic resonance performed with ultrafast, breath-hold, heavily T2-weighted sequences (HASTE) demonstrated a bronchial fistula.


Ultrastructural identification of the splenic follicular dendritic cells in the chicken.
There is a need to identify the follicular dendritic cells (FDC) of the chicken spleen at the ultrastructural level during a secondary immune response. The cells were identified after intravenous priming BSA and boosting with biotinylated BSA conjugated to colloidal gold particles. Monoclonal antibodies raised specifically either to chicken IgG or IgM were used to characterize these immune complex-trapping cells. The FDC had an irregular morphology which varied through time, supporting the existence of two types of FDC in the chicken spleen, one showing filiform cell processes, the other provided with beaded dendrites. When the filiform dendrites were observed, the FDC bound the antigen on their surfaces. These dendrites showed an intrincate convoluted configuration, forming tightly wrapped networks near the cell body. The networks had the same features as those described in mammals as antigen retaining reticulum (ARR). In chickens, the ARR, which represents sites of antigen localization on FDC, reached maximum development on day 5 after the second injection of BSA and had disappeared by day 8. At this time FDC had beaded dendrites. Antigen is retained on FDC in the chicken spleen for long periods of time.


[Synopsis of a four-year research on the "maculipennis" complex (author's transl)].
The authors have carry out during four summers a study of the "maculipennis complex" on the Languedoc-Roussillon coast line. They have determined three sibling species: Anopheles maculipennis subalpinus (very abundant, with an important eggs ornementation' poly-morphism), Anopheles maculipennis maculipennis (found only once in that region) and Anopheles maculipennis atroparvus found only the last year of our research.


Stop consonant production in isolated and repeated syllables in Parkinson's disease.
To determine if Parkinson's disease (PD) patients have increasing difficulty as speech tasks become longer or more complex, the timing and accuracy of isolated syllables and repeated sequences of syllables were studied. Acoustic measures of PD patient's syllables were similarly impaired relative to normal controls for both isolated and repeated syllable sequences. Listeners' identification scores were equally high for both types of productions. Unlike previous studies of other types of movements in PD, speech accuracy and timing does not deteriorate as items become longer or more complex.


Differences in 7th and 8th edition American Joint Committee on Cancer staging for periocular sebaceous carcinoma.
To examine the clinicopathological features of periocular sebaceous carcinoma and describe the differences in T category between the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging system for eyelid carcinoma in a Canadian population. This study is a single-centre retrospective review of consecutive patients diagnosed with periocular sebaceous carcinoma at Vancouver General Hospital over a 24-year period. Medical records and pathological slides were reviewed. Clinicopathological features, management, and outcomes were recorded. Each carcinoma was staged as per both the seventh and eighth editions AJCC staging system for eyelid carcinoma. Forty-five patients (25 women, 20 men) were identified with a median age of 74 years (range 42-91 years). Tumour size was with a median of 4 mm (range 1-30 mm) and a mean of 6.7 mm. Using the seventh edition, patients were assigned the following T categories: Tis = 10, T1 = 9, T2 = 11, T3 = 8, T4 = 0. Under the eighth edition, 18 of 45 patients (40%) were restaged, with the majority of these (15 patients, 33%) being downstaged. The eighth edition categories were as follows: Tis = 10, T1 = 22, T2 = 3, T3 = 0, T4 = 3. Three patients developed disease recurrence, 2 of whom (staged T2c and T4b) died of disease. There were substantial differences in the seventh and eighth editions of AJCC for the staging of periocular sebaceous carcinoma. Our series had small tumours at presentation with infrequent recurrences or metastases. We found a high number of patients with in-situ-only disease.


The 'A' is the Weakest Link: What Local Health Departments are Doing to Improve Adolescent Health.
Although adolescence is a critical developmental period, there has not been coordinated effort to comprehensively address adolescent health within the field of maternal and child health (MCH). In order to inform future adolescent health efforts, MCH leaders in local health departments were asked to reflect on the greatest health challenges facing adolescents in their communities, the causes of these health challenges, the interventions currently implemented to promote adolescent health, and additional intervention needs. 15 interviews were conducted in 2018 with 13 city and county health departments and two community-based agencies (N = 19). Interviews were recorded and transcribed verbatim. Mutually agreed upon themes were determined by the research team and these themes were used to code the transcripts. Mental and behavioral health and sexual and reproductive health issues were perceived to be the greatest health challenges facing adolescents. Participants attributed these health issues to the social determinants of health and adverse childhood experiences. Although all health departments offered sexual and reproductive health interventions, few implemented mental and behavioral health interventions. Insufficient funding and collaboration challenges were the major barriers impeding the implementation of additional coordinated adolescent health interventions. Coordinated funding and technical assistance will be needed to enable MCH professionals in local health to realize their potential to improve the health of adolescents. Specific observations and opportunities were addressed in efforts to create conversation that would lead to an improvement in adolescent health services within local health departments, as well as communities and the field of MCH.


The localization of oxytocin and mesotocin in the reproductive tract of the male marsupial bandicoot Isoodon macrourus.
The cellular localization of oxytocin and mesotocin within the testis and prostate of the Northern brown bandicoot, Isoodon macrourus, was examined. Tissues were fixed in 4% paraformaldehyde and immunoreactive cells and tissues were detected with antibodies to oxytocin and mesotocin. Immunoreactive oxytocin was present in the Leydig cells and in the spermatids of the adult and the 263-day bandicoots and there was faint staining in the 123-day bandicoot. Mesotocin was not present in the testes of the bandicoot. Immunoreactive oxytocin and mesotocin were present in the ventral portion of the prostate. The oxytocin within the testis may play a role in spermatogenesis and in seminiferous tubule contractility whereas the hormones present in the accessory glands may have a role in sperm transport in the female reproductive tract.


Clinical, histologic and quantitative angiographic predictors of restenosis after directional coronary atherectomy: a multivariate analysis of the renarrowing process and late outcome.
To characterize predictors of restenosis after successful directional atherectomy, we reviewed the clinical, angiographic and procedural data obtained during 132 consecutive procedures. Clinical and angiographic follow-up data were obtained in a prospectively collected and consecutive series of 125 patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic (11%) lesions in native coronary arteries. Restenosis was assessed clinically and by quantitative coronary angiography. A dual approach to data analysis was taken to gain insight into factors affecting the clinical outcome and vessel wall healing response. Therefore, multivariate analysis was performed to 1) determine the correlates of residual lumen diameter at follow-up (angiographic outcome), and 2) characterize the determinants of the late lumen loss (renarrowing process). Clinical and angiographic follow-up data after successful atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an acute lumen gain of 1.28 +/- 0.48 mm (mean +/- SD), resulting in a minimal lumen diameter of 2.44 +/- 0.47 mm. At follow-up, the minimal lumen diameter decreased to 1.78 +/- 0.64 mm. The angiographic restenosis rate was 28% if the traditional 50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy minimal lumen diameter and right coronary or left circumflex artery lesions were independent predictors of a larger minimal lumen diameter (angiographic outcome). Lumen loss during follow-up (renarrowing process) was independently predicted by relative lumen gain and preprocedural minimal lumen diameter. In analyzing the long-term results of new interventional techniques such as directional atherectomy, the late lumen loss during follow-up (renarrowing process), which is characterized by the vessel wall healing response after an intervention, should be considered together with the residual lumen diameter at follow-up (clinical outcome). It is clear that whereas improved clinical outcome is associated with larger vessel size and postprocedural lumen diameter and non-left anterior descending artery location, greater relative gain at intervention is predictive of more extensive lumen renarrowing.


