External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer.
One hundred fifty-nine patients with unresectable but localized pancreatic cancer, as defined at exploratory laparotomy, were treated at the Mayo Clinic between February 1974 to April 1985. Postoperative therapy consisted of 4000 to 6000 cGy external beam irradiation (XRT) alone in 122 patients or 4500 to 5500 cGy XRT in combination with an intraoperative electron boost in 37. In addition, 132 (both groups) received 5-fluorouracil (5-FU) chemotherapy. Local control (LC) at 1 year was 82% with XRT + intraoperative radiation therapy (IORT) versus 48% with XRT and 66% versus 20% at 2 years respectively (P less than 0.0005). Due to the high incidence of hematogenous and/or peritoneal spread in both groups (abdominal failure in 54 and 56% of patients at risk), the decreased frequency of local progression did not translate into an improved survival. Neither median nor long-term survival of the two treatment groups (XRT versus XRT + IORT) was statistically different (median 12.6 months versus 13.4 months, P = 0.25). With tumor arising in the head of the pancreas, survival at 2 years was 18% as opposed to 0% for other locations (P less than 0.01). On the basis of a Cox multivariate analysis, no other treatment or prognostic factor significantly altered survival. Until the problem with systemic failure (usually abdominal) can be resolved, the median and long-term survival of patients with pancreatic carcinoma is likely to remain unchanged. Since IORT appears to improve local control, we will continue to utilize IORT in phase 1, 2 studies which also attempt to decrease the incidence of abdominal failures. Even with IORT + XRT combinations, the incidence of local progression is excessive and radiation dose modifiers need to be evaluated.


A hybrid coloboma and optic disc pit associated with macular retinoschisis.
To report and describe an unusual case of a patient with optic disc pit in one eye and optic disc coloboma with a focal pit associated with macular retinoschisis in the other eye. A 21-year-old woman presented with optic disc pit in the right eye and optic disc coloboma with a focal pit like excavation in the left eye. Macular spectral domain optical coherence tomography (SD-OCT) of the left eye revealed macular retinoschisis, without serous detachment. Proper monitoring of patients with disc anomalies associated with maculopathy is mandatory. The use of OCT imaging during follow-up can help to identify involvement of the fovea or enlargement of the retinoschisis area.


Genetic diversity of transmission blocking vaccine candidate (Pvs25 and Pvs28) antigen in Plasmodium vivax clinical isolates from Iran.
The leading candidates for a Transmission Blocking Vaccine (TBV) in Plasmodium vivax parasite are the ookinete surface protein 25 (Pvs25) and Pvs28, which their phase I clinical trial is ongoing. Therefore, we carried out survey of polymorphisms of the pvs25 and pvs28 genes in P. vivax populations that are circulating in the two malaria areas of contrasting endemicity in Iran, before field application of the TBV. To characterize the polymorphisms of pvs25 and pvs28 genes, 50 isolates were analyzed by sequencing method and their gene structure was compared with parasite populations from India, Bangladesh, Indonesia, Thailand, Mexico and Brazil. Three mutations were detected in pvs25 and pvs28 including Q87K, E97Q, I130T and M52L, T65K, T140S with two and four distinct haplotypes, in comparison with the Sal I sequence type, respectively. Both haplotypes of Pvs25 were found among northern and southern P. vivax isolates; however, only two and three of the Pvs28 variants were observed among the northern and southern isolates, respectively. In conclusion, the present results show the limited sequence polymorphism of the pvs25 and pvs28 genes among field P. vivax population in Iran. These results highly encourage with respect to applicability of Pvs25 and Pvs28-based vaccine against P. vivax infection in the region, where these parasites are prevalent, whether these occur in the temperate or tropical zones.


Exploring directed functional connectivity based on electroencephalography source signals using a global cortex factor-based multivariate autoregressive model.
Partial directed coherence (PDC) computed from multivariate autoregressive (MVAR) model coefficient is increasingly being used to study directed functional connectivity between brain regions in the frequency domain based on electroencephalography (EEG) source signals. However, directly fitting MVAR model to the high-dimensional source signals is difficult. Besides, although PDC measurement often shows good results for simulated data, it is not clear to what extent the results for real data are physiologically plausible. We propose a new method termed global cortex factor-based MVAR (GCF-MVAR) to study directed functional connectivity based on EEG source signals. It avoids directly fitting MVAR model to high-dimensional EEG sources, instead using low-dimensional global cortex factor signals derived from the source signals by principle component analysis (PCA). To validate its physiological efficacy, we weight the PDC with source spectral power (SP) which reflects the true frequency activity in a source region. The performance of GCF-MVAR is compared with FMVAR, ROI-MVAR, and MVAR by applying to both simulated and resting-state EEG data. The simulation results show that GCF-MVAR has the lowest estimation error. By using the source SP to weight the PDC, GCF-MVAR improves the physiological interpretation of the source connectivity for both simulated and resting-state EEG data. The new method is proved to outperform than the state-of-the-art methods, and can be feasible not only for resting state studies, but also task-related connectivity and neurological disorder analysis.


Surgical repair of the boutonnière deformity of the fingers.
Boutonnière is discussed. The results of twenty-seven digits operated on are presented. The operative technique used was that directed to the central tendon. The results were analysed according to the digit affected, to the type of lesion, if closed or opened, to the association with other lesions and to the time between the lesion and the surgery.


6,7-Di-hydro-5H-pyrrolo-[1,2-a]imidazole.
The crystal structure of 6,7-di-hydro-5H-pyrrolo-[1,2-a]imidazole, C6H8N2, at 100 K has monoclinic (P21/n) symmetry. The mol-ecule adopts an envelope conformation of the pyrrolidine ring, which might help for the relief torsion tension. The crystal cohesion is achieved by C-H⋯N hydrogen bonds. Inter-estingly, this fused ring system provides protection of the α-C atom (attached to the non-bridging N atom of the imidazole ring), which provides stability that is of inter-est with respect to electrochemical properties as electrolytes for fuel cells and batteries, and electrodeposition.


Transfer RNA splicing in Saccharomyces cerevisiae. Secondary and tertiary structures of the substrates.
Secondary and tertiary structures of four yeast tRNA precursors that contain introns have been elucidated using limited digestion with a variety of single-strand- and double-strand-specific nucleases. The pre-tRNAs, representing the variety of intron sizes and potential structures, were: pre-tRNALeuCAA, pre-tRNALeuUAG, pre-tRNAIleUAU, and pre-tRNAPro-4UGG. Conventional tRNA cloverleaf structure is maintained in these precursors except that the anticodon loop is interrupted by the intron. The intron contains a sequence which is complementary to a portion of the anticodon loop and allows the formation of a double helix often extending the anticodon stem. The 5' and 3' splicing cleavage sites are located at either end of this helix and are single-stranded. The intron is the most sensitive region to nuclease cleavage, suggesting that it is on the surface of the molecule and available for interaction with the splicing endonuclease. Absence of Mg2+ or spermidine renders the dihydrouridine and T psi C loops of these precursors highly sensitive to nuclease digestion. These ionic effects mimic those observed for tRNAPhe and suggest that the tRNA portion of these precursors has native tRNA structure. We propose consensus secondary and tertiary structures which may be of significance to eventual understanding of the mechanism of yeast tRNA splicing.


The global unmet need of congenital cardiac care: a quantitative analysis of the global burden of disease.
CHDs are one of the most frequent congenital malformations, affecting one in hundred live births. In total, 70% will require treatment in the first year of life, but over 90% of cases in low- and middle-income countries receive no treatment or suboptimal treatment. As a result, CHDs are responsible for 66% of preventable deaths due to congenital malformations in low- and middle-income countries. This study examines the unmet need of congenital cardiac care around the world based on the global burden of disease. CHD morbidity and mortality data for 2006, 2011, and 2016 were collected from the Institute for Health Metrics and Evaluation Global Burden of Disease Results Tool and analysed longitudinally to assess trends in excess morbidity and mortality. Between 2006 and 2016, a 20.7% reduction in excess disability-adjusted life years and 20.6% reduction in excess deaths due to CHDs were observed for children under 15. In 2016, excess global morbidity and mortality due to CHDs remained high with 14,788,418.7 disability-adjusted life years and 171,761.8 paediatric deaths, respectively. In total, 90.2% of disability-adjusted life years and 91.2% of deaths were considered excess. This study illustrates the unmet need of congenital cardiac care around the world. Progress has been made to reduce morbidity and mortality due to CHDs but remains high and largely treatable around the world. Limited academic attention for global paediatric cardiac care magnifies the lack of progress in this area.


Antagonistic properties of two recombinant strains of Streptomyces melanosporofaciens obtained by intraspecific protoplast fusion.
Intraspecific protoplast fusion was used to produce stable prototrophic recombinants of Streptomyces melanosporofaciens EF-76, a biocontrol agent of plant disease producing geldanamycin. Two recombinant strains (FP-54 and FP-60) that differed with regard to their antagonistic properties against Bacillus cereus ATCC 14579, Streptomyces scabies EF-35 and Phytophthora fragariae var. rubi 390 were characterized. FP-60 lost the ability to inhibit the in vitro growth of these microbial strains while FP-54 exhibited higher antagonistic activities against them. FP-60 was deficient in geldanamycin biosynthesis whereas FP-54 was shown to produce, in addition to geldanamycin, at least two other antimicrobial compounds that were absent in the culture supernatants of strain EF-76. Like the wild-type strain EF-76, strain FP-54 reduced common scab symptoms on potato tuber but no significant difference was observed between the disease index attributed to tubers treated with strain EF-76 or with strain FP-54. Strain FP-60 showed no protective effect against common scab. The disease index of tubers treated with this recombinant was worse than the index associated with potato tubers from control treatments.


