miR-20b attenuates airway inflammation by regulating TXNIP and NLRP3 inflammasome in ovalbumin-induced asthmatic mice.
Asthma is a chronic inflammatory disorder of the airway and is associated with pyroptosis. microRNAs (miRNAs) underlie pathogenic mechanism in asthma. This study is expected to evaluate the role of miR-20b in asthma-induced airway inflammation via regulating thioredoxin-interacting protein (TXNIP) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. The asthmatic mouse model was established via ovalbumin (OVA) induction. Expressions of miR-20b, TXNIP, and NLRP3 in lung tissues were determined. Bronchial hyperresponsiveness was appraised, cells in bronchoalveolar lavage fluid were counted and categorized, and histopathological damage was observed. Levels of inflammatory and pyroptotic cytokines were measured. The binding relationship of miR-20b and TXNIP was testified. Co-location and interaction between TXNIP and NLRP3 were detected. Mice were infected with the lentivirus packaged with pcDNA3.1-TXNIP or pcDNA3.1-NLRP3 for joint experiments to observe the pathological changes of mice. miR-20b was poorly expressed, while TXNIP and NLRP3 were highly expressed in OVA-induced mice. miR-20b overexpression attenuated airway inflammation and pyroptosis, manifested by alleviation of histopathological damage, declined numbers of total cells and inflammatory cells, lowered bronchial hyperresponsiveness, decreased levels of pro-inflammatory and pyroptotic cytokines, and increased anti-inflammatory cytokines. miR-20b targeted TXNIP and inhibited TXNIP expression, and TXNIP can bind to NLRP3 and upregulated NLRP3 expression. Upregulation of TXNIP or NLRP3 could reverse the protecting role of miR-20b overexpression in OVA-induced mice. miR-20b inhibited TXNIP expression to reduce the binding of TXNIP and NLRP3, thus restricting pyroptosis and airway inflammation of asthmatic mice.


Cross-fertilization between Syrian and Chinese hamsters.
The role of the zona pellucida in the specificity of fertilization was studied by cross-inseminations between Syrian (Golden) and Chinese hamster gametes. Cumulus-enclosed eggs from both Syrian and Chinese hamsters were placed together in one dish and inseminated with spermatozoa from either one or the other species. Fertilization always took place between gametes of homologous species. Chinese hamster spermatozoa failed to bind to the zona pellucida of Syrian hamster eggs; hence, fertilization was never observed. However, Chinese hamster spermatozoa could fertilize zona-free Syrian hamster eggs. In the reciprocal cross, a large number of Syrian hamster spermatozoa could bind to and penetrate the zonae of Chinese hamster eggs. However, fusion of Syrian hamster spermatozoa with the vitellus of zona-intact Chinese hamster eggs was never observed. After removal of the zona pellucida, only a small percentage (31%) of Syrian hamster spermatozoa could fuse with Chinese hamster vitelli. Thus, in these species, the mechanisms of interspecific gamete recognition and the prevention of interspecies fertilization seem to differ according to the direction of the cross. In Syrian hamster eggs, the block to interspecies fertilization seems to exist at the level of the zona pellucida, while in Chinese hamster eggs the block is at the level of the egg plasma membrane. The implications of these results in analyses of the genetics of spermatozoa, the molecular basis of sperm-egg recognition, and mechanisms of reproductive isolation leading to speciation, are discussed.


Social desirability scale values of locus of control scale items.
Three groups of subjects rated each item in Rotter's I-E Scale for its social desirability value. Social desirability scale values (SDSV) of paired items were compared with one another. Results indicated that paired items are not sufficiently similar in their SDSVs, thus enabling subjects to respond on the basis of social desirability. All three groups rated internal items as being significantly more socially desirable than external items. The correlations between the SDSV ratings of the three groups were highly significant. The results indicate that the scale, as it is currently used, is seriously deficient.


Effect of barium ions on excitation-contraction coupling of frog twitch muscle fibres.
The mechanism for the Ba2(+)-induced potentiation of the twitch tension in frog skeletal muscle was investigated. No significant difference in the peak amplitude of the calcium transients evoked by voltage-clamp depolarizing pulse was found between the fibres bathed in Ca2+ (control) and Ba2+ Ringer's solution, whereas the calcium transients evoked by the action potentials from the fibres in Ba2+ Ringer's solution were increased by about 64%, compared with control. In comparison with control, the action potentials of the fibres in Ba2+ Ringer's solution had a similar overshoot but a significantly longer time course. Our results suggest that excitation-contraction coupling in frog twitch muscle fibres is not altered by replacing Ca2+ with Ba2+. The Ba2(+)-induced potentiation of contraction may be accounted for by broadening of the action potentials.


Facile preparation of toluidine blue-loaded DNA nanogels for anticancer photodynamic therapy.
Photodynamic therapy (PDT) provides an effective therapeutic option for different types of cancer in addition to surgery, radiation, and chemotherapy. The treatment outcome of PDT is largely determined by both the light and dark toxicity of photosensitizers (PSs), which can be technically improved with the assistance of a drug delivery system, especially the nanocarriers. Toluidine blue (TB) is a representative PS that demonstrates high PDT efficacy; however, its application is largely limited by the associated dark toxicity. Inspired by TB's noncovalent binding with nucleic acids, in this study, we demonstrated that DNA nanogel (NG) could serve as an effective TB delivery vehicle to facilitate anticancer PDT. The DNA/TB NG was constructed by the simple self-assembly between TB and short DNA segments using cisplatin as a crosslinker. Compared with TB alone, DNA/TB NG displayed a controlled TB-releasing behavior, effective cellular uptake, and phototoxicity while reducing the dark toxicity in breast cancer cells MCF-7. This DNA/TB NG represented a promising strategy to improve TB-mediated PDT for cancer treatments.


Dynamics of pH modification of an acidic protein bait used for tropical fruit flies (Diptera: Tephritidae).
Several species of Anastrepha and Bactrocera fruit flies (Diptera: Tephritidae) are captured in traps baited with the protein bait NuLure combined with borax (sodium tetraborate decahydrate) in an aqueous solution, typically 9% NuLure (vol:vol) with 3% borax (wt:vol). NuLure is an acid hydrolysate of corn and has an acidic pH. Addition of borax makes the solution more alkaline, and increase in alkalinity results in increase of ammonia release from the bait solution. This is a very dynamic system, with resultant pH affected by factors such as the amount of borax added, the pH of the water used for preparation, the age of the bait solution, and the development of microbial growth. Problems with borax include amount needed to increase alkalinity of NuLure solutions, which creates difficulties in disposing of spent bait in fruit fly trapping programs. Therefore, research was conducted to evaluate NaOH as an alternative method to increase alkalinity of NuLure solutions. Laboratory experiments compared effect of NaOH versus borax for pH modification on changes in pH and ammonia content of NuLure solutions over time. Although NuLure/NaOH solutions could be adjusted to a more alkaline pH than NuLure/borax solutions, borax plays a critical role in pH stability over time. However, the pH of NuLure/NaOH is stabilized when propylene glycol (10% vol:vol) was used to prepare the bait solution. The use of NaOH can provide an alternative to the use of borax to increase bait solution alkalinity.


Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle.
 Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.


Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4 endonuclease complex formation and nuclear localization.
The Saccharomyces cerevisiae Mms4 and Mus81 proteins form a specific complex, which functions as an endonuclease specific for branched DNA molecules and protects cells from killing by DNA alkylation damage, but not damage induced by ionizing radiations. In an effort to further understand the structure and functions of the Mus81-Mms4 complex, we attempted to define domains required for complex formation and nuclear localization through deletion and mutagenesis analyses. Combined yeast two-hybrid and co-immunoprecipitation experiments indicate that the C-terminal 100 amino acids of both Mus81 and Mms4 are required and sufficient for heterodimer formation. However, a single amino acid substitution in Mms4 in the N-terminal region is able to abolish the interaction, which suggests that the three-dimensional structure is also important for Mms4 to interact with Mus81. By fusion to green fluorescent protein and in vivo subcellular localization studies, we demonstrate that Mms4 and Mus81 are nuclear proteins and can be localized to the nucleus independently. Deletion analyses indicate that one of two putative nuclear localization signals (residues 244-263) in Mms4 is required for localization, whereas the N-terminal half of Mus81 is necessary and sufficient for its localization to the nucleus.


Characteristics of Pakistani women seeking abortion and a profile of abortion clinics.
A study of the characteristics of Pakistani women seeking abortion and a profile of abortion clinics was conducted in 32 abortion clinics in three provincial capitals of the country. All 452 women who had their pregnancies terminated between October and December 1997 were interviewed. Except for 39 women (8.6%), all study subjects were married. A majority of the women (36.6%) were aged >35 years, 61.0% had given birth to > or =5 children, and 40.2% were illiterate. The predominant reasons for abortion were "too many children" (64.4%), contraceptive failure (20.3%), premarital affairs (8.6%), medical reasons (5.4%), and extramarital affairs (1.3%). Nearly two thirds of the abortions were induced by inadequately trained persons. Only 22% of the abortion clinics met the World Health Organization (WHO) standards required for safe termination of pregnancy. At all these clinics, the procedure used to terminate the pregnancy was dilatation and curettage (D&C). Only one clinic was using manual vacuum aspiration (MVA). Induced abortion seems to be fairly common among married women of high parity, advanced age, and low educational status. Keeping in view the large number of terminations, new medical and surgical techniques of pregnancy termination should be introduced to those already providing abortion services.