[18F]MFBG PET/CT outperforming [123I]MIBG SPECT/CT in the evaluation of neuroblastoma.
Iodine 123 labeled meta-iodobenzylguanidine ([123I]MIBG) scan with SPECT/CT imaging is one of the most commonly used imaging modalities in the evaluation of neuroblastoma. [18F]-meta-fluorobenzylguanidine ([18F]MFBG) is a novel positron emission tomography (PET) tracer which was reported to have a similar biodistribution to [123I]MIBG. However, the experience of using [18F]MFBG PET/CT in the evaluation of patients with neuroblastoma is limited. This preliminary investigation aims to assess the efficacy of [18F]MFBG PET/CT in the evaluation of neuroblastomas in comparison to [123I]MIBG scans with SPECT/CT. In this prospective, single-center study, 40 participants (mean age 6.0 ± 3.7 years) with history of neuroblastoma were enrolled. All children underwent both [123I]MIBG SPECT/CT and [18F]MFBG PET/CT studies. The number of lesions and the Curie scores revealed by each imaging method were recorded. Six patients had negative findings on both [123I]MIBG and [18F]MFBG studies. Four of the 34 patients (11.8%) were negative on [123I]MIBG but positive on [18F]MFBG, while 30 patients were positive on both [123I]MIBG and [18F]MFBG studies. In these 34 patients, [18F]MFBG PET/CT identified 784 lesions while [123I]MIBG SPECT/CT detected 532 lesions (p < 0.001). The Curie scores obtained from [18F]MFBG PET/CT (11.32 ± 8.18, range 1-27) were statistically higher (p < 0.001) than those from [123I]MIBG SPECT/CT (7.74 ± 7.52, range 0-26). 30 of 34 patients (88.2%) with active disease on imaging had higher Curie scores based on the [18F]MFBG study than on the [123I]MIBG imaging. [18F]MFBG PET/CT shows higher lesion detection rate than [123I]MIBG SPECT/CT in the evaluation of pediatric patients with neuroblastoma. Clinicaltrials.gov : NCT05069220 (Registered: 25 September 2021, retrospectively registered); Institute Review Board of Peking Union Medical College Hospital: ZS-2514.


Making connections at DNA replication forks: Mrc1 takes the lead.
In a recent issue of Molecular Cell, Lou et al. (2008) demonstrate that the Mrc1 protein associates with the DNA polymerase that acts on the leading strand at replication forks, suggesting a potential mechanism that could help to preserve genome stability.


The kinetics of methaemoglobin substitution reactions have been investigated by the stopped-flow technique. Biphasic reactions have been observed with adult and fetal methaemoglobin. This behaviour is attributed to different reactivities of the chain types. The investigations give evidence of an increasing chain reactivity in the sequence alpha-chain < beta-chain < gamma-chain. The differences increase with the size of the substituting ligand, indicating steric effects.


Retrograde double-labeling demonstrates convergent afferent innervation of the prostate and bladder.
Prostatic inflammation is a common histologic finding in men with lower urinary tract symptoms (LUTS). It has been postulated that prostatic inflammation could sensitize afferent neurons innervating the bladder and thereby produce changes in voiding behavior. In support of this, we demonstrate an anatomic basis for pelvic cross-talk involving the prostate and bladder. Retrograde labeling was performed by an application of a neuro-tracer Fast Blue (FB) to one side of either the anterior prostate (AP), dorsal lateral prostate (DLP)/ventral prostate (VP), bladder, or seminal vesicle (SV). Examination of dorsal root ganglion (DRG) neuron labeling revealed shared afferent innervation of the prostate and bladder at spinal segments of T13, L1, L2, L6, and S1. Dual labeling was performed by an application of FB and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyaine perchlorate (DiI) to the AP and bladder, respectively. We observed double-labeled DRG neurons at T13, L1, L2, L6, and S1--a finding that proves convergent innervation of prostate and bladder. Our observations demonstrate the potential for neural cross-talk between the prostate and bladder and support a postulated mechanism that prostatic inflammation may induce hyper-sensitization of bladder afferents and produce irritative LUTS.


Conformational dynamics of the μ-opioid receptor determine ligand intrinsic efficacy.
The μ-opioid receptor (μOR) is an important target for pain management and the molecular understanding of drug action will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance (DEER) and single-molecule fluorescence resonance energy transfer (smFRET), how ligand-specific conformational changes of the μOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several cytoplasmic receptor conformations interconverting on different timescales, including a pre-activated receptor conformation which is capable of G protein binding, and a fully activated conformation which dramatically lowers GDP affinity within the ternary complex. Interaction of β-arrestin-1 with the μOR core binding site appears less specific and occurs with much lower affinity than binding of G protein Gi.


Age differences in cytokine expression under conditions of health using experimental pain models.
Older adults are at an increased risk to develop frequent and prolonged pain. Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory of aging and the increased incidence of age-related diseases. This study tested the hypothesis that older adults show greater immune responses to experimental pain compared to younger individuals. Study subjects (8 younger and 9 older healthy adults) underwent 3 experimental sessions using well-validated human experimental pain models: the cold pressor task (CPT), focal heat pain (FHP), and a non-painful thermal control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, 60, and 90 min post-stimuli administration. Pro-inflammatory cytokines (TNF-α IL-6 and IL-8) peaked at the same time points for both groups, with greater elevations among older subjects for TNF-α and IL-8 in both pain models and elevations in IL-6 only for CPT. Anti-inflammatory cytokines (IL-4, IL-5, and IL-10) generally peaked later for the older subjects, with increased elevations for FHP but not the CPT. These data are consistent with the assertion that age-related immune system dysregulation may account for the increased prevalence of pain in older adults.


HCN channels: structure, cellular regulation and physiological function.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization. In addition, voltage-dependent opening of these channels is directly regulated by the binding of cAMP. HCN channels are encoded by four genes (HCN1-4) and are widely expressed throughout the heart and the central nervous system. The current flowing through HCN channels, designated I(h) or I(f), plays a key role in the control of cardiac and neuronal rhythmicity ("pacemaker current"). In addition, I(h) contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration and synaptic transmission. In this review we give an overview on structure, function and regulation of HCN channels. Particular emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity.


