A defective Vkappa A2 allele in Navajos which may play a role in increased susceptibility to haemophilus influenzae type b disease.
The antibody response to H. influenzae type b (Hib) is pauciclonal, and is dominated by antibodies using the VkappaA2 gene. Navajos have a 5-10-fold increased incidence of Hib disease compared with control populations. We hypothesized that a polymorphism in one of the genes in this oligoclonal response may lead to increased disease susceptibility. Since the predominant A2+ anti-Hib antibodies have high avidity for Hib and can be unmutated, the A2 Vkappa gene was analyzed. Over half of the Navajos studied, but only one control individual, had a new allele of A2, termed A2b, with three changes from the published A2 germline sequence. One of the changes was in the recombination signal sequence, suggesting that the A2b allele might not undergo V-J rearrangement very frequently. This possibility was confirmed by analyzing the relative frequency of non-productive A2 rearrangements in A2a/b heterozygous Navajos. Many fewer A2b rearrangements were observed, showing that the A2b allele is defective in its ability to undergo rearrangement. The prevalence of this allele in Navajos may play a role in their increased susceptibility to invasive Hib disease. If so, it would underscore the importance of the germline Ig repertoire for protective antibody responses to pathogenic bacteria in unimmunized children.


Periodontal considerations in prosthodontic treatment.
This paper reviews the relationship of periodontics to restorative dentistry. Specific emphasis is placed on the relationship of the restorative margin to the periodontium and the frequent need to alter the placement of the gingival margin so that the restoration will be constructed on sound tooth structure. The prognosis of the sectioned multirooted tooth and other alternatives of treating a shortened dental arch are considered. However, all treatment modalities conclude that a compliant patient and a strong periodontal maintenance program are integral to success, which, with a coordinated effort by the periodontist and the restorative dentist, best assures a successful long-term dental treatment.


Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes.
Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are increasingly recognized as valuable for determining the effects of drugs on ion channels but they do not always accurately predict contractile responses of the human heart. This is in part attributable to their immaturity but the sensitivity of measurement tools may also be limiting. Measuring action potential, calcium flux or contraction individually misses critical information that is captured when interrogating the complete excitation-contraction coupling cascade simultaneously. Here, we develop an hypothesis-based statistical algorithm that identifies mechanisms of action. We design and build a high-speed optical system to measure action potential, cytosolic calcium and contraction simultaneously using fluorescent sensors. These measurements are automatically processed, quantified and then assessed by the algorithm. Multiplexing these three critical physical features of hiPSC-CMs allows identification of all major drug classes affecting contractility with detection sensitivities higher than individual measurement of action potential, cytosolic calcium or contraction.


STEAP4, a gene associated with insulin sensitivity, is regulated by several adipokines in human adipocytes.
We previously identified a six-transmembrane epithelial antigen of the prostate (STEAP) 4 as a novel plasma membrane protein that is downregulated in obese patients and may play a significant role in the development of human obesity. This study was designed to identify the biological characteristics of the STEAP4 gene in human adipocytes. On the basis of oil red O staining and the expression profiles of specific markers, we demonstrated that overexpression of STEAP4 did not affect adipogenesis. 2-Deoxy-D-[3H]-glucose uptake tests showed that STEAP4 promoted insulin-stimulated glucose uptake in mature human adipocytes. Further data from quantitative real-time RT-PCR and Western blotting revealed that the adipokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4. Our results demonstrate that STEAP4 does not influence human adipocyte differentiation, but it participates in regulating the insulin sensitivity of human adipocytes.


Phosphite translocation in soybean and mechanisms of Phytophthora sojae inhibition.
Although phosphite (Phi)-based fertilizers are used in large quantities in agriculture, the use of Phi-based fungicides against soybean root rot caused by Phytophthora sojae are limited. While, their low toxicity are of high ecological and economic focus. Limited attention has been paid to Phi translocation efficiency in soybeans and the efficacy of Phi as a fungicide against P. sojae. In this study, we evaluated the efficiency of Phi translocation in the Williams soybean cultivar by determining the Phi concentrations in roots, stems, and leaves using high-performance ion chromatography after the application of Phi to the roots. Phi was translocated from roots to leaves within 1 h and its concentration increased significantly in leaves within 36 h after Phi application. Results of an in vitro growth inhibition assay and an in vivo infection assay showed that Phi inhibited P. sojae. Additionally, we examined the activation of the salicylic acid (SA) and ethylene (ET) defense pathways by Phi. The expression of SA and ET pathway-related genes was upregulated in most soybean tissues after Phi application. Our results provide evidence that Phi translocation suppresses root rot caused by P. sojae in soybean.


Silencing of heat shock protein 70 expression enhances radiotherapy efficacy and inhibits cell invasion in endometrial cancer cell line.
To investigate the role of heat shock proteins 70 (HSP70) in radiosensitivity and invasiveness of endometrial cancer in vitro. HSP70 expression was silenced in relatively radioresistant, well-differentiated human endometrial cancer cell line ISK, using small interference RNA method, or by HSP70 overexpression after transfecting a HSP70-expressing vector. The effect of HSP70 on ISK cell line response to irradiation was evaluated. The surviving fraction was measured using colony-formation assay. Apoptosis was detected by flow cytometry and HSP70 expression was determined by quantitative real-time polymerase chain reaction, western-blot, and/or immunocytochemistry. Cell invasiveness was measured using transwell invasion assay. HSP70 silencing caused a significant increase in irradiation-induced cell killing in comparison with control cells, with an enhancement factor of 1.27, and in the percentage of apoptotic cells (14.22% vs 6.74%, P = 0.021). After 4 Gy irradiation, mean +/- standard deviation survival fraction in ISK cells was reduced to 0.32 +/- 0.04 in comparison with control values but in ISK/siRNA-HSP70 cells the survival fraction was higher and amounted to 0.51 +/- 0.08 (P = 0.026). Silencing HSP70 significantly inhibited cell invasion before and after irradiation (106 +/- 19 vs 219 +/- 18 and 119 +/- 16 vs 256 +/- 31, P = 0.007). On the contrary, ectopic overexpression of HSP70 attenuated irradiation-induced apoptosis (7.15% vs 4.08%, P = 0.043) and induced more ISK/HSP70 cells invaded through the filters than mock-infected cells before and after irradiation (274 +/- 21 vs 194 +/- 16 before irradiation, and 298 +/- 24 vs 227 +/- 19 after irradiation, respectively, P = 0.032). Disruption of HSP70-induced cytoprotection during irradiation enhances therapeutic effect of irradiation, which makes HSP70 a promising target in the research of endometrial cancer.


[Comparison between AngII receptor antagonist and ACE inhibitor].
Angiotensin II(AII) accelerates the progress of cardiovascular diseases. This was proved by the fact that the blockade of renin-angiotensin system provided clinical benefits for patients with cardiovascular diseases. This review focuses on the differences between AT1-receptor antagonist and ACE inhibitor in basic and clinical aspects. Beside decreased AII concentration, increased tissue bradykinin concentration may contribute to the beneficial effect of ACE inhibitor, on the other hand, this increases the rate of cough to decrease the compliance. Increased AII concentration by AII receptor antagonist may antagonize the binding of the drug as well as stimulate AT2 receptor subtype. ACE inhibitor can not block the effect of non-ACE AII formation, but AII receptor does. These differences should be considered for their clinical use.


Serum from heifer calves treated with bovine growth hormone affects the rate of proliferation of C2C12 myogenic cells dependent on the plane of nutrition: the role of insulin-like growth factor-I and IGF-binding proteins-2 and -3.
The present in vitro experiments were carried out in order to study whether variations in the bovine growth hormone (bGH)/insulin-like growth factor (IGF)-I axis induced by plane of nutrition and bGH treatment of heifer calves caused variations in serum-induced proliferation of C2C12 myoblasts. Serum was obtained from two groups each of six heifer calves (195 +/- 8 kg) before (d -1) and after treatment with 15 mg/day of bGH for 6 days (d 6) fed either a low (GHL) or a high plane (GHH) of nutrition. Preceding the experiment all 12 heifer calves were fed at the low plane of nutrition. At d 6, serum concentrations of insulin and IGF-I were increased while that of IGF-binding proteins (IGFBP)-2 was decreased in GHH, but unchanged in GHL calves. Serum-induced proliferation of C2C12 myoblasts, was elevated at d 6 by GHH treatment. Especially human IGFBP-3 but also bovine IGFBP-2 added to cell cultures inhibited the rate of proliferation of C2C12 myoblasts stimulated by human IGF-I. The present results showed that GH treatment causes changes in the GH/IGF axis, which leads to changes in serum-induced growth of C2C12 muscle cells dependent on the plane of nutrition that mimic in vivo effects of GH treatment, which indicate an endocrine contribution of the IGF system. However, drawbacks of this suggestion are discussed.


A comprehensive platform for quality control of botanical drugs (PhytomicsQC): a case study of Huangqin Tang (HQT) and PHY906.
Establishing botanical extracts as globally-accepted polychemical medicines and a new paradigm for disease treatment, requires the development of high-level quality control metrics. Based on comprehensive chemical and biological fingerprints correlated with pharmacology, we propose a general approach called PhytomicsQC to botanical quality control. Incorporating the state-of-the-art analytical methodologies, PhytomicsQC was employed in this study and included the use of liquid chromatography/mass spectrometry (LC/MS) for chemical characterization and chemical fingerprinting, differential cellular gene expression for bioresponse fingerprinting and animal pharmacology for in vivo validation. A statistical pattern comparison method, Phytomics Similarity Index (PSI), based on intensities and intensity ratios, was used to determine the similarity of the chemical and bioresponse fingerprints among different manufactured batches. Eighteen batch samples of Huangqin Tang (HQT) and its pharmaceutical grade version (PHY906) were analyzed using the PhytomicsQC platform analysis. Comparative analysis of the batch samples with a clinically tested standardized batch obtained values of PSI similarity between 0.67 and 0.99. With rigorous quality control using analytically sensitive and comprehensive chemical and biological fingerprinting, botanical formulations manufactured under standardized manufacturing protocols can produce highly consistent batches of products.