Acute urinary retention caused by OVHIRA syndrome.
Obstructed hemivagina and ipsilateral renal anomaly (OVHIRA) syndrome is a congenital urogenital malformation that associates a bifid uterus with a longitudinal vaginal septum, resulting in a blind hemivagina and an ipsilateral renal agenesis. The clinical presentation is highly variable, delaying diagnosis and leading to important complications. An 18-year-old woman was diagnosed with OVHIRA syndrome following acute urinary retention. An agenesis in the left-sided renal system and an enormous pelvic mass compressing the adjacent structures were revealed in the intravenous urography. Nuclear magnetic resonance was the imaging modality that provided most diagnostic information, defining the pelvic mass as a giant left hematometrocolpos contained with a longitudinal vaginal septum. Resection of the septum was performed draining all reduced hematic content and both hemiuteri communicated with a single vagina, resulting in an asymptomatic patient. OVHIRA syndrome is a little known entity that can occur atypically, which makes the diagnosis difficult and delays the treatment. It is important to maintain a high degree of clinical suspicion to avoid irreversible complications.


False positive reaction for carboxyhemoglobin in blood from liver tissue.
On spectrophotometric determination of carboxyhemoglobin in blood collected from the liver of three bodies at three days post-mortem, false positive results were found (5--15 per cent saturation), since samples of heart blood collected a few hours after death did not contain carboxyhemoglobin.


Cost-minimization analysis of alternative diagnostic approaches in a modeled patient with non-small cell lung cancer and subcarinal lymphadenopathy.
To evaluate the costs of alternative diagnostic evaluations of enlarged subcarinal lymph nodes (SLNs) in modeled patients with non-small cell lung cancer (NSCLC). A cost-minimization model was used to compare 5 diagnostic approaches in the evaluation of enlarged SLNs in modeled patients with NSCLC. Values for the test performance characteristics and prevalence of malignancy in patients with SLN were obtained from the medical literature. The target population was adult patients known or suspected to have NSCLC with SLNs with a short axis length of at least 10 mm on thoracic computed tomography (CT). The lowest-cost diagnostic work-up was by initial evaluation with endoscopic ultrasonography-guided fine-needle aspiration (EUS FNA) biopsy ($11,490 per patient) compared with mediastinoscopy (with biopsy) ($13,658), transbronchial FNA biopsy ($11,963), CT-guided FNA biopsy ($13,027), and positron emission tomography ($12,887). The results were sensitive to rate of SLN metastases and EUS FNA sensitivity. The EUS FNA biopsy remained least costly if the probability of SLN metastases exceeded 24% or EUS FNA sensitivity was higher than 76%. Primary mediastinoscopy was the most economical if not. Which testing strategy is least costly for SLN evaluation in a modeled patient with NSCLC may be determined by the pretest probability of nodal metastases. Use of EUS FNA biopsy minimizes the cost of diagnostic evaluation in most cases.


Nitrate assimilation in coexisting vascular plants in mire and swamp forest habitats in Central Sweden.
In order to monitor the nitrate assimilation capability of mire plants, in vivo current and maximally induced nitrate reductase activity (NRA) were investigated in 14 species of vascular plants from four different sites in a central Swedish mire. One of the sites was a swamp forest. The plants studied included species with both wide and restricted ecological ranges, and the mire sites selected covered a wide range of plant productivity. At the most productive site, current NRA differed among coexisting species. This differentiation in the use of nitrate as a source of nitrogen suggested the possibility of resource partitioning with regard to nitrogen acquisition. Maximally induced NRA, measured 3 days after an addition of nitrate, was highest at the most productive sites and differed among coexisting species. Plant species characteristic of rich fens had the highest maximally induced NRA. In all species, there was a positive correlation between the ability to assimilate peaks of available nitrate and total leaf nitrogen concentration.


Evaluación semicuantitativa de gliomas cerebrales en adultos: un enfoque de las características neuropatológicas.
Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. To develop a semi-quantitative scale to numerically grade gliomas morphological characteristics. A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.


Observer-based control for nonlinear parameter-varying systems: A sum-of-squares approach.
This paper investigates the design problem of nonlinear and time-varying observer-based controllers for nonlinear parameter-varying systems without/with input constraints. With the aid of Lyapunov stability theory, the state-and-parameter-dependent linear matrix inequality conditions are obtained. These conditions are developed as convex programming problems. And a feasible solution can be obtained via sum-of-squares techniques. Thus, the commonly used backstepping/iterative methods are avoided. In addition, the effect of the bilinear product forms for the controller gain matrix and the Lyapunov functional are eliminated. A remarkable advantage of this proposed approach is that the state-and-parameter-dependent observer and the state-feedback controller can be designed independently, which significantly reduces the computational complexity. Finally, the feasibility and validity of the proposed method can be illustrated by simulation results.


Serrulatane diterpenoids from the leaves of Eremophila glabra and their potential as antihyperglycemic drug leads.
Eremophila (Scrophulariaceae) is a genus of Australian desert plants, which have been used by Australian Aboriginal people for various medicinal purposes. Crude extracts of the leaf resin of Eremophila glabra (R.Br.) Ostenf. showed α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values of 19.3 ± 1.2 μg/mL and 11.8 ± 2.1 μg/mL, respectively. Dual α-glucosidase/PTP1B high-resolution inhibition profiling combined with HPLC-PDA-HRMS and NMR were used to isolate and identify the compounds providing these activities. This resulted in isolation of seven undescribed serrulatane diterpenoids, eremoglabrane A-G, together with nine previously identified serrulatane diterpenoids and flavonoids. Three of the serrulatane diterpenoids showed PTP1B inhibitory activities with IC50 values from 63.8 ± 5.8 μM to 104.5 ± 25.9 μM.


Building immunization decision-making capacity within the World Health Organization European Region.
A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provides evidence-based recommendations to policy-makers, assisting them in making sound immunization policy and programme decisions. The World Health Organization (WHO) Regional Office for Europe is working to strengthen the capacity of newly-established NITAGs and has targeted efforts on low- and middle-income countries. The Regional Office, in collaboration with WHO Headquarters and USA Centers for Disease Control and Prevention (CDC), developed a new training strategy and held training workshops to improve NITAGs' functioning and ability to make evidence-based recommendations. Feedback from countries that participated in trainings indicated that the updated training materials and interactive approach with follow-up technical support enabled them to align their NITAG charters and processes with WHO recommendations. To ensure continued progress, global and regional partners such as WHO and CDC should continue providing technical support to recently established NITAGs.


Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy.
We sought to illustrate improvement of cerebral white matter changes in metachromatic leukodystrophy after treatment with hematopoietic stem cell transplant (HSCT). We conducted serial magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) as standard follow-up after HSCT with cord blood in 1 patient with juvenile metachromatic leukodystrophy diagnosed before frank degenerative symptoms developed. We measured MRI and 1H-MRS changes. The white matter changes first increased after HSCT, then decreased in relation to the pre-HSCT MRI and 1H-MRS. Hematopoietic stem cell transplant, if performed early in metachromatic leukodystrophy, can not only stabilize but even improve cerebral white matter abnormalities. Our findings suggest a biological effect of HSCT.


Content Validation of the Athletic Training Milestones: A Report from the Association for Athletic Training Education Research Network.
The Athletic Training Milestones were developed as a comprehensive framework to assess athletic trainers' knowledge, skill, and behavior acquisition across the continuum of athletic training practice. However, without established content validity, it is unclear whether the Athletic Training Milestones can be used effectively as a clinical evaluation and research tool to evaluate competence and performance across multiple users and sites. We conducted a highly conservative content validity index (CVI) with data from 12 content experts. Our findings revealed an extremely high overall scale CVI of 0.99, and CVI scores of the 28 individual subcompetency items assessed ranged from 0.83 to 1.00. For the athletic training profession to truly embrace competency-based evaluation and performance assessments, we need a highly valid and comprehensive instrument, such as the Athletic Training Milestones.


Characterization and potential of three temperature ranges for hydrogen fermentation of cellulose by means of activity test and 16s rRNA sequence analysis.
A series of standardized activity experiments were performed to characterize three different temperature ranges of hydrogen fermentation from different carbon sources. 16S rRNA sequences analysis showed that the bacteria were close to Enterobacter genus in the mesophilic mixed culture (MMC) and Thermoanaerobacterium genus in the thermophilic and hyper-thermophilic mixed cultures (TMC and HMC). The MMC was able to utilize the glucose and cellulose to produce methane gas within a temperature range between 25 and 45 °C and hydrogen gas from 35 to 60°C. While, the TMC and HMC produced only hydrogen gas at all temperature ranges and the highest activity of 521.4mlH2/gVSSd was obtained by TMC. The thermodynamic analysis showed that more energy is consumed by hydrogen production from cellulose than from glucose. The experimental results could help to improve the economic feasibility of cellulosic biomass energy using three-phase technology to produce hythane.