The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity.
Islet β-cell dysfunction that leads to impaired insulin secretion is a principal source of pathology of diabetes. In type 2 diabetes, this breakdown in β-cell health is associated with compromised islet-enriched transcription factor (TF) activity that disrupts gene expression programs essential for cell function and identity. TF activity is modulated by recruited coregulators that govern activation and/or repression of target gene expression, thereby providing a supporting layer of control. To date, more than 350 coregulators have been discovered that coordinate nucleosome rearrangements, modify histones, and physically bridge general transcriptional machinery to recruited TFs; however, relatively few have been attributed to β-cell function. Here, we will describe recent findings on those coregulators with direct roles in maintaining islet β-cell health and identity and discuss how disruption of coregulator activity is associated with diabetes pathogenesis.


Characterization of saline dust emission resulted from Urmia Lake drying.
Compared with common dust storms, saline dust storms transport high concentrations of fine-grain saline and alkaline material. The saline dust storm differs from common dust storm, especially considering the sources of the suspended particulate matter (PM), chemical composition, grain size, and circulation processes. Atmospheric particulate matters (TSP, PM10, PM2.5, and PM1) and their water-soluble ions were concurrently measured at two sites located at north and southeast part of Urmia lake from January 2013 to September 2013. Particulate matters (PMs) were measured using high volume sampler and HAZ-DUST EPAM-5000 particulate air monitors. In both of the sampling sites, the highest concentration of PM was observed during the summer season (521.6, 329.1, 42.6, and 36.5 for TSP, PM10, PM2.5, and PM1, respectively). A total of 11 inorganic water-soluble ions in the TSP and PM10 were identified by ion chromatography (IC). No statistically significant difference was found between PM's ions concentrations of two sampling sites. The average of the total measured water-soluble ions in the sampling sites was 28.75 ± 12.9 μg/m(3) (11.9 ± 4.8% of total TSP mass) for TSP and 14.65 ± 7.1μg/m(3) (8.7 ± 4.4 of total PM10 mass) for PM10. Among all detected ions, sulfate was the dominant constituent followed by nitrate and sodium. This study showed that the water soluble salts compose 3-20% of the total mass of TSP and PM10. The PCA analysis showed that saline particulates formed from Urmia lake bed were the dominant source (57.6 %) of TSP. In addition, saline particulates together with crustal materials resulted from resuspension were the main source (59.9%) of PM10.


Colchicine does not provide a sustained blockage of collagen and plasma protein secretion by rat hepatocytes.
Colchicine has been reported to disrupt microtubules and thereby inhibit collagen secretion. Because of this "anti-collagen" activity, colchicine has been suggested for use in the treatment of hepatic fibrosis. Using biochemical and immunohistochemical techniques, our laboratory has identified the hepatocyte as one possible source of collagen in the liver. The present study examined the direct effect of colchicine on collagen secretion by hepatocytes in culture. Parenchymal cells were isolated from the livers of adult rats four days following a two-thirds hepatectomy. Total collagen and the fraction secreted into the medium were quantitated as incorporation of [3H]-proline into bacterial collagenase-sensitive protein. Treatment of the hepatocytes with 100 microM colchicine (2-3 hours) resulted in a substantial inhibition of collagen secretion. However, upon longer exposure of the hepatocytes to the drug (24 hours and 8 days), the inhibitory effect on collagen secretion was abolished. The anti-protein secretion activity of the colchicine in the conditioned medium removed from the hepatocytes was still present as verified by a 2.5 hour fibroblast-collagen secretion bioassay. The secretion of the plasma proteins albumin, fibrinogen and the third component of complement was not altered by the presence of colchicine. We conclude that the hepatocyte is a highly efficient secretory cell, and is not entirely dependent upon microtubules as organelles for protein secretion. Therefore, to the extent that hepatocytes may contribute to the hepatic fibrosis, the therapeutic use of colchicine to block collagen secretion might be expected to have only limited effectiveness.


A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues.
We compared the streptavidin-peroxidase conjugate (SP) method of immunoperoxidase histochemistry to the unlabeled antibody (PAP) and avidin-biotin-peroxidase complex (ABC) techniques in human colorectal carcinoma tissues stained with a monoclonal antibody for expression of carcinoembryonic antigen. Compared to the ABC and PAP method, the SP method produced stronger staining intensity and very low background staining. This was true when other antibody isotypes, other antibody species, other organs, and another tumor-associated antigen were used. Moreover, the SP procedure time could be reduced to one third that of the ABC or PAP methods without compromising accuracy, and the SP reagent is stable for several months. The chemical nature of the streptavidin molecule accounts, in large part, for the advantages of the SP method.


Neural activation during successful and unsuccessful verbal learning in schizophrenia.
Successful and unsuccessful intention to learn words was assessed by means of event-related functional MRI. Eighteen patients with schizophrenia and 15 healthy control participants were scanned while being given two word lists to read and another seven to learn with immediate recall. Neural activation patterns were segregated according to whether words were subsequently recalled or forgotten and these conditions were contrasted with each other and reading. Compared to controls, patients with schizophrenia showed deficits with regard to neural recruitment of right hippocampus and of cerebellar structures during successful verbal learning. Furthermore, a reversal of activated structures was evident in the two groups: Controls showed activation of right frontal and left middle temporal structures during the unsuccessful intention to learn. During successful learning, there was additional activation of right superior parietal lobule. In contrast, patients showed activation of right superior parietal lobule during unsuccessful and successful intention to learn. There were additional frontal and left middle temporal lobe activations during successful learning. We conclude that increased parietal activity may reflect a mechanism which compensates for the lack of hippocampal and cerebellar contributions to verbal learning in schizophrenia.


Imaging strategies for MR of the spine.
Magnetic resonance (MR) imaging has rapidly evolved as a primary modality for evaluating the spine. Following routine radiographs, MR is currently the preferred examination in evaluating patients presenting with myelopathy, suspected congenital abnormalities, discitis/osteomyelitis, and myeloradiculopathy. It is becoming the examination of choice in evaluating patients with radiculopathy as well when fast-scan techniques are available. MR of the spine will prove increasingly important as the technology advances. It is likely that MR will replace myelography entirely for many indications.


[Nephretic colic in patients with arrhythmia (author's transl)].
The authors relate one case of obstruction by emboly in the renal artery. The diagnosis were too late for conservative surgery. In this case, they insist on the particulary signs of that nephretic colic and they show the diagnosis measures which are able to permit a conservative surgery in urgency.