New quantification methods for carotid intra-plaque neovascularization using contrast-enhanced ultrasound.
As carotid intra-plaque neovascularization (IPN) is linked to progressive atherosclerotic disease and plaque vulnerability, its accurate quantification might allow early detection of plaque vulnerability. We therefore developed several new quantitative methods for analyzing IPN perfusion and structure. From our analyses, we derived six quantitative parameters-IPN surface area (IPNSA), IPN surface ratio (IPNSR), plaque mean intensity, plaque-to-lumen enhancement ratio, mean plaque contrast percentage and number of micro-vessels (MVN)-and compared these with visual grading of IPN by two independent physicians. A total of 45 carotid arteries with symptomatic stenosis in 23 patients were analyzed. IPNSA (correlation r = 0.719), IPNSR (r = 0.538) and MVN (r = 0.484) were found to be significantly correlated with visual scoring (p < 0.01). IPNSA was the best match to visual scoring. These results indicate that IPNSA, IPNSR and MVN may have the potential to replace qualitative visual scoring and to measure the degree of carotid IPN.


A randomized and longitudinal study of human menopausal gonadotropin with intrauterine insemination in the treatment of infertility.
To study in a randomized and longitudinal manner the efficacy of human menopausal gonadotropin (hMG) superovulation combined with intrauterine insemination (IUI) versus IUI alone in the treatment of various causes of infertility in the presence of normal ovulation. An initially randomized and subsequently longitudinal study of infertile couples was performed at a university-based clinical research center. One hundred nineteen couples with longstanding infertility (average duration 3.7 years) associated with male factor infertility, unexplained infertility, and/or endometriosis were enrolled. All patients were randomized in the initial cycle to treatment with either hMG/IUI or urine LH-timed IUI alone. They were then followed longitudinally as they alternated subsequent cycles between the two modalities. Outcome indices measured were cycle fecundity, pregnancy outcome, and cumulative pregnancy rates evaluated by life-table analysis. Human menopausal gonadotropin/IUI therapy was consistently more effective than IUI alone in the treatment of endometriosis, male factor infertility, and unexplained infertility, with cycle fecundities ranging from 7.1-19.0% versus 0-6.7%, respectively, during the first seven cycles. Human menopausal gonadotropin/IUI is a more effective therapy for enhancing fertility than is IUI alone for the treatment of endometriosis, male factor infertility, and unexplained infertility.


Minimally-invasive valve surgery.
Minimally-invasive approaches have become increasingly important in cardiac valve surgery. Smaller incisions have become commonplace in many major centers. We reviewed the existing literature and present the current state-of-the-art of minimally-invasive valve operations in this paper.


Patient safety culture and associated factors among health care professionals at public hospitals in Dessie town, north east Ethiopia, 2019.
Patient safety culture is defined as the attitudes, perceptions, and values that staffs share within an organization related to patient safety. The safety of health care is now a major global concern. It is likely that millions of people suffer disabling injuries or death directly related to medical care. Particularly in developing and transitional countries, patient harm is a global public health problem. The objective of the study is to assess patient safety culture and associated factors among health care professionals working in public hospitals in Dessie town, North East Ethiopia, 2019. Facility based quantitative study was employed from March 15 -April 30, 2019 in public hospitals in Dessie town. Four hundred and twenty two health care professionals were recruited to complete a structured pretested self-administered questionnaire. The data was cleaned, coded and entered in to Epi Info-7 and exported to SPSS version 20. Data was further analyzed using bivariate and multivariate logistic regression analyses. Variables with P value of less than 0.05 in multivariate analysis were declared as statistically significant at 95% CI. Of the 422 recruited a total of 411 participants completed the survey with a response rate of 97.4%. Close to half (184(44.8%)) of the participants indicated good patient safety culture. Good patient safety culture was positively associated with working in primary hospital (AOR = 2.56, 95% CI = 1.56, 4.21). On the other hand, good patient safety culture was negatively associated with health professional's age between 25-34 year (AOR = 0.25, 95% CI = 0.08-0.74) and working in Pediatrics ward (AOR = 0.39, 95% CI = 0.17-0.9) and in emergency ward (AOR = O.25, 95%CI = 0.09-0.67). The overall level of patient safety culture was under 50%. Good patient safety culture had positive association with working in primary hospital and negative association with professionals' age between 25-29 year, 30-34 year and working in pediatrics and emergency ward. Implementing actions that support all dimensions of safety culture should be promoted at all levels of hospitals.


Effects of Kampo herbal medicine on plasma melatonin concentration in patients.
There are studies reporting that some natural products containing melatonin. Sleep disturbance and nocturnal polyuria are related to abnormal biorhythm. It is possible that kampo medicine may influence biorhythm. We therefore examined the symptoms and plasma melatonin of patients treated with rokumi-gan, hachimi-jio-gan, gosha-jinki-gan and seishinrenshi-in. Furthermore, the concentration of four kampo medicines and crude drugs making up these formulations were investigated. Diurnal plasma melatonin was not affected by Rokumi-gan, but tended to be lowered by treatment with hachimi-jio-gan, gosha-jinki-gan and seishinrenshi-in. Melatonin was present in several extracts from crude drugs, namely Rehmanniae radix, Moutan cortex, Cinnamomi cortex, Aconiti tuber, Plantaginis semen, Scutellariae radix and Lycii radicis cortex.


Transplant outcomes in acute leukemia. II.
Currently, it is possible to find a hematopoietic stem cell (HSC) donor for virtually all patients with acute leukemia who have an indication to receive an allogeneic hematopoietic stem cell transplant (HSCT) and lack a human leukocyte antigen (HLA)-identical sibling or a well-matched HLA unrelated donor (URD). According to the ethnicity of the patients and the donor registry, approximately 25% to 60% of patients will not find an 8/8 HLA-matched unrelated donor. Other alternative donors, such as HLA-mismatched related donor or unrelated donor umbilical cord blood (UCB), have emerged to solve the lack of a sibling or well-matched URD. In the haploidentical HSCT setting, new techniques of T-cell depletion, new approaches using combinations of immunosuppressive drugs or different conditioning regimens, and developments on immunotherapy have focused attention on this option. Therefore, any physician has to carefully evaluate, for each patient in need of an allograft, all of the possible alternatives in order to choose the best HSC donor, taking into account type of disease to be transplanted, urgency of transplantation, donor characteristics, and center experience. This review evaluates the current status of haploidentical HSCT in acute leukemia, its advantages and remaining limitations compared to other stem cell sources, and how these data may be used in the development of donor selection algorithms.


The prolabial unwinding flap method for one-stage repair of bilateral cleft lip, nose, and alveolus.
This paper describes a one-stage reconstruction of the complete bilateral cleft lip, nose, and alveolus using an asymmetrically designed prolabial flap. The columella of the nose and the central lip are produced by "unwinding" the columellar and labial sections of the prolabium around a small central tab, which is used to center the junction between the lip and columella. Only two scars are produced, both of which run vertically along each philtral column. Accurate preoperative orthopedics without lip adhesion is considered essential to this repair. The principal advantage/disadvantage to the method is its asymmetrical design. If asymmetries result, they have been easily corrected. Eight consecutive cases are presented with follow-up ranging from 1.5 to 6.3 years.


Cloning and relational analysis of 15 novel fungal endoglucanases from family 12 glycosyl hydrolase.
Cellulases belong to the large family of glycosyl hydrolases (GHs) and are produced by a variety of bacteria and fungi. These extracellular enzymes act as endoglucanases (EGs), cellobiohydrolases or beta-glucosidases. In this paper, we describe molecular screening for EGs from the GH family 12. Using three homologous sequence boxes deduced from five previously known members of the family, we analysed 22 cellulase-producing fungal strains obtained from a diverse area of the fungal kingdom. Polymerase chain reactions using degenerate primers designed to the homologous protein boxes were used to identify the family 12 homologues. Several fungi showed the presence of multiple versions of the gene, while amino acid sequence analysis showed diversity in 15 novel members of the family, ranging from 26% to 96% similarity. Our sequence analysis shows that the phylogenetic tree of family 12 EGs can be divided into four subfamilies: 12-1 (fungal group I), 12-2 (fungal group II), 12-3 ( Streptomyces group in which Rhodothermus marinus fits) and 12-4 ( Thermophiles group). Erwinia carotovora may form a new subgroup.


Neurotransmitter modulation of small-conductance Ca2+-activated K+ channels by regulation of Ca2+ gating.
Small-conductance Ca2+-activated K+ (SK) channels are widely expressed in neuronal tissues where they underlie post-spike hyperpolarizations, regulate spike-frequency adaptation, and shape synaptic responses. SK channels constitutively interact with calmodulin (CaM), which serves as Ca2+ sensor, and with protein kinase CK2 and protein phosphatase 2A, which modulate their Ca2+ gating. By recording coupled activities of Ca2+ and SK2 channels, we showed that SK2 channels can be inhibited by neurotransmitters independently of changes in the activity of the priming Ca2+ channels. This inhibition involvesSK2-associated CK2 and results from a 3-fold reduction in the Ca2+ sensitivity of channel gating. CK2phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating SK2 channels. We extended these observations to sensory neurons by showing that noradrenaline inhibits SK current and increases neuronal excitability in aCK2-dependent fashion. Hence, neurotransmitter-initiated signaling cascades can dynamically regulate Ca2+ sensitivity of SK channels and directly influence somatic excitability.


Synthetic peptides of hepatitis G virus (GBV-C/HGV) in the selection of putative peptide inhibitors of the HIV-1 fusion peptide.
The GB virus C or hepatitis G virus (GBV-C/HGV) is a single-stranded positive sense RNA virus that belongs to the Flaviviridae family. Recent years have seen the publication of numerous works in which coinfection with GBV-C/HGV and HIV has been associated with slower progression of the illness and a higher survival rate of patients once AIDS has developed. The mechanism by which the GBV-C/HGV virus has a "protective effect" in patients with HIV has still not been defined. Study of the interaction of the GBV-C/HGV and HIV viruses could lead to the development of new therapeutic agents for the treatment of AIDS. Given that the mechanism responsible for the beneficial effect exercised by the GBV-C/HGV virus in the course of HIV infection has not been defined, the present work is intended as a study of the structure and interactions between the fusion peptide of HIV-1, gp41(1-23), and synthetic peptide sequences of the E2 envelope protein of GBV-C/HGV using biophysical techniques. Our results highlight that the E2(269-286) sequence interacts with the target fusion peptide of HIV-1 and modifies its conformation.