The electroencephalographic effects of desflurane in humans.
The electroencephalographic (EEG) effects of a new inhaled anesthetic are of interest because of the potential of such agents to produce excitatory (convulsant) activity and because of the potential usefulness of the EEG as an indicator of anesthetic depth and cerebral activity. Accordingly, we examined the EEG in 12 healthy, young male volunteers during desflurane anesthesia. Each subject had a baseline recording and then steady-state exposure to 6, 9, and 12% (0.83, 1.24, and 1.66 MAC) desflurane in O2 alone, and to 3, 6, and 9% desflurane in O2 with 60% N2O. The sequence of doses and the presence of N2O were randomized. We used mechanical ventilation to maintain normocapnia at each dose level. We also tested the effects of hypercapnia secondary to spontaneous ventilation. Additionally, at 1.24 MAC, subjects' lungs were hyperventilated to a PCO2 of 25.8 +/- 0.7 mmHg and exposed to rhythmic, loud clapping to attempt to provoke excitatory phenomena. Finally, after at least 6 h exposure to desflurane, we repeated measurements at 0.83 and 1.66 MAC to assess possible tolerance. Four channels of EEG were monitored visually, and at each dose, a quantitative EEG analysis was performed. Desflurane produced EEG changes comparable to those observed with equipotent levels of isoflurane. No epileptiform activity was seen. Desflurane significantly suppressed EEG activity; prominent burst suppression was seen at 1.24 MAC and higher. Substitution of N2O for 0.42 MAC desflurane reduced the degree of EEG suppression relative to the equipotent administration of desflurane and O2. Quantitative EEG measures for the early doses and for the later, repeated exposures did not differ.


Psychosocial adjustment process of mothers caring for young men with traumatic brain injury: focusing on the mother-son relationship.
This study focuses on the mother-son relationship of 13 mothers caring for single sons between the ages of 15 and 30 years who have higher brain dysfunction due to a traumatic brain injury. We aimed to elucidate the psychosocial adjustment process of mothers for 5 years following the injury to facilitate the social rehabilitation of both mother and son. Data obtained through a semistructured interview method were analyzed using a modified grounded theory approach. After 56 concepts were identified, 18 categories and then 8 core categories were semantically created. The 8 core categories were (a) avoid contact with son, (b) support son based on mother's own desire, (c) support son alone without external support, (d) realize mother's care limits and seek external support sources, (e) request and utilize external support, (f) support and work toward son's independence while monitoring his interactions with others, (g) mother considers own feelings and reenters society, and (h) strive for continued care of son with mother's acquired energy and efficient management skills. These were grouped into the following five stages: (a) avoidance, (b-c) closed, (d) support seeking, (e-f) withdrawal, and (g-h) reconstruction.


Distribution of ammonia-oxidizing bacteria in sewage activated sludge: analysis based on 16S rDNA sequence.
This study carried out analysis of ammonia-oxidizing bacteria (AOB) communities in 12 sewage activated sludge systems standing in eight sewage treatment plants located in Tokyo. The systems were different in the treatment process configuration: anaerobic/anoxic/aerobic (A20), anaerobic/aerobic (AO), and conventional activated sludge (AS) processes. AOB communities were analyzed by sequences of 16S rDNA amplicons, which were separated by denaturing gradient gel eletrophoresis (DGGE) after specific polymerase chain reaction (PCR) amplification. The results demonstrated that low ammonium concentrations in the influents of the 12 sewage activated sludge systems resulted in the dominance of Nitrosomonas oligotropha-like sequences. Further, Nitrosomonas europaea- and Nitrosomonas cryotolerans-like sequences were recovered from only one A20 system of which the influent contained higher ammonium and chloride concentrations than those of other systems. Nitrosomonas communis-like sequences were found in every A20 and AO system, but mostly not found in every AS system. In summary, influent characteristics and treatment process configuration affected the AOB communities in the 12 sewage activated sludge systems.


Acupuncture regulates the aging-related changes in gene profile expression of the hippocampus in senescence-accelerated mouse (SAMP10).
To examine molecular events in hippocampus associated with aging and acupuncture effect, we employed cDNA arrays providing data of 588 genes to define transcriptional patterns. Male 8-month-old SAMP10 and its homologous SAMRl were selected and randomly divided into four groups: R1 control group (Rc), P10 control group (Pc), P10 acupuncture group (Pa) and P10 non-acupoint group (Pn). The points consisted Shanzhong (CV17), Zhongwan (CV12), Qihai (CV6), Zusanli (ST36) and Xuehai (SP10). In Pa, we found that points stimuli could completely or partly reverse some genes expression profiles in hippocampus with aging. Simultaneously, some genes not related with brain aging were affected by acupuncture as well. Meanwhile, non-acupoint had some effect on aging-unrelated genes expression and little or negative effect on aging-related genes. We verified array results with RT-PCR and Northern blotting for three genes which are related to oxidative damage closely, including Hsp84, Hsp86 and YB-1. In conclusion, acupuncture could be a potential intervention to retard molecular events with aging in mammals.


Imaging of congenital heart disease in adults: choice of modalities.
Major advances in noninvasive imaging of adult congenital heart disease have been accomplished. These tools play now a key role in comprehensive diagnostic work-up, decision for intervention, evaluation for the suitability of specific therapeutic options, monitoring of interventions and regular follow-up. Besides echocardiography, magnetic resonance (CMR) and computed tomography (CT) have gained particular importance. The choice of imaging modality has thus become a critical issue. This review summarizes strengths and limitations of the different imaging modalities and how they may be used in a complementary fashion. Echocardiography obviously remains the workhorse of imaging routinely used in all patients. However, in complex disease and after surgery echocardiography alone frequently remains insufficient. CMR is particularly useful in this setting and allows reproducible and accurate quantification of ventricular function and comprehensive assessment of cardiac anatomy, aorta, pulmonary arteries and venous return including complex flow measurements. CT is preferred when CMR is contraindicated, when superior spatial resolution is required or when "metallic" artefacts limit CMR imaging. In conclusion, the use of currently available imaging modalities in adult congenital heart disease needs to be complementary. Echocardiography remains the basis tool, CMR and CT should be added considering specific open questions and the ability to answer them, availability and economic issues.


Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma.
Hybrid cell vaccination is a new cancer immune therapy approach that aims at recruiting T cell help for the induction of tumour specific cytolytic immunity. The vaccines are generated by fusion of the patients' tumour cells with allogeneic MHC class II bearing cells to combine the tumour's antigenicity with the immunogenicity of allogeneic MHC molecules. Safety and anti-tumour activity of this treatment were assessed in a clinical trial that has yielded one complete and one partial remission, and 5 cases of stable disease among 16 patients with advanced stage metastatic melanoma. As evidenced by histology, the vaccination induced T cell relocation into tumour nodules. Stable disease could be maintained by repeated booster injections for more than 24 months in some patients. The side effects were minor. Occasional occurrences of vitiligo spots after vaccination were indicative of a restricted therapy induced auto-immune reactivity. The results suggest that hybrid cell vaccination is a safe cancer immune therapy potentially effective for induction of acute anti-tumour response as well as long-term maintenance.


Aspirin absorption from a feeding jejunostomy.
In a 67-year-old man who had a feeding jejunostomy because of dysphagia paralytica, the absorption of aspirin was measured in terms of serum salicylate concentration. A 975-mg dose of aspirin was given as a slurry in water directly into the feeding tube. Peak serum levels of salicylate were well correlated with those in previous studies of aspirin absorption by the oral route in a geriatric population. However, unexpectedly, the half-life of the drug in this patient was twice as long (7.5 hours) as that found in six previous studies (3.7 hours) of elderly patients given similar doses.


IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways.
Endometriosis (EMs) is a chronic inflammatory condition. Interleukin (IL)-37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study aimed to evaluate the possible role of IL-37 in the EMs pathogenesis. We investigated the in vivo effect of IL-37 on EMs by injection with recombinant human IL-37 (rhIL-37) into EMs mice. Furthermore, we evaluated the in vitro effects of IL-37 on proliferation, adhesion, migration and invasiveness of endometrial stromal cells (ESCs), and explored whether Wnt/β-catenin and mitogen-activated protein kinase (MAPK) pathways were involved in this process. In cultured ESCs, IL-37 overexpression significantly suppressed both protein and mRNA expression of the inflammation-associated cytokines, including IL-1β, IL-6, IL-10 and tumor necrosis factor (TNF-α). Furthermore, IL-37 overexpression significantly inhibited ESCs proliferation, adhesion, migration, invasion and the activity of matrix metalloproteinase (MMP)-2 and MMP-9. In contrast, knockdown of IL-37 exerted the opposite effects. Importantly, the IL-37-mediated action in ESCs was through inactivation of Wnt/β-catenin, p38 MAPK, extracellular signal-related kinases MAPK and c-Jun N-terminal kinase MAPK pathways. Moreover, EMs mice treated with rhIL-37 showed the decreased endometriotic-like lesion size and lesion weight, lower expression of IL-1β, IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-I (ICAM-I) and MMP-2/9 activity in peritoneal fluid compared with the wide type (WT) EMs mice. These findings suggest that IL-37 suppresses cell proliferation, adhesion, migration and invasion of human ESCs through multiple signaling pathways, thereby affecting the occurrence and development of EMs.