Bone development.
The development of the vertebrate skeleton reflects its evolutionary history. Cartilage formation came before biomineralization and a head skeleton evolved before the formation of axial and appendicular skeletal structures. This review describes the processes that result in endochondral and intramembranous ossification, the important roles of growth and transcription factors, and the consequences of mutations in some of the genes involved. Following a summary of the origin of cartilage, muscle, and tendon cell lineages in the axial skeleton, we discuss the role of muscle forces in the formation of skeletal architecture and assembly of musculoskeletal functional units. Finally, ontogenetic patterning of bones in response to mechanical loading is reviewed.This article is part of a Special Issue entitled "Muscle Bone Interactions".


The Autism-Related lncRNA MSNP1AS Regulates Moesin Protein to Influence the RhoA, Rac1, and PI3K/Akt Pathways and Regulate the Structure and Survival of Neurons.
Autism spectrum disorder (ASD) is a complex disease involving multiple genes and multiple sites, and it is closely related to environmental factors. It has been gradually revealed that long noncoding RNAs (lncRNAs) may regulate the pathogenesis of ASD at the epigenetic level. In neuronal cells, the lncRNA moesin pseudogene 1 antisense (MSNP1AS) forms a double-stranded RNA with moesin (MSN) to suppress moesin protein expression. MSNP1AS overexpression can activate the RhoA pathway and inhibit the Rac1 and PI3K/Akt pathways; however, the regulation of Rac1 by MSNP1AS is not associated with MSN, and the effect on the RhoA pathway may also be associated with other factors. MSNP1AS can decrease the number and length of neurites, inhibit neuronal cell viability and migration, and promote apoptosis. Downregulation of MSN expression functions similarly to MSNP1AS, and its overexpression can block the above functions of MSNP1AS. In addition, in vivo experiments show that MSN improves social interactions and reduces repetitive behaviors in BTBR mice, decreases the activity of RhoA and restores the activity of PI3K/Akt pathway. Therefore, the abnormal expression of MSNP1AS in ASD patients might influence the structure and survival of neuronal cells through the regulation of moesin protein expression to facilitate the development and progression of ASD. These findings provide new evidence for studying the mechanisms of lncRNAs in ASD. LAY SUMMARY: Autism spectrum disorder (ASD) is a common neurodevelopmental disease and its neurodevelopmental mechanisms have not been elucidated. More and more studies have found that long noncoding RNAs (lncRNAs) can regulate the development of central nervous system in many ways and affect the pathogenic process of ASD. Moesin pseudogene 1 antisense (MSNP1AS) is an up-regulated lncRNA in ASD patients. In-depth functional experiments showed that MSNP1AS inhibited moesin protein expression and regulated the activation of multiple signaling pathways, thus decreasing the number and length of neurites, inhibiting neuronal cell viability and migration, and promoting apoptosis. Therefore, MSNP1AS is an important lncRNA related to ASD and can regulate the biological function of neurons.


"Comparing the effectiveness, acceptability and oral hygiene status between vacuum formed retainer and Begg's retainer": a pilot study.
Recently, Vacuum formed retainers (VFRs) are preferred as an Orthodontic retention appliance over conventional Begg's retainers. Very few studies have been conducted between VFRs and Begg's retainers. Hence, this study aims at assessing the effectiveness, oral hygiene and acceptability between VFRs and Begg's retainers with a follow up period of 1 year. Eighty patients who completed fixed Orthodontic treatment were included. Retainers were delivered on the same day of debonding. Retainer 1/ R1 stands for VFRs and Retainer 2/ R2 stands for Begg's retainers. The retainers were randomly allocated to both the arches. 40 VFRs and Begg's retainers in maxillary and mandibular arch were given respectively. Effectiveness, oral hygiene condition were performed at T0 (After debonding), T1 (3 months after using retainers), T2 (6 months after using retainers), T3 (9 months after using retainers), T4 (12 months after using retainers) follow up stages, except the feedback form and the breakage of retainers that were filled at T4 stage. Both R1 and R2 retainers showed improvement in teeth alignment in both the arches at follow up stages. Interproximal contacts in maxillary and mandibular arch with VFRs and Begg's retainers improved to 77.5% and 82.5% respectively. Considering the marginal ridge, Begg's retainers and VFRs showed 95%, 55% increased proportion at T4 respectively (p < 0.05). Patients wearing Beggs's retainers had significantly better (p < 0.05) oral hygiene status. Significant differences were observed with Begg's retainers in teeth biting, whereas no significant difference was found with fitting of appliance (p = 0.180) and gingival irritation (p = 1.000). VFRs were well accepted aesthetically that was significant. Retainers were prone to breakage but was not significant (p = 0.162). Begg's wrap around retainers maintain good oral hygiene, improve the teeth alignment, interproximal contact and marginal ridges post Orthodontic treatment with better fitting of the appliance. VFRs are also preferred as they are good in maintaining proper teeth alignment with progressive improvement in the interproximal contacts and are aesthetically pleasing.


Extracting human antibody sequences from public databases for antibody humanization: high frequency of species assignment errors.
In antibody humanization, complementarity determining regions from a 'donor' antibody are often grafted onto a human framework selected by high sequence identity with the donor. In our own humanization experiments, we have found that species information is often incorrect. Here we take three mouse antibodies and perform BLAST searches against sequences annotated as being human. We find that the first genuine human hits for the six chains appear at Positions 30, 4, 11, 24, 18 and 29 in the hit lists. This illustrates both the need for caution in performing humanization and for improvements in annotation.


Ultrafine Flexible Endoscope Visualization to Assist in the Removal of a Huge Spinal Extradural Arachnoid Cyst: Case Report and Literature Review.
Arachnoid cysts are one of the benign spinal cystic lesions. Multiple nerve roots and spinal cord may be compressed by it, and operating is often recommended. Traditional surgical procedures often choose the posterior median approach, separating the paravertebral muscles, milling the lamina, fully exposing the cyst, partially or completely removing the cyst wall, looking for the leak, and then suturing and sealing. Here we present a case of giant spinal extradural arachnoid cyst in which a ultrafine flexible endoscope was used to visualize cystic spaces and identity the leaks. We repaired the leak after removing part of the cyst wall under the operating microscope, and the patient had an excellent recovery.


Production of Recombinant Polypeptides Binding α2-Macroglobulin and Analysis of Their Ability to Bind Human Serum α2-Macroglobulin.
Many streptococcal strains bind to two main human blood plasma proteins: IgG and human serum albumin (HSA). Protein G expressed in group C and G streptococci has specific binding regions for these proteins. Protein G in group G streptococcal strains also contains a region binding another human plasma protein, α2-macroglobulin (α2-М), upstream to the HSA-binding domain. Two recombinant polypeptides GM and GM1 capable of binding to α2-М were obtained using the G4223 strain of a group G Streptococcus, protein G molecule of which interacts with three human blood serum proteins (IgG, HSA, and α2-М). However, polypeptide GM containing three IgG-binding and three HSA-bindings domains and the region binding α2-М has higher molecular mass and higher affinity to α2-М than polypeptide GM1 that includes only the α2-М binding region.


Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.
The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.


Detection of CYP2D6 polymorphism using Luminex xTAG technology in autism spectrum disorder: CYP2D6 activity score and its association with risperidone levels.
CYP2D6 is involved in the biotransformation of a large number of drugs, including risperidone. This study was designed to detect CYP2D6 polymorphisms with a Luminex assay, including assessment the relationship of CYP2D6 polymorphisms and risperidone plasma concentration in autism spectrum disorder children (ASD) treated with risperidone. All 84 ASD patients included in this study had been receiving risperidone at least for 1 month. The CYP2D6 genotypes were determined by Luminex assay. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Among the 84 patients, there were 46 (55.42%) classified as EM, 33 (39.76%) as IM, and 4(4.82%) as UM. The plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients were significant differences among the CYP2D6 predicted phenotype group (P = 0.001 and P < 0.0001 respectively). Moreover, the plasma concentration of risperidone and risperidone/9-hydroxyrisperidone ratio in the patients with CYP2D6 activity score 0.5 were significantly higher than those with the CYP2D6 activity score 2.0 (P = 0.004 and P = 0.002 respectively). These findings suggested that the determination of the accurate CYP2D6 genotype-predicted phenotype is essential in the clinical setting and individualization of drug therapy. The use of the Luminex assay for detection of CYP2D6 polymorphisms could help us more accurately identify an individual's CYP2D6 phenotype.


Non-resective surgery and radiosurgery for treatment of drug-resistant epilepsy.
Epilepsy surgery is an effective treatment for properly selected patients with intractable seizures. However, many patients with medically intractable epilepsy are not excellent candidates for surgical resection of the epileptogenic zone. Due to recent advances in computer technology and bioengineering, several novel techniques are receiving increasing interest for their role in the care of people with epilepsy. Neuromodulation is an emerging surgical option to be used when conventional resective surgery is not indicated. We review the indications and expected outcomes of neuromodulatory treatments currently available for the treatment of refractory epilepsy, i.e., vagus nerve stimulation, deep brain stimulation, stereotactic radiosurgery, and multiple subpial transections.


Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment.
Leptomeningeal involvement in patients with CLL is relatively rare and the prognosis is usually considered to be poor. The authors reviewed all CLL patients treated in a tertiary referral center to assess the incidence and outcome of leptomeningeal involvement (LI) in CLL. They found an incidence of 1-2% of LI. Most of the patients with LI had a longterm survival, despite failure to clear the cerebrospinal fluid from tumor cells.


Role of G protein-coupled receptors in inflammation.
G protein-coupled receptors (GPCRs) play important roles in inflammation. Inflammatory cells such as polymorphonuclear leukocytes (PMN), monocytes and macrophages express a large number of GPCRs for classic chemoattractants and chemokines. These receptors are critical to the migration of phagocytes and their accumulation at sites of inflammation, where these cells can exacerbate inflammation but also contribute to its resolution. Besides chemoattractant GPCRs, protease activated receptors (PARs) such as PAR1 are involved in the regulation of vascular endothelial permeability. Prostaglandin receptors play different roles in inflammatory cell activation, and can mediate both proinflammatory and anti-inflammatory functions. Many GPCRs present in inflammatory cells also mediate transcription factor activation, resulting in the synthesis and secretion of inflammatory factors and, in some cases, molecules that suppress inflammation. An understanding of the signaling paradigms of GPCRs in inflammatory cells is likely to facilitate translational research and development of improved anti-inflammatory therapies.


Parameter optimization model of learning in stepping motion.
In this study we combine the representation of motion by a finite number of hardwired functions with parameter optimization to model learning during a stepping motion. Representation of experimental kinematic data by a finite number of predetermined functions and undetermined coefficients was analyzed. Least squares approximation was used to represent experimental data of stepping motions over obstacles of different heights. Functional relationships between coefficients and obstacles heights were also obtained. Learning of stepping over an obstacle was then formulated as a finite dimensional optimization problem. The pattern of foot path, and joint angles trajectories obtained by this learning model, were then compared to the experimental data. The results of the data fitting analysis and of the optimization process as a model for motion learning, indicate that motion can be adequately represented by a set of hardwired functions, and a finite number of task dependent coefficients.


Prevention of pulmonary embolism by inferior vena cava filters: results in 62 cases.
The most effective methods of preventing recurrent pulmonary embolism involve interruption of the pathway of emboli through the inferior vena cava. Of the several procedures that interrupt vana caval blood flow, percutaneous implantation of a screen filter is associated with the lowest risk and appears to be as effective as any of the other procedures in preventing recurrent emboli. This article describes the experience with 62 cases of screen filter implantation performed between 1971 and 1975. Pulmonary embolism recurred in 1.6% of the patients, and 10% of the patients developed swelling of the lower extremities that did not exist preoperatively. Inferior vena cava phlebography performed 6 to 24 months postoperatively in 25 patients showed a patent inferior vena cava in 9 patients, partial occlusion of the vana cava in 8 patients, and complete occlusion of the vena cava with extensive collateral veins in 8 patients.


Structural insights into melatonin receptors.
The long-anticipated high-resolution structures of the human melatonin G protein-coupled receptors MT1 and MT2 , involved in establishing and maintaining circadian rhythm, were obtained in complex with two melatonin analogs and two approved anti-insomnia and antidepression drugs using X-ray free-electron laser serial femtosecond crystallography. The structures shed light on the overall conformation and unusual structural features of melatonin receptors, as well as their ligand binding sites and the melatonergic pharmacophore, thereby providing insights into receptor subtype selectivity. The structures revealed an occluded orthosteric ligand binding site with a membrane-buried channel for ligand entry in both receptors, and an additional putative ligand entry path in MT2 from the extracellular side. This unexpected ligand entry mode contributes to facilitating the high specificity with which melatonin receptors bind their cognate ligand and exclude structurally similar molecules such as serotonin, the biosynthetic precursor of melatonin. Finally, the MT2 structure allowed accurate mapping of type 2 diabetes-related single-nucleotide polymorphisms, where a clustering of residues in helices I and II on the protein-membrane interface was observed which could potentially influence receptor oligomerization. The role of receptor oligomerization is further discussed in light of the differential interaction of MT1 and MT2 with GPR50, a regulatory melatonin coreceptor. The melatonin receptor structures will facilitate design of selective tool compounds to further dissect the specific physiological function of each receptor subtype as well as provide a structural basis for next-generation sleeping aids and other drugs targeting these receptors with higher specificity and fewer side effects.


Correction: Brázda, V. and Coufal, J. Recognition of Local DNA Structures by p53 Protein. Int. J. Mol. Sci. 2017, 18, 375.
The authors wish to make the following corrections to their paper [1] [...].