Visuomotor velocity transformations for smooth pursuit eye movements.
Smooth pursuit eye movements are driven by retinal motion signals. These retinal motion signals are converted into motor commands that obey Listing's law (i.e., no accumulation of ocular torsion). The fact that smooth pursuit follows Listing's law is often taken as evidence that no explicit reference frame transformation between the retinal velocity input and the head-centered motor command is required. Such eye-position-dependent reference frame transformations between eye- and head-centered coordinates have been well-described for saccades to static targets. Here we suggest that such an eye (and head)-position-dependent reference frame transformation is also required for target motion (i.e., velocity) driving smooth pursuit eye movements. Therefore we tested smooth pursuit initiation under different three-dimensional eye positions and compared human performance to model simulations. We specifically tested if the ocular rotation axis changed with vertical eye position, if the misalignment of the spatial and retinal axes during oblique fixations was taken into account, and if ocular torsion (due to head roll) was compensated for. If no eye-position-dependent velocity transformation was used, the pursuit initiation should follow the retinal direction, independently of eye position; in contrast, a correct visuomotor velocity transformation would result in spatially correct pursuit initiation. Overall subjects accounted for all three components of the visuomotor velocity transformation, but we did observe differences in the compensatory gains between individual subjects. We concluded that the brain does perform a visuomotor velocity transformation but that this transformation was prone to noise and inaccuracies of the internal model.


Democratic People's Republic of Korea. Population programme paves the way for better flow of and use of population information.
The population program of DPRK is currently generating census data, a number of demographic and contraceptive research studies, and various IEC materials. However, these have not been widely disseminated. At the same time, policymakers and professionals engaged in population and development activities expressed the need for more information and materials to assist them in their tasks. To address these needs, the government represented by the National Coordinating Committee for Population Programs, proposed the establishment of a Population Information Center that will facilitate the collection, processing, dissemination, and use of population information and materials in order to support the work of the population personnel. In a fact-finding and project development mission undertaken with the assistance of the UNFPA (UN Population Fund), Beijing, UNDP (UN Development Programme) Pyongyang, and CST for East and Southeast Asia Adviser on Population Information, it was agreed upon that a Population Information Center be set up at the Grand People's Study House which serves as the central document information center in the country as well as correspondence university rendering re-education programs for the working people. The project document basically lays the foundation for a nationwide population information networking by building first the centerpiece of the network. It will develop the capability of the Grand People's Study House in collecting, organizing, analyzing, repackaging and disseminating population information as well as in managing a nationwide network. Four activities will be envisaged to achieve this goal. The first requires the establishment of the Population Information Center structure and organization. The rest necessitate the collection of materials and creation of a bibliographic database, the training of personnel in various information-handling tools and techniques and service provision, and facilitating dissemination of information through a repackaging and lecture series program.


Mathematical learning difficulties and PASS cognitive processes.
This study examined the relationships between mathematical learning difficulties (MLD) and the planning, attention, simultaneous, successive (PASS) theory of cognitive processing. The Cognitive Assessment System (CAS) was used to measure the PASS processes for a group of 267 Dutch students with MLD who attended either general or special education. The results showed that students with MLD performed lower than their peers on all CAS scales and that the MLD group contained many students with cognitive weaknesses in planning or successive processing. Moreover, students who had specific difficulties with the acquisition of basic math facts, the automatization of such facts, or word-problem solving were found to have distinct PASS cognitive profiles. In order to investigate the relationships between cognitive abilities and improvement in the mastery of basic math facts and problem solving, 165 of the students with MLD were given a special multiplication intervention. It appeared that the effectiveness of this particular intervention did not differ across the groups of students with specific cognitive weaknesses.


[Gastric lipoma presenting as intestinal obstruction].
Gastric lipoma is a rare benign tumor. The symptoms are correlated with the size and the dimensions of neoplasm. It can be the cause of bleeding, gastroduodenal intussusception and intestinal obstruction, as in case reported and surgically treated. The Authors make a literature review to define the better diagnostic and surgical approach.


[Surveillance of soil-borne nematodiasis in Yancheng City from 2016 to 2020].
To understand the prevalence of soil-transmitted nematode infections in Yancheng City from 2016 to 2020, so as to provide insights into the development of the scheme for further soil-transmitted nematodiasis surveillance. Soil-borne nematode infections were detected using the modified Kato-Katz method (two slides for one sample) among the permanent residents living in Yancheng City from 2016 to 2020, and Enterobius vermicularis infection was additionally detected among children at ages of 12 years and lower using the adhesive cellophane-tape perianal swab method. The prevalence and intensity of human soil-borne nematode and E. vermicularis infections were descriptively analyzed. A total of 51 259 person-time residents were detected for soil-borne nematode infections in Yancheng City from 2016 to 2020, and 48 egg-positives were identified, with a 0.09% prevalence. The soil-borne nematodes infecting residents included Ascaris lumbricoides, hookworm and Trichuris trichiura, with 0.04%, 0.05% and 0.002% prevalence rates of infections, and all infections were mild. There was a region-specific prevalence of soil-borne nematode infections in Yancheng City (χ2 = 18.21, P = 0.02), with the highest prevalence seen in Funing County (0.21%), while no infections were detected in Dafeng District for five successive years. The overall prevalence of E. vermicularis infections was 0.22% among children at ages of 12 years and lower in Yancheng City. The prevalence of soil-borne nematode infections appears a gradual decline in residents living in Yancheng City from 2016 to 2020, and is at an extremely low level. Further surveillance of soil-transmitted nematodiasis requires to be intensified targeting key regions and populations to consolidate the control achievements.


The Expression Pattern of Hypoxia-Related Genes Predicts the Prognosis and Mediates Drug Resistance in Colorectal Cancer.
Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. However, due to the heterogeneity of CRC, the clinical therapy outcomes differ among patients. There is a need to identify predictive biomarkers to efficiently facilitate CRC treatment and prognosis. Methods: The expression profiles from Gene Expression Omnibus (GEO) database were used to identify cancer hallmarks associated with CRC outcomes. An accurate gene signature based on the prognosis related cancer hallmarks was further constructed. Results: Hypoxia was identified to be the primary factor that could influence CRC outcomes. Sixteen hypoxia-related genes were selected to construct a risk gene signature (HGS) associated with individuals' prognosis, which was validated in three independent cohorts. Further, stromal and immune cells in tumor microenvironment (TME) were found to be associated with hypoxia. Finally, among the 16 hypoxia-related genes, six genes (DCBLD2, PLEC, S100A11, PLAT, PPAP2B and LAMC2) were identified as the most attributable ones to drug resistance. Conclusion: HGS can accurately predict CRC prognosis. The expression of the drug resistance-related genes is critical in CRC treatment decision-making.


Mouth protectors and oral trauma: a study of adolescent football players.
A total of 754 junior high school and high school football players from the Birmingham, AL, area were studied to determine the extent of sports-related oral trauma among players. More than half the oral injuries and more than a third of the concussions were reported in sports other than football. Basketball and baseball players had a high prevalence of hard tissue oral trauma with virtually none of the players wearing mouth protectors. The results of this study indicate that current mouth protector designs are helpful in preventing hard tissue trauma, yet additional soft tissue protection is indicated in football mouth protector design.


Air-stable operation of transparent, colloidal quantum dot based LEDs with a unipolar device architecture.
We report a novel unipolar light-emitting device architecture that operates using direct-current, field-driven electroluminescence of colloidally synthesized quantum dots (QDs). This device architecture, which is based only on transparent ceramics and QDs, enables emission from different color QDs and, for the first time, constant QD electroluminescence during extended operation in air, unpackaged.


Glycolaldehyde Inhibits CO(2) Fixation in the Cyanobacterium Synechococcus UTEX 625 without Inhibiting the Accumulation of Inorganic Carbon or the Associated Quenching of Chlorophyll a Fluorescence.
When studying active CO(2) and HCO(3) (-) transport by cyanobacteria, it is often useful to be able to inhibit concomitant CO(2) fixation. We have found that glycolaldehyde was an efficient inhibitor of photosynthetic CO(2) fixation in Synechococcus UTEX 625. Glycolaldehyde did not inhibit inorganic carbon accumulation due to either active CO(2) or HCO(3) (-) transport. When glycolaldehyde (10 millimolar) was added to rapidly photosynthesizing cells, CO(2) fixation was stopped within 15 seconds. The quenching of chlorophyll a fluorescence remained high (</= 82% control) when CO(2) fixation was completely blocked by glycolaldehyde. This quenching was relieved upon the addition of a glucose oxidase oxygentrap. This is consistent with our previous finding that q-quenching in the absence of CO(2) fixation was due to O(2) photoreduction. Photosynthetic CO(2) fixation was also inhibited by d,l,-glyceraldehyde but a sixfold higher concentration was required. Glycolaldehyde acted much more rapidly than iodoacetamide (15 seconds versus 300 seconds) and did not cause the onset of net O(2) evolution often observed with iodoacetamide. Glycolaldehyde will be a useful inhibitor when it is required to study CO(2) and HCO(3) (-) transport without the complication of concomitant CO(2) fixation.