A comparison of three organisational levels in one health care region in Sweden implementing person-centred care: coupled, decoupled or recoupled in a complex organisation.
Establishing more substantial patient involvement in the health care has become fundamental to Western health care services. Person-centred care (PCC) has been developed as a way of working that involve the patients and family members. However, the implementation of PCC in clinical practice has proven to be challenging. The aim of this study was to explore the congruence of managers' perceptions and understanding of various aspects of PCC across three organisational levels in one health care region in Sweden in terms of coupling, decoupling and recoupling. A policy on increased patient participation in health care was adopted in one health care region in Sweden. This policy was embodied in the form of PCC and a support strategy for the implementation was put in place. Participants representing three organisational levels (senders: politicians, n = 3; messengers: senior management, n = 7; and receivers: middle- and frontline managers, n = 13) were interviewed and documents collected. A deductive qualitative content analysis was performed and findings from the three organisational levels compared. Descriptions of PCC at all the three organisational levels included health care provided in partnership between provider and patient. However, messengers and receivers also included aspects of how work was organised as part of the concept. Representatives at all levels expected high-quality care while reducing health care costs as an outcome, however, messengers and receivers also anticipated improvements in the work environment and reduced staff turnover. Strategies to support implementation included continuation and enhancement of existing routines that were considered person-centred and development of new ones. A need to make PCC less 'fuzzy' and ambiguous and instead communicate a more tangible care process was described. Representatives among messengers and receivers also suggested that no actions were needed because the practice was already considered person-centred. The findings indicated that congruence between organisational levels existed in some aspects, suggesting coupling between policy and practice. However, also incongruences were identified that might be due to the fuzziness of definitions and the application of PCC in practice, and the difficulty in assessing the level of patient-centredness in clinical practice.


Ligand-Mediated Hydrogenic Defects in Two-Dimensional Electrically Conductive Metal-Organic Frameworks.
Compared to dense analogues, high-surface-area metals offer several key advantages in electrocatalysis and energy storage. Of the porous manifolds, metal-organic frameworks (MOFs) boast the highest known surface area of any material class, and a subset of known frameworks also conduct electricity. The premier conductive scaffolds, Ni3(HITP)2 and Ni3(HIB)2, are both predicted to be metallic, but experiments have yet to measure bulk metallicity. In this paper, we explore the thermodynamics of hydrogen vacancies and interstitials and demonstrate that interstitial hydrogen is a plausible and prevalent defect in the conductive MOF family. The existence of this defect is predicted to render both Ni3(HITP)2 and Ni3(HIB)2 as bulk semiconductors, not metals, and emphasizes that hydrogenic defects play a critical role in determining the bulk properties of conductive MOFs.


Help to Family and Friends: Are There Gender Differences at Older Ages?
This paper uses recent data from the Wisconsin Longitudinal Study (N = 5,220) to explore gender differences in the extent to which adults in their 50s and 60s provide informal help to their adult children, elderly parents and friends We find that both men and women report very high levels of helping kin and nonkin alike, though women do more to assist elderly parents and women provide much more emotional support to others than do men. Men provide more assistance than do women with "housework, yard work and repairs." As they retire from the workforce, married men become significantly more involved in the care of their grandchildren, virtually eliminating any gender difference by the time they are in their 60s.


Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004.
Widespread use of pneumococcal conjugate vaccine (PCV7) resulted in decreases in invasive disease among children and elderly persons. The benefits may be offset by increases in disease due to serotypes not included in the vaccine (hereafter, "nonvaccine serotypes"). We evaluated the effect of PCV7 on incidence of disease due to nonvaccine serotypes. Cases of invasive disease were identified in 8 geographic areas through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Serotyping and susceptibility testing of isolates were performed. We calculated the incidence of disease for children aged <5 years and adults aged > or =65 years. We compared rates of serotype-specific disease before and after PCV7 was licensed for use. The annual incidence of disease due to nonvaccine serotypes increased from an average of 16.3 cases/100,000 population during prevaccine years (1998-1999) to 19.9 cases/100,000 population in 2004 for children aged <5 years (P=.01) and from 27.0 cases/100,000 population during prevaccine years to 29.8 cases/100,000 population in 2004 for adults aged > or =65 years (P=.05). Significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period (P<.05 for each serotype); serotype 19A has become the predominant cause of invasive disease in children. The incidence of disease due to these serotypes also increased among elderly persons. The incidence of pneumococcal disease caused by nonvaccine serotypes is increasing. Ongoing surveillance is needed to monitor the magnitude of disease caused by nonvaccine serotypes, to ensure that future vaccines target the appropriate serotypes.


Increase in CD95 (Fas/APO-1)-positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena.
The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). The CD95 and Bcl-2 expressions within CD4+ T, CD8+ T, and CD19+ B cell subsets were analysed by two-colour flow cytometry. The surface expression of CD95 was significantly high in both the CD4+ T and CD8+ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO- to primed CD45RO+ CD4+ T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl-2-positive cells in the CD4+ T cell, CD8+ T cell and CD19+ B cell subsets among the patient groups and normal subjects. These results indicate that an increase in CD4+ T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non-specific activation of T lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI).


How to implement an office-based vein program.
Peripheral venous disease is a highly prevalent problem affecting over 25-30 million people in the United States. Office-based treatment of superficial veins for chronic venous insufficiency is a fast-growing area with a recent surge of interest by cardiologists in this field. We describe our own experience with establishing a vein clinic in a single-specialty, cardiology-based office, and provide tips and tricks on how you can start your own vein program. A program based on the mission of providing high-quality, appropriate care to patients and with knowledgeable providers and staff is of paramount importance for the reputation and growth of the clinic. Other important factors needed for success include diligent oversight by a director and/or supervisor, an efficient precertification process, prompt billing and coding, and establishing an internal database or participation in a national venous database to track outcomes and complications. Regular meetings of all clinic participants that discuss quality, outcomes, and operational issues are essential to help standardize care and meet the recently launched Intersocietal Accreditation Commission standards.


Decreasing influenza vaccine coverage among adults with high-risk chronic diseases in Spain from 2014 to 2017.
The objectives of this study were to estimate coverage of influenza vaccination in Spain among adults suffering chronic conditions, to assess time trends from 2014 to 2017 and to identify vaccine uptake predictors. We used individualized data of persons ≥15 y interviewed in the 2017 Spanish National Health Survey. Vaccine uptake and the presence of the chronic conditions analyzed (diabetes; cancer; chronic respiratory disease; chronic heart disease and cerebrovascular disease) were self-reported. Independent variables included sex, age and nationality. In 2017 overall influenza vaccination uptake among subjects with high-risk chronic conditions remained low (40.3%) and decreased significantly from 2014 (41.7%, adjusted OR 0.98 95%CI 0.84-0.98). The highest coverage was found among those with cerebrovascular disease (52.2%), diabetes (51.5%) and heart disease (51.4%) and the lowest figures for those suffering cancer (34.9%) and respiratory disease (35.1%). Coverage for cancer patients declined a 25% from 2014 to 2017. Older persons had higher coverages whereas females and immigrant population had lower uptakes.We conclude that influenza vaccination coverage among the high-risk population in Spain for suffering chronic conditions remains at a low level and has decreased significantly from 2014 to 2017, this affects more intensely to females and immigrants.


Detection of incoherent joint state due to inaccurate bone motion estimation.
In biomechanical modelling and motion analysis, the use of personalised data such as bone geometry would provide more accurate and reliable results. However, there are still a limited number of tools used to measure the evolution of articular interactions. This paper proposes a coherence index to describe the articular status of contact surfaces during motion. The index relies on a robust estimation of the evolution of surfacic interactions between the joint surfaces. The index is first compared to distance maps on simulated motions. It is then used to compare two motion capture protocols (two different localisations of the markers for scapula tracking). The results show that the index detects progressive modifications in the joint and allows distinguishing the two protocols, in accordance with the literature. In the future, the index could, among other things, be used to compare/improve biomechanical models and motion analysis protocols.


Theta oscillations are sensitive to both early and late conflict processing stages: effects of alcohol intoxication.
Prior neuroimaging evidence indicates that decision conflict activates medial and lateral prefrontal and parietal cortices. Theoretical accounts of cognitive control highlight anterior cingulate cortex (ACC) as a central node in this network. However, a better understanding of the relative primacy and functional contributions of these areas to decision conflict requires insight into the neural dynamics of successive processing stages including conflict detection, response selection and execution. Moderate alcohol intoxication impairs cognitive control as it interferes with the ability to inhibit dominant, prepotent responses when they are no longer correct. To examine the effects of moderate intoxication on successive processing stages during cognitive control, spatio-temporal changes in total event-related theta power were measured during Stroop-induced conflict. Healthy social drinkers served as their own controls by participating in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg women) and placebo conditions in a counterbalanced design. Anatomically-constrained magnetoencephalography (aMEG) approach was applied to complex power spectra for theta (4-7 Hz) frequencies. The principal generator of event-related theta power to conflict was estimated to ACC, with contributions from fronto-parietal areas. The ACC was uniquely sensitive to conflict during both early conflict detection, and later response selection and execution stages. Alcohol attenuated theta power to conflict across successive processing stages, suggesting that alcohol-induced deficits in cognitive control may result from theta suppression in the executive network. Slower RTs were associated with attenuated theta power estimated to ACC, indicating that alcohol impairs motor preparation and execution subserved by the ACC. In addition to their relevance for the currently prevailing accounts of cognitive control, our results suggest that alcohol-induced impairment of top-down strategic processing underlies poor self-control and inability to refrain from drinking.


The potential role of gene expression in the management of primary and metastatic colorectal cancer.
Although there have been recent advances in treatment of colorectal cancer, microarray technology has the potential to improve the application of these therapies by interrogating tumor-specific molecular "fingerprints." The future applications and benefits of gene expression profiling are discussed. Potential uses include determining who will benefit from chemotherapy, further classifying patients into responders and nonresponders, predicting apoptotic response, developing classifiers to recognize chemosensitive tumors, identifying genes that portend a poor prognosis, revealing genes associated with metastases, predicting the outcome according to clinical stage, and avoiding surgery in patients who would not benefit from resection. Recent research has been aimed at not only finding new molecularly targeted agents, but also identifying specific signatures to predict sensitivity and resistance to therapy. Future care may soon incorporate the data derived from a single microarray chip or similar technology that will describe a patient's tumor, predict prognosis, and direct specific therapy.


