Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden 1990-2003: occurrence, origin and survival compared to ovarian cancer.
The aim of this register study was to determine occurrence of non-genital ovarian metastasis detected by gynecologic surgery presented as ovarian neoplasm in Sweden from 1 January 1990 to 31 December 2003. Origin of metastases and time of detection in relation to surgery were recorded. Age at diagnosis, survival for ovarian metastasis compared to ovarian cancer and prognostic factors were evaluated. Utilizing the population-based Swedish In-Patient Registry, Cancer Registry and Causes of Death Registry, we identified 255 cases with non-genital tract metastases to the ovaries detected at gynecological surgery. During the study period, 10,955 newly diagnosed cases of ovarian cancer were reported to the Swedish Cancer Registry. The proportion of ovarian metastases detected at surgery of all ovarian neoplasm increased from 1.7% to 3.0% during the study period. The patients with ovarian metastasis of non-GI origin were younger than patients with primary ovarian cancer. The most common primary diseases were breast cancer (29%), colon cancer (27%) and gastric cancer (16%). Ovarian metastasis of GI origin preceded primary diagnosis in 51% of patients but for women with disease of non-GI origin the primary diagnosis was made in 18% of patients after surgery. Five-year survival for patients with ovarian metastasis of GI origin was 11% and it was 24% if metastases were of non-GI origin. Five-year survival for women with ovarian metastases from breast cancer was 26%. In a multivariate analysis, GI surgery at primary surgery for ovarian metastasis was unfavorable prognostic factor. Diagnosis of primary disease known before surgery, primary disease of non-GI or unknown origin and operation at university hospital all had favorable prognostic impact for overall survival. Detection of non-genital ovarian metastasis at gynecologic surgery is associated with poor prognosis, and prognosis is worse in tumors with GI origin and if the primary is not detected prior to surgery. The results indicate that a thorough patient evaluation is very important before surgery for suspected ovarian neoplasm.


The in vivo and in vitro effects of antibodies against rabbit beta 2-integrins.
Beta 2-integrins play a crucial role in the development of an inflammatory response. In ours study, Abs have been used to investigate the role of individual members of this family of adhesion molecules in both in vivo and in vitro assays. An Ab against rabbit LFA-1 effectively inhibited the adhesion of rabbit polymorphonuclear leukocytes to rabbit endothelial cells in culture and was also effective in blocking cell recruitment to the peritoneum and vascular leakage at dermal sites of inflammation. An Ab that inhibited rabbit complement receptor type 3 function in vitro failed to inhibit cell recruitment to the peritoneum or vascular leakage in response to intradermal FMLP. Histologic studies suggested that the anti-complement receptor type 3 Ab may have modified the cell migration process.


Beyond chi-square: log-linear analysis and related methods of qualitative analysis.
Advanced methods of qualitative analysis hold great potential for nursing and health-related research. In this article, recent advances in qualitative analysis techniques are discussed and illustrated using data from a study of professional attitudes regarding nurse practitioner prescribing. Implications for in-depth multivariate analysis and theory building are discussed.


Diverse roles for axon guidance pathways in adult tissue architecture and function.
Classical axon guidance ligands and their neuronal receptors were first identified due to their fundamental roles in regulating connectivity in the developing nervous system. Since their initial discovery, it has become clear that these signaling molecules play important roles in the development of a broad array of tissue and organ systems across phylogeny. In addition to these diverse developmental roles, there is a growing appreciation that guidance signaling pathways have important functions in adult organisms, including the regulation of tissue integrity and homeostasis. These roles in adult organisms include both tissue-intrinsic activities of guidance molecules, as well as systemic effects on tissue maintenance and function mediated by the nervous and vascular systems. While many of these adult functions depend on mechanisms that mirror developmental activities, such as regulating adhesion and cell motility, there are also examples of adult roles that may reflect signaling activities that are distinct from known developmental mechanisms, including the contributions of guidance signaling pathways to lineage commitment in the intestinal epithelium and bone remodeling in vertebrates. In this review, we highlight studies of guidance receptors and their ligands in adult tissues outside of the nervous system, focusing on in vivo experimental contexts. Together, these studies lay the groundwork for future investigation into the conserved and tissue-specific mechanisms of guidance receptor signaling in adult tissues.