The impact of emergent infections on the fetal state.
To study the impact of emergent infections (human herpesvirus type 6) on the fetal state. The study involved examination of 90 pregnant women in the 2nd and 3rd trimesters of gestation (Group 1 (25 pregnant) consisted of patients with a viral infection, CMV carriers, Group 2 (25 pregnant) included women with a viral infection, herpes simplex virus types 1/2, Group 3 amounted for 20 patients with a viral infection, herpes simplex virus type 6, Group 4 comprised 20 patients with normal pregnancy and no signs of infection. Concentration of IgM and IgG to herpes simplex virus types 1/2, IgM and IgG to herpesvirus type 6 in venous blood of the pregnant was determined by enzyme-immunoassay. Giant cells typical for CMV were determined by cytological examination of saliva sediment. All the pregnant underwent ultrasound somatogenetic examination, Doppler evaluation of maternal-placental-fetal hemodynamics and biophysical profile (BPP) assessment. Results and their discussion: Ultrasound examination of Group 1, 2 and 3 pregnant showed signs of intrauterine infection. Pregnant women with a viral infection were found to have intrauterine growth retardation (IUGR) and Group 3 patients more commonly had symmetrical 3rd degree IUGR. BPP indices showed initial signs of fetal distress in 5 (20%) Group 1 pregnant, 7 (27%) Group 2 pregnant and 11 (55%) Group 3 pregnant women. Doppler examination of uterine-feto-placental hemodynamics revealed a more pronounced increase in vascular resistance indices in Group 3 patients. Emergent infections (herpesvirus type 6) of pregnant trigger more pronounced changes in the feto-placental system than other viral infections. Herpesvirus type 6 is a common cause of fetal state deterioration, which manifests in intrauterine growth retardation, changes in biophysical profile and hemodynamic disorders in the mother-placenta-fetus system.


Urban and non-urban differences in community living and participation among individuals with serious mental illnesses.
Despite a wealth of studies examining the relationship between urbanicity (i.e., living in an urban area) and psychological distress, there is a paucity of research examining the relationship between urbanicity, community living, and community participation of adults with serious mental illnesses. This study addresses this knowledge gap by assessing urban and non-urban differences in community participation, sense of community, mental health stigma, and perceptions of the neighborhood environment among individuals with serious mental illnesses living independently throughout the United States. A total of 300 individuals with serious mental illnesses recruited from 21 outpatient mental health service organizations in 15 states completed a phone survey about their community living and participation experiences. Urbanicity was examined at two spatial scales (block group and county), and independent-samples t-tests were employed to assess urban and non-urban differences in community living and participation variables. Levels of community participation and perceptions of neighborhood quality and crime were higher in urban block groups; sense of community was higher in urban counties; and perceptions of mental health stigma were higher in non-urban counties. Results inform the methodological literature on best practices for assessing urbanicity, as well as interventions aimed at increasing community participation and improving aspects of the built and social environment that affect individuals who experience mental health distress.


Assessment of haptic memory using somatosensory change-related cortical responses.
Haptic memory briefly retains somatosensory information for later use; however, how and which cortical areas are affected by haptic memory remain unclear. We used change-related cortical responses to investigate the relationship between the somatosensory cortex and haptic memory objectively. Electrical pulses, at 50 Hz with a duration of 500 ms, were randomly applied to the second, third, and fourth fingers of the right and left hands at an even probability every 800 ms. Each stimulus was labeled as D (preceded by a different side) or S (preceded by the same side). The D stimuli were further classified into 1D, 2D, and 3D, according to the number of different preceding stimuli. The S stimuli were similarly divided into 1S and 2S. The somatosensory-evoked magnetic fields obtained were divided into four components via a dipole analysis, and each component's amplitudes were measured using the source strength waveform. The results showed that the preceding event did not affect the amplitude of the earliest 20-30 ms response in the primary somatosensory cortex. However, in the subsequent three components, the cortical activity amplitude was largest in 3D, followed by 2D, 1D, and S. These results indicate that such modulatory effects occurred somewhere in the somatosensory processing pathway higher than Brodmann's area 3b. To the best of our knowledge, this is the first study to demonstrate the existence of haptic memory for somatosensory laterality and its impact on the somatosensory cortex using change-related cortical responses without contamination from peripheral effects.


Chitosan and procyanidin composite films with high antioxidant activity and pH responsivity for cheese packaging.
Chitosan-procyanidin composite films (CS-PC films) with different mass ratios were prepared by solution casting method. Their structural, thermal, physical, and antioxidant properties, antibacterial activity and pH responsivity were determined. Compared with CS-control film, CS-PC films exhibited lower solubility and higher tensile strength. The antimicrobial properties against Escherichia coli and Aspergillus niger were improved by 20.0% and 30.4%, respectively. CS-PC films indicated good antioxidant activity through their DPPH and ABTS+ scavenging rates, which were 2.45 times higher than CS-control film. pH responsivity was represented by the outstanding changes in color, which were visible to the naked eye. Food packaging film with high antioxidant activity, bacteriostatic properties and pH responsivity was prepared by CS and PC. Compared with the initial properties of cheese, the characteristics of cheese packaged with CS-PC films were obviously better than those of the control groups.


Microbial Diversity and Sulfur Cycling in an Early Earth Analogue: From Ancient Novelty to Modern Commonality.
Life emerged and diversified in the absence of molecular oxygen. The prevailing anoxia and unique sulfur chemistry in the Paleo-, Meso-, and Neoarchean and early Proterozoic eras may have supported microbial communities that differ from those currently thriving on the earth's surface. Zodletone spring in southwestern Oklahoma represents a unique habitat where spatial sampling could substitute for geological eras namely, from the anoxic, surficial light-exposed sediments simulating a preoxygenated earth to overlaid water column where air exposure simulates oxygen intrusion during the Neoproterozoic era. We document a remarkably diverse microbial community in the anoxic spring sediments, with 340/516 (65.89%) of genomes recovered in a metagenomic survey belonging to 200 bacterial and archaeal families that were either previously undescribed or that exhibit an extremely rare distribution on the current earth. Such diversity is underpinned by the widespread occurrence of sulfite, thiosulfate, tetrathionate, and sulfur reduction and the paucity of sulfate reduction machineries in these taxa. Hence, these processes greatly expand lineages mediating reductive sulfur-cycling processes in the tree of life. An analysis of the overlaying oxygenated water community demonstrated the development of a significantly less diverse community dominated by well-characterized lineages and a prevalence of oxidative sulfur-cycling processes. Such a transition from ancient novelty to modern commonality underscores the profound impact of the great oxygenation event on the earth's surficial anoxic community. It also suggests that novel and rare lineages encountered in current anaerobic habitats could represent taxa that once thrived in an anoxic earth but have failed to adapt to earth's progressive oxygenation. IMPORTANCE Life on earth evolved in an anoxic setting; however, the identity and fate of microorganisms that thrived in a preoxygenated earth are poorly understood. In Zodletone spring, the prevailing geochemical conditions are remarkably similar to conditions prevailing in surficial earth prior to oxygen buildup in the atmosphere. We identify hundreds of previously unknown microbial lineages in the spring and demonstrate that these lineages possess the metabolic machinery to mediate a wide range of reductive sulfur processes, with the capacity to respire sulfite, thiosulfate, sulfur, and tetrathionate, rather than sulfate, which is a reflection of the differences in sulfur-cycling chemistry in ancient versus modern times. Collectively, such patterns strongly suggest that microbial diversity and sulfur-cycling processes in a preoxygenated earth were drastically different from the currently observed patterns and that the Great Oxygenation Event has precipitated the near extinction of a wide range of oxygen-sensitive lineages and significantly altered the microbial reductive sulfur-cycling community on earth.


Probing influence of mesophasic transformation on performance of self-emulsifying system: effect of ion.
Self-emulsifying systems are mixtures of oils and surfactants, ideally isotropic, sometimes including cosolvents, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastrointestinal tract. The process of self-emulsification has remained the center of attraction for most researchers. Controlled hydration of self-emulsifying systems shows formation of an intermediate gel phase which upon rupture forms an emulsion. Current work was undertaken to understand and explore the microstructural properties of intermediate gel phase which are believed to influence the performance (droplet size) of the final formulation. The effect of additives on microstructural properties of intermediate gel phase has also been investigated. Microstructural elucidation of hydrated samples of intermediate regimes was done by using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. Samples from intermediate regimes showed formation of local lamellar structure which swelled with hydration. In the present work, the effect of addition of salt form of naproxen (sodium and potassium) and naproxen (base) on microstructural properties of intermediate regimes was investigated. Systems containing naproxen salts formed larger droplets whereas naproxen base formed smaller ones. Microstructural properties of intermediate lamellar structures were well correlated with performance of the final formulation. The current studies indicate that by controlling the properties of intermediate regimes optimized formulations with desired performance can be tailor-made.


Elevated MMP-12 protein levels in induced sputum from patients with COPD.
Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate. Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1-42.1) v 6.7 (3.9-10.4) v 4.2 (2.4-11.3) v 6.1 (4.5-7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4-8.0) v 0.14 (0.1-0.2) microg/microl, p = 0.0002). MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.


The ovaries of Cicadomorpha: distribution of microfilaments and microtubules in terminal filament cells.
The ovaries of the investigated homopterans are telotrophicmeroistic and consist of several (7-21 ) ovarioles. Each ovariole is composed of three elements: an anteriorly localized terminal filament, a tropharium, and a posterior vitellarium. The latter comprises several developing ovarian follicles in a linear arrangement. The terminal filaments are relatively solid and composed of two distinct types of cells: the apical cells (ApCs) and the basal cells (BaCs). The BaCs are disc-shaped and oriented perpendicularly to the long axis of the ovariole, whereas the ApCs are strongly elongated and arranged parallel to this axis. The distribution of cytoskeletal elements has been studied with the use of electron microscope and histochemical methods. We show that the ApCs house prominent bundles of highly ordered microfilaments and/or parallel arranged microtubules. In contrast, BaCs contain only individual microtubules that are predominantly located in peripheral regions of the cells. It is suggested that microfilaments and microtubules present in the ApCs are responsible for the mechanical rigidity of the terminal filaments.