Velutin, an Aglycone Extracted from Korean Mistletoe, with Improved Inhibitory Activity against Melanin Biosynthesis.
The abnormal regulation of melanin synthesis leads to a wide range of pigmentary disorders. Although various melanin biosynthesis inhibitors have been developed, their efficacy and long-term safety needs to be further improved, and thus the goal of this study is to develop promising natural compound inhibitors of melanin biosynthesis. Here, we obtained aglycone flavonoid extract through the microwave-assisted hydrolysis of glycoside extract from Korean mistletoe in acidic condition. The aglycone extract inhibited tyrosinase activity more efficiently with better antioxidant activity than glycoside extract in vitro. The microwave-assisted aglycone extract of mistletoe was further analyzed for in vivo activity, and the results showed the aglycone extract inhibited both early melanocyte development and melanin synthesis more efficiently in zebrafish embryo in a dose-dependent manner. Our in vivo toxicity assay quantitatively measured cell death in zebrafish embryos and showed that the microwave-assisted aglycone extract of mistletoe had no significant effect on cell death (p < 0.001), indicating that aglycone extract is more biocompatible than glycoside extract. Furthermore, our in vitro and in vivo analyses successfully identified and characterized velutin, an aglycone of a homoflavoyadorinin B glycoside, as a major inhibitory component in the microwave-assisted mistletoe extract. Ultimately, this study showed that the novel natural compound inhibitor velutin, which was generated through microwave-assisted extraction from mistletoe, improved the efficacy of melanin biosynthesis inhibition with little toxicity.


Acute pancreatitis occurring in gastric aberrant pancreas treated with surgery and proved by histological examination.
We describe a case of gastric aberrant pancreas with acute pancreatitis. Barium meal examination, endoscopic examination and computed tomography of a 32-year-old man with abdominal pain revealed a submucosal tumor, about 3.5 cm in diameter, at the angulus of his stomach. Endoscopic ultrasonography revealed a hypoechoic mass with anechoic capillary areas. His serum amylase level was high at 262 IU/l. Laparoscopy-assisted local resection was carried out. The resected tumor revealed pancreatic tissue with extensive neutrophil infiltration in the gastric wall and fat necrosis in the subserosa. There are few cases of histologically proven acute pancreatitis in gastric aberrant pancreatic tissue.


A comparison of drug coverage in alberta before and after the introduction of the national common drug review process.
The integration of the Common Drug Review (CDR) was a substantial change for Canada's public drug plans. Detailed comparisons of time-to-listing and proportion of medications covered by the province of Alberta's drug plans within the context of the CDR process have not been rigorously conducted. New drugs approved by Health Canada were identified five years prior to the CDR's first recommendation (May 2004) and five years after. The time-to-listing and proportion of new drugs covered on the Alberta Health and Wellness Drug Benefit List (AHWDBL) was compared between these periods. The level of agreement between CDR recommendations and coverage in Alberta was calculated using a kappa score. Two hundred and twenty new drugs were identified and met the study eligibility criteria (118 pre-CDR, 102 post-CDR). The median time-to-listing was 312 vs. 524 days in the pre-CDR and post-CDR periods, respectively, with the difference largely driven by time from notice of compliance (NOC) to the CDR recommendation. The level of agreement between 73 drugs with CDR recommendations and coverage in Alberta was fair (kappa 0.55). Following the implementation of the CDR, the proportion of drugs covered has decreased and overall median time-to-listing of new drugs has increased in the province of Alberta. For drugs listed on the AHWDBL, the proportion of time attributable to the CDR process (NOC to CDR recommendation) was 63% of the overall time-to-listing.


Obstetrical management of maternal listeremia.
A case is reported of fetal survival after maternal listeremia. Transplacental fetal infection may have been prevented by early delivery. Review of the literature suggests that management be based on cultures of the maternal and fetal compartments. We believe that the considerations for immediate delivery as opposed to medical therapy should rest on the fetal maturity and the sensitivity of the organism to antibiotics which will reach therapeutic levels in the fetal compartment.


Agricultural Insurance and Agricultural Economic Growth: The Case of Zhejiang Province in China.
Based on the theories of welfare economics, this paper analyzed the mechanism of agricultural insurance (AI) affecting agricultural economic growth (AEG), theoretically, and carried out an empirical analysis by using the random effects model and thirteen years of panel data, which included the annual data of 11 cities in Zhejiang Province, China, from 2007 to 2019. The gross output value of agriculture, forestry, animal husbandry, and fishery (GOVA) of 11 cities in Zhejiang Province is selected as the explained variable, agricultural insurance premium income (AIPI) as an explanatory variable. We selected area of waterlogging removal (AWR), rural electricity consumption (REC), total power of agricultural machinery (TPAM), and crop-sown area (CSA) as control variables. The study shows that: (1) the AIPI has a significant positive impact on the growth of GOVA. When other conditions remain unchanged, a 1% increase in AIPI increases the GOVA by 0.166%, accordingly; (2) The control variables of REC, TPAM, and CSA are statistically significant for the growth of the GOVA. The elasticity coefficient of REC is 0.325, the elastic coefficient of the TPAM is 0.287, and the elasticity coefficient of CSA is -0.281.


Timing in the normal pharyngeal swallow. Prospective selection and evaluation of 16 normal asymptomatic patients.
A review of timing of pharyngeal events with radiography has been made. A prospective selection of normal asymptomatic patients presenting for a gastrointestinal evaluation was made and timing of 55 events in the videorecorded pharyngeal swallow in these patients was performed. Only 16 normal asymptomatic patients as defined for selection were found among 870 patients presenting for gastroesophageal examination. A detailed description of their timing observations is presented. The timing data were used to temporally order events in the pharyngeal swallow. This ordering of events in the pharyngeal swallow and the data upon which it is based are reported here in detail.


Neurological sequelae of hypoxic-ischemic brain injury.
Hypoxic-ischemic brain injury (HI-BI) after cardiac arrest commonly results in neurological injury and long term dysfunction, with outcomes ranging from coma and vegetative states to functional disability with various degrees of dependence. Increased rates of bystander CPR and cardiac defibrillation has led to a rapid increase in successful resuscitations. Patients who reach the hospital after cardiac arrest may develop various neurological deficits or clinical syndromes that may preclude recovery to their premorbid baseline. Consequently, clinicians are faced with not only predicting outcome regarding wakefulness and independence but also with long term therapeutic management. Several neurological syndromes have been reported as consequences of HI-BI. This review will describe some of the more common syndromes seen after HI-BI, including the various levels of arousal, seizures, myoclonus, movement disorders, cognitive impairments, and other specific neurological abnormalities.


Waste washing pre-treatment of municipal and special waste.
Long-term pollution potential in landfills is mainly related to the quality of leachate. Waste can be conveniently treated prior to landfilling with an aim to minimizing future emissions. Washing of waste represents a feasible pre-treatment method focused on controlling the leachable fraction of residues and relevant impact. In this study, non-recyclable plastics originating from source segregation, mechanical-biological treated municipal solid waste (MSW), bottom ash from MSW incineration and automotive shredder residues (ASR) were treated and the removal efficiency of washing pre-treatment prior to landfilling was evaluated. Column tests were performed to simulate the behaviour of waste in landfill under aerobic and anaerobic conditions. The findings obtained revealed how waste washing treatment (WWT) allowed the leachability of contaminants from waste to be reduced. Removal rates exceeding 65% were obtained for dissolved organic carbon (DOC), chemical oxygen demand (COD) and Total Kjeldahl Nitrogen (TKN). A percentage decrease of approximately 60% was reached for the leachable fraction of chlorides, sulphates, fluoride and metals, as proved by a reduction in electric conductivity values (70%).


Clinical Profile and Survival Rate of Interstitial Lung Disease in a Tertiary Care Center of Eastern Nepal.
Background The clinical profiles of interstitial lung diseases are reported mainly from developed world. There have been no data from Nepal. Objective The objective of this study is to describe clinical profile and survival in Eastern Nepal. Method Prospectively collected clinical, radiological and laboratory data of consecutive patients with Interstitial lung disease from an eastern regional tertiary care center were analyzed. The recommended official criteria for diagnosing different types of interstitial lung diseases were followed accordingly. Result The study revealed that, 68.0% of the patient's age was of above 60 years with male predominance (66.0%). Idiopathic pulmonary fibrosis (79.5%) was the commonest interstitial lung disease followed by connective tissue disease associated interstitial lung disease. Persistent cough (97.7%) and dyspnea (95.5%) were the commonest presentations. Renal impairment, ischemic Heart Disease and anasarca were significant co morbidities contributing to mortality. Survival rate of the patients was found to be maximum at 5 months (95%) and minimum at 24 months (42%) from the diagnosis of the disease. Conclusion Widespread use of High-resolution computed tomography has made early recognition of interstitial lung disease in elderly patients. Well planned large scale multicenter prospective studies are needed to broaden our understanding about this serious pulmonary disorder.


RB49-like Bacteriophages Recognize O Antigens as One of the Alternative Primary Receptors.
The power of most of the enterobacterial O antigen types to provide robust protection against direct recognition of the cell surface by bacteriophage receptor-recognition proteins (RBP) has been recently recognized. The bacteriophages infecting O antigen producing strains of E. coli employ various strategies to tackle this nonspecific protection. T-even related phages, including RB49-like viruses, often have wide host ranges, being considered good candidates for use in phage therapy. However, the mechanisms by which these phages overcome the O antigen barrier remain unknown. We demonstrate here that RB49 and related phages Cognac49 and Whisky49 directly use certain types of O antigen as their primary receptors recognized by the virus long tail fibers (LTF) RBP gp38, so the O antigen becomes an attractant instead of an obstacle. Simultaneously to recognize multiple O antigen types, LTFs of each of these phages can bind to additional receptors, such as OmpA protein, enabling them to infect some rough strains of E. coli. We speculate that the mechanical force of the deployment of the short tail fibers (STF) triggered by the LTF binding to the O antigen or underneath of it, allows the receptor binding domains of STF to break through the O polysaccharide layer.