Predictability of combined effects of eight chloroacetanilide herbicides on algal reproduction.
Chloroacetanilides are pre-emergence herbicides for the control of annual grasses and broadleaf weeds. As a result of their extensive use, residues are often found in surface waters. Observed simultaneous occurrence of different chloroacetanilide herbicides gives reason for concern about potential combination effects on aquatic non-target organisms. This study aimed to clarify whether joint effects of various chloroacetanilide herbicides may be predictable from knowledge of concentration-response relationships of single substances. Whether the chloroacetanilides all share the same mode of action is unclear. Therefore we investigated the predictive value of two alternative concepts for the prediction of combined effects: concentration addition, which assumes a similar mode of action, and independent action, which is based on the idea of a dissimilar mode of action of the mixture components. Eight chloroacetanilides (acetochlor, alachlor, butachlor, dimethachlor, metazachlor, metolachlor, pretilachlor and propachlor) were experimentally tested for their individual as well as for their combined effects in mixtures on the reproduction of the green alga Scenedesmus vacuolatus. Individual chloroacetanilides impaired algal reproduction, with EC50 values ranging from 3 to 232 microg litre(-1). The differences in EC50 values were strongly correlated with the lipophilicities of the compounds. Effects of chloroacetanilide mixtures were considerably higher than those of the individual components: a complete inhibition of algal reproduction was observed when every mixture component was present in a concentration that would cause only 5% effect if applied singly. However, the combined effects proved to be predictable by using the concept of concentration addition. The alternative concept, independent action, distinctly underestimated the mixture toxicity. These findings (1) indicate a similar mechanism of action of chloroacetanilides in algae and (2) reinforce the view that concentration addition is a reasonable assumption for the predictive hazard assessment of groups of similarly acting herbicides.


Videography-Based Unconstrained Video Analysis.
Video analysis and understanding play a central role in visual intelligence. In this paper, we aim to analyze unconstrained videos, by designing features and approaches to represent and analyze videography styles in the videos. Videography denotes the process of making videos. The unconstrained videos are defined as the long duration consumer videos that usually have diverse editing artifacts and significant complexity of contents. We propose to construct a videography dictionary, which can be utilized to represent every video clip as a sequence of videography words. In addition to semantic features, such as foreground object motion and camera motion, we also incorporate two novel interpretable features to characterize videography, including the scale information and the motion correlations. We then demonstrate that, by using statistical analysis methods, the unique videography signatures extracted from different events can be automatically identified. For real-world applications, we explore the use of videography analysis for three types of applications, including content-based video retrieval, video summarization (both visual and textual), and videography-based feature pooling. In the experiments, we evaluate the performance of our approach and other methods on a large-scale unconstrained video dataset, and show that the proposed approach significantly benefits video analysis in various ways.


Physiological behavior of bean's seeds and grains during storage.
Beans are one of the most used foods to meet the energy needs of the Brazilian diet, requiring farmers to use high seed physiological potential. The aim was to evaluate the physiological quality of beans stored for 360 days. Analyses were performed at 0, 30, 90, 180, 270, and 360 days after receiving the seeds (S1 and S2) and grains (G1 and G2) of BRS Splendor. Tests of germination, accelerated aging, cold, speed of germination, average length of shoots, and root were performed. The experimental design was completely randomized split-plot in time and the means were compared through Tukey test at 5% probability. Seed germination was not affected in S2, while the drop in S1 and G1 was significant. The vigor of grains from field 1 declined from 91 to 50% and from 93% to 76% by accelerated aging and cold, respectively, after 360 days. The germination speed tests performed showed a decreased during the experiment. The grains from field 1 had lower physiological quality. The accelerated aging and cold tests, through the speed of germination parameter, showed decrease in the vigor of the Splendor BRS. The storage period influenced the physiological quality of the beans tested.


The phenomenon of vertebral body drift in neurofibromatosis and its implications for surgical safety.
To report on the phenomenon of body drift in neurofibromatosis scoliosis and discuss its implication on surgical safety. Ten dystrophic neurofibromatosis scoliosis (NF) and ten adolescent idiopathic scoliosis (AIS) were studied by radiographs, CT, and MRI. The curve characteristics and a detailed analysis of the morphology of the apical and three adjacent vertebral segments above and below were done. The coronal alignment and the presence of a drift of the vertebral body in relationship to the lamina were carefully studied in both groups and compared. The mean cobb angle in the NF group was 77.6°, and 63.7° in the AIS group. All the studied vertebra in the NF group had extensive pedicle changes, which were more severe at the apical and periapical regions. Body drift was noted in 29 vertebral segments, with 9/10 of apical segments showing a significant drift. The body drift was associated with significant pedicle dystrophic changes and was independent of the curve magnitude. In comparison, in AIS, no body drift was noted despite a larger deformity and more severe vertebral rotation. The 'body drift' phenomenon was unique to neurofibromatosis scoliosis and was secondary to severe pedicle morphology changes. This was present even in curves less than 60° and could result in cord injury while instrumenting the concave pedicle. Therefore, a thorough preoperative assessment and planning by a 3D CT are mandatory.