The effects of long-term herbal treatment for pediatric AIDS.
This paper presents our long-term (1992-2000) treatment of pediatric Acquired Immune Deficiency Syndrome (AIDS) patients (maximum 100 children, last three years 65) using native herbal remedies in a voluntary medical assistance program in Constanta, Romania. We primarily report the progress of 10 children at a facility called the "House of Tomorrow" and three other facilities. The long-term (8 years and 8 months) treatment contributed to a drop of the amount of Human Immunodeficiency Virus Ribonucleic Acids (HIV-RNA) below the measurable level for 9 out of 10 patients at the "House of Tomorrow." Furthermore, the treatment led to preservation and increase of the cluster of differentiation (CD4) count, a remarkable decrease in mortality rate, as well as the maintenance of a good quality of life. It took one to three years for the beneficial effects of the treatment to emerge. No side-effects were recognized either clinically or biochemically, nor was there any emergence of drug-resistant strains of HIV as seen with anti-HIV chemical treatments. This paper also refers to which herbal remedies were used and their general mechanism of action.


Taxonomy and phylogeny of the novel rhytidhysteron-like collections in the Greater Mekong Subregion.
During our survey into the diversity of woody litter fungi across the Greater Mekong Subregion, three rhytidhysteron-like taxa were collected from dead woody twigs in China and Thailand. These were further investigated based on morphological observations and multi-gene phylogenetic analyses of a combined DNA data matrix containing SSU, LSU, ITS, and tef1-α sequence data. A new species of Rhytidhysteron, R.xiaokongense sp. nov. is introduced with its asexual morph, and it is characterized by semi-immersed, subglobose to ampulliform conidiomata, dark brown, oblong to ellipsoidal, 1-septate, conidia, which are granular in appearance when mature. In addition to the new species, two new records from Thailand are reported viz. Rhytidhysterontectonae on woody litter of Betula sp. (Betulaceae) and Fabaceae sp. and Rhytidhysteronneorufulum on woody litter of Tectonagrandis (Lamiaceae). Morphological descriptions, illustrations, taxonomic notes and phylogenetic analyses are provided for all entries.


Extracorporeal membrane oxygenation as a bridge to definite surgery in recurrent postinfarction ventricular septal defect.
A recurrent shunt after a postinfarction ventricular septal defect (PI-VSD) repair is common. We treated a case of cardiogenic shock caused by a large recurrent shunt after the patch repair of an apical PI-VSD with percutaneous extracorporeal membrane oxygenation (ECMO) for 4 days until a secondary definite repair. This suggests that percutaneous ECMO support is reliable before and after secondary definitive surgery in recurrent PI-VSD and may imply using a delayed surgical strategy with ECMO support to restore hemodynamic stability and avoid primary surgery on freshly fragile infarcted myocardium.


Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes.
Inhibitory effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated. These cannabinoids inhibited 7-ethoxyresorufin O-deethylase activity of recombinant CYP1A1, CYP1A2, and CYP1B1 in a competitive manner. CBD most potently inhibited the CYP1A1 activity; the apparent K(i) value (0.155microM) was at least one-seventeenth of the values for other CYP1 isoforms. On the other hand, CBN more effectively decreased the activity of CYP1A2 and CYP1B1 (K(i)=0.0790 and 0.148microM, respectively) compared with CYP1A1 (K(i)=0.541microM). Delta(9)-THC less potently inhibited the CYP1 activity than CBD and CBN, and showed low selectivity against the CYP1 inhibition (K(i)=2.47-7.54microM). The preincubation of CBD resulted in a time- and concentration-dependent decrease in catalytic activity of all the recombinant CYP1 enzymes and human liver microsomes. Similarly, the preincubation of Delta(9)-THC or CBN caused a time- and concentration-dependent inhibition of recombinant CYP1A1. The inactivation of CYP1A1 by CBD indicated the highest k(inact)/K(I) value (540l/mmol/min) among the CYP1 enzyme sources tested. The inactivation of recombinant CYP1A1 and human liver microsomes by CBD required NADPH, was not influenced by dialysis and by glutathione, N-acetylcysteine, and superoxide dismutase as trapping agents. These results indicated that CBD and CBN showed CYP1 isoform-selective direct inhibition and that CBD was characterized as a potent mechanism-based inhibitor of human CYP1 enzymes, especially CYP1A1.


Adventitial cystic disease of the popliteal artery: diagnosis and treatment. A case report.
Adventitial cystic disease of the popliteal artery (ACDPA) is an unusual cause of a unilateral progressive intermittent claudication in young or middle-aged men. In the case described here, ultrasound (US) examination provided the preoperative diagnosis. The lesion was dealt with by simple evacuation of the cyst and excision of the wall. This simple treatment is all that is required in the majority of cases and provides good long-term results.


Tracking mechanical wave propagation within tissue using phase-sensitive optical coherence tomography: motion artifact and its compensation.
We describe theoretical and experimental investigations of motion artifacts that can arise in the detection of shear wave propagating within tissue with phase-sensitive optical coherence tomography. We find that the motion artifact is a combined product of sample surface motion and refractive index difference between sample and air, which cannot be neglected when estimating the tissue motion within tissue. A method of compensating the motion artifact is demonstrated, the results of which emphasize the need for surface motion compensation when measuring the mechanical response for elastography or other biomedical applications.


Effect of growth conditions on extracellular products (ECPs) of Aeromonas hydrophila.
Owing to the significant role in gastrointestinal illness of A. hydrophila, frequently detected in various raw and ready-to eat foods, its pathogenetic mechanisms are particularly studied. In this paper we report the results obtained studying in vitro the effect of O2 tension and inoculum age on the extra cellular products (ECPs) of seven strains food-borne isolated and cultured at 37 degrees. The considered factors influenced markedly bacterial growth as well as ECPs production and the more notable differences were detected among 15 hours old strains let grown slowly shaking (15SH), that showed the highest bacterial yield, and 24 h old strains cultured statically (24ST), whose haemolysin and cytotoxin production was favoured. Wilcoxon test shows as, in these latter conditions, the strains needed short time to adapt the haemolysin and cytotoxin production. The oxygen tension reduction, extending the replication time, induces the bacterial metabolism toward secondary products, as verified by Spearman test applied to ECPs indexes. The increased production per cell of virulence-associated factors could be responsible of gastrointestinal disorders caused by food-borne A. hydrophila strains, even without a massive gut colonization, especially when immunocompromised individuals ingest contaminated foods.


A comparison of cerebral oxygenation as measured by the NIRO 300 and the INVOS 5100 Near-Infrared Spectrophotometers.
In this study cerebral oxygenation was measured using the NIRO 300 and the INVOS 5100 spectrophotometers in 10 healthy adult volunteers, exposed to varying degrees of hyperoxia and hypoxia. The results showed similar baseline values for tissue oxygenation index and regional cerebral oxygen saturation with mean (SD) values being 64.9% (5.1) and 62.3% (6.0), respectively. The overall bias was -2.1%, with the INVOS 5100 under-reading cerebral oxygenation compared to the NIRO 300, with limits of agreement of +/-14.7%. Both monitors demonstrated similar changes in response to hyperoxia and hypocapnia (coefficient of variance for FIo2 0.45 = 10.0%, FIo2 1.0 = 10.1%, hypocapnia = 14.5%). The reasons for the bias and variability may relate to differences in the methodological approaches of the two monitors. The correlation between the monitors in response to changes in cerebral oxygenation implies that they may be useful as trend monitors in clinical practice.


Donor preparation using pneumatic dissection in endothelial keratoplasty: DMEK or DSEK?
To determine if residual stroma remains on the Descemet membrane when pneumatic dissection is used to prepare donor tissue for endothelial keratoplasty. Pneumatic dissection using a posterior peripheral needle insertion was carried out on 5 eye bank corneas. Samples were then sent for histological analysis. A thin layer of stroma remained on the Descemet membrane in all the samples. The average central stromal thickness was 12.4 μm (range 6.5-20.0 μm). Endothelial keratoplasty using pneumatic dissection to prepare donor tissue should be considered a form of Descemet stripping endothelial keratoplasty and not Descemet membrane endothelial keratoplasty. If future studies show excellent visual results using pneumatic dissection for endothelial keratoplasty, then removal of all donor stroma may be unnecessary.


Genotoxic evaluation of workers employed in pesticide production.
Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless exposure to pesticides can represent a potential risk to humans. Pesticide manufacturing unit workers are prone to possible occupational pesticide exposure. Therefore, this study was performed to evaluate the genotoxic effect of pesticide exposure in these workers. In the present investigation 54 pesticide workers and an equal number of control subjects were assessed for genome damage in blood lymphocytes utilizing the chromosomal aberration analysis and the buccal epithelial cell by adopting the micronucleus test. The results suggested that pesticide workers had a significantly increased frequency of chromosomal aberrations when compared with controls (mean+/-S.D., 8.43+/-2.36 versus 3.32+/-1.26; P<0.05). Similarly, the pesticides exposed workers showed a significant increase in micronucleated cells compared with controls (1.24+/-0.72 versus 0.32+/-0.26; P<0.05). Analysis of variance revealed that occupational exposure to pesticides had a significant effect on frequency of micronuclei (P<0.05), whereas smoking, age, gender and alcohol consumption had no significant effect on genetic damage (P>0.05). However, no association was found between years of exposure, smoking, age, gender, alcohol consumption and higher levels of genetic damage as assessed by the chromosomal aberration assay (P>0.05). Our findings indicate that occupational exposure to pesticides could cause genome damage in somatic cells.


Historical development of the Archives of Environmental & Occupational Health and its predecessor journals, 1919-2009.
The Archives of Environmental & Occupational Health (AEOH) has a long and distinguished history that has so far involved a total of 7 journal titles since 1919. This article provides a detailed historical review of the AEOH, from its seminal precursors of the early 20th century, into the distinguished periodical of today. As editorial leadership is known to influence journal quality, considerable discussion focuses on the careers and professional achievements of the Editors-in-Chief, as well as key members of the editorial board who served the AEOH and its predecessor journals over the past 90 years.


First record of the thread-legged assassin bug Myiophanes greeni Distant, 1903 (Heteroptera: Reduviidae: Emesinae) from India.
While surveying bugs and spiders in the caves of Satara District, Maharashtra, one of us (SK) collected a thread-legged bug associated with a spider web. A Sri Lankan Emesinae bug, Myiophanes greeni Distant (Heteroptera: Reduviidae: Emesinae) is reported for the first time from India. The species is redescribed with several illustrations including male genitalia.