Extracellular Lipids in the Lung and Their Role in Pulmonary Fibrosis.
Lipids are major actors and regulators of physiological processes within the lung. Initial research has described their critical role in tissue homeostasis and in orchestrating cellular communication to allow respiration. Over the past decades, a growing body of research has also emphasized how lipids and their metabolism may be altered, contributing to the development and progression of chronic lung diseases such as pulmonary fibrosis. In this review, we first describe the current working model of the mechanisms of lung fibrogenesis before introducing lipids and their cellular metabolism. We then summarize the evidence of altered lipid homeostasis during pulmonary fibrosis, focusing on their extracellular forms. Finally, we highlight how lipid targeting may open avenues to develop therapeutic options for patients with lung fibrosis.


Noninvasive evaluation of the hemodynamic status in patients after heart transplantation or left ventricular assist device implantation.
Hemodynamic assessment is crucial after heart transplantation (HTX) or left ventricular assist device (LVAD) implantation. Gold-standard is invasive assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is a new technology that is supposed to determine hemodynamics completely noninvasive. We aimed to validate this technology in HTX and LVAD patients and conducted a prospective single-center cohort study. Patients after HTX or LVAD implantation underwent right heart catheterization including TD. NPCA using the CNAP Monitor (V.5.2.14; CNSystems Medizintechnik AG, Graz, Austria) was performed simultaneously. Three TD measurements were compared with simultaneous NPCA measurements for hemodynamic assessment. To describe the agreement between TD and NPCA, Bland-Altman analysis was done. In total, 28 patients were prospectively enrolled (HTX: n = 10, LVAD: n = 18). Bland-Altman analysis revealed a mean bias of +1.05 l/min (limits of agreement ± 4.09 l/min, percentage error 62.1%) for cardiac output (CO). In LVAD patients, no adequate NPCA signal could be obtained. In 5 patients (27.8%), any NPCA signal could be detected, but was considered as low signal quality. In conclusion, according to our limited data in a small cohort of HTX and LVAD patients, NPCA using the CNAP Monitor seems not to be suitable for noninvasive evaluation of the hemodynamic status.


[Analysis of bite marks].
Precise photographs, supplemented by impressions are used to research and compare bite marks. Different materials for impressions are available to the forensic odontologist. Subsequently, the acquired information of the bite mark will be compared with the dentition of a suspect through photographs, intra- and extra oral examination and impressions. The overlay, which can be created using a variety of methods, allows the comparison between the bite mark and the dentition of the suspect. Among the most commonly used are hand-tracing of study models, wax bites or photocopies, or the radio-opaque wax bite method. Thanks to modern technology and the use of computers, analyses of bite marks have gradually become more accurate. Current research carried out at the Katholieke Universiteit Leuven will demonstrate whether the computer program ForensicIQ is able to offer an even more precise comparison between a given bite mark and the dentition of a suspect. By no means should bite mark analysis alone be allowed to lead to a guilty verdict, but it will offer the opportunity to exclude a suspect from a crime when the data do not correspond.


Improving lipid control following myocardial infarction.
Following a myocardial infarction, lipid-lowering therapy is an established intervention to reduce the risk of recurrent cardiovascular events. Prior studies show a need to improve clinical practice in this area. Here, we review the latest research and perspectives on improving postmyocardial infarction lipid control. Dyslipidemia and myocardial infarction remain leading causes of global disability and premature mortality throughout the world. The processes of care in lipid control involve multiple patient-level, provider-level, and healthcare system-level factors. They can be challenging to coordinate. Recent studies show suboptimal use of early high-intensity statin therapy and overall lipid control following myocardial infarction. Encouragingly, lipid control has improved over the last decade. Implementation science has identified checklists as an effective tool. At the top of the checklist for reducing atherogenic lipids and recurrent event risk postmyocardial infarction is early high-intensity statin therapy. Smoking cessation and participation in cardiac rehabilitation are also priorities, as are lifestyle counseling, promotion of medication adherence, ongoing lipid surveillance, and medication management. Optimizing lipid control could further enhance clinical outcomes after myocardial infarction.


Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes.
Gene transcription is associated with local changes in chromatin, both in nucleosome positions and in chemical modifications of the histones. Chromatin dynamics has mostly been studied on a single-gene basis. Those genome-wide studies that have been made primarily investigated steady-state transcription. However, three studies of genome-wide changes in chromatin during the transcriptional response to heat shock in the budding yeast Saccharomyces cerevisiae revealed nucleosome eviction in promoter regions but only minor effects in coding regions. Here, we describe the short-term response to nitrogen starvation in the fission yeast Schizosaccharomyces pombe. Nitrogen depletion leads to a fast induction of a large number of genes in S. pombe and is thus suitable for genome-wide studies of chromatin dynamics during gene regulation. After 20 min of nitrogen removal, 118 transcripts were up-regulated. The distribution of regulated genes throughout the genome was not random; many up-regulated genes were found in clusters, while large parts of the genome were devoid of up-regulated genes. Surprisingly, this up-regulation was associated with nucleosome eviction of equal magnitudes in the promoters and in the coding regions. The nucleosome loss was not limited to induction by nitrogen depletion but also occurred during cadmium treatment. Furthermore, the lower nucleosome density persisted for at least 60 min after induction. Two highly induced genes, urg1(+) and urg2(+), displayed a substantial nucleosome loss, with only 20% of the nucleosomes being left in the coding region. We conclude that nucleosome loss during transcriptional activation is not necessarily limited to promoter regions.


A Novel, Rapid, and Validated Stability-Indicating UPLC Method for the Estimation of Drotaverine Hydrochloride and Ibuprofen Impurities in Oral Solid Dosage Form.
A novel, stability-indicating, reversed-phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of pure drotaverine hydrochloride and ibuprofen in the presence of their impurities and degradation products. The method was developed using a Waters UPLC BEH C18, 100 × 2.1 mm, 1.7 µm column with a flow rate of 0.3 mL/min and detector wavelength at 210 nm. The mobile phase consisted of potassium dihydrogen orthophosphate buffer and acetonitrile. Drotaverine hydrochloride and ibuprofen were subjected to the stress conditions of oxidative, acid, base, photolytic, and thermal degradation. Degradation products resulting from the stress studies were well-resolved, thus confirming the test method as stability-indicating. Validation of the method was carried out as per International Conference on Harmonization guidelines.


High expression of Stabilin-2 predicts poor prognosis in non-small-cell lung cancer.
Stabilin-2 has been found to regulate the progression of cancer. It was not fully understood whether it shows some roles in non-small-cell lung cancer (NSCLC). We used the immunohistochemical staining to evaluate Stabilin-2 protein expression in formalin-fixed paraffin-embedded tissue of NSCLC patients' primary lesion. And we carried out χ2 test to detect relationships between Stabilin-2 expression and various clinical factors. Besides, the survival difference between patients with high and low Stabilin-2 expression was also analyzed. The expression of Stabilin-2 was associated with N stage and age. Higher Stabilin-2 expression exists in poorer survival patients. It revealed that Stabilin-2 expression was a significant predictor for both OS and DFS by univariate and multivariate analyses. High stabilin-2 expression in NSCLC predicts poor tumor prognosis.


Geometrical conditions indispensable for muscle contraction.
Computer simulation has uncovered the geometrical conditions under which the vertebrate striated muscle sarcomere can contract. First, all thick filaments should have identical structure, namely: three myosin cross-bridges, building a crown, should be aligned at angles of 0°, 120°, 180°, and the successive crowns and the two filament halves should be turned around 120°. Second, all thick filaments should act simultaneously. Third, coordination in action of the myosin cross-bridges should exist, namely: the three cross-bridges of a crown should act simultaneously and the cross-bridge crowns axially 43 and 14.333 nm apart should act, respectively, simultaneously and with a phase shift. Fifth, six thin filaments surrounding the thick filament should be turned around 180° to each other in each sarcomere half. Sixth, thin filaments should be oppositely oriented in relation to the sarcomere middle. Finally, the structure of each of the thin filaments should change in consequence of strong interaction with myosin heads, namely: the axial distance and the angular alignment between neighboring actin monomers should be, respectively, 2.867 nm and 168° instead of 2.75 nm and 166.15°. These conditions ensure the stereo-specific interaction between actin and myosin and good agreement with the data gathered by electron microscopy and X-ray diffraction methods. The results suggest that the force is generated not only by the myosin cross-bridges but also by the thin filaments; the former acts by cyclical unwrapping and wrapping the thick filament backbone, and the latter byelongation.


[Regional enterocolitis--a problem rich disease picture in diagnosis and therapy].
Etiology, symptoms and diagnosis of Crohn's disease are described in a clinical study based on 37 patients. Drug therapy, surgery and their indications are discussed. Among 37 patients suffering from Crohn's disease of the complicated chronic type postoperative lethality amounted to 8.1%, the rate of complications came up to 37.8%. Recurrences after surgical therapy were observed in 40%. Toxic megacolon should be treated by the procedure of Turnbull.