Factors Associated with Clinical Research Recruitment in a Pediatric Academic Medical Center--A Web-Based Survey.
One of the most difficult aspects of conducting clinical research is the ability to successfully recruit participants. Pediatric clinical research presents unique recruitment challenges that relate to the need for parental consent on behalf of a minor, child assent, and school attendance. Yet, this has been less well studied. We conducted a survey of investigators performing human subjects research in a single large academic pediatric hospital to better understand characteristics of studies with successful recruitment. We conducted a web-based survey from September 2011 to December 2011 of all principal investigators with an Institutional Review Board approved human subjects protocol at Boston Children's Hospital, a pediatric Academic Medical Center. The survey captured various characteristics of the protocols including study design, staffing, resources, and investigator experience and training as well as respondents' perceived barriers and facilitators to recruitment. We used chi square tests and Mantel-Haenszel test for linear trend to examine the relationship between selected predictor variables and the binary outcome of successful vs. unsuccessful recruitment and multivariable logistic regression analyses to examine the simultaneous influence of potential predictors on each outcome. Among the 349 eligible investigators, 52% responded to the survey, and 181 with valid data were included in the analyses. Two-thirds of the 87 protocols closed to enrollment reached 80% or more of their target enrollment, whereas, only one-third of the 94 protocols actively recruiting were meeting 80% of their target. Recruitment method appeared to be the only significant and independent factor associated with achieving 80% or more of target enrollment in closed to enrollment protocols. Closed to enrollment protocols that used recruitment in person were 4.55 times (95% CI 1.30 to 15.93; p = 0.02) more likely to achieve 80% or more of their target enrollment when compared to those that used other recruitment methods. Other potentially modifiable factors such as number of study visits, study duration and investigator experience were suggestive of being meaningfully related to recruitment. Recruiting in person may promote reaching an acceptable target enrollment in pediatric as well as adult clinical research. Future research is needed on larger and more diverse samples to gain a better understanding of how the characteristics and qualifications of the individuals who conduct recruitment influence participant enrollment as well as how best to approach patient and families for their participation.


Peak shift and rules in human generalization.
Two experiments tested whether a peak-shifted generalization gradient could be explained by the averaging of distinct gradients displayed in subgroups reporting different generalization rules. Across experiments using a causal judgment task (Experiment 1) and a fear conditioning paradigm (Experiment 2), we found a close concordance between self-reported rules and generalization gradients using a continuous stimulus dimension (hue). Both experiments also showed an overall peak-shifted gradient after differential conditioning, but not after single cue conditioning. Importantly, the peak shift could be decomposed into linear and peaked gradients when participants were divided into rule subgroups. Our results highlight the need to consider individual differences in the rules that participants derive in human generalization studies and suggest that in some situations, peak shift may be a consequence of averaging across diverse rule subgroups. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Recent advances in benign gynecological laparoscopic surgery.
Minimally invasive surgery continues to transform the field of gynecological surgery and is now the standard of care for the surgical treatment of many diseases in gynecology. Owing to minimally invasive surgery's clear advantages, new advances in technology are being employed rapidly and enabling even the most complicated procedures to be performed less invasively. We examine recent literature on minimally invasive surgical innovations, advances, and common practices in benign gynecology that, from our point of view, made an impact on the way laparoscopic surgery is performed and managed in the last decade.


Psychiatric Morbidity in Chinese Adults with Type 1 Diabetes in Hong Kong.
To determine the prevalence of psychiatric morbidity and identify the correlates, as well as to evaluate the effectiveness of the Hospital Anxiety and Depression Scale and the 12-item General Health Questionnaire to screen for psychiatric morbidity in Chinese adults with type 1 diabetes. Subjects were recruited from a local public diabetes specialist outpatient clinic from August 2013 to January 2014. Demographic and clinical factors were recorded. Psychiatric diagnosis was established using the Chinese-bilingual version of the Structured Clinical Interview for the DSM-IV Axis I disorders. Scores for the Hospital Anxiety and Depression Scale and the 12-item General Health Questionnaire were compared with the psychiatric diagnosis. Of the 136 patients, the point prevalence of overall psychiatric, depressive, and anxiety disorders was 39.7%, 23.5%, and 25.7%, respectively. Family history of mental illness, smoking status, history of mental illness, presence of social problems, perceived absence of confidant, presence of neuropathy and hyperlipidaemia, as well as higher level of glycosylated haemoglobin were found to be the associated factors. Psychiatric disorders were common in Chinese adults with type 1 diabetes. Finding out associated factors and using the Hospital Anxiety and Depression Scale and the 12-item General Health Questionnaire as a screening tool helped to identify patients in a diabetes clinic with psychiatric disorders.