Pivmecillinam plus pivampicillin versus co-trimoxazole in patients undergoing transurethral prostate resection.
Patients undergoing transurethral prostate resection received a 10-day or a 20-day treatment with a combination of pivmecillinam/pivampicillin or with co-trimoxazole starting 1 day before surgery. The results were evaluated in 139 patients. Fifty-three patients had bacteriuria prior to the operation, and the bacteriological cure rate was 22 out of 25 on pivmecillinam/pivampicillin and 22 out of 28 on co-trimoxazole. Eighty-six patients had no bacteriuria pre-operatively and received treatment prophylactically. Two out of 40 patients on co-trimoxazole developed urosepsis, while pivmecillinam/pivampicillin was effective in preventing septicaemic episodes in all 46 patients treated. Tolerance was good with mild side-effects in 5 patients on pivmecillinam/pivampicillin and in 2 patients on co-trimoxazole.


[Skin tests as immunologic parameters in cervical cancer].
Immunological skin-tests in 158 patients admitted at the 1st Department of Gynaecology and Obstetrics, University of Vienna, and in 25 healthy controls were done in a long-term prospective study. 123 examined patients were suffering from invasive cervical cancer stage I or Ii (group 1), 17 patients were suffering from preinvasive lesions of the cervix (group 2) and 18 patients were admitted for treatment of benign disorders (group 3). Recall-antigens--streptokinase-streptodornase (SKSD), purified protein derivate (PPD) and candida (CAND)--and a primary antigen (DNCB) were used testing cutaneous delayed hypersensitivity reactions. Preoperative total reactivity to recall-antigens calculated by a score was significantly reduced in cancer patients in comparison to other groups. Subdividing the cancer patients according to histological criteria of the malignancy we could find significantly differences in particular tests (SKSD and CAND) but not in total reactivity score. Comparing the preoperative reactivity of cancer patients with or without recurrence of malignancy within two years less pronounced differences were found. Reactivity to recall-antigens in all tests and in all patient groups were better three weeks after surgical treatment than preoperatively. The prior found differences between the groups remained significant (p less than 0,05). In contrast, cancer patients demonstrated severe anergy in postoperative DNCB sensitization test as only 1 of 33 patients exhibited normal hypersensitivity reaction. 113 out of 24 patients of group 2 and 3 (54%) demonstrated delayed hypersensitivity to DNCB in operative sensitization test.(ABSTRACT TRUNCATED AT 250 WORDS)


Anti-invasion and anti-migration effects of miR-199a-3p in hepatocellular carcinoma are due in part to targeting CD151.
Several studies have reported reduced miR-199a-3p expression in hepatocellular carcinoma (HCC). In an effort to discover important target genes for miR-199a-3p that may be related to HCC development or progression, we identified the tetraspanin, transmembrane glycoprotein CD151. Luciferase reporter assays and western blotting identified CD151 as a bona fide miR-199a-3p target gene. While CD151 protein was increased in the mesenchymal but not the epithelial HCC cell lines, CD151 knockdown with siRNA did not reduce HCC cell proliferation in either group of cells. miR-199a-3p reduced in vitro invasion and migration of CD151-positive HCC cells. Examination of the mRNA and protein expression in pairs of primary HCC tumors and adjacent benign tissues showed that not only was CD151 mRNA and protein increased in the tumors but also that an inverse correlation exists between the miR-199a-3p and CD151 RNA expression. We report that CD151 is a target of miR-199a-3p and that increased CD151 protein resulting from reduced miR-199a-3p could contribute to the development of metastatic HCC.


Act No. 61, 29 September 1987.
This Act amends Article 10 of Act No. 1263 of 1974 to double to $20.00 (pesos) the lowest amount of maternity allowance that a worker can receive per week in Cuba.


Neuropsychological sequelae of light head injuries in older children 6 months after trauma.
Fifty-six children, 9-13 years of age, underwent neuropsychological testing 4-8 months after concussion. They were individually matched with a control group on the variables of school grade, sex, and academic achievement. On 29 of the 32 test variables, the results of the control group were superior to those of the experimental group. Analysis of variance showed that the concussion factor explained most of the differences between the groups. The differences tended to decrease with increasing age, and to increase with increasing complexity of the tests. The results indicate that neuropsychological sequelae after concussion may be demonstrated, even when there are few subjective complaints and no perceptible lags in academic achievement.


Circular RNAs: Novel Regulators of Neuronal Development.
Circular RNAs (circRNAs) are highly stable, circularized long non-coding RNAs. circRNAs are conserved across species and appear to be specifically enriched in the nervous system. Recent studies show that many circRNAs are expressed in a tissue- and developmental-stage-specific manner, reveal a striking regulation of circRNAs during neuronal development, and detect their presence at synaptic sites. The exact functions of circRNAs remain poorly understood, but evidence from analysis of some circRNA molecules suggests that they could substantially contribute to the regulation of gene expression, particularly in architecturally complex and polarized cells such as neurons. Emerging evidence also indicates that circRNAs are involved in the development and progression of various neurological disorders. In this review, we summarize the molecular characteristics of circRNAs and discuss their proposed functions and mechanism-of-action in developing neurons.


Virus-like particles as antigenic nanomaterials for inducing protective immune responses in the lung.
The lung is a major entry point for many of the most detrimental pathogens to human health. The onslaught of pathogens encountered by the lung is counteracted by protective immune responses that are generated locally, which can be stimulated through vaccine strategies to prevent pathogen infections. Here, we discuss the use of virus-like particles (VLPs), nonpathogen derivatives of viruses or protein cage structures, to construct new vaccines exploiting the lung as a site for immunostimulation. VLPs are unique in their ability to be engineered with near molecular level detail and knowledge of their composition and structure. A summary of research in developing VLP-based vaccines for the lung is presented that suggests promising results for future vaccine development.


Oxytocin, Tolerance, and the Dark Side of Addiction.
Substance use disorders blight the lives of millions of people and inflict a heavy financial burden on society. There is a compelling need for new pharmacological treatments as current drugs have limited efficacy and other major drawbacks. A substantial number of animal and recent clinical studies indicate that the neuropeptide, oxytocin, is a particularly promising therapeutic agent for human addictions, especially alcohol use disorders. In preliminary trials, we found that oxytocin administered by the intranasal route, which produces some neuropeptide penetration into the CNS, potently blocked withdrawal and reduced alcohol consumption in heavy drinkers. A considerable body of earlier animal studies demonstrated that oxytocin inhibits tolerance to alcohol, opioids, and stimulants as well as withdrawal from alcohol and opioids. Based on these preclinical findings and our clinical results, we hypothesize that oxytocin may exert therapeutic effects in substance dependence by the novel mechanism of diminishing established tolerance. A newer wave of studies has almost unanimously found that oxytocin decreases self-administration of a number of addictive substances in several animal models of addiction. Reduction of established tolerance should be included among the potential explanations of oxytocin effects in these studies and changes in tolerance should be examined in future studies in relationship to oxytocin influences on acquisition and reinstatement of self-administration as well as extinction of drug seeking. Oxytocin efficacy in reducing anxiety and stress responses as well as established tolerance suggests it may be uniquely effective in reducing negative reinforcement (Koob's "dark side" of addiction) that maintains chronic substance use.


Influence of nonsystemic transmission on the epidemiology of insect borne arboviruses: a case study of vesicular stomatitis epidemiology in the western United States.
Nonsystemic transmission, where a pathogen is transmitted between infected and uninfected vectors without the vertebrate host becoming viremic, may provide an explanation for transmission in systems where the vertebrate hosts have been difficult to identify. This transmission pathway had been previously demonstrated for tick-borne viruses and bacteria, but the recent demonstration for Simulium and vesicular stomatitis virus is the first for a blood-feeding insect. The epidemiology of vesicular stomatitis viruses has been difficult to understand, and nonsystemic transmission may be important. We use mathematical formulations of the basic reproduction number, R(0), to compare systemic and nonsystemic transmission. The absence of a latent period before host infectiousness in nonsystemic transmission may allow a more rapid increase in prevalence in the biting flies early in the development of a new outbreak. Aggregation of flies between hosts and at favored feeding sites on hosts will be important, but further data on nonsystemic transmission as a function of space and time are required to fully assess this pathway. The data needed to compare the two pathways and their relative roles in virus epidemiology are discussed.


Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells.
Vitamin D Receptor (VDR) is expressed in both animal and human ovarian tissue, however, the role of vitamin D in human ovarian steroidogenesis is unknown. Cultured human ovarian cells were incubated in tissue culture medium supplemented with appropriate substrates, with or without 50 pM-150 pM or 50 nM-150 nM of 1,25-(OH)2D3, and in the presence or absence of insulin. Progesterone, testosterone, estrone, estradiol, and IGFBP-1 concentrations in conditioned tissue culture medium were measured. Vitamin D receptor was present in human ovarian cells. 1,25-(OH)2D3 stimulated progesterone production by 13% (p<0.001), estradiol production by 9% (p<0.02), and estrone production by 21% (p<0.002). Insulin and 1,25-(OH)2D3 acted synergistically to increase estradiol production by 60% (p<0.005). 1,25-(OH)2D3 alone stimulated IGFBP-1 production by 24% (p<0.001), however, in the presence of insulin, 1,25-(OH)2D3 enhanced insulin-induced inhibition of IGFBP-1 production by 13% (p<0.009). Vitamin D stimulates ovarian steroidogenesis and IGFBP-1 production in human ovarian cells likely acting via vitamin D receptor. Insulin and vitamin D synergistically stimulate estradiol production. Vitamin D also enhances inhibitory effect of insulin on IGFBP-1 production.