Validity and reproducibility of a revised semi-quantitative food frequency questionnaire (SQFFQ) for women of age-group 12-44 years in Chengdu.
To find a credible nutritional screening tool for evaluating relationship between nutritional status and diseases in Chengdu female residents, the reliability and validity of a revised semi-quantitative food frequency questionnaire (SQFFQ) were tested. The validity was assessed by comparing the SQFFQ with the 'standard' method of 3 days' dietary recall, and the reliability was assessed by comparing the first SQFFQ with the second SQFFQ at 4 weeks interval. Correlation analysis showed that, for reliability, the average correlation coefficient (CC) of 22 kinds of nutrients was 0.66 and reduced to 0.60 after adjusting for energy; the average of intra-class correlation coefficients (ICC) was 0.65. For validity, the average CC was 0.35 and remained stable after adjusting for CC of energy or nutrients. Validity of 17 nutrients in SQFFQ survey had correlation with result of 3 days' dietary recall. The results showed that the revised SQFFQ can be used for investigating the role of nutrients in development of disease in Chengdu female residents.


Facile and rapid synthesis of highly luminescent nanoparticles via pulsed laser ablation in liquid.
This paper demonstrates the usefulness of pulsed laser ablation in liquids as a fast screening synthesis method able to prepare even complex compositions at the nanoscale. Nanoparticles of Y2O3:Eu3+, Lu2O2S:Eu3+, Gd2SiO5:Ce3+, Lu3TaO7:Gd3+ and Tb3+ are successfully synthesized by pulsed laser ablation in liquids. The phase and stoichiometries of the original materials are preserved while the sizes are reduced down to 5-10 nm. The optical properties of the materials are also preserved but show some small variations and some additional structures which are attributed to the specificities of the nanoscale (internal pressure, inhomogeneous broadening, surface states, etc).


Filamentous fungi with high paraquat-degrading activity isolated from contaminated agricultural soils in northern Thailand.
The contamination of paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) herbicide from the farming area has become a public concern in many countries. This herbicide harms to human health and negatively effects the soil fertility. Several methods have been introduced for the remediation of paraquat. In this study, 20 isolates of the paraquat-tolerant fungi were isolated from the contaminated soil samples in northern Thailand. We found that isolate PRPY-2 and PFCM-1 exhibited the highest degradation activity of paraquat on synthetic liquid medium. About 80 and 68% of paraquat were removed by PRPY-2 and PFCM-1 respectively after 15 days of cultivation. Based on the morphological characteristic and molecular analysis, the fungal isolate PRPY-2 and PFCM-1 were identified as Aspergillus tamarii and Cunninghamella sp. respectively. The biosorption of paraquat on these fungal mycelia was also investigated. It was found that only 8-10% of paraquat could be detected on their mycelia, while 24-46% of paraquat was degraded by fungal mycelia. This is the first report on paraquat degrading ability by A. tamarii and Cunninghamella sp. It is demonstrated that these filamentous fungi are promising microorganisms available for remediation of paraquat contaminated environment.


A Mechanism of Synaptic Clock Underlying Subjective Time Perception.
Temporal resolution of visual information processing is thought to be an important factor in predator-prey interactions, shaped in the course of evolution by animals' particular ecology. Here I show that light can be considered to have a dual role of a source of information, which guides motor actions, and an environmental feedback for those actions. I consequently show how temporal perception might depend on feedback-based behavioral adaptations realized in the nervous system through activity-dependent synaptic plasticity. I propose an underlying mechanism of synaptic clock, with every synapse having its characteristic time unit, determined by the persistence of memory traces of synaptic inputs, which is used by the synapse to tell time, and postulate the existence of a specific brain-wide distribution of synaptic clocks with different time units. The present theory offers a simple, testable link between the fields of neurobiology of memory, time perception and ecology, which may account for numerous experimental findings, including the interspecies variation in the temporal resolution and the properties of subjective time perception in humans, specifically the variable speed of perceived time passage, depending on emotional or attentional states or tasks performed.


General anesthesia does not impair simulator driving skills in volunteers in the immediate recovery period - a pilot study.
The current recommendations to refrain from driving for 24 hr after general anesthesia (GA) lack evidence. Our objective was to measure impairment of driving performance at various time intervals after anesthesia using driving impairment at different blood alcohol concentrations (BAC) as a gold standard for comparison. Institutional Review Board approval was obtained. A cross-over design, within subject comparison was used. Twelve volunteers were randomized to three treatments: GA, alcohol, and no drug. Psychomotor recovery was assessed by Digit Symbol Substitution Test (DSST) and Trieger Dot Test (TDT). On the anesthetic day, GA was induced with propofol 2.5 mg x kg(-1) and fentanyl l micro g x kg(-1) and maintained with N(2)O-O(2) 50:50 and approximately one minimum alveolar concentration of desflurane by spontaneous ventilation for 30 min. Driving simulator test runs occurred at two, three, four, and 24 hr postanesthesia. On the alcohol treatment day, a vodka and orange juice beverage was administered to reach the legal limit for BAC in the province of Ontario, Canada (BAC 0.08%). On the control day, no drug was given. Driving simulator test runs corresponded to the same time of day as the postanesthetic test runs. Two-way analysis of variance for dependent samples (ANOVA) was performed using the SAS program. P values of less than 0.05 were considered significant. There was no significant difference in postanesthetic driving skills at two, three, and four hours postanesthesia, and the corresponding control sessions. There was no significant difference among the three sessions with respect to pen and paper tests of psychomotor performance. Performance during the alcohol session differed significantly from that during the control and postanesthetic sessions. Certain driving skills return by two hours after one half hour of GA of propofol, desflurane, and fentanyl in a group of young volunteers.


PM2.5 components and outpatient visits for asthma: A time-stratified case-crossover study in a suburban area.
The effects of fine particles (PM2.5) on asthma have been widely confirmed by epidemiological research studies. However, a limited number of studies have investigated the relationship between exposure to different PM2.5 components and asthma. We characterized the PM2.5 components in a suburban site of central Taiwan and conducted a time-stratified case-crossover study to elaborate the effects of daily concentration of each PM2.5 component on asthma outpatient visits. We retrieved asthma outpatient claims for individuals less than 20 years old with a residential address in the Shalu district, Taiwan, from the National Health Insurance Research Database during 2000-2010. Multiple linear regression models were used to back extrapolate the historic concentration of individual components of PM2.5 from 2000 through to 2010, including black carbon (BC) and eight ions, namely, sulfate, nitrate (NO3-), ammonium, chloride, potassium (K+), magnesium, calcium, sodium. The odds ratio (OR) with a 95% confidence interval (CI) of individual PM2.5 components on asthma was estimated by conditional logistic regression. A total of 887 asthma outpatient visits with individuals who have an average age of 7.96±3.88 years were selected. After adjusting for confounders, we found an interquartile range (IQR) increase in BC level, an IQR increase in NO3- level, and an IQR increase in K+ level that were all associated with the increased risk of asthma outpatient visits from the current day (OR = 1.18, 95% CI: 1.05-1.34; OR = 1.11, 95% CI: 1.01-1.21; and OR = 1.16, 95% CI: 1.04-1.30, respectively). The effects of these components on asthma were stronger in the cold season than in the warm season. However, we did not find any lagging effects. The results suggest that exposure to NO3-, BC, and K+ derived from industry-related combustion or motor vehicles emission sources may increase the risk of asthma outpatient visits, particularly during the cold season.


The photographic emulsion layer as a three-dimensional recording medium.
In order to understand how a photographic material responds to radiation, its depth must be taken into account. For analysis the material is imagined to be built up of "elementary layers." The three characteristics: modulation transfer function, density, and granularity, completely characterize the material and the resulting image. For parallel light both in exposure and density readout these characteristics are additive from those of the elementary layers. Methods for realizing and measuring the properties of elementary layers in any given material are described. The modulation transfer function is found to be considerably degraded for the lower elementary layers, which also make a relatively large contribution to the lower spatial frequencies of the noise power spectrum.


Axial presacral lumbar interbody fusion and percutaneous posterior fixation for stabilization of lumbosacral isthmic spondylolisthesis.
Case series. To describe a minimally invasive surgical technique for treatment of lumbosacral spondylolisthesis. Traditional surgical management of lumbosacral spondylolisthesis is technically challenging and associated with significant complications. Minimally invasive surgical techniques offer patients treatment alternatives with lower operative morbidity risk. The combination of percutaneous pedicle screw reduction and an axial presacral approach for lumbosacral discectomy and fusion is an option for the surgical management of low-grade lumbosacral spondylolisthesis. Twenty-six consecutive patients with symptomatic L5-S1 level isthmic spondylolisthesis (grade 1 or grade 2) underwent axial presacral lumbar interbody fusion and percutaneous posterior fixation. Study outcomes included visual analogue scale for axial pain severity, Odom criteria, and radiographic fusion. The procedure was successfully completed in all patients with no intraoperative complications reported. Intraoperative blood loss was minimal (range, 20-150 mL). Median hospital stay was 1 day (range, <1-2 d). Spondylolisthesis grade was improved after axial lumbar interbody fusion (P<0.001) with 50% (13 of 26) of patients showing a reduction of at least 1 grade. Axial pain severity improved from 8.1±1.4 at baseline to 2.8±2.3 after axial lumbar interbody fusion, representing a 66% reduction from baseline (95% confidence interval, 54.3%-77.9%). At 2-year posttreatment, all patients showed solid fusion. Using Odom criteria, 81% of patients were judged as excellent or good (16 excellent, 5 good, 3 fair, and 2 poor). There were no perioperative procedure-related complications including infection or bowel perforation. During postoperative follow-up, 4 patients required reintervention due to recurrent radicular (n=2) or screw-related (n=2) pain. The minimally invasive presacral axial interbody fusion and posterior instrumentation technique is a safe and effective treatment for low-grade isthmic spondylolisthesis.