Development of a serum-free culture medium for the large scale production of recombinant protein from a Chinese hamster ovary cell line.
A serum-free medium, WCM5, has been developed for the large scale propagation of CHO (Chinese hamster ovary) cells which express recombinant protein using dihydrofolate reductase as a selectable marker. WCM5 was prepared by supplementing Iscoves medium without lecithin, albumin or transferrin with a number of components which were shown to benefit growth. WCM5 medium contained 5 mg l(-1) human recombinant insulin (Nucellin) but was otherwise protein-free. CHO 3D11(*) cells which had been engineered to express a humanised antibody, CAMPATH(*)-1H, were routinely grown using serum-containing medium. From a seeding density of 10(5) cells ml(-1), cells grown in static culture with serum reached a maximal cell density of 6.5×10(5) cells ml(-1) after 6 days in culture and produced a maximal antibody concentration of 69 mg l(-1) after 11 days in culture. CHO 3D11(*) cells grown with serum were washed in serum-free medium then cultured in WCM5 medium. Following a period of adaptation the cell growth and product yield was superior to that achieved with serum-containing medium. CHO cells producing CAMPATH-1H grown in an 8000 l stirred bioreactor seeded with 2×10(5) cells ml(-1) reached a maximal viable cell density of 2.16×10(6) cells ml(-1) after 108 h in culture and a maximal antibody concentration of 131.1 mg l(-1) after 122 h in culture.


Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine.
Research on the biochemistry and physiology of l-arginine has remained an attractive area for scientists over the last 100 years due to its diverse physiological functions in mammals. Research on l-arginine was boosted after the identification of nitric oxide (NO) and agmatine and their physiological importance. NO directly modulates ion channels, activates soluble guanylyl cyclase and other important proteins by ADP ribosylation and nitrosylation and binding to heme or iron-sulfur clusters. These modifications and interaction with heme might activate or inhibit various protein kinases, phosphatases and modulate transcription of various nuclear factors to possibly cause cardiovascular diseases like hypertension, ischemia, diabetes, atherosclerosis and angiogenesis. Agmatine holds the key to prevent the toxic effects associated with induction of NO synthesis by its ability to inhibit inducible nitric oxide synthase (iNOS). Agmatine is also synthesized from l-arginine by the enzyme arginine decarboxylase and displays a significant potential in cardiovascular system. Agmatine, with the myriad of effects on calcium homeostasis, seems to modulate various functions in the heart, brain and vasculature. The present review compiles the recent development to improve the understanding the role played by l-arginine-metabolic pathways in cardiovascular system. Though l-arginine and its metabolites are well known to affect various cardiovascular physiologies, the currently available literature is still not sufficient to validate the prophylactic/therapeutic efficacy of l-arginine. l-Arginine and its metabolites, NO and agmatine still hold the key for future research in cardiovascular system.


Striatal projections from the rat lateral posterior thalamic nucleus.
The dorsocentral striatum (DCS) has been implicated as an associative striatal area receiving inputs from several cortical areas including medial agranular cortex (AGm), posterior parietal cortex (PPC), and visual association cortex to form a cortical-subcortical circuit involved in directed attention and neglect. The lateral posterior thalamic nucleus (LP) may also play a role in directed attention and neglect because LP has robust reciprocal connections with these cortical areas and projects to DCS. We used anterograde axonal tracing to map thalamostriatal projections from LP and surrounding thalamic nuclei, with a focus on projections to DCS. The thalamic nuclei investigated included LP, laterodorsal thalamic nucleus (LD), central lateral nucleus (CL), and posterior thalamic nucleus (Po). We found that the mediorostral part of LP (LPMR) projects strongly to DCS as well as to the dorsal peripheral region of the striatum. Further, there is topography within LPMR and DCS such that the far medial LPMR projects to the central region of DCS (projection area of AGm) and the central LPMR projects to the dorsal region of DCS (projection area of PPC and Oc2M). In contrast, the laterorostral part of LP (LPLR) and other thalamic nuclei surrounding LP project to dorsolateral to dorsomedial peripheral regions of the striatum but do not project to DCS. These findings indicate that DCS is a region of convergence for thalamostriatal and corticostriatal projections from regions that are themselves interconnected, serving as the key element of the corticostriatal-thalamic network mediating spatial processing and directed attention.


[Prevalence and chief variants of the course of schizophrenia with a predominance of delusional and hallucinatory-delusional disorders throughout the course of the disease (clinico-epidemiologic study)].
A nonselective group of 971 schizophrenic patients was studied. The development of the disease in these patients was characterized by the prevalence of hallucinative disorders during the whole duration of the disease. This group totalled 19.1% of the whole population of patients. The cases with continuous paranoid schizophrenia totalled 42.4% of the studied group (8.1% of the population). The rest observations formed the continual range between paranoid and attack-like schizophrenia.


Single Cell Biology: Exploring Somatic Cell Behaviors, Competition and Selection in Chronic Disease.
The full range of cell functions is under-determined in most human diseases. The evidence that somatic cell competition and clonal imbalance play a role in non-neoplastic chronic disease reveal a need for a dedicated effort to explore single cell function if we are to understand the mechanisms by which cell population behaviors influence disease. It will be vital to document not only the prevalent pathologic behaviors but also those beneficial functions eliminated or suppressed by competition. An improved mechanistic understanding of the role of somatic cell biology will help to stratify chronic disease, define more precisely at an individual level the role of environmental factors and establish principles for prevention and potential intervention throughout the life course and across the trajectory from wellness to disease.


"Between a rock and the mitral valve space": Transcatheter mitral valve-in-valve implantation for paravalvular leak and refractory hemolysis complicated by circumflex coronary occlusion.
Transcatheter mitral valve implantation (TMVI) is an emerging field in structural cardiology. A particularly difficult group to treat is high-risk patients requiring valve in mitral annular calcification (ViMAC) intervention, with overall poor procedural success and outcomes in recent registries. This case highlights an unusual complication of paravalvular regurgitation (PVL) through the uncovered stent frame of a balloon expandable transcatheter heart valve (THV) on the left ventricular side of the prosthesis, leading to mechanical hemolysis and subsequent anuric renal failure post a ViMAC procedure. Attempts to treat the PVL with an occlusion plug device were unsuccessful and led to left circumflex coronary occlusion secondary to mechanical compression of the vessel in the posterior mitral valve annulus, a previously unreported phenomenon. A repeat valve-in-valve procedure was performed to treat the PVL, and immediate angioplasty resolved the left circumflex occlusion. High-risk patients requiring TMVI pose multiple challenges to Heart Teams in the treatment of valve pathology. Optimal procedural planning, multimodality imaging, improved THVs, and the awareness of potential complications are fundamental in overcoming the learning curve of TMVI and improved outcome for patients requiring ViMAC.