Donor-host Lymphatic Anastomosis After Murine Lung Transplantation.
Establishing lung lymphatic drainage is thought to be important for successful lung transplantation. To date, there has been a complete absence of knowledge of how lymphatic connections are reestablished after lung transplant, despite evidence suggesting that this does indeed occur. The present study aimed to elucidate whether and how lymphatic anastomosis occurs after lung transplant. An orthotopic murine model of lung transplant using lymphatic reporter mice and whole mount immunohistochemistry was used to evaluate the lymphatic vasculature and donor-host connections after lung transplantation. Immunohistochemistry of transplanted lungs demonstrated robust lymphatic vessels, and functional assays demonstrated lymphatic drainage in the transplanted lung that was comparable with that in native lungs. Lymphatic vessels in the donor lung exhibited active sprouting toward the host at the anastomosis within the first 3 days after lung transplantation, with more numerous and complex lymphatic sprouting developing thereafter. Donor lymphatic vessels were numerous at the site of anastomosis by day 14 after lung transplantation and formed physical connections with host lymphatic vessels, demonstrating a mechanism by which lymphatic drainage is reestablished in the transplanted lung. Lymphatic drainage after lung transplantation is established by active sprouting of donor lymphatic vessels towards the host and the formation of donor-host lymphatic connections at the level of the transplant anastomosis.


Mapping schizophrenic negative symptoms onto measures of the patient's speech: set correlational analysis.
We describe a system designed to assess the speech behaviors that inform clinicians about their patients' negative symptoms. Measures are formed into scales to reflect the patient's Pausing, Speech Rate, and Dyadic Interaction with the interviewer. Using set correlation, we examined the associations between the acoustic scales and the clinician's ratings of Flat Affect, Alogia, and Asociality. Over half of the multivariance in the clinical scales was accounted for by the acoustic scales. Unique isomorphisms between the acoustic and rating scales were found for: Dyadic Interaction with Flat Affect; Pause Production with Alogia; and Rate with Asociality.


Stereoselective synthesis of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol derivatives that are highly selective alpha-L-fucosidase inhibitors.
N-Phenylaminomethyl benzimidazolyl moieties attached at C-2 of (2S,3S,4R,5S)-5-methylpyrrolidine-3,4-diol increase the potency and selectivity of the inhibitory activity of these systems towards alpha-L-fucosidases.


Echocardiographic evaluation of wheelchair-bound basketball players.
Cardiopulmonary function in sedentary men whose lower limbs have been immobilized for years has been shown to be markedly lower than normal. However, the cardiopulmonary function of paraplegics who regularly activate their upper limps and trunk has been suggested to be almost normal in a few studies. The purpose of the present study was to evaluate the left ventricular dimensions, left ventricular mass, systolic and diastolic function in adolescent wheelchair-bound basketball players using echocardio-graphy, and to compare the results with those of sedentary adolescents unable to use their lower extremities and the results of able bodied controls. The study group consisted of 22 male adolescent high school students who were unable to use their lower extremities: 11 were members of a high school basketball team who had been regularly playing basketball for at least 2 years, and 11 were sedentary adolescents none of whom was engaged in any kind of routine training program. The control group consisted of 11 healthy able-bodied male adolescents of similar age. There were no significant differences in left ventricular dimensions and wall thickness, aortic root, left atrium diameters, or left ventricular filling characteristics between the three groups. Wheelchair-bound basketball players had increased left ventricular ejection fraction and shortening fraction compared with the sedentary unable-bodied individuals. Although left ventricular ejection fractions were significantly lower than in normal adolescents, all ejection fraction values except one were within the normal limits in the unable-bodied basketball players. The results of the present study suggest that an upper extremity exercise program and sports such as basketball can improve the cardiac functions and additional echocardiographic functions of people unable to use their lower extremities, potentially to normal levels.


A Rare Case of Basal Cell Adenocarcinoma of Parotid Gland with Intracranial Extension.
Basal cell adenocarcinoma (BCAC) is a rare tumour entity. Despite its tendency to be infiltrative and destructive tumour with propensity to recur, it rarely metastasizes and long-term outcome following surgery is favourable. This paper presents a 42-year-old male with residual BCAC of parotid gland that had extended into infratemporal fossa and intracranial. The important aspect of this case is the rarity occurrence of BCAC of parotid with intracranial extension and its surgical approaches to achieve tumour clearance.


Calcium independence of phosphoinositide hydrolysis-induced increase in cyclic AMP accumulation in SK-N-SH human neuroblastoma cells.
Previous work has shown that stimulation of muscarinic receptors in various cell lines increases intracellular cyclic AMP (cAMP) levels. This unusual response has been hypothesized to be mediated by stimulation of calcium/calmodulin-sensitive adenylate cyclase, secondary to inositol trisphosphate (IP3)-mediated calcium mobilization. To test this hypothesis, we stimulated muscarinic receptors in SK-N-SH human neuroblastoma cells while blocking the IP3-mediated rise in intracellular calcium concentration using two different methods. Loading cells with the intracellular calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) abolished the carbachol-mediated intracellular calcium release without abolishing the carbachol-mediated increase in cAMP level. Similarly, in cells preexposed to carbachol, the agonist-induced change in intracellular calcium level was blocked, but the cAMP response was not. Thus, both of these methods failed to block the muscarinic receptor-mediated increase in cAMP level, thereby demonstrating that this cAMP level increase is not mediated by a detectable rise in intracellular calcium concentration.


The Orientation of Social Support measure.
In this study we proposed and tested the theory that behavior is affected by the orientation of the members of one's social network. We collected data from 98 women (some drug users) with the Orientation of Social Support (OSS) scale and two other widely used measures: the Social Support Questionnaire (SSQ), and the Multidimensional Scale of Perceived Social Support (MSPSS). Drug use was measured with the Addiction Severity Index (ASI). Pairwise correlations showed that the OSS had no correlation with the SSQ or the MSPSS. Subjects' ASI scores were regressed on the three measures of support. The only variable that entered stepwise regression was the OSS scale. This study confirmed our theory that it is important to examine the orientation of and not just the extent of social support. The paper provides the questionnaire and the scoring procedures for measurement of extent of peer pressure.


Combating photoaging with percutaneous collagen induction.
Medical clinicians are used to being consulted by patients who want to restore their youthful appearance. Although structural changes to the face and body may be achieved with surgery, for example, face lifts, the impression of youth also relies heavily on young-looking skin. It is desirable to have thicker and tighter skin to properly fulfill the desire for youth. Percutaneous collagen induction offers an antiaging effect to improve the appearance of old skin. It allows us to improve our patients' skin from the inside outward as well as from the surface. Experience has shown that percutaneous collagen induction works optimally when combined with a scientific skin care program to restore a youthful appearance. In addition, the same technique has proven to be very effective in minimizing acne scars and burn scars by removing scar collagen and replacing it with normal collagen. Consequently, scar contractures and depressed scars are improved. With the introduction of percutaneous collagen induction therapy in 1997, a simple and fast method was developed with regard to safely treating wrinkles and scars and producing lasting smoothness. As opposed to ablative laser treatments, the epidermis remains intact and is not damaged. For this reason, the operation can be safely repeated if needed, and it can be also applicable to regions where laser treatments or deep peelings cannot be done.


Overthinking skilled motor performance: or why those who teach can't do.
Skilled athletes often maintain that overthinking disrupts performance of their motor skills. Here, we examined whether these experiences have a basis in verbal overshadowing, a phenomenon in which describing memories for ineffable perceptual experiences disrupts later retention. After learning a unique golf-putting task, golfers of low and intermediate skill either described their actions in detail or performed an irrelevant verbal task. They then performed the putting task again. Strikingly, describing their putting experience significantly impaired higher skill golfers' ability to reachieve the putting criterion, compared with higher skill golfers who performed the irrelevant verbal activity. Verbalization had no such effect, however, for lower skill golfers. These findings establish that the effects of overthinking extend beyond dual-task interference and may sometimes reflect impacts on long-term memory. We propose that these effects are mediated by competition between procedural and declarative memory, as suggested by recent work in cognitive neuroscience.


[An autopsy case of double cancer (Hepatocellular carcinoma and mixed germ cell tumor of the testis)--significance of alpha-fetoprotein and human chorionic gonadotropin as tumor markers].
A 43-year-old male suffering from liver cirrhosis was admitted with complaints of general malaise and anorexia. Admission laboratory data evidenced high levels of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). Histopathologically, the resected left testis and supraclavicular enlarged lymph nodes revealed mixed germ cell tumor. After castration, the serum HCG level normalized, but AFP continued to increase. Autopsy findings did not unequivocally show mixed germ cell tumor, however, massive type hepatocellular carcinoma was present. These findings suggest that the hepatocellular carcinoma produced AFP, while the mixed germ cell tumor produced HCG.


Characterisation of metabolites after the microbial degradation of A- and B-trichothecenes by BBSH 797.
This work deals with the characterisation of trichothecene metabolites after the microbial degradation by the bacterial strain BBSH 797. Besides deoxynivalenol (DON), also the degradation of other trichothecenes was investigated. In the case of nivalenol, its metabolite deepoxy nivalenol could be identified. Useful methods for the structural characterisation are GC-MS or LC-PB-MS which were used in this particular case.