The usefulness of antiplatelet prescriptions for the identification of patients with atherothrombosis in primary care: a Dutch cross-sectional study.
Patients with atherothrombotic cardiovascular disease (ACD) should receive specific treatments, including lipid-lowering medication. In order to optimize treatment for patients with ACD in primary care, an efficient method to identify all these patients is needed. We aimed to assess which method serves best to identify all patients with ACD in Dutch primary care: morbidity records, antiplatelet prescribing records or a combination of these. In a cross-sectional study in 45 Dutch general practices, computerized medical records of all patients with any cardiovascular disease, cardiovascular symptoms or cardiovascular medication were analysed. Of the 7280 patients with a recorded indisputable indication for antiplatelet therapy, 4715 (64.8%) could be identified by means of antiplatelet prescriptions. Of the patients with a recorded indisputable indication for antiplatelets but without any antiplatelet prescription, 28.9% received a vitamin K antagonist. Of the 8718 patients with antiplatelet therapy, 5697 (65.3%) could be identified by means of a recorded indisputable or possible indication for antiplatelet therapy. Female patients, patients younger than 60 years old and patients having a recorded diagnosis of angina pectoris or diabetes had a higher risk to be missed by antiplatelet prescribing records. Morbidity records and prescribing records should be used both in order to identify all patients with ACD in primary care. Patients who use antiplatelet prescriptions but do not have a recorded ACD deserve extra attention, because they are either treated without a good indication for antiplatelet therapy (overtreatment) or need a correction of their morbidity records.


A note from a survey of some knowledge aspects of leptospirosis among a sample of rural villagers in the highly endemic area, Thailand.
The main purpose of this pilot study was to assess knowledge of leptospirosis among a sample of rural villagers in the highly endemic area, Thailand. This cross-sectional descriptive study was conducted among a sample of 300 rural villagers in the highly endemic area of leptospirosis, Buriram Province in Thailand. A self-administered questionnaire on some knowledge aspects of leptospirosis was used. The response rate was 100%. Most participants (80%) had a poor knowledge of leptospirosis. There was no significant correlation of sex and age of the subjects as to the level of knowledge (chi2, p > 0.05); however, there was significant correlation of level of education and occupation of the subjects to the level of their knowledge (chi2, p < 0.05). Although this was a limited pilot study, the results imply that the present leptospirosis control program is not successful, and that the main problem is the knowledge level of people in endemic areas. A program to improve the basic knowledge of leptospirosis of rural villagers in endemic areas must be initiated.


Rituximab combined with GDP regimen can effectively improve the efficacy and immune function of non-Hodgkin lymphoma.
To evaluate the efficacy of rituximab combined with GDP regimen (gemcitabine + cisplatin + dexamethasone) in the treatment of non-Hodgkin lymphoma and its impact on the immune function of patients. Clinical data of 88 patients with non-Hodgkin lymphoma (NHL) treated in Affiliated Hospital of Yan'an University from February 2017 to February 2019 were analyzed retrospectively. Among them, 40 patients treated with the second-line regimen (gemcitabine + cisplatin + dexamethasone) were served as the control group, and 48 patients received additional rituximab were as the observation group. The therapeutic effect, incidence of adverse reactions, levels of complement (C3, C4) and immunoglobulin [immunoglobulin (Ig) G, IgM, IgA] before and after treatment were compared between the two groups. Cox regression analysis was used to analyze the prognostic factors of patients. The total response rate of patients in observation group was higher than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions (hair loss, nausea and vomiting, thrombocytopenia, anemia and bone marrow suppression) between the two groups (P>0.05). After treatment, the levels of C3 and C4 in both groups were lower than those before treatment, and the decrease in observation group were more evident than that in control group (P<0.05). No notable fluctuation was observed in the levels of IgG, IgM and IgA in both groups between before and after treatment (P>0.05). Cox regression analysis found that Ann Arbor stage and pretreatment disease status were the factors affecting the prognosis of patients. Rituximab combined with GDP regimen has a significant effect on the treatment of non-Hodgkin lymphoma, and Ann Arbor stage and pretreatment disease state are prognostic factors for patients with NHL.


Body mass index and age at natural menopause: a meta-analysis.
There is no universal consensus on the relationship between body mass index (BMI) and age at natural menopause (ANM). The primary bias was confounding by cigarette smoking because smoking was a strong confounding factor related to lower BMI and earlier menopause. This meta-analysis was conducted to estimate the effect of BMI on ANM. Medline and EMBASE databases were searched for relevant studies up to December 2013. Studies were selected for analysis based on certain inclusion and exclusion criteria. Hazard ratios (HRs) with 95% CI were extracted to assess the association between BMI and early ANM. Nine studies were selected for this meta-analysis. The HR of early ANM was 1.08 (95% CI, 1.03-1.14; P < 0.01) in underweight women compared with women of normal BMI. Compared with women of normal BMI, overweight women (HR, 0.93; 95% CI, 0.91-0.96; P < 0.001) and obese women (HR, 0.95; 95% CI, 0.79-1.15; P = 0.59) were associated with late ANM. In addition, the HRs of early ANM in overweight and obese women were 0.92 (95% CI, 0.90-0.94; P < 0.001) and 0.88 (95% CI, 0.82-0.95; P < 0.001), respectively, compared with underweight women. A separate meta-analysis indicated that the results (HR, 0.85; 95% CI, 0.81-0.90; P < 0.001) changed markedly in the comparison of obese versus normal-weight women in studies that controlled for smoking. The results of our study indicate that increased BMI modestly associates with later ANM. The relationship between BMI and ANM needs further clarification in well-designed studies, especially studies well-controlled for smoking status.


Separation of periportal and perivenous rat hepatocytes by fluorescence-activated cell sorting: confirmation with colloidal gold as an exogenous marker.
Periportal and perivenous hepatocytes are known to display various functional differences. In this study we present a new method to separate periportal and perivenous cells: after selectively loading zone 1 or zone 3 with the fluorescent label acridine orange in an antegrade or retrograde perfusion, respectively, we separated the isolated hepatocytes on a fluorescence-activated cell sorter. The common way to check on proper separation is to estimate activities of enzymes known to exhibit a heterogeneous acinar distribution. Using enzyme histochemistry, however, we found that already on short collagenase perfusion, some enzymes displayed a more shallow gradient than in vivo, making enzyme activities less suitable as zonal markers. We therefore used colloidal gold granules (17 nm) injected intravenously (2.5 mg) into the rat 2 to 3 hr before cell isolation. The gold is taken up predominantly by perivenous hepatocytes, probably because of the efficient removal of gold granules in zone 1 by competing Kupffer cells. We compared acridine orange fluorescence, presence of gold particles and activities of six marker enzymes, three biochemically and three histochemically determined. Acridine orange and gold both pointed to a high enrichment of the fractions, whereas most enzyme activities were more randomly distributed among the cells as a result of the isolation procedure. Our separation procedure yielded fractions highly enriched in either viable periportal or perivenous cells, both from one liver. The use of colloidal gold as a marker to monitor separation is a valuable alternative to the more risky estimation of enzyme activities.


The Widespread Use of Nanomaterials: The Effects on the Function and Diversity of Environmental Microbial Communities.
In recent years, as an emerging material, nanomaterials have rapidly expanded from laboratories to large-scale industrial productions. Along with people's productive activities, these nanomaterials can enter the natural environment of soil, water and atmosphere through various ways. At present, a large number of reports have proved that nanomaterials have certain toxic effects on bacteria, algae, plants, invertebrates, mammalian cell lines and mammals in these environments, but people still know little about the ecotoxicology of nanomaterials. Most relevant studies focus on the responses of model strains to nanomaterials in pure culture conditions, but these results do not fully represent the response of microbial communities to nanomaterials in natural environments. Over the years, the effect of nanomaterials infiltrated into the natural environment on the microbial communities has become a popular topic in the field of nano-ecological environment research. It was found that under different environmental conditions, nanomaterials have various effects on the microbial communities. The medium; the coexisting pollutants in the environment and the structure, particle size and surface modification of nanomaterials may cause changes in the structure and function of microbial communities. This paper systematically summarizes the impacts of different nanomaterials on microbial communities in various environments, which can provide a reference for us to evaluate the impacts of nanomaterials released into the environment on the microecology and has certain guiding significance for strengthening the emission control of nanomaterials pollutants.


Denaturing RNA electrophoresis in TAE agarose gels.
Current methods of analytical RNA electrophoresis are based on the utilization of either complicated laboratory instrumentation or toxic, carcinogenic, or expensive chemicals. We suggest here the use of classical Tris-acetate-ethylenediamine tetraacetic acid (TAE) agarose gels combined with prior denaturation of RNA samples in hot formamide for the electrophoretic separation of RNA species. We present a brief comparison of the proposed TAE/formamide method with the most common 3-(N-morpholino)propanesulfonic acid/formaldehyde agarose gel protocol and show that both methods produce comparable results for size determination of RNA molecules and subsequent Northern blotting of gels. In addition to purified RNA samples, the robustness of the TAE/formamide protocol is demonstrated by its suitability for the analysis of RNA quality in crude yeast cell lysates containing large amounts of proteins, DNA, and other contaminating molecules. We therefore propose the TAE/formamide agarose electrophoresis as a rapid, simple, and cheaper alternative to current methods of RNA electrophoresis. Additionally, another benefit is the reduced exposure of laboratory personnel to hazardous chemicals.


Associated red cell enzyme deficiencies and their significance in a case of congenital enzymopenic methemoglobinemia.
Examination of the red cell enzyme profile in a case of congenital methemoglobinemia has shown associated deficiencies of glutathione reductase (GR) and glutathione peroxidase (GSHPx) in addition to NADH-methemoglobin reductase deficiency. Contrary to expectations, GR and GSHPx deficiencies do not seem to have contributed to the methemoglobinemia in this case. The lack of symptoms in spite of a high methemoglobin (Hi) level (35%) appears to be due to the restriction of Hi to a small percentage of red cells.