Mimicking myofibrillar protein denaturation in frozen-thawed meat: Effect of pH at high ionic strength.
This study aims at providing new insight on protein denaturation in freezing-thawing. Freezing-thawing minced pork reduced water-holding of myofibrils and increased surface hydrophobicity. One additional freezing-thawing cycle at slow freezing rate caused appearance of a 160 kDa myosin-4 fragment in SDS-PAGE, further decreased water-holding of myofibrils and increased surface hydrophobicity. Fresh minced pork was exposed to either high salt (2 M KCl) only or high salt with lower pH to mimic conditions in freezing. Exposure to high salt only increased water-holding of myofibrils and hence did not reproduce myofibrillar protein changes in freezing. Exposure to combinations of lower pHs and high salt decreased water-holding and increased surface hydrophobicity, suggesting myofibrillar protein denaturation occurred by a comparable mechanism as in freezing-thawing. We propose that exposure to decreased pH combined with high solute concentrations in the unfrozen water of frozen meat is the primary cause of myofibrillar protein denaturation in frozen-thawed meat.


Measurement of refractive-index change at a liquid-solid interface close to the critical angle.
We measured the refractive-index change on a liquid sample, using the reflection of a polarized Gaussian laser beam close to the angle of total reflection. We applied this technique to a solution of nickel (ii) phthalocyanine tetrasulfonated (NiPTS) in water-ethanol (1/1 v/v), in which the nonlinearity of the refractive index is due to optically induced thermal effects. We show that close to the angle of total reflection the sensitivity of this technique is four times bigger than at normal incidence.


Is periapical surgery follow-up with only two-dimensional radiographs reliable? A retrospective cohort type sensitivity study.
Two-dimensional (2D) radiographic techniques are commonly used for assessing lesion prognosis after endodontic surgery. The present retrospective cohort study analyzes the sensitivity and ability of different radiographic techniques in obtaining area and volume measurements of periapical lesions. Preoperative and follow-up (6-48 months) periapical and panoramic radiographs (index test) and cone-beam computed tomography (CBCT) images (reference standard) were selected from an endodontic microsurgery database. Sensitivity was analyzed independently by two examiners. The areas of the 2D radiographic images and CBCT volumes were studied using Itk-Snap software and Romexis viewer. The sample comprised 105 patients and 105 teeth, with a mean follow-up of 21 months (range 6-48). Preoperatively, CBCT detected all the periapical areas, periapical radiography detected 67, and panoramic radiography detected 60. Postoperatively, of the 52 cases in which CBCT detected remains of the periapical area, periapical radiography detected 22, and panoramic radiography detected 17. The measurements of the areas obtained by the 2D methods, and the volumes obtained by CBCT, had to be transformed into linear measures for comparison purposes. The measurements were found to be significantly different in both the preoperative and the follow-up images. Periapical radiography showed greater sensitivity than panoramic radiography, both preoperatively and at follow-up. The lesions measured with CBCT were larger, with significant differences than as evidenced by the periapical and panoramic radiographs.


Investigation of the non-small cell lung cancer patients with bronchus involvements: A population-based study.
We aimed to explore the prognostic differences among T1-4N0-2M0 non-small cell lung cancer (NSCLC) patients with bronchus involvements and to validate the T category of these patients in an external cohort. Univariable and multivariable Cox analysis was performed to determine the prognostic factors. Kaplan-Meier method with a log-rank test was used to compare overall survival differences between groups. Propensity score matching method was used to minimize the bias caused by the imbalanced covariates between groups. A total of 169 390 eligible T1-4N0-2M0 NSCLC cases were included. There were 2354, 3367, 1638, 75, 87 585, 42 056, 19 246, and 13 069 cases in the group of superficial tumors of any size with invasive component limited to bronchial wall (T1-bronchus), tumors involving main stem bronchus ≥2 cm from carina (T2-main bronchus [≥2 cm]), tumors involving main stem bronchus <2 cm from carina (T2-main bronchus [<2 cm]), tumors with carina invasion (T4-carina), T1, T2, T3, and T4, respectively. Multivariable Cox analysis indicated that T1-bronchus patients had the best prognosis; T2-main bronchus (≥2 cm) and T2-main bronchus (<2 cm) patients had similar prognosis both in the entire cohort and in several subgroups. Survival curves showed that T1-bronchus and T1 patients had similar survival rates; the survivals of T2-main bronchus patients regardless of the distance from carina were comparable to those of T2 patients, and the survivals of T4-carina patients were also similar to those of T4 patients. Our results validated and supported the current T category for the patients with bronchus involvements, which might provide certain reference value for the revisions of T category in the next version of the tumor-node-metastasis stage classification.


Triphasic effects of short chain n-alcohols on synaptic membrane transport of choline and of gamma-aminobutyric acid.
n-Alcohols, when added in increasing concentrations, had an unusual triphasic effect on the uptake of choline and of gamma-aminobutyric acid by isolated synaptosomes. There was slight inhibition of these uptakes at low n-alcohol concentrations, followed by a sharp peak of uptake enhancement, and then greater inhibition. The n-alcohol concentrations required for these effects were proportional to published n-alcohol membrane/buffer partition coefficients, with the peaks of uptake enhancement occurring at 60 mM n-propanol, 20 mM n-butanol and 7.5 mM n-pentanol. Synaptosomal membrane potential, as estimated from synaptosomal accumulation of the permeant cation [3H]tetraphenylphosphonium, was not affected by n-alcohols in the concentrations used in this study, suggesting that neither the inhibitory or enhancing effects of these n-alcohols were attributable to changes in trans-synaptosomal membrane ion gradients. The inhibiting and enhancing effects of n-alcohols could be reproduced in determinations of gamma-aminobutyric acid uptake by isolated synaptic plasma membranes, suggesting that the observed effects are due to a direct action of the n-alcohols on the synaptosomal plasma membrane. These effects may be attributable to a change in membrane binding of these alcohols from the membrane core to the membrane surface as alcohol concentration is increased.


Expression of nitric oxide synthase in mucosal cells of the canine colon.
The expression of nitric oxide synthase (NOS) in the mucosa of the canine colon was investigated with in situ hybridzation, immunohistochemistry (using isoform specific antibodies), western analysis, and NADPH diaphorase (NADPH-d) histochemistry. In situ hybridization using a common probe for known isoforms of NOS showed that NOS mRNA was strongly expressed in mucosal cells. A gradient in the degree of hybridization was noted from the base of the crypts to the luminal surface. This gradient was also apparent using an endothelial NOS (eNOS)-specific probe. Neural NOS-like immunoreactivity (nNOS-LI) was observed in columnar epithelial cells, and the same population of cells was stained with NADPH-d. Endothelial NOS-like immunoreactivity (eNOS-LI) was also found in mucosal cells; however, this eNOS-LI was confined to mucous cells. These cells were not stained with NADPH-d. The existence of eNOS in mucosal cells was confirmed by in situ hybridization using the probe which specifically hybridized with mRNA of eNOS and by western blots which demonstrated the expression of a 135-kDa protein in mucosal homogenates. The differential expression of NOS isoforms and the gradient in expression along the length of the crypts suggest complex roles for NO in the development of colonic epithelial cells and in secretion and transport functions of the colonic mucosa.