Increased cortical excitability induced by transcranial DC and peripheral nerve stimulation.
This study investigated the effect of short periods of simultaneous weak anodal direct current (DC) stimulation and peripheral ulnar nerve (ES) stimulation on corticospinal excitability. The experiments involved repeated testing of ten normal subjects with four different protocols: (1) No Stimulation; (2) DC only; (3) ES only; (4) DC plus ES. Motor evoked potentials (MEP) were recorded from the First Dorsal Interosseous (FDI); Abductor Digiti Minimi (ADM) and Flexor Carpi Ulnaris (FCU). The baseline MEP amplitude was compared with that obtained immediately after the first set of stimulation, after the second set of stimulation, 15 min post stimulation and 30 min after stimulation. No significant change was seen with the No Stimulation and ES Only protocols. FDI showed a significant change in the DC protocol after the second set of stimulation but the changes were not present 15 or 30 min after. The DC plus ES protocol showed FDI changes that were significant after the second set of stimulation with the elevations persisting when tested 15 and 30 min post intervention. These observations show that a period of anodal DC stimulation preceding a period of ulnar nerve stimulation resulted in significant and persistent elevations in cortical excitability.


Access to Improved Water Sources and Sanitation in Minority Ethnic People in Vietnam and Some Sociodemographic Associations: A 2019 National Survey.
Achieving access to clean water and basic sanitation remains as major challenges in Vietnam, especially for vulnerable groups such as minority people, despite all the progress made by the Millennium Development Goal number 7.C. The study aimed to describe the access to improved water sources and sanitation of the ethnic minority people in Vietnam based on a national survey and to identify associated factors. A cross-sectional study was conducted in 2019 with a sample size of 1385 ethnic minority households in 12 provinces in Vietnam. Multivariate logistic regression modeling was performed to examine the probability of having access to improved water sources and sanitation and sociodemographic status at a significance level of P < .05. The access to improved water sources and sanitation was unequal among the ethnic minority people in Vietnam, with the lowest access rate in the northern midland and mountainous and Central Highland areas and the highest access rate in the Mekong Delta region. Some sociodemographic variables that were likely to increase the ethnic minority people's access to improved water sources and/or sanitation included older age, female household heads, household heads with high educational levels, religious households, and households in not poor status. The study suggested more emphasis on religion for improving the ethnic minority's access to improved water sources and sanitation. Besides, persons of poor and near-poor status and with low educational levels should be of focus in future water and sanitation intervention programs.


Blockade of interleukin-6 receptor suppresses inflammatory reaction and facilitates functional recovery following olfactory system injury.
We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in an olfactory nerve injury model. Clinically, however, steroid administration is not recommended in the acute phase of head injury because of concerns regarding side effects and no evidence of its efficacy. Recently, it has been reported that interleukin-6 (IL-6) plays an important role in the inflammatory reaction. The present study investigates if anti-IL-6 receptor (IL-6R) antibody can facilitate functional recovery in the olfactory system following injury. Rat anti-mouse IL-6R antibody (MR16-1) was intraperitoneally injected to severe olfactory nerve injury model mice immediately after the nerve transection (NTx). Histological assessment of recovery within the olfactory bulb was made at 5-70 days. X-gal staining labeled the degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. MR16-1-injected animals showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential testing showed improved functional recovery in MR16-1-injected mice. These findings suggest that blockade of IL-6R could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.


Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.
Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.


mPEGylated solanesol micelles as redox-responsive nanocarriers with synergistic anticancer effect.
We prepared an amphiphilic redox-responsive conjugate based on mPEGylated solanesol, solanesyl poly(ethylene glycol) dithiodipropionate (SPDP), along with its inert counterpart solanesyl poly(ethylene glycol) succinate (SPGS), which self-assembled in aqueous solution to form redox-responsive micelles. Used as efficient drug carriers for doxorubicin (DOX), the micelles acted as synergistic agents for cancer therapy. Dynamic light scattering (DLS) measurements showed that the SPDP micelles had average diameters of 111nm, which decreased to 88nm after the encapsulation of DOX. The mean diameters and size distribution of the disulfide-containing micelles changed obviously in the presence of the reducing agent glutathione (GSH), whereas no changes occurred in the case of redox-insensitive SPGS micelles. DOX could be loaded into both types of micelles, with drug loading content of about 4.0%. A significantly accelerated release of DOX was triggered by GSH for DOX-loaded SPDP micelles, compared with DOX-loaded SPGS micelles. Blank SPGS and SPDP micelles displayed higher inhibition of HeLa and MCF-7 cell proliferation but less cytotoxicity to normal L-02 cells at similar concentrations. Confocal microscopic observation indicated that a greater amount of DOX was delivered into the nuclei of cells following 9 or 12h incubation with DOX-loaded micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded SPDP micelles over free DOX and DOX-loaded SPGS micelles. All of the data presented here suggested that these SPDP micelles may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs. Various nanoscale drug carriers were used to enhance therapeutic effect of many drugs. While, the metabolites of high quantities of carriers may cause additional short- or long-term toxicities. In this study, a new systems based on solanesol derivatives was developed for anticancer drug delivery. There are two features for this system. One is solanesol originated bioactivity of the carrier, which will synergistically facilitate therapeutic effect of the encapsulated drug. The other is the redox-responsive drug release behavior adaptable to the glutathione-rich atmosphere of tumor cell. All the hypothesis have been elucidated in this work through in vitro and in vivo studies. It was found that this drug delivery system may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs.


Differentiation between cancerous and normal hyperplastic lobules in breast lesions.
Determining the risk that a particular area of hyperplastic breast tissue will progress to cancer is difficult and is currently expressed only as a general risk factor within the population. Using an antibody against the apoptotic purinergic receptor P2X7, we examined 40 cases each of the following histological categories: normal, moderate, florid and atypical hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive lobular and invasive ductal carcinoma. These were previously diagnosed by H&E and supplied by clinical laboratories as tissue sections. Normal and mildly hyperplastic epithelium was devoid of the cytolytic P2X7 receptors whereas all epithelial cells in all cases of in situ or invasive lobular or ductal carcinoma labelled intensely. The lobular and ductal in situ cases labelled intracellularly while the invasive epithelial cancer cells showed intense cell surface label indicating an attempt was being made to induce apoptosis. All these receptors however are non-functional and thus unable to induce apoptosis. Approximately 10% of all hyperplastic lobules examined in the biopsied tissue, regardless of H&E classification, labelled for P2X7, which is suggestive of early metabolic cancerous change. The acini within lobules were either completely labelled with P2X7 or were completely devoid of the receptor. A potential advantage of this method lies in identifying early cancerous change in hyperplastic lobules and in establishing the true extent of cancerous spread in infiltrating lesions, thus facilitating the task of reporting clear surgical margins.


Evaluation of antitussive potential of Ionidium suffruticosam Ging. (Violaceae) extract in albino mice.
The present study was carried out to evaluate the antitussive potential of methanol extract of Ionidium suffruticosam Ging. (Violaceae) which was investigated for its effect on a cough model induced by sulfur dioxide gas in albino mice. It exhibited significant dose-dependent antitussive activity when compared with the control, 250 and 500 mg/kg (p.o.) of the extract showing 28.37% and 54.16% inhibition of the cough with respect to control group. The antitussive activity of the extract was comparable to that of codeine phosphate, a prototype antitussive agent.


Restoration of elbow extension power in the tetraplegic patient using the Moberg technique.
In tetroplegic patients extensor power can be restored to the elbow by transferring the posterior deltoid muscle to the triceps aponeurosis. Thirteen patients representing 14 posterior deltoid muscle transfers were evaluated 13.8 months later. Using a 0 to 5 muscle grading system, the average preoperative muscle grade for elbow extension power was 0.5. After operation the average had increased to 3.6. All patients were satisfied with their results and noted a significant improvement in the activities of daily living. In no case was there a loss of preoperative functional capacity.


Histopathological assessments reveal retinal vascular changes, inflammation, and gliosis in patients with lethal COVID-19.
The purpose of this study is to assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the SARS-CoV-2 infection. Eyes from seven COVID-19-positive and six similar age-matched control donors with a negative test for SARS-CoV-2 were assessed. Globes were evaluated ex vivo with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for Epon embedding and immunocytochemistry. Fundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the controls. OCT-based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes; however, the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples. In situ analysis of the retinal tissue suggests that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.


Risk factors for lung infection in stroke patients: a meta-analysis of observational studies.
The aims of this meta-analysis were to evaluate the risk factors associated with lung infections in stroke patients and to provide evidence for prevention decisions. We searched the Embase, PubMed, EBSCO and Web of Science databases to collect studies from January 2000 to July 2015. The meta-analysis identified 23 risk factors for lung infections in stroke patients, and the top 5, ranked by order according to odds ratio values (95% confidence interval), were as follows: multiple vertebrobasilar stroke, 22.99 (4.04, 130.83); National Institutes of Health Stroke Scale score >15 points, 14.63 (8.54, 25.08); mechanical ventilation, 10.20 (7.15, 14.57); nasogastric tube use, 9.87 (6.21, 15.70); and dysphagia, 7.50 (2.60, 21.65). Preventive measures should be taken against these risk factors to reduce the incidence of lung infection.


Infectivity and sporogony of Caryospora-type oocysts of Isospora rivolta obtained by heating.
The infectivity and sporogony of Caryospora-type oocysts of Isospora rivolta obtained by heat treatment were examined. Fresh unsporulated oocysts of I. rivolta were heated at 50 degrees C for 5 min, then poured into a cold 2% potassium dichromate solution and incubated at 25 degrees C. To observe the stage of sporulation, 100 oocysts were examined at 2-h intervals after incubation. The earliest sporulated oocysts were observed at 14 h and the sporulation time was 22 h, similar to that of nontreated oocysts. To determine the infectivity, only Caryospora-type oocysts were collected after sporulation and inoculated orally into cats and mice. The mice were killed at 7 days after inoculation, and their mesenteric lymph nodes and spleens were fed to other cats. All of these cats shed oocysts. The newly discharged oocysts developed into the Isospora type after sporulation. These results suggest that the Caryospora-type oocysts transformed only morphologically after heat treatment and were as infective as the nontreated oocysts to host animals.