Subgroups and differences of fixation in 3-part proximal humerus fractures.
This study aimed to determine the morphological differences of three-part proximal humerus fractures, the group in which plate screw fixation is most frequently used, and to evaluate the functional and radiological results of the methods applied for different subgroups. Twenty-nine patients (6 males and 23 females) with three-part proximal humerus fractures were in the study, with an average age of 64. The patients were in three groups according to their fracture types. Group 1 included eight patients with valgus impaction fracture. Group 2 included eleven patients with easily achieved stability after reduction. Group 3 consisted of ten patients with procurvatum varus angulation, a significant displacement between fragments, and in whom medial cortical continuity was not maintained without fixation. All patients underwent surgery with a minimally invasive deltoid split approach method and locked ana-tomic plate screw osteosynthesis. In group 1 patients, the space in the area where valgization is present in the head was filled with cortico-cancellous allografts. No grafting or metaphyseal compression took place in Group 2 patients. In group 3 patients, the metaphyseal compression technique was applied to the bone defect area. Cephalodiaphyseal angles (CDA) were measured at the postoperative and final follow-up. The constant Murley score made the functional evaluation. The patients were followed for an average of 27.6 months, and the union was present in all patients for an average of 3.6 months. Early screw migration was present in three patients, and late screw migration was in one patient. There were twenty-four excellent and 5 good results. CDA decreased from 139.42° to 136.13°. A statistically significant difference was present between the values of Groups 2 and 3 in the final control CDA of the groups. In this study, the functional scores of grafting stable valgus-impacted fractures and metaphyseal compression of unstable fractures with insufficient medial support were as good as stable 3-part fractures. Considering neer type 3 fractures should be evaluated with their subgroups, and fixation and stability-enhancing solutions specific to the groups are essential.


[Clinical evaluation of various tumor markers in pleural effusion and in the serum].
Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.


[Microcatheterization with gadolinium and glue embolization for post-biopsy arteriovenous fistula in a patient with renal failure].
Percutaneous renal biopsy is frequently used in diagnosis of renal dysfunction. Nevertheless, complications, mostly vascular, may occur. Treatment must be minimally invasive with nephron preservation, especially in kidney failure. We present an interesting therapeutic approach with highly selective catheterization under gadolinium and glue embolization, leading to total cure of iatrogenic fistula without renal deterioration.


Conservation of gene co-regulation between two prokaryotes: Bacillus subtilis and Escherichia coli.
We measured conservation of gene co-regulation between two distantly related prokaryotes, B. subtilis and E. coli. The co-regulation between genes was extracted from knowledge of regulation of genes stored in databases. For B. subtilis operons, we obtained the data set from ODB which we have developed and, for the regulons, we used DBTBS. For E. coli data set, we used known regulons derived from RegulonDB. We obtained a reliable data set of co-regulated genes in B. subtilis and E. coli. About 60-80 % of gene pairs conserved co-regulation relationships, so co-regulation between genes are highly conserved even between distantly related species. To measure the functional relationship between these conserved genes, we used KEGG PATHWAY and COG. When two co-regulated genes are in the same biological pathway in KEGG or share the same functional category in COG, we assume that they have the same function. As a result, we also found that many conserved co-regulated gene pairs share the same functions. These observations would help to predict gene co-regulation and protein functions.


Apophatic love, contagion, and surveillance: Orthodox Christian responses to the global pandemic.
As the COVID-19 pandemic hit, Orthodox Christians globally reacted to the possibility of contagion and risk in dialogue with theological positions about materials, their own long history which includes surviving previous pandemics and plagues, governmental and civil expectations and edicts, and pious - but often unofficial - understandings about protection and the sacrality of religious artefacts and the space of the temple. This article draws upon primary ethnographic research amongst Orthodox Christians in the UK, Serbia, Greece and Russia, as well as news articles about and primary ecclesiastical documents from Orthodox Churches more widely, to highlight commonalities and divergences in Orthodox Christian responses to the pandemic. Examining both the theological basis, and socio-political differences, this article considers how the Orthodox theology of apophaticism and relationality impacts wider discourses of contagion (both positive and negative), and consequently compliance with public health initiatives. Comparison across diverse Orthodox settings suggests that Orthodox Christians are concerned with the neighbour - both in terms of who may be watching (and reporting) them, and who may fall sick because of them.


Molecular insights in repurposing selective COX-2 inhibitor celecoxib against matrix metalloproteinases in potentiating delayed wound healing: a molecular docking and MMPB/SA based analysis of molecular dynamic simulations.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a role in healing, including reducing inflammation, promoting fibroblast and keratinocyte migration, and modifying scar tissue. Due to their pleiotropic functions in the wound-healing process in diabetic wounds, MMPs constitute a significant cause of delayed wound closure. COX-2 inhibitors are proven to inhibit inflammation. The present study aims to repurpose celecoxib against MMP-2, MMP-8 and MMP-9 through in silico approaches, such as molecular docking, molecular dynamics, and MMPB/SA analysis. We considered five selective COX-2 inhibitors (celecoxib, etoricoxib, lumiracoxib, rofecoxib and valdecoxib) for our study against MMPs. Based on molecular docking study and hydrogen bonding pattern, celecoxib in complex with three MMPs was further analyzed using 1 µs (1000 ns) molecular dynamics simulation and MMPB/SA techniques. These studies identified that celecoxib exhibited significant binding affinity -8.8, -7.9 and -8.3 kcal/mol, respectively, against MMP-2, MMP-8 and MMP-9. Celecoxib formed hydrogen bonding and hydrophobic (π-π) interactions with crucial substrate pocket amino acids, which may be accountable for their inhibitory nature. The MMPB/SA studies showed that electrostatic and van der Waal energy terms favoured the total free binding energy component, while polar solvation terms were highly disfavored. The in silico analysis of the secondary structures showed that the celecoxib binding conformation maintains relatively stable along the simulation trajectories. These findings provide some key clues regarding the accommodation of celecoxib in the substrate binding S1' pocket and also provide structural insights and challenges in repurposing drugs as new MMP inhibitors with anti-inflammatory and anti-inflammatory wound-healing properties.Communicated by Ramaswamy H. Sarma.


Humanistic Spirit Training of Medical Students Based on Multisource Medical Data Fusion.
Medical colleges need to strengthen the cultivation of medical students' humanistic and spiritual literacy. First of all, schools need to change the current educational concept and the cultivation mode of humanistic quality. In educational work, schools should pay attention to the social cognitive skills of medical students, and at the same time pay attention to the cultivation of students' basic qualities. Schools need to find problems in time, and schools need to take corresponding measures to deal with these problems. Medical colleges need to strengthen the training of medical students' comprehensive quality and incorporate humanistic education into the goal of all-round development of medical students. Specifically, schools need to adopt a work method of distributed implementation and distributed guidance to fully mobilize the enthusiasm and initiative of school leaders, teachers, and students themselves. Schools need to strengthen inspection and supervision and summarize the experiences and lessons that students have learned in their learning. On this basis, schools need to improve the quality and efficiency of students' humanities education work. Through the analysis of multisource medical data, this paper conducts research on the working mode of humanistic quality cultivation in medical colleges. Specifically, school education will be people-centered. Schools need to cultivate the humanistic spirit of medical students in the ideological and political education work. This paper conducts mathematical statistical analysis based on multisource medical data and analyzes the differences in the effect of different teaching modes and training methods on the cultivation of medical students' humanistic spiritual literacy. Based on this, the research proposes recommendations for the future development of medical schools. First of all, schools need to build a humanized classroom, combine skills education with moral education, and improve the learning efficiency of student groups. In addition, schools need to teach students to feel respected and valued. Secondly, schools need to implement human-oriented teaching work to give full play to students' own talents and personalities. During school education work, schools need to organically combine classroom education and social practice. Schools need to link teaching and real society and link students' learning process with real life. Schools need to organically combine reading and learning with life, so as to promote the all-round development of students' humanistic quality.


Intramedullary nailing with supplemental plate and screw fixation of long bones of patients with osteogenesis imperfecta: operative technique and preliminary results.
Although intramedullary fixation is the standard form of surgical fixation of the long bones of children with osteogenesis imperfecta (OI), it remains fraught with complications. Implant breakage, implant cut out, long bone fracture, nonunion, and rod bending have all been described as complications of intramedullary long bone fixation in children with OI. Supplemental fixation techniques represent an attempt to decrease these risks of surgical implant failure of intramedullary devices. A supplemental plate and screw construct at a fracture or an osteotomy site in addition to an intramedullary device in the long bone segment is one such form of supplemental fixation. The aim of this study is to describe the surgical technique and early results of plate and screw fixation used to supplement intramedullary fixation in a subset of our OI patient population. This is a retrospective review and report on 14 long bone segments of 11 children with OI who have undergone intramedullary fixation as well as supplemental fixation at osteotomy or fracture sites with a plate and screw construct. The long bone segments treated with intramedullary fixation and a supplemental plate and screw construct included 11 femurs, two tibias, and one humerus. Intramedullary devices included a combination of telescoping and nontelescoping implants. The mean follow-up duration was 10 months. All 14 long bone segments have gone on to radiographic union. The average time to union was 8.8 weeks (range: 6.5-17 weeks). In 11 of the long bone segments, the supplemental plate fixation was applied to the site of a fracture or osteotomy. In one case, supplemental plate fixation was applied to the site of a nonunion (distal humerus nonunion). We describe various options of this surgical technique and early results. Although further follow-up and investigation will provide further insight into long-term outcomes, supplemental plate and screw fixation is a valuable and versatile option for this challenging patient population.