Streamlining the dental care during COVID-19 pandemic: updated clinical recommendations and infection control management framework.
Several guidelines for dental practice have been published by dental associations and regulatory boards since the beginning of the pandemic. Initially, all non-emergency dental treatment were suspended. Healthcare personnel around the world are gradually expanding back to elective procedures. International updated recommendations alert that professionals must maintain regular observation of local health department reports, ensure personal protective equipment, and screen all patients for COVID-19 signs and symptoms. Telehealth strategies, patient screening, rescheduling when presenting COVID-19 symptoms and/or history of contact with infected people and hand/environment hygiene practices are reinforced. Appropriate cleaning and surface disinfection are mandatory. The dental staff must be trained to use appropriate Personal Protective Equipment (PPE), following a risk assessment and standard precautions: gloves; fluid resistant disposable gown, eye protection (face shield or goggles) and a medical mask. A fit tested N95 or KN95 respirator (or higher) is recommended when aerosol generating procedures are performed. Only essential accompanying persons should attend to dental appointment with the patient and must wear a cloth face covering or facemask. Social distancing and mask wearing by all staff are necessary in all areas of the office. Dental health care providers should keep up to date to the current guidance of clinical practice during the pandemic.


Pleuroperitoneal shunt for recurrent malignant pleural effusions.
The therapeutic options available for the management of malignant pleural effusions associated with a restricting malignant cortex remain unsatisfactory. The efficacy of pleuroperitoneal shunts was evaluated in 16 patients with recurrent malignant effusions. There were no operative deaths; one patient died on the third postoperative day as a result of lymphangitis carcinomatosa. The median hospital stay was five (range 3-21) days. Palliation was obtained in all but one of the other 15 patients. There was no appreciable reaccumulation of pleural fluid as judged by radiography. Two patients developed occlusion of the shunt. In one case this was due to blood clots in the pleural catheter and necessitated insertion of a new shunt. The other shunt was removed because of obstructing infected fibrin debris, and a rib resection was performed. There were eight deaths related to the underlying malignancy after a mean interval of 7.3 (range 1.5-23) months. The other six patients are still alive, with a mean survival of 11.0 (range 5-20) months, and have achieved good symptomatic relief. The insertion of a pleuroperitoneal shunt can offer effective palliation for patients with recurrent malignant pleural effusions.


Using bovine pituitary extract to increase proliferation of keratocytes and maintain their phenotype in vitro.
To investigate the effects of bovine pituitary extract on the proliferation of keratocytes and maintaining the keratocyte phenotype in vitro. Single keratocytes were isolated by enzyme digestion for in vitro culture. Three groups were designed according to the different culture media: a bovine pituitary extract (BPE) group, a fetal bovine serum (FBS) group and the control group. The phenotypes and proliferation of cultured cells were evaluated by morphology, immunofluorescent staining and mRNA expression of CD34, Lumican, VSX1, α-SMA and proliferating cell nuclear antigen (PCNA). In the BPE group, cells underwent serial subcultivation, and their phenotypes were identified by immunofluorescent staining. To analyze the proliferation of keratocytes in different concentrations of BPE, six different concentrations were designed to ascertain the most appropriate amount. In the BPE group, the cells spread out and presented dendritic morphology, and their dendrites connected to one another to form networks. On the third passage, most cells maintained their phenotype. In the FBS group, the cells exhibited a dendritic appearance in early cultured stages, but their morphology subsequently changed into a fibroblast-like shape. The number of dendritic cells in BPE group was more than FBS and control groups. Immunofluorescent staining and real-time polymerase chain reaction (PCR) confirmed that few keratocytes underwent fibroblastic transformation in the BPE and control groups, and that proliferation was higher in the BPE group than in the control group. Although the proliferation was higher in the FBS group, many keratocytes underwent fibroblastic transformation. The analysis of cell morphology and mRNA expressions of CD34, PCNA and VSX1 in six group showed that different concentrations of BPE affected the proliferation obviously but didn't affect the keratocyte phenotype, and the concentration of 40µg/mL was the most appropriate one. BPE can improve the proliferation of keratocytes and maintain their phenotype in vitro. Many keratocytes can be harvested rapidly and provide seeds for the construction of corneal stroma.