The Feasibility of Ultrasonography in Defining the Size of Jaw Osseous Lesions.
Jaw bone lesions are common pathologic conditions. The role of ultrasonography in evaluation of the extra-osseous lesions is confirmed, however, this imaging modality is not the diagnostic routine for the intra-osseous jaw lesions. The purpose of this study was to evaluate the efficiency of ultrasonography in diagnosis of intra-osseous jaw lesions concerning their size and content and also to study its correlation with the histopathological findings. For this study, 15 patients with intra-osseous jaw lesions in the maxilla and mandible were selected from those referred to the Department of Oral Surgery. Panoramic imaging, computed tomography (CT) or cone beam computed tomography (CBCT) and ultrasonography (USG) were performed for all the lesions. The size of the lesions was measured by USG and then compared with CT or CBCT. Moreover, the correlation amongst the echographic patterns and histopathologic results was evaluated. In 12 cases, size values were in complete agreement with CT or CBCT. The size of 3 lesions could not be measured by the radiologist due to the thickness of buccal cortical plate. Findings of this study suggested that USG might be feasible in estimating the size of intra-osseous jaw lesions with little underestimation. This study also confirmed that ultrasound imaging was a very useful imaging technique which could provide significant diagnostic information regarding the content of jaw bone lesions where the buccal bone thickness was thin enough.


SSBP1 drives high fructose-induced glomerular podocyte ferroptosis via activating DNA-PK/p53 pathway.
High fructose consumption is a significant risking factor for glomerular podocyte injury. However, the causes of high fructose-induced glomerular podocyte injury are still unclear. In this study, we reported a novel mechanism by which high fructose induced ferroptosis, a newly form of programmed cell death, in glomerular podocyte injury. We performed quantitative proteomic analysis in glomeruli of high fructose-fed rats to identify key regulating proteins involved in glomerular injury, and found that mitochondrial single-strand DNA-binding protein 1 (SSBP1) was markedly upregulated. Depletion of SSBP1 could alleviate high fructose-induced ferroptotic cell death in podocytes. Subsequently, we found that SSBP1 positively regulated a transcription factor p53 by interacting with DNA-dependent protein kinase (DNA-PK) and p53 to drive ferroptosis in high fructose-induced podocyte injury. Mechanically, SSBP1 activated DNA-PK to induce p53 phosphorylation at serine 15 (S15) to promote the nuclear accumulation of p53, and thereby inhibited expression of ferroptosis regulator solute carrier family 7 member 11 (SLC7A11) in high fructose-exposed podocytes. Natural antioxidant pterostilbene was showed to downregulate SSBP1 and then inhibit DNA-PK/p53 pathway in its alleviation of high fructose-induced glomerular podocyte ferroptosis and injury. This study identified SSBP1 as a novel intervention target against high fructose-induced podocyte ferroptosis and suggested that the suppression of SSBP1 by pterostilbene may be a potential therapy for the treatment of podocyte ferroptosis in glomerular injury.


Validation of the B3LYP/N07D and PBE0/N07D Computational Models for the Calculation of Electronic g-Tensors.
Calculations on a large set of free radicals containing atoms of the second and third row show that the computational model defined by the new N07D basis set and hybrid density functionals (B3LYP and PBE0) provides remarkably accurate g-tensor values at reasonable computational costs. Since in previous works it has been shown that the same computational model delivers reliable results also for structural parameters and hyperfine couplings, the route seems paved toward full a priori computation of EPR spectra of large free radicals both in vacuo and in condensed phases.


Anatomical evaluation of facial nerve pathways and dissection of "premasseter space" for rhytidectomy in Asians.
Partial detachment of the superficial musculoaponeurotic system (SMAS) by dissection of the premasseter space (PMS) is an option for enhancing the effectiveness of SMAS-based rhytidectomy. The aim of this study was to identify the underlying cause of the potential risk of motor nerve impairment sometimes caused by PMS dissection and to consider the effective use of PMS dissection, especially in Asians. Detailed dissection was carried out on six fixed Japanese cadavers to evaluate facial nerve pathways around the PMS. The anterior wall of the PMS was opaque because each face exhibited fibers of various thicknesses within and around the anterior border of the masseter. The ascending ramifications of the buccal trunk ran through the fibers, outside the anterior border of the masseter in some faces but within it in others. This study revealed the presence of a danger zone when dissecting the PMS in Asians. Severing the fibers that fix the SMAS to the masseter fascia around the anterior border of the masseter is sometimes unavoidable to attain good mobility of the SMAS. Surgeons must be mindful of the fibers near the anterior border of the masseter because they may be outside the PMS and contain buccal trunk ramifications; the anterior wall of the PMS tends to be opaque in Asians. Nonetheless, the extent of PMS dissection should be determined on an individual basis. The present findings may help to reduce relevant risks in Asian patients and standardize procedures for effective rhytidectomy. This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors at www.springer.com/00266.


Nickel and iron-based metal-organic frameworks for removal of organic and inorganic model contaminants.
Metal-organic frameworks (MOFs) are a promising class of porous nanomaterials in the field of environmental remediation. Ni-MOF and Fe-MOF were chosen for their advantages such as structural robustness and ease of synthesis route. The structure of prepared MOFs was characterized using FE-SEM, XRD, FTIR, and N2 adsorption-desorption. The efficiency of MOFs to remove organic model contaminants (anionic Alizarin Red S (ARS) and cationic malachite green (MG) and inorganic fluoride was studied. Fe-MOF and Ni-MOF adsorbed 67, 88, 6% and 32, 5, and 9% of fluoride, ARS, and MG, respectively. Further study on ARS adsorption by Fe-MOF showed that the removal efficiency was high in a wide range of pH from 3 to 9. Moreover, dye removal was directly increased by adsorbent mass (0.1-0.75 g/L) and decreased by ARS concentration (25-100 mg/L). The pseudo-first-order kinetic model and Langmuir isotherm model with a qmax of 176.68 mg/g described the experimental data well. The separation factor, KL, was in the range of 0-1, which means the adsorption process was favorable. In conclusion, Fe-MOF showed remarkable adsorption of organic and inorganic model contaminants.


Spontaneous zona reaction in the mouse as a limiting factor for the time in which an oocyte may be fertilized.
This study evaluated the effect of ovum aging on the in vitro fertilizability of mouse ova. Over 1347 ova were evaluated. Serial trypsin digestion of in vitro and in vivo aged ova revealed an increase in zona digestion time (0.25% trypsin) beginning at 40 hr, which increased over a 40-hr period and resulted in the unfertilized zona becoming as "hard" as the fertilized embryo zona. In vitro fertilizability showed a rapid decrease as zona hardening occurred with loss of cortical granules as assessed by electron microscopy. These data suggest that the window of fertilizability is "closed" by a spontaneous zona reaction occurring at about 55 hr post-human chorionic gonadotropin with loss of cortical granules and zona hardening as manifested by increasing zona digestion time with 0.25% trypsin.


Association of urinary monomethylated arsenic concentration and risk of hypertension: a cross-sectional study from arsenic contaminated areas in northwestern China.
Although some studies mainly from Taiwan, Bangladesh and the United States, have suggested a consistent dose-response increase in the prevalence of hypertension with increasing arsenic exposure, the association between chronic environmental arsenic exposure and the risk of hypertension is still inconclusive. Most of the studies discussed the association from the point of view of arsenic concentration in drinking water or cumulative arsenic exposure (CAE), few involved arsenic speciation into the discussion. In this cross-sectional study, we evaluated the potential association between environmental arsenic exposure through drinking water and the prevalence of hypertension by analyzing not only CAE but also urinary arsenic speciation, and provided data on arsenic exposure and hypertension from mainland of China. A cross-sectional study was conducted in one of the arsenic contaminated areas in the northwest of China. Among a total of 1005 residents who voluntarily participated in the study, 604 of eligible subjects were confirmed and interviewed door to door. Standing height, body weight, and blood pressure were measured. First void urine was collected and measured for the concentration of urinary arsenic speciation. CAE was calculated in a subpopulation of 360 subjects with detailed water consumption history. The association between urinary arsenic speciation, CAE and the risk of hypertension were analyzed by multiple logistic regressions. We found that the levels of urinary arsenic species of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (tAs) were significantly correlated with systolic or pulse blood pressure. A positive relationship was found between the highest tertile of CAE and hypertension in a dose-dependent manner. Subjects with higher concentration of urinary MMA or lower percentage of DMA tended to be liable to suffer from hypertension. A significant increasing trend of the risk of hypertension with increasing tertiles of MMA concentration was also observed in the logistic regression models both before and after adjustment for confounders. Our findings suggested that arsenic exposure, especially high level of CAE, was positively associated with the prevalence of hypertension, and that higher concentration of urinary MMA might be related to the increased susceptibility to hypertension.


Simple method for preparing superhydrophobic paper: spray-deposited hydrophobic silica nanoparticle coatings exhibit high water-repellency and transparency.
Superhydrophobic and transparent coatings are deposited onto paper by spraying alcohol suspensions of SiO(2) nanoparticles. Superhydrophobicity depends on the aggregation states of nanoparticles, which are determined by the type of alcohol used in the suspensions. The superhydrophobicity of the paper is maintained after touching the paper with a bare finger.