Photoprocesses of photosensitizing drugs within cyclodextrin cavities.
Recently some interest has been focused on the photobehavior of CD-drug inclusion complexes in relation to the problem of the biological photosensitization by drugs. This review is dedicated to the illustration of the mechanistic aspects of the photoprocesses occurring in some non-steroidal anti-inflammatory drugs (NSAIDs), with photosensitising side effects, within CD cavities. It is shown how the photobehavior of the CD-drug associates can help to model the photoreactivity of the drugs in biological sites. The limitations for the use of CDs as protective systems for the clinical administration of photosensitising drugs is also evidenced.


miR-181b-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization by directly targeting YWHAG.
Epithelial-mesenchymal transition (EMT) is essential for increased invasion and metastasis during cancer progression. Among the candidate EMT-regulating microRNAs that we previously identified, miR-181b-3p was found to induce EMT in MCF7 breast cancer cells, as indicated by an EMT-characteristic morphological change, increased invasiveness, and altered expression of an EMT marker. Transfection with a miR-181b-3p inhibitor reduced the expression of mesenchymal markers and the migration and invasion of highly invasive breast cancer cells. miR-181b-3p induced the upregulation of Snail, a master EMT inducer and transcriptional repressor of E-cadherin, through protein stabilization. YWHAG was identified as a direct target of miR-181b-3p, downregulation of which induced Snail stabilization and EMT phenotypes. Ectopic expression of YWHAG abrogated the effect of miR-181b-3p, including Snail stabilization and the promotion of invasion. In situ hybridization and immunohistochemical analyses indicated that YWHAG expression was inversely correlated with the expression of miR-181b-3p and Snail in human breast cancer tissues. Furthermore, transfection with miR-181b-3p increased the frequency of metastatic nodule formation in the lungs of mice in experimental metastasis assays using MDA-MB-231 cells. Taken together, our data suggest that miR-181b-3p functions as a metastasis activator by promoting Snail-induced EMT, and may therefore be a therapeutic target in metastatic cancers.


Retinoblastoma susceptibility gene product (pRb) and p107 functionally separate the requirements for serum and anchorage in the cell cycle G1-phase.
Growth factors and cell anchorage are both required for cell cycle G(1)-phase progression, but it is unclear whether their function is mediated through the same set of cell cycle components and whether they are both required during the same periods of time. We separately analyzed the requirements of serum and anchorage during G(1)-phase progression and found that human dermal fibroblasts as well as wild type, pRb(-/-), and p107(-/-) mouse embryonic fibroblasts needed serum (growth factors) until mid-G(1)-phase but required cell anchorage until late G(1)-phase to be competent for S-phase entry. Importantly, however, pRb/p107 double-null mouse embryonic fibroblasts lacked serum requirement in mid-G(1)-phase but still required cell anchorage until late G(1)-phase to enter S-phase. Our results indicate that pRb and p107 do not constitute the last control point for extracellular factors during G(1)-phase progression, and they functionally separate the requirements for serum and cell anchorage in terms of involved cell cycle components.


Neural control of jejunal and ileal motility and transmural potential difference in the ferret.
The aim of the present study was to examine the vagal control of motor activity and transmural potential difference in the anaesthetized ferret jejunum and ileum in vivo. The data suggest that in the jejunum fluctuations in transmural potential difference occur secondary to spontaneous bursts of contractions and both are controlled by activity in the vagus nerve. However, in the ileum, spontaneous contractile activity and transmural potential difference are not under the tonic influence of the vagus nerve, although transmural potential difference may be under tonic sympathetic control. Furthermore, it appears that vagally induced motor activity and transmural potential difference responses are independent phenomena. Finally the changes in transmural potential difference and the long latency motor responses to vagal nerve stimulation in the small intestine of the ferret are mediated at least in part by noncholinergic transmitters.


Ultraviolet-visible transient spectroscopy of bacteriorhodopsin mutants. Evidence for two forms of tyrosine-185----phenylalanine.
The photocycle kinetics of the bacteriorhodopsin mutant Tyr-185----Phe has been investigated by UV-visible transient spectroscopy. Flash-induced spectral changes were measured from 100 ns to 500 ms using a gated optical multichannel analyzer on protein samples that were reconstituted in vesicles with Halobacterium halobium lipids. Tyr-185----Phe exhibits a pH-dependent absorbance spectrum reflecting contributions from two different species. At pH 6, the dominant photocycling species has a lambda max near 610 nm although the absorption maximum of light-adapted Tyr-185----Phe is at 581 nm. This red-shifted species does not form any M-like intermediate and undergoes a photocycle similar to that observed for deionized blue membrane. At pH 8, the dominant photoactive form exhibits a lambda max near 550 nm. This purple species, which is blue shifted 20 nm relative to wild-type bacteriorhodopsin, exhibits a photocycle similar to the wild type. However, M formation occurs in 8 microseconds, approximately three times faster than wild-type bacteriorhodopsin at pH 8. In addition, an unusually long lived intermediate absorbing at 610 nm is observed at high pH. In the UV region, a broad band near 300-310 nm is absent in the mutant relative to wild type, consistent with earlier measurements made at low temperature which suggest that Tyr-185 undergoes a change in protonation. Steady-state proton pumping action spectra indicate that the 550 nm species does transport protons but that the blue species is inactive. These results are discussed in terms of a model that hypothesizes that Tyr-185 is located close to the bacteriorhodopsin chromophore and stabilizes the interaction of helices F and G through formation of a polarizable bond with Asp-212.


[Artificial blood: the future of blood transfusion? II. Blood substitutes other than hemoglobin solutions].
Part 2 discusses the state-of-the-art in oxygen-transporting blood substitutes other than hemoglobin solutions (Part 1); these are the fluorocarbon emulsions, the hemoglobin liposomes and other products such as oxygen-chelating agents. The substitutes reviewed here may play an important future role; before then, their stability, ease of administration, innocuity and value in human clinical medicine must be ensured.


Health disparities in pediatric sleep-disordered breathing.
Sleep-disordered breathing reflects a continuum of overnight breathing difficulties, ranging from mild snoring to obstructive sleep apnea syndrome. Sleep-disordered breathing in childhood is associated with significant adverse outcomes in multiple domains of functioning. This review summarizes the evidence of well-described ethnic, racial, and socioeconomic disparities in pediatric sleep-disordered breathing, from its prevalence to its treatment-related outcomes. Research on potential socio-ecological contributors to these disparities is also reviewed. Critical future research directions include the development of interventions that address the modifiable social and environmental determinants of these health disparities.


Modern treatment of pulmonary embolism.
Modern treatment of acute pulmonary embolism requires rapid and accurate diagnosis followed by risk stratification to devise an optimal management strategy. Patients at low risk have good outcomes simply with intensive anticoagulation treatment. Higher-risk patients may require more aggressive intervention with thrombolysis or embolectomy. Clinical risk factors for an adverse outcome include increasing age, cancer, congestive heart failure, systemic arterial hypotension, chronic obstructive pulmonary disease and right ventricular dysfunction. A promising approach is the Geneva Prognostic Score, which is based upon a rapid clinical assessment. On physical examination, signs of right ventricular failure, including distended jugular veins and a right-sided S3 gallop, should be looked for. The electrocardiogram may show evidence of right ventricular strain with a new right bundle branch block or T wave inversion in leads V1-V4. The troponin level may be elevated as a marker of cardiac injury and right ventricular microinfarction, even in the absence of coronary artery disease. The most useful imaging marker of high risk is the presence of moderate or severe right ventricular dilatation and hypokinesis on the echocardiogram, especially with progressively worsening right ventricular function despite intensive anticoagulation treatment. Patients at high risk should be considered for thrombolytic therapy or embolectomy rather than management with anticoagulation therapy alone. Special care must be taken to avoid thrombolytic therapy among patients who might be susceptible to intracranial haemorrhage. Intracranial haemorrhage reached a surprisingly high rate of 3.0% in the International Cooperative Pulmonary Embolism Registry of 2,454 prospectively evaluated acute pulmonary embolism patients at 52 hospitals in seven countries. An alternative approach to patients at high risk is a catheter-based or open surgical embolectomy. It is crucial to refer these patients as quickly as possible, rather than delaying intervention until cardiogenic shock has ensued. Fortunately the current tools for risk stratification provide an "early window" for prognostication and can help the coordination of a definitive treatment plan with optimal results.


Potent effector function of tumor-sensitized L-selectin(low) T cells against subcutaneous tumors requires LFA-1 co-stimulation.
Animal tumor models have demonstrated that adoptive transfer of tumor-draining lymph node (TDLN) T lymphocytes can cure established tumors in many anatomic sites. However, subcutaneous tumors are relatively refractory and have required maximally tolerated doses of cells. The goals of this study were to determine whether a subset of TDLN T lymphocytes varying in expression of the cell adhesion molecule L-selectin (CD62L) had augmented therapeutic efficacy and to determine the co-stimulatory requirements for trafficking and anti-tumor effector function. TDLNs were recovered from mice bearing progressive MCA 205 fibrosarcomas, and the T lymphocytes were segregated into CD62L(low) and CD62L(high) subsets and activated ex vivo with anti-CD3 mAb and IL-2. Mice bearing established subcutaneous MCA 205 tumors were treated with activated T cell subsets and in some experiments with additional mAb against cell adhesion molecules. Adoptive transfer of as few as 5 x 10(6) activated cells cured mice bearing 3-day subcutaneous MCA 205 tumors initiated with 6 x 10(6) cells, and the tumors demonstrated a dense infiltrate of CD62L(low) cells. In marked contrast, adoptive transfer of 10 times as many T cells derived from the reciprocal CD62L(high) compartment had no effect on tumor growth. The effector function of the CD62L(low) T cells was clearly dependent on co-stimulation through the cell adhesion molecule LFA-1, because anti-LFA-1 mAb completely abrogated the anti-tumor reactivity of the transferred cells against subcutaneous tumors and inhibited tumor infiltration. In contrast, blockade of ICAM-1, VLA-4, or VCAM-1 had no inhibitory effect on the anti-tumor function. These studies demonstrate the high therapeutic activity of the CD62L(low) subset of tumor-draining LN T cells against subcutaneous tumors, a relatively refractory site, and confirm the essential role of LFA-1 for effector T cell function. Identification of the phenotype and requirements for effector function of T lymphocytes sensitized to tumor antigens has implications for clinical trials of adoptive immunotherapy for head and neck carcinoma using a similar approach.