The expression of activin receptor-like kinase 1 among patients with head and neck cancer.
We investigated the expression and clinical significance of activin receptor-like kinase 1 (ACVRL1) in patients with head and neck squamous cell carcinoma (HNSCC). Case series with chart review. Academic Institute of Otolaryngology, Kaohsiung, Taiwan. Patients diagnosed with HNSCC (n = 169) underwent surgical resection followed by radiotherapy and/or chemotherapy for aggressive tumors between November 2000 and March 2004. ACVRL1 expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry approaches. High levels of ACVRL1 expression were significantly correlated with advanced T classification (P < .001), positive N classification (P = .002), advanced TNM stage (P < .001), lymphovascular invasion (P < .001), and extracapsular spread of lymph node metastasis (P = .021). A poor 5-year overall survival rate was correlated with high ACVRL1 expression (P = .0048), advanced T classification (P = .0075), positive N classification (P = .0024), advanced TNM stage (P = .0077), and extracapsular spread of lymph node (P = .0002), but a multivariate analysis using the Cox regression model revealed that the only independent prognostic factors for survival were ACVRL1 expression (P = .043; odds ratio [OR], 1.635; 95% confidence interval [CI], 1.017-2.629) and extracapsular spread of lymph node metastasis (P = .003; OR, 2.052; 95% CI, 1.270-3.315). A high level of ACVRL1 expression in tumor tissue is significantly correlated with advanced T classification, positive N classification, advanced TNM stage, and poorer prognosis.


Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model.
Studies performed to identify early events of ovarian cancer and to establish molecular markers to support of early detection and the development of chemopreventive regimens have been hindered by a lack of adequate cell models. Taking advantage of the spontaneous transformation of mouse ovarian surface epithelial (MOSE) cells in culture, we isolated and characterized distinct transitional stages of ovarian cancer as the cells progressed from a premalignant nontumorigenic phenotype to a highly aggressive malignant phenotype. Transitional stages were concurrent with progressive increases in proliferation, anchorage-independent growth capacity, in vivo tumor formation, and aneuploidy. During neoplastic progression, our ovarian cancer model underwent distinct remodeling of the actin cytoskeleton and focal adhesion complexes, concomitant with downregulation and/or aberrant subcellular localization of two tumor-suppressor proteins E-cadherin and connexin-43. In addition, we demonstrate that epigenetic silencing of E-cadherin through promoter methylation is associated with neoplastic progression of our ovarian cancer model. These results establish critical interactions between cellular cytoskeletal remodeling and epigenetic silencing events in the progression of ovarian cancer. Thus, our MOSE model provides an excellent tool to identify both cellular and molecular changes in the early and late stages of ovarian cancer, to evaluate their regulation, and to determine their significance in an immunocompetent in vivo environment.


Perceived need and use of oral health services among adolescents and adults in Tanzania.
The perceived need and use of oral health services among adolescents and adults in Tanzania were studied. One region from each of the country's five zones was chosen at random. Final sample selection (n = 1061) was done in the main towns of the selected regions. Participants were interviewed using a structured questionnaire which dealt with perceived need for dental treatment and use of oral health services and several demographic variables. Frequency tables were computed and analyzed. Odds ratios were calculated based on 2 x 2 tables and logistic regression models. The majority, 82% (95% CI: 79-85%) had sought treatment due to pain or for tooth extraction. Perceived need, dissatisfaction with own oral health status and use of oral health services were slightly more frequent among women. Bleeding gums had no explanatory value on the dependent variables. The strongest explanatory variable in a logistic regression model for perceived need and dissatisfaction with own oral health status was previous dental treatment with an estimated odds ratio of 6.4 (95% CI: 4.7-8.7) and 7.2 (95% CI: 5.3-9.9), respectively. People living nearest a treatment facility tended to use the services more [odds ratio 1.3 (95% CI: 0.8-2.1)]. A very strong relation between previous dental problems and use of oral health services was found, namely an odds ratio of 68.8 (95% CI: 39.0-121.4). The findings in the study may be useful in the attempts to implement Tanzania's National Plan for Oral Health.


Chromenes - A Novel Class of Heterocyclic Compounds: Recent Advancements and Future Directions.
Chromenes are an important class of oxygen-containing heterocyclic compounds with intriguing biological activity, a simple structure with mild adverse effects. Chromenes are abundantly found in nature in the form of alkaloids, tocopherols, flavone, and anthocyanins. The Chromene nucleus is an important moiety for the discovery of new drug candidates. Chromene derivatives have shown various pharmacological activities like antiviral, anticancer, anti-inflammatory, antitumour, antimicrobial, antiproliferative, anticholinesterase, EPR-1 (Effector cell Protease Receptor-1) antagonist and MAO (Mono-Amine Oxidase) inhibitors. In SAR (Structure Activity Relationship) studies with chromene nucleus, it was found that 4-aryl moiety, 3-cyano group, and 2-amino group are essential for the cytotoxic activity. Substitution at the 7th position with electron donating group enhances the pharmacological activity whereas the electron withdrawing group decreases the pharmacological activity. Structural modifications at the chromene ring, middle aliphatic portion, and terminal aromatic ring yielded more potential 5-HT1A (5-Hydroxytryptamine 1A) receptor affinity and antidiabetic activity. Chromenes with cyclic secondary amine and 4-hydroxy phenyl substituents yielded potent antimicrobial compounds. This review summarizes the importance of chromenes in rational drug design and the development of novel molecules with a variety of pharmacological activities.