Predictors of motor tasks essential for daily activities among persons with heart failure.
To engage in daily activities, persons must be able to perform basic motor tasks, such as walking around the house, climbing up stairs, standing up from the sofa, and so forth. For patients with heart failure (HF), activity intolerance, symptoms of HF, muscle strength, and balance contribute to the "ability" to perform daily activities. Many patients with HF reported that they are able to perform motor tasks, but they modify how they do the tasks. The purpose of the study was to identify factors that predict modification in motor tasks essential to daily activities. Forty-eight men and 54 women aged more than 18 years (mean 59.6 years) were recruited from an outpatient HF clinic. By using hierarchic multiple regression, 90% of the variance in modifications in motor tasks (Late Life Function and Disability Instrument-Function component) was explained, and significant predictors were dyspnea with motor tasks (beta = 0.87), age (beta = 0.12), and gender (beta = 0.11). Older women had significantly greater modifications in these tasks than men. Modifications of motor tasks may provide information on those at high risk of developing disability and assist clinicians to identify interventions to improve dyspnea and prevent or reverse decline.


Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-alpha-Demethylase Ihibitors.
Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3-0.5 mug/mL. The mechanism of antifungal action of these coordination compounds is probably connected to an inhibition of lanosterol-14-alpha-demethylase, a metallo-enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes.


Ageing as well as you can in place: Applying a geographical lens to the capability approach.
Despite policy commitments to support ageing in place, we know very little about the everyday realities and experiences of older people living in different environmental circumstances, with varying personal capabilities. This paper: 1) examines the valued place-based functionings of older people through the use of geo-spatial and in-situ methods, where functionings are defined as states of being and doing, and place-based functionings are defined as places, activities, interactions, routes, and routines that support these beings and doings; and 2) demonstrates the utility of a capability approach by amalgamating the interconnected concepts 'ageing in place' and 'ageing well'. Three in-depth individual experiences of ageing at home in a Dublin (Ireland) suburb show how differing health and mobility challenges are managed, and illustrate how conceptions of ageing well in place can be identified from geographically-grounded lifeworlds. Participants' place-based functionings are identified by combining qualitative and geo-spatial approaches through the use of annotated maps, using data obtained from traditional interviews, go-along interviews, and mapping exercises. Results demonstrate the diversity of place-based functionings valued by each individual, and how functionings are negotiated depending on different needs, wishes, and health or mobility challenges. Results also highlight the importance of supportive environments and social supports in enabling older people to realise their most valued functionings over time, which include being able to get out and about, engage and connect with others, carry out daily tasks and errands confidently, and remain independent. By paying attention to subjectively valued place-based functionings, as well as the specific supports required to sustain them, we can facilitate older people to not just age in place, or age well, but to age - as well as they can - in place.


2-(2-phenylethyl)chromones from Chinese eaglewood.
2-(2-Phenylethyl) chromones and a 2-(2-phenylethenyl) chromone, were isolated from the ethanolic extract of Chinese eaglewood. Their structures were determined on the basis of extensive analyses of spectroscopic data. Among those, one showed significant neuroprotective activities against both glutamate-induced and corticosterone-induced neurotoxicity in P12 pheochromocytoma and human U251 glioma cells at a concentration of 10 μM and increased cell viability by 82.2% and 86.9%, respectively.


Bipolar disorder in the Bulgarian Gypsies: genetic heterogeneity in a young founder population.
We report the results of follow-up analyses of 12 genomic regions showing evidence of linkage in a genome-wide scan (GWS) of Gypsy families with bipolar affective disorder (BPAD). The Gypsies are a young founder population comprising multiple genetically differentiated sub-isolates with strong founder effect and limited genetic diversity. The BPAD families belong to a single sub-isolate and are connected by numerous inter-marriages, resulting in a super-pedigree with 181 members. We aimed to re-assess the positive GWS findings and search for evidence of a founder susceptibility allele after the addition of newly recruited subjects, some changes in diagnostic assignment, and the use of denser genetic maps. Linkage analysis was conducted with SimWalk2, accommodating the full complexity of pedigree structure and using a conservative narrow phenotype definition (BPAD only). Six regions were rejected, while 1p36, 13q31, 17p11, 17q21, 6q24, and 4q31 produced nominally significant results in both the individual families and the super-pedigree. Haplotypes were reconstructed and joint tests for linkage and association were done for the most promising regions. No common ancestral haplotype was identified by sequencing a strong positional and functional candidate gene (GRM1) and additional STR genotyping in the top GWS region, 6q24. The best supported region was a 12 cM interval on 4q31, also implicated in previous studies, where we obtained significant results in the super-pedigree using both SimWalk2 (P = 0.004) and joint Pseudomarker analysis of linkage and linkage disequilibrium (P = 0.000056). The size of the region and the characteristics of the Gypsy population make it suitable for LD mapping.


Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates.
It is well established that gonadal hormonal manipulation results in morphologic changes in the rat hippocampus. The great similarities in the hippocampal formation between nonhuman primates and humans, as well as the differences in this structure between humans and rats, led to this investigation of whether hormonal manipulation in female subhuman primates influences pyramidal cell spine density in the CA1 hippocampal subfield, as it does in rats. African green monkeys (Cercopithecus aethiops sabaeus) were ovariectomized, and half of the animals received estrogen replacement therapy. One month later, the monkeys were killed. In the first group of experiments, pyramidal cell spines were analyzed on Golgi-impregnated material taken from the CA1 hippocampal subfield. In the second experiment, unbiased electron microscopic stereologic calculations were performed to estimate the volumetric density of spine synapses in the same hippocampal subfield. Analysis of the Golgi-impregnated material showed that the spine density of CA1 pyramidal cells is much lower in the ovariectomized animals than in ovariectomized and estrogen-replaced monkeys. The unbiased, electron microscopic, stereologic calculation confirmed the light microscopic observation. The volumetric density (number of spine synapses/microm(3)) of spine synapses was significantly lower (43.33%) in the ovariectomized animals than in ovariectomized and estrogen-replaced monkeys. Because the hippocampus is involved in specific mnemonic functions, this observation highlights the importance of hormone replacement therapy in postmenopausal conditions.


Evidence for prejunctional alpha- and beta-adrenoceptors in the canine saphenous vein: influence of frequency of stimulation and external calcium concentration.
Most studies of adrenergic neurotransmission have utilized 3H-labeled transmitter-preloaded isolated tissues. The present study has employed a radioenzymatic assay to measure field-stimulated endogenous norepinephrine overflow from the canine saphenous vein preparation. The presence of prejunctional alpha- and beta-adrenoceptors was documented in experiments conducted at two frequencies of stimulation (1 and 5 Hz) and three external calcium concentrations (1.25, 2.5, and 5 mM). There was a direct relationship between frequency of stimulation or external calcium concentration and per pulse norepinephrine overflow. Diminution of stimulated norepinephrine overflow in the presence of clonidine (10(-6) M) was taken as evidence for prejunctional alpha-adrenoceptors. Enhanced overflow in the presence of isoproterenol (10(-6) M) was evidence for prejunctional beta-adrenoceptors. The effects of these alpha- and beta-adrenergic agonists were partially reversed by antagonists, phentolamine (10(-6) M) and propranolol (10(-6) M), respectively. The influence of clonidine or isoproterenol on stimulated norepinephrine overflow was inversely related to frequency of stimulation and external calcium concentration. Enhanced stimulated norepinephrine overflow in the presence of phentolamine is evidence for negative feedback prejunctional alpha-adrenoceptor tone in the canine saphenous vein.


EEG and intelligence: relations between EEG coherence, EEG phase delay and power.
There are two inter-related categories of EEG measurement: 1, EEG currents or power and; 2, EEG network properties such as coherence and phase delays. The purpose of this study was to compare the ability of these two different categories of EEG measurement to predict performance on the Weschler Intelligence test (WISC-R). Resting eyes closed EEG was recorded from 19 scalp locations with a linked ears reference from 442 subjects aged 5-52 years. The Weschler Intelligence test was administered to the same subjects but not while the EEG was recorded. Subjects were divided into high IQ (> or = 120) and low IQ (< or = 90) groups. EEG variables at P<.05 were entered into a factor analysis and then the single highest loading variable on each factor was entered into a discriminant analysis where groups were high IQ vs. low.Q. Discriminant analysis of high vs. low IQ was 92.81-97.14% accurate. Discriminant scores of intermediate IQ subjects (i.e. 90 < IQ < 120) were intermediate between the high and low IQ groups. Linear regression predictions of IQ significantly correlated with the discriminant scores (r = 0.818-0.825, P < 10(-6)). The ranking of effect size was EEG phase > EEG coherence > EEG amplitude asymmetry > absolute power > relative power and power ratios. The strongest correlations to IQ were short EEG phase delays in the frontal lobes and long phase delays in the posterior cortical regions, reduced coherence and increased absolute power. The findings are consistent with increased neural efficiency and increased brain complexity as positively related to intelligence, and with frontal lobe synchronization of neural resources as a significant contributing factor to EEG and intelligence correlations. Quantitative EEG predictions of intelligence provide medium to strong effect size estimates of cognitive functioning while simultaneously revealing a deeper understanding of the neurophysiological substrates of intelligence.