Oversight of Genomic Data Sharing: What Roles for Ethics and Data Access Committees?
Discussions regarding responsible genomic data sharing often center around ethical and legal issues such as the consent, privacy, and confidentiality of individuals, families, and communities. To ensure the ethical grounds of genomic data sharing, oversight by both research ethics and Data Access Committees (DACs) across the research lifecycle is warranted. In this article, we review these oversight practices and argue that they reveal a compelling need to clarify the scope of ethical considerations by oversight bodies and to delineate core elements such as "objectionable" data uses. Ethical oversight of genomic data sharing would be considerably improved if the relevant ethical considerations by research ethics and DACs were coordinated. We therefore suggest several mechanisms to achieve greater clarification of ethical considerations by these committees, as well as greater communication and coordination between both to ensure robust and sustained ethical oversight of genomic data sharing.


Molecular dynamics and NMR spin relaxation in proteins.
Molecular dynamics simulations often play a central role in the analysis of biomolecular NMR data. The focus here is on NMR spin-relaxation, which can provide unique insights into the time-dependence of conformational fluctuations, especially on picosecond to nanosecond time scales which can be directly probed by simulations. A great deal has been learned from such simulations about the general nature of such motions and their impact on NMR observables. In principle, relaxation measurements should also provide valuable benchmarks for judging the quantitative accuracy of simulations, but there are a variety of experimental and computational obstacles to making useful direct comparisons. It seems likely that simulations on time scales that are just now becoming generally feasible may provide important new information on internal motions, overall rotational diffusion, and the coupling between internal and rotational motion. Such information could provide a sound foundation for a new generation of detailed interpretation of NMR spin-relaxation results.


Embryonic resetting of the parental vernalized state by two B3 domain transcription factors in Arabidopsis.
Some overwintering plants acquire competence to flower, after experiencing prolonged cold in winter, through a process termed vernalization. In the crucifer plant Arabidopsis thaliana, prolonged cold induces chromatin-mediated silencing of the potent floral repressor FLOWERING LOCUS C (FLC) by Polycomb proteins. This vernalized state is epigenetically maintained or 'memorized' in warm rendering plants competent to flower in spring, but is reset in the next generation. Here, we show that in early embryogenesis, two homologous B3 domain transcription factors LEAFY COTYLEDON 2 (LEC2) and FUSCA3 (FUS3) compete against two repressive B3-containing epigenome readers and Polycomb partners known as VAL1 and VAL2 for the cis-regulatory cold memory element (CME) of FLC to disrupt Polycomb silencing. Consistently, crystal structures of B3-CME complexes show that B3FUS3, B3LEC2 and B3VAL1 employ a nearly identical binding interface for CME. We further found that LEC2 and FUS3 recruit the scaffold protein FRIGIDA in association with active chromatin modifiers to establish an active chromatin state at FLC, which results in resetting of the silenced FLC to active and erasing the epigenetic parental memory of winter cold in early embryos. Following embryo development, LEC2 and FUS3 are developmentally silenced throughout post-embryonic stages, enabling VALs to bind to the CME again at seedling stages at which plants experience winter cold. Our findings illustrate how overwintering crucifer annuals or biennials in temperate climates employ a subfamily of B3 domain proteins to switch on, off and on again the expression of a key flowering gene in the embryo-to-plant-to-embryo cycle, and thus to synchronize growth and development with seasonal temperature changes in their life cycles.


Osteoarthritis 1991. Current drug treatment regimens.
Osteoarthritis, the most common rheumatic disease, presents the clinician with a major therapeutic and management task. The chronic and progressive course of the disease is punctuated by pain, declining function and escalating disability. This article attempts to deal with the pharmacological therapeutic options available to use in the management of osteoarthritis. Other non-pharmacological therapeutic modalities are also briefly discussed, including patient education, joint protection, physiotherapy, occupational therapy and surgery. Drug therapy as discussed focuses on the control of pain and inflammation. For this intermittently painful condition analgesic drugs assume a very important role. Non-steroidal anti-inflammatory drugs (NSAIDs) have combined analgesic and anti-inflammatory properties which are particularly useful in many patients who manifest inflammation in addition to pain. While systemic steroids have no role in the treatment of osteoarthritis, intra-articular steroid injections may be of benefit. In trying to slow the degenerative process chondroprotective agents such as glycosaminoglycan may also assume increasing importance in the future. Choosing one drug over another must be done after consideration of many factors including the therapeutic and toxicity profile of the drugs involved, their pharmacology and dose regimen, the patient profile, cost and the desired effect.


Pharmacokinetics of dalfampridine extended release 7.5-mg tablets in healthy subjects and individuals with mild and moderate renal impairment: an open-label study.
Dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) are available to improve walking in patients with multiple sclerosis (MS). D-ER is mainly renally eliminated; the approved 10-mg twice daily dose is contraindicated in the United States in patients with moderate or severe renal impairment. This study evaluated single-dose and steady-state pharmacokinetics of a 7.5-mg dose of D-ER in healthy subjects (n = 13) and subjects with mild (n = 17) and moderate (n = 12) renal impairment. D-ER plasma concentrations were consistently higher in subjects with renal impairment relative to healthy individuals with a significant (P < .0001) inverse linear relationship between creatinine clearance and drug exposure. Steady-state AUC0-12 among healthy subjects, 167.0 ± 55.3 ng h/mL, increased 74% and 151% with mild and moderate renal impairment, respectively. The overall incidence of adverse events was 61.5%, 47.1%, and 33.3% in healthy subjects, and subjects with mild and moderate renal impairment, respectively, and for treatment-related adverse events the rates were 0%, 17.6%, and 8.3%, respectively. The most common adverse events were headache, dizziness, and arthralgia. The pharmacokinetics of D-ER 7.5-mg twice daily in subjects with mild renal impairment was comparable to 10-mg twice daily in patients with MS who had normal renal function. Exposure was significantly higher in moderate renal impairment.


Methotrexate in chronic-recurrent calcium pyrophosphate deposition disease: no significant effect in a randomized crossover trial.
Calcium pyrophosphate deposition (CPPD) may cause severe arthropathy, major joint destruction and treatment options are limited. The aim of this study was to test the therapeutic efficacy of methotrexate (MTX) in chronic or recurrent CPPD arthropathy. Patients with CPPD arthropathy were randomized to receive either weekly subcutaneous injections of 15 mg/week of MTX or placebo (PBO) for three months, in a double-blind, crossover randomized controlled trial. Inclusion criteria comprised definite CPPD disease, recurrent arthritis or persistent polyarthritis, and an insufficient response to NSAIDs, glucocorticoids or colchicine. The primary outcome was an improvement in the disease activity scores based on 44 joints (DAS44). The analysis was performed on an intent-to-treat basis. We randomized 26 patients, and compared 25 treatment periods on MTX with 21 treatment periods on PBO. Baseline characteristics were balanced between the groups. The evolution of the DAS44 was not statistically significantly different between groups (median DAS44 decreased by -0.08 on MTX versus -0.13 on PBO, after three months, P = 0.44). Furthermore, pain levels remained stable in both groups (median change in VAS Pain -1 unit on MTX and 0 on PBO, P = 0.43), and none of the secondary outcomes was significantly different between the two groups. Minor adverse events (AE) did not differ in frequency between the groups, but the only serious AE occurred on MTX (bicytopenia). The results of this trial with MTX in this older population with chronic or recurrent CPPD arthropathy suggest no strong effect of MTX on disease activity. EudraCT No: 2007-003479-37. Registered 26 April 2008.


Adult Posterior Fossa Anaplastic Ependymoma, Case Series and Literature Review.
Ependymomas are rare central nervous system tumors. The current treatment strategy is gross total tumor removal. Whether adjuvant therapy will be beneficial is controversial. We retrospectively analyzed 3 cases of World Health Organization (WHO) grade III posterior fossa anaplastic ependymomas treated with different treatment modalities. We aimed to identify possible treatment options for infratentorial WHO grade III anaplastic ependymoma in adults. We performed a retrospective analysis of 3 patients diagnosed with infratentorial anaplastic ependymomas in our institution from 2016 to 2020. The demographic data were documented. This case series of 3 patients does not meet the Department of Health and Human Services definition of research and does not need Institutional Review Board approval. All patients' informed consents have been obtained. One patient underwent subtotal tumor resection combined with adjuvant radiotherapy and Gamma Knife radiosurgery while the other 2 patients underwent gross total tumor removal combined with Gamma Knife radiosurgery or adjuvant radiotherapy. Tumors recurred in the first patient 20 months later, while the other 2 patents did not develop recurrence. The modified Rankin scale scores of these patients were 1, 0, and 0. All patients are followed up with regular magnetic resonance imaging at our facility. The strategy for treating WHO grade III anaplastic ependymomas is controversial, but gross total tumor resection remains the key element. Adjuvant stereotactic radiosurgery after tumor removal might be considered if radiotherapy is not an option. The role of chemotherapy is unclear, and the use of chemotherapy should be tailored to individual patients.


Hospital governance and market share.
The organizational structure of nonprofit hospitals has remained fixed while hospital technology and financing have changed. Caught between competitive pressures from other organizations not subject to the same government regulation to contain costs and assure quality, and physician resistance to organizational change, hospital boards lack the capacity to make effective and timely decisions to retain market share. Governing structure will have to change for nonprofit hospitals to sustain growth and to achieve adequate standards of cost containment, quality assurance, and patient service. Accountability for hospital performance should be maintained through increased control of the governing board by physicians and managers. The board and medical official should agree on the nature of the latter's accountability for departmental or committee performance. The board should hold medical officials so accountable. If regulators, trustees, physicians, and managers are genuinely interested in sustaining the nonprofit hospital's share of the market, they must pay more attention to the structure and function of hospital governance, so that boards can more effectively respond to market opportunities, contain costs, and assure quality.


Assisted Oocyte Activation With Calcium Ionophore Improves Pregnancy Outcomes and Offspring Safety in Infertile Patients: A Systematic Review and Meta-Analysis.
This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38-3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53-4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.