Dietary phosphatidylcholine and risk of all-cause and cardiovascular-specific mortality among US women and men.
The trimethylamine-containing nutrient phosphatidylcholine is the major dietary source for the gut microbiota metabolite trimethylamine-N-oxide (TMAO), which has been related to cardiovascular diseases (CVDs) and mortality. Previous research suggested that the relation of TMAO with CVD risk might be stronger in diabetic than in nondiabetic populations. However, the evidence for an association of dietary phosphatidylcholine with CVD and mortality is limited. We aimed to examine whether dietary consumption of phosphatidylcholine, which is mainly derived from eggs, red meat, and fish, is related to all-cause and CVD mortality in 2 cohorts of US women and men. In particular, we also tested if such an association was modified by diabetes status. We followed 80,978 women from the Nurses' Health Study (1980-2012) and 39,434 men from the Health Professionals Follow-Up Study (1986-2012), who were free of cancer and CVD at baseline, for mortality. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We used Cox proportional hazards models to estimate HRs and 95% CIs. We documented 17,829 all-cause and 4359 CVD deaths during follow-up. After multivariate adjustment for potential confounders, including demographic factors, disease status, lifestyle, and dietary intakes, higher phosphatidylcholine intakes were associated with an increased risk of all-cause and CVD mortality. HRs (95% CIs) comparing the top and bottom quintiles of phosphatidylcholine intake were 1.11 (1.06, 1.17; P-trend across quintiles < 0.0001) for all-cause mortality and 1.26 (1.15, 1.39; P-trend < 0.0001) for CVD mortality in the combined data of both cohorts. The associations of phosphatidylcholine with all-cause and CVD mortality were stronger in diabetic than in nondiabetic participants (P-interaction = 0.0002 and 0.001, respectively). These data suggest that higher phosphatidylcholine consumption is associated with increased all-cause and CVD mortality in the US population, especially in patients with diabetes, independent of traditional risk factors.


Surgical treatment of a 56-year-old woman with an intracardiac type of total anomalous pulmonary venous connection.
Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac anomaly. Death usually occurs in the first 3 months of life in about 50% of neonates with this disease, and no more than 20% of patients survive to the age of 1 year. The patient with the longest recorded survival is 49 years old. Here, we report successful surgical treatment of this disease in a 56-year-old female patient. This patient was discharged in good health about 1 month after operation, with no evidence of recurrence of heart failure at 13 months' follow-up.


Inhibition of HBsAg immunologic reactivity and intestinal aerobic flora.
Cultures of human intestinal aerobic flora did not have any inhibiting action on the immunologic reactivity of hepatitis B antigen even after disruption of bacterial cells by freezing and thawing. This suggests that the inhibitor is elaborated by the human intestinal mucosa.


The sci-commodity sensibilities of performative Covid-19 face masking.
This article explores how extravagantly visible mask-wearing relates with consumer culture. Methodologically, three purposively chosen case studies of spectacular or performative mask-wearing are used to show what the face mask can teach us about consumer culture in a pandemic. First, a Daily Mail (UK) article in which an 'elderly shopper' is shamed for wearing a sanitary towel as a face mask is used to explore the politics of disposable commodities. Second, the multiplying portraits of people wearing masks archived under Instagram's #MaskSelfie hashtag allows an examination of how consumer-citizenship is performed. Third, the presence of extremely expensive luxury designer masks, as evidenced by Rich Mnisi's Swarovski-encrusted offering, is a base for considering how virtue signalling has become a platform for luxury branding. Building on these three examples, the argument is made that waste, selfies and luxury are modalities for a pandemic commodity politics that is layered over and into the scientific citizenship signalled by the wearing of face masks. Together these create what I call a 'sci-commodity' sensibility, in which the face mask as a technology has become integrated with the modalities of consumption. This has resonance with ongoing debates about the object, subject and brand in consumer culture.


Benchmarking DNA isolation kits used in analyses of the urinary microbiome.
The urinary microbiome has been increasingly characterized using next-generation sequencing. However, many of the technical methods have not yet been specifically optimized for urine. We sought to compare the performance of several DNA isolation kits used in urinary microbiome studies. A total of 11 voided urine samples and one buffer control were divided into 5 equal aliquots and processed in parallel using five commercial DNA isolation kits. DNA was quantified and the V4 segment of the 16S rRNA gene was sequenced. Data were processed to identify the microbial composition and to assess alpha and beta diversity of the samples. Tested DNA isolation kits result in significantly different DNA yields from urine samples. DNA extracted with the Qiagen Biostic Bacteremia and DNeasy Blood & Tissue kits showed the fewest technical issues in downstream analyses, with the DNeasy Blood & Tissue kit also demonstrating the highest DNA yield. Nevertheless, all five kits provided good quality DNA for high throughput sequencing with non-significant differences in the number of reads recovered, alpha, or beta diversity.


Central Integration of Canal and Otolith Signals is Abnormal in Vestibular Migraine.
Vestibular migraine (VM), a common cause of vestibular symptoms within the general population, is a disabling and poorly understood form of dizziness. We sought to examine the underlying pathophysiology of VM with three studies, which involved the central synthesis of canal and otolith cues, and present preliminary results from each of these studies: (1) VM patients appear to have reduced motion perception thresholds when canal and otolith signals are modulated in a co-planar manner during roll tilt; (2) percepts of roll tilt appear to develop more slowly in VM patients than in control groups during a centrifugation paradigm that presents conflicting, orthogonal canal and otolith cues; and (3) eye movement responses appear to be different in VM patients when studied with a post-rotational tilt paradigm, which also presents a canal-otolith conflict, as the shift of the eye's rotational axis was larger in VM and the relationship between the axis shift and tilt suppression of the vestibulo-ocular reflex differed in VM patients relative to control groups. Based on these preliminary perceptual and eye movement results obtained with three different motion paradigms, we present a hypothesis that the integration of canal and otolith signals by the brain is abnormal in VM and that this abnormality could be cerebellar in origin. We provide potential mechanisms that could underlie these observations, and speculate that one of more of these mechanisms contributes to the vestibular symptoms and motion intolerance that are characteristic of the VM syndrome.


[Live birth resulting from abdominal pregnancy].
Advanced abdominal pregnancy is extremely rare. Symptoms are often nonspecific, and the diagnosis is frequently missed. Maternal mortality and morbidity are also very high especially if the condition is not diagnosed and managed properly. In abdominal pregnancy there is a high incidence of fetal malformations. We are presenting a case of a 38 year old primigravida with an undiagnosed advanced abdominal pregnancy carried beyond 36 weeks of gestation. We delivered a 2090 g baby from the abdomen. A relaparotomy was necessary on the third postoperative day because of abdominal bleeding. At the time of discharge both mother and baby were doing well. The publication also provides a literature overview, including definition, epidemiology, diagnosis and therapy. Orv. Hetil., 2017, 158(13), 508-511.


Communicating With School Nurses About Sexual Orientation and Sexual Health: Perspectives of Teen Young Men Who Have Sex With Men.
Black and Latino young men who have sex with men (YMSM) are at disproportionate risk for sexually transmitted diseases (STDs), including HIV. This study informs school-centered strategies for connecting YMSM to health services by describing their willingness, perceived safety, and experiences in talking to school staff about sexual health. Cross-sectional data were collected from Black and Latino YMSM aged 13-19 through web-based questionnaires (N = 415) and interviews (N = 32). School nurses were the staff members youth most often reported willingness to talk to about HIV testing (37.8%), STD testing (37.1%), or condoms (37.3%), but least often reported as safe to talk to about attraction to other guys (11.4%). Interviews revealed youth reluctance to talk with school staff including nurses when uncertain of staff members' perceptions of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) people or perceiving staff to lack knowledge of LGBTQ issues, communities, or resources. Nurses may need additional training to effectively reach Black and Latino YMSM.


A Systematic Review of Exercise Intervention Program for People With Substance Use Disorder.
Addiction has been attributed to development of habit-based neural circuits that promote continued substance use despite a conscious wish to abstain. The goal of this study was to determine if physical exercise could serve as an alternative habit to replace habitual substance use, and whether this exercise intervention methods differed for opioid vs. amphetamine Dependents. A total of 14 randomized controlled experimental literatures on exercise intervention in people with opioid and amphetamine use disorder were screened, the 14 literature included 4 opioids and 10 amphetamines. From the 14 literature, the information of intervention program elements were counted, respectively. Independent sample t-test was used to compare the similarities and differences between the two intervention methods, and intervention mechanism of dependents were discussed. All rehabilitation exercises for opioid dependents use aerobic exercise, while most rehabilitation exercises for amphetamine dependents use aerobic exercise, and a few use aerobic and anaerobic mixed exercise. There is no significant difference in exercise time, exercise frequency and cycle between the two intervention schemes (P > 0.05). The rehabilitation indicators of opioid and amphetamine dependents generally include psychological indicators and physiological indicators, and most of the tests mainly focus on measuring psychological indicators such as mood and drug craving of dependents. The goal of exercise intervention for opioid and amphetamine dependents is similar, the first is to improve mood, reduce craving, improve sleep, and the second is to enhance physical fitness. In the treatment of Substance use disorder, exercise intervention can be used as an auxiliary treatment. Exercise intervention emphasizes low intensity and high frequency. Exercise intervention tends to cultivate long-term exercise habits or exercise lifestyle. Based on this "habit" mechanism, exercise can complete the substitution of material dependence.


Comparative clinical and pharmacokinetic aspects of cefotetan versus cefoxitin plus metronidazole in vaginal hysterectomy.
In a randomised clinical trial, 102 women who underwent vaginal hysterectomy were given a single preoperative 2g dose of cefotetan (CTT) (52 pts) or three perioperative 2g doses of cefoxitin (CFX) plus 0.5g metronidazole (50 pts) as antibiotic prophylaxis. No statistically significant differences between the groups were detected in the clinical response (100% for both groups). The incidence of major wound infection (2% CTT and 0% CFX) were also comparable between the two treatment groups; post-operative changes in body temperature, duration of hospitalisation and post-operative urinary tract infections (16% CTT and 20% CFX) were similar. Both drugs were well tolerated. Twenty nine of the 102 patients were further investigated to determine the pharmacokinetics following a single 2g dose of CTT or CFX, in both serum and tissue. Although both antibiotics provided good concentrations during the early phase of surgery, CTT levels persisted for a longer time period. These results confirm that single dose cefotetan is equally as effective and safe as multiple dose cefoxitin plus metronidazole for prophylaxis in patients undergoing vaginal hysterectomy.


Conformation of Lac repressor tetramer in solution, bound and unbound to operator DNA.
We tested whether the Steitz et al. [(1974) Proc. Natl. Acad. Sci. U.S.A., 71:593-597] model of lactose repressor (LacR) (14 x 6.0 x 4.5 nm) represented the shape of free or operator-bound LacR in solution. The model predicts a 14 nm length for bound LacR. Direct measurement, using Pt-C shadow width standards, was 9.6 +/- 0.2 nm long. Using the Steitz model, we generated a distribution of measurements and converted them into a distribution of shadow widths using gold ball standards. Direct measurement of LacR produced a narrower shadow width distribution with a larger mean size than the Steitz model predicted. Measurement along two orthogonal axes of negatively stained LacR images generated a size distribution, also converted into a shadow width distribution using the gold ball standards. Since the experimental shadow width distribution exactly matched the shadow width distribution derived theoretically from negatively stained LacR, our negative-stained images are representative of LacR's conformation in solution. Approximately 56% of negatively stained LacR had a V-shaped fold around an axis orthogonal to its length, bringing the DNA binding domains of each dimer adjacent. This open end of the V binds single operator DNA. The other 44% of the LacR tetramer is in the extended form with its DNA binding sites at opposite ends. Although the V-shaped conformation has a closed hinge with the dimers associated along a side, the extended open-hinged state remains important since LacR must bind two distant operator sites for full repression. Our measurements predict the normal presence of both conformations in nearly equal amounts, suggesting that both are equally active in repressing the lac operon.


Characterisation and identification of chemical constituents in aqueous extract of Fomes officinalis Ames based on ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry.
Fungal species are an attractive resource for physiologically functional food and drug precursor. Fomes officinalis Ames, a medicinal fungus, is traditionally used as a folk medicine in traditional Chinese medicine prescription for the therapy of cough and asthma. The water-soluble substances in Chinese herbal medicines are likely to play an important physiological function. However, information on probing and identifying chemical components of the aqueous extract of Fomes officinalis Ames (AFO) remains unknown. This study was conducted to screen and characterise the chemical components of AFO. An effective and sensitive ultrahigh-performance liquid chromatography tandem quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) method with the Full MS/PIL/dd-MS2 acquisition approach was applied for the profiling of chemical components in AFO. An HSS T3 column was used for component separation, and a strategy of simultaneous targeted and untargeted multicomponent characterisation was implemented. Multiple identification approaches were used, including accurate molecular mass