A comparison of endocrine pancreatic tissue in adults of four species of lampreys in British Columbia: a morphological and immunohistochemical study.
Histological techniques and immunohistochemistry with antisera against insulin and somatostatin were used in a study of the identification and the distribution of endocrine pancreatic tissue in adults of four species of lampreys in British Columbia. The fine structure of the pancreatic cells of one of the species was also examined. The four species (Lampetra ayresi, Lampetra tridentata, Lampetra macrostoma, and Lampetra richardsoni) all possess cranial and caudal pancreatic masses and an intervening intermediate cord, but there are variations in amount and deposition of the pancreatic tissue with respect to the alimentary canal and the liver which appear to be species specific. There is also some variation in the distribution of pancreatic tissue between L. richardsoni of different stream populations. A newly identified parasitic variety of L. richardsoni in Morrison Creek, called L. richardsoni var. marifuga, usually has no cranial pancreas but has an extensive intermediate cord. The distribution of pancreatic tissue in these lampreys is of relevance to taxonomy and to variations in development of the endocrine pancreas during lamprey metamorphosis. The pancreatic tissue of all species and var. marifuga is composed of cells which are immunoreactive to either insulin or somatostatin antisera. The fine structure of cells from the cranial and caudal pancreatic tissue from L. ayresi does not vary with saltwater and freshwater acclimation. Insulin-containing B cells and somatostatin-containing D cells are present in equal numbers in both pancreatic regions and the cells each have characteristic cytoplasmic granules. A third cell type is most abundant in the cranial pancreas but it is of unknown function.


Synthesis and evaluation of antifungal activity of C21-steroidal derivatives.
The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034 μM, respectively.


Reappraising the evolutionary history of the largest known gecko, the presumably extinct Hoplodactylus delcourti, via high-throughput sequencing of archival DNA.
Hoplodactylus delcourti is a presumably extinct species of diplodactylid gecko known only from a single specimen of unknown provenance. It is by far the largest known gekkotan, approximately 50% longer than the next largest-known species. It has been considered a member of the New Zealand endemic genus Hoplodactylus based on external morphological features including shared toe pad structure. We obtained DNA from a bone sample of the only known specimen to generate high-throughput sequence data suitable for phylogenetic analysis of its evolutionary history. Complementary sequence data were obtained from a broad sample of diplodactylid geckos. Our results indicate that the species is not most closely related to extant Hoplodactylus or any other New Zealand gecko. Instead, it is a member of a clade whose living species are endemic to New Caledonia. Phylogenetic comparative analyses indicate that the New Caledonian diplodactylid clade has evolved significantly more disparate body sizes than either the Australian or New Zealand clades. Toe pad structure has changed repeatedly across diplodactylids, including multiple times in the New Caledonia clade, partially explaining the convergence in form between H. delcourti and New Zealand Hoplodactylus. Based on the phylogenetic results, we place H. delcourti in a new genus.


Associations between diet and health behavior: results from the 1992 Rhode Island Behavioral Risk Factor Survey.
The 1992 Rhode Island Behavioral Risk Factor Surveillance System was used to assess self-reported health behaviors of consumers of finfish and raw shellfish. We hypothesized that consumers of finfish, foods considered to be healthy, were more likely than nonconsumers of finfish to partake in health-promoting behaviors. Similarly, we postulated that consumers of raw molluscan shellfish, foods linked to an elevated risk of acquiring various illnesses, were more likely than nonconsumers of raw-shellfish to partake in risk-taking behaviors. Finfish eaters were significantly more likely than abstainers to report recent exercise, efforts to lose weight, periodic monitoring of serum cholesterol, and not currently being smokers. Raw shellfish eaters were significantly more likely than abstainers to report recent acute and chronic alcohol consumption. The results suggest that inquiry into dietary patterns may be an avenue for exploring other health behaviors.


Chemical composition and methane yield of reed canary grass as influenced by harvesting time and harvest frequency.
This study examined the influence of harvest time on biomass yield, dry matter partitioning, biochemical composition and biological methane potential of reed canary grass harvested twice a month in one-cut (OC) management. The regrowth of biomass harvested in summer was also harvested in autumn as a two-cut management with (TC-F) or without (TC-U) fertilization after summer harvest. The specific methane yields decreased significantly with crop maturity that ranged from 384 to 315 and from 412 to 283 NL (normal litre) (kgVS)(-1) for leaf and stem, respectively. Approximately 45% more methane was produced by the TC-F management (5430Nm(3)ha(-1)) as by the OC management (3735Nm(3)ha(-1)). Specific methane yield was moderately correlated with the concentrations of fibre components in the biomass. Larger quantity of biogas produced at the beginning of the biogas assay from early harvested biomass was to some extent off-set by lower concentration of methane.


Therapeutic drug monitoring in Italian psychiatry.
Therapeutic drug monitoring (TDM) aims to optimize pharmacotherapy treatment. Knowledge, availability and use of TDM for psychiatric patients, however, differ between countries. In this survey we analysed the practice in Italy of TDM for psychoactive drugs. A semi-structured questionnaire was sent out to 211 mental health centres (centro di salute mentale) and 10 university hospitals from each region in Italy. Feedback was obtained from 44 centres. Information collected by the questionnaires indicated that in Italian psychiatry TDM is used for lithium, valproic acid and carbamazepine. With regard to clozapine, TDM was regarded as the blood cell counting which is obligatory when prescribing this drug. TDM was not employed for antidepressant or antipsychotic drug prescribing. Moreover, it appeared that only a few laboratories in Italy offer TDM services for psychiatric patients. Nevertheless, interest was expressed about receiving further information about TDM in psychiatry and participating in training programmes. This nationwide survey revealed that in Italy, TDM of psychoactive drugs is restricted to only a few drugs. In response to interest expressed, mental health workers should be educated about TDM and more laboratories should be encouraged to establish TDM services for psychotropic drugs.


Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum.
In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of preterm delivery, hemorrhage, and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The messenger RNA (mRNA) encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly up-regulated molecule in PAS samples. Overexpression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up-regulate a cancer-like proinvasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.


Cesarean delivery for abnormal labor.
Cesarean delivery is indicated at any stage in the labor process in the presence of nonreassuring fetal status or when conservative measures fail in the setting of abnormal labor. In the absence of maternal or fetal indications for expedited delivery, cesarean delivery is not indicated for latent phase disorders. When to intervene for protracted labor is arguable, but slow rates of labor progress are consistent with safe vaginal delivery. Cesarean delivery in the second stage should be avoided for at least 4 hours if there is progressive fetal descent.


Tautomeric mixture coordination enables efficient lead-free perovskite LEDs.
Lead halide perovskite light-emitting diodes (PeLEDs) have demonstrated remarkable optoelectronic performance1-3. However, there are potential toxicity issues with lead4,5 and removing lead from the best-performing PeLEDs-without compromising their high external quantum efficiencies-remains a challenge. Here we report a tautomeric-mixture-coordination-induced electron localization strategy to stabilize the lead-free tin perovskite TEA2SnI4 (TEAI is 2-thiopheneethylammonium iodide) by incorporating cyanuric acid. We demonstrate that a crucial function of the coordination is to amplify the electronic effects, even for those Sn atoms that aren't strongly bonded with cyanuric acid owing to the formation of hydrogen-bonded tautomeric dimer and trimer superstructures on the perovskite surface. This electron localization weakens adverse effects from Anderson localization and improves ordering in the crystal structure of TEA2SnI4. These factors result in a two-orders-of-magnitude reduction in the non-radiative recombination capture coefficient and an approximately twofold enhancement in the exciton binding energy. Our lead-free PeLED has an external quantum efficiency of up to 20.29%, representing a performance comparable to that of state-of-the-art lead-containing PeLEDs6-12. We anticipate that these findings will provide insights into the stabilization of Sn(II) perovskites and further the development of lead-free perovskite applications.


Lengthening of the ulna in radial agenesis: a preliminary report.
In two patients with bilateral radial agenesis, the ulnas were divided and lengthened in a modified Abbott-Anderson device with a gear box controlled by an electric motor to obtain from one to 2 mm. per day of gradual distraction. Three centimeters of length was achieved in 3 weeks. Bone bridged the gap in 3 months and was mature in 6 months. Repeat osteotomy and lengthening was done 12 to 18 months later. All secondary lengthening operations required bone grafts. Total length gained ranged from 5.4 to 6.4 cm.


Transmission rate of Ureaplasma urealyticum, Mycoplasma spp., Gardnerella vaginalis, B-streptococci, Candida spp. and Chlamydia trachomatis from the mother to the newborn.
In a preliminary study of the transmission rate of Ureaplasma urealyticum, Mycoplasma species, Gardnerella vaginalis, B-Streptococci, Candida species and Chlamydia trachomatis from the mother to the newborn, swabs were taken from 45 parturients and their neonates and cultured by suitable methods. Out of 30 parturients with a positive culture, 8 harboured more than one microorganism investigated. U. urealyticum was found in 11 newborn and all of them had a positive mother. Candida spp. were found in 4 newborn, but 3 of these had a negative mother. G. vaginalis was detected in only 1 infant and the mother was negative. C. trachomatis was not isolated from any mother but was present in 2 newborn infants. Thus only U. urealyticum showed clear evidence of transmission from mother to baby.


Genetic diversity of Mycobacterium tuberculosis complex isolates circulating in an area with high tuberculosis incidence: Using 24-locus MIRU-VNTR method.
We aimed to determine the genetic diversity, phylogenetic relationship and transmission dynamics of Mycobacterium tuberculosis complex (MTBC) genotypes in an area with high tuberculosis (TB) incidence. A set of 164 MTBC isolates from new TB patients of Golestan province, Iran, were subjected to genotyping using the standard 24-locus MIRU-VNTR method. Recent TB transmission was evaluated and phylogenetic relationships were analysed by minimum spanning tree and cluster-graph methods. Among the 164 isolates, 132 distinct patterns were detected. The 48 clustered isolates (29.3%) were distributed into 16 clusters ranging in size from 2 to 12 isolates. The most frequent genotype was Central Asian Strain/Delhi (CAS/Delhi) (n = 67, 40.8%), followed by NEW-1 (n = 53, 32.3%) and Beijing (n = 19, 11.6%) genotypes. Thirty five (72.9%) of NEW-1 isolates were recovered from immigrant patients and 84.2% (n = 16) of Beijing genotypes recovered from native cases. Statistically significant association was found between clustering and smoking (p = 0.047), drug addiction (p = 0.01) and prison history (p = 0.003). The estimated proportion of recent transmission was 19.5%. Presence of highly diverse MTBC isolates circulating in this province without a dominant genotype might be a consequence of importation of various genotypes in this area.


Forecasting of AQI (PM2.5) for the three most polluted cities in India during COVID-19 by hybrid Daubechies discrete wavelet decomposition and autoregressive (Db-DWD-ARIMA) model.
Air pollution has emerged as a significant environmental challenge at the global level, and India is majorly affected by it. Numerous emission sources, such as automobiles, industries, fuel-burning for household and commercial activities, and dust due to construction activities, are responsible for air pollution. The lockdown in India which was clamped for controlling the spread of virulent disease also brought down the level of pollutants in air significantly. The proposed approach deals with the application of the hybrid model of Daubechies discrete wavelet decomposition (Db-DWD) and the autoregressive integrated moving average (ARIMA) model for modeling and forecasting the chaotic data of air quality index (PM2.5) from the three most polluted cities (Agra, New Delhi, and Varanasi) in India for pre and within lockdown periods. The estimated outputs of the component series are then reconstructed to obtain the final forecast of the AQI data. The statistical evaluation compares the performance of the simple ARIMA model and the joint Db-DWD-ARIMA model. Also, the coupled model has been applied for forecasting efficacy with Daubechies mother wavelet of orders 5, 8, 10, and 12. The hybrid model reduced forecasting errors and improved accuracy significantly. Secondly, the forecasting efficiencies in this hybrid model have enhanced with the increase in wavelet order. This study will help to assess and take appropriate steps to control air pollution levels and to monitor the growing air pollutants, which will be significant for our existence.


Characteristics and expression profiles of MHC class Ⅰ molecules in Carassius auratus.
Major histocompatibility complex class Ⅰ (MHC Ⅰ) molecules play a vital role in adaptive immune systems in vertebrates by presenting antigens to effector T cells. Understanding the expression profiling of MHC Ⅰ molecules in fish is essential for improving our knowledge of the relationship between microbial infection and adaptive immunity. In this study, we conducted a comprehensive analysis of MHC Ⅰ gene characteristics in Carassius auratus, an important freshwater aquaculture fish in China that is susceptible to Cyprinid herpesvirus 2 (CyHV-2) infection. We identified approximately 20 MHC Ⅰ genes discussed, including U, Z, and L lineage genes. However, only U and Z lineage proteins were identified in the kidney of Carassius auratus using high pH reversed-phase chromatography and mass spectrometry. The L lineage proteins were either not expressed or present at an extremely low level in the kidneys of Carassius auratus. We also used targeted proteomics to analyze changes in protein MHC Ⅰ molecules abundance in healthy and CyHV-2-infected Carassius auratus. We observed that five MHC Ⅰ molecules were upregulated, and Caau-UFA was downregulated in the diseased group. This study is the first to reveal the expression of MHC Ⅰ molecules at a large scale in Cyprinids, which enhances our understanding of fish adaptive immune systems.


Functionalization and higher-order organization of liposomes with DNA nanostructures.
Small unilamellar vesicles (SUVs) are indispensable model membranes, organelle mimics, and drug and vaccine carriers. However, the lack of robust techniques to functionalize or organize preformed SUVs limits their applications. Here we use DNA nanostructures to coat, cluster, and pattern sub-100-nm liposomes, generating distance-controlled vesicle networks, strings and dimers, among other configurations. The DNA coating also enables attachment of proteins to liposomes, and temporal control of membrane fusion driven by SNARE protein complexes. Such a convenient and versatile method of engineering premade vesicles both structurally and functionally is highly relevant to bottom-up biology and targeted delivery.


Electrocardiographic abnormalities in patients with heart failure.
The morbidity and mortality from heart failure (HF) differ between patients with reduced (< 50%) and with preserved ( >or= 50%) left ventricular ejection fraction (LVEF) on account of many factors, including abnormalities detected in the electrocardiogram (ECG). The aim of this study was to determine and compare the ECG abnormalities between HF patients with reduced and with preserved LVEF. The study was cross-sectional in design and carried out in Aminu Kano teaching hospital and Murtala Mohammed specialist hospital, Kano, Nigeria, from April 2005 to June 2006. We studied the resting electrocardiograms of all HF patients aged 15 years and older who were referred to the two centres for echocardiography. A total of 113 patients were studied and 98.2% of them had abnormal ECGs. Forty-two patients (37.2%) had preserved LVEF while the remaining 71 (62.8%) had reduced LVEF. Left ventricular hypertrophy (LVH) was the commonest ECG abnormality, found among 55 patients (77.5%) with reduced LVEF, and 21 patients (50%) with preserved LVEF (p = 0.0026). The commonest arrhythmia was atrial fibrillation, found among 10 patients (14.1%) with reduced LVEF and eight patients (19.1%) with preserved LVEF (p = 0.486). Prolonged corrected QT interval was found among 30 (71.4%) and 56 patients (78.9%) with preserved and reduced LVEF, respectively (p 5 0.370). Most of the patients with heart failure studied in Kano, Nigeria had abnormal electrocardiograms, and the most common abnormality was LVH.


Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells.
Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy drug for ACC. Mitotane induces adrenal cortex necrosis, mitochondrial membrane impairment, and irreversible binding to CYP proteins. In this study, we explored the molecular effect of mitotane on steroidogenesis in human adrenocortical cancer NCI-H295 cells. Mitotane (10-40μM) inhibited basal and cAMP-induced cortisol secretion but did not cause cell death. Mitotane exhibited an inhibitory effect on the basal expression of StAR and P450scc protein. Furthermore, 40μM of mitotane significantly diminished StAR, CYP11A1 and CYP21 mRNA expression. HSD3B2 and CYP17 seem to be insensitive to mitotane. The stimulatory effects of mitotane on CYP11B1 were more remarkable than its inhibitory effects. In contrast, the activation of cAMP signaling strongly elevated the expression of all these genes. Mitotane (40μM) almost completely neutralized this positive effect and returned 8-Br-cAMP-induced StAR, CYP11A1, CYP17 and CYP21 mRNA to control levels. After cAMP activation, mitotane did not change the levels of CYP11B1 mRNA. The present study demonstrates that mitotane can inhibit cortisol biosynthesis due to a non-specific interference with the gene transcription of steroidogenic enzymes under both basal and 8-Br-cAMP-activated conditions in NCI-H295 cells. We also identified that StAR and CYP11A1 key enzymes that participate in the rate-limiting step of steroidogenesis, were more sensitive to mitotane. In addition, the biphasic effect of mitotane on CYP11B1 was also elucidated.


Adult identity mentoring: reducing sexual risk for African-American seventh grade students.
This study was undertaken to determine whether the Adult Identity Mentoring (AIM) project successfully promotes abstinence, delays initiation of sex, and decreases intention to engage in sex. Twenty middle school classes of African-American seventh graders were randomly assigned to receive either the AIM intervention or a standard health education control curriculum. The AIM is a 10-session curriculum based on the theory of possible selves. Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills. Surveys about sexual activity were conducted before the intervention, 19 weeks after baseline, and again at 1 year after the intervention. Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions, abstinence, and a trend toward fewer virgins initiating intercourse for the first time, 19 weeks after baseline. Specifically, students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention. Effects for 1-year follow-up, with smaller sample size, showed only that AIM male participants maintained the significant abstinence effect. A new intervention, AIM was evaluated among African-American seventh graders. This program, by focusing students on positive future selves, effectively modified sexual risk without directly providing instruction on sexually explicit topics.


Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced arthritis in DBA/1 mice.
Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1β and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted β-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.


Case report: A novel pathogenic FRMD7 variant in a Turner syndrome patient with familial idiopathic infantile nystagmus.
Infantile idiopathic nystagmus (IIN) is an oculomotor disorder characterized by involuntary bilateral, periodic ocular oscillations, predominantly on the horizontal axis. X-linked IIN (XLIIN) is the most common form of congenital nystagmus, and the FERM domain-containing gene (FRMD7) is the most common cause of pathogenesis, followed by mutations in GPR143. To date, more than 60 pathogenic FRMD7 variants have been identified, and the physiopathological pathways leading to the disease are not yet completely understood. FRMD7-associated nystagmus usually affects male patients, while it shows incomplete penetrance in female patients, who are mostly asymptomatic but sometimes present with mild ocular oscillations or, occasionally, with clear nystagmus. Here we report the first case of a patient with Turner syndrome and INN in an XLIIN pedigree, in which we identified a novel frameshift mutation (c.1492dupT) in the FRMD7 gene: the absence of one X chromosome in the patient unmasked the presence of the familial genetic nystagmus.