Isolation and identification of C-19 fatty acids with anti-tumor activity from the spores of Ganoderma lucidum (reishi mushroom).
We previously showed that ethanolic extracts of spores of Ganoderma lucidum inhibit tumor cell proliferation and induce apoptosis of HL-60 cells. The active constituents appeared to be long-chain fatty acids, particularly carbon-19 (C-19) fatty acids which have not been reported in spores of Ganoderma lucidum. In the present study, two of these C-19 fatty acids which are key compounds in the activities, were identified as their 2-naphthyl ester derivatives after esterification of a mixture of fatty acids obtained from the spores. The active compounds were determines as nonadecanoic acid and cis-9-nonadecenoic acid. The location of the double bond of cis-9-nonadecenoic acid was demonstrated by GC-MS analysis, based on the fragmentation pattern of the adduct prepared from the fatty acid and dimethyl disulfide.


Glomerular basement membrane polyanion distribution and nitric oxide in spontaneous hypertensive rats: effects of salt loading and antihypertensive therapy with propranolol.
Cationic colloidal gold (CCG), a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, mainly heparan sulfate proteoglycan in spontaneous hypertensive rats (SHR) with or without salt loading and antihypertensive treatment with propranolol. The changes of mean GBM width and anionic sites distribution were assessed by electron microscopy. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO2) + nitrate (NO3), stable metabolites of NO. SHR had decreased NO production and increased GBM width (27%) compared with the control Wistar-Kyoto (WKY) rats. The chronic high dietary salt intake resulted in a significant increase in blood pressure, proteinuria, and renal function in the SHR rats. The chronic high salt dietary intake resulted in a decrease in NO in the WKY and a further reduction in NO production in the SHR. The GBM anionic sites count was similar in the SHR and WKY nonsalt-loaded groups, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/microm GBM, respectively, but significantly lower in both salt-loaded SHR and WKY, 9.9 +/- 0.55 (P < .01) and 9.6 +/- 0.55 (P < .01) CCG counts/microm GBM, respectively. Antihypertensive treatment with propranolol in the salt-loaded SHR group resulted in lower blood pressure, a further decrease in NO production, but no significant changes in GBM width and anionic sites count. It is concluded that chronic high salt intake may be deleterious to the permselectivity of the GBM. A low NO production state that results from chronic salt loading in already hypertensive rats will result in more severe organ (renal) damage, most probably by the addition of the loss of GBM permselectivity to the existing pathomorphologic changes.


Inhibition of 17-beta-estradiol on neuronal excitability via enhancing GIRK1-mediated inwardly rectifying potassium currents and GIRK1 expression.
Catamenial epilepsy is a common central nervous system disease in female, which is influenced by the 17-β-estradiol (estrogen) level during the menstrual cycle. Low level (<0.05ng/ml) of estrogen normally accompanies with the perimenstrual classification of catamenial epilepsy, however, without clear mechanism. In previous studies, estrogen has been demonstrated to possess widely regulatory effects on potassium channels. Here, the effect of 17-β-estradiol on modulating inwardly rectifying K+ (Kir) currents was investigated in cultured hippocampal neurons. The underlying mechanism was also detected. In this research, null-estrogen cultures and spaying animals were used to mimicked the low level estrogen condition in menstrual period. Patch clamp recordings, western blotting and pharmacological experiments were performed to detect the effects of estrogen receptors and the underlying mechanisms. Compared to those neurons in normal medium (with 0.1ng/ml estrogen), null-estrogen cultures or neurons treated by estrogen receptor blocker (ICI 182,780) both had significant suppressed Kir currents. The expression level of G protein-gated inwardly rectifying K+ channel subunit 1 (GIRK1) was significantly decreased in spaying animals. Furthermore, a GIRK channel inhibitor (TPQ) similarly suppressed the Kir currents. Lastly, estrogen deficiency, estrogen receptor blocker and GIRK channel inhibitor all promoted the epileptiform bursting activities in neurons, as a result of Kir current suppression. Taken together, 17-β-estradiol, by the activation of estrogen receptors, is essential for the maintenance of Kir currents, and thus has an inhibitory effect on the epileptiform bursting activities in cultured hippocampal neurons, whereas GIRK1 is the major intermedial mediator. This research provides a new mechanism for the pathogenesis of catamenial epilepsy, particularly in the menstrual period and the early section of follicular phase.


Double contrast knee arthrography in children.
The indications for knee arthrography in children consist of: suspected internal derangement; osteochondritis dissecans; Blount's disease; popliteal cysts; loose bodies; synovial tumors; and miscellaneous abnormalities including unexplained knee pain.


Granulocyte-colony stimulating factor (G-CSF) improves motor recovery in the rat impactor model for spinal cord injury.
Granulocyte-colony stimulating factor (G-CSF) improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function.


Long Non-coding RNA JHDM1D-AS1 Interacts with DHX15 Protein to Enhance Non-Small-Cell Lung Cancer Growth and Metastasis.
JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC.


Diallyl tetrasulfane activates both the eIF2α and Nrf2/HO-1 pathways.
Diallyl polysulfanes have been shown to exert cell cycle arrest, anti-tumor and anti-inflammatory activities in a variety of in vitro and in vivo models. Although diallyl polysulfanes cause oxidative stress, little is known about the underlying signaling cascades leading to antioxidant defense or apoptosis. Cells were treated with DATTS at different concentrations and for different time periods. Reactive oxygen species and thiol concentrations were determined by commercially available kits. The expression levels of signal molecules were determined by Western Blot analysis. A direct influence of Nrf2 on the promoter of HO-1 gene was determined by a luciferase assay with the StRE promoter element from the HO-1 gene. We found an immediate increase in the level of the superoxide anion radical O(2)(-) and hydrogen peroxide H(2)O(2) and an overall thiol depletion. DATTS treatment of HCT116 cells also caused an up-regulation of phospho-eIF2α, nuclear Nrf2 and HO-1 protein levels in a time and concentration-dependent manner. Pre-treatment of cells with antioxidants significantly reduced the elevated expression levels of these proteins. A direct contribution of Nrf2 was shown by its interaction with the stress-response element of the HO-1 promoter. DATTS activates the ROS-eIF2α/Nrf2 HO-1 signaling cascades leading to the up-regulation of HO-1. However, this antioxidant defense is not sufficient to protect HCT116 cells from apoptosis. This study shows for the first time a parallel but not equal activation of signaling pathways by DATTS with a competitive ultimate cellular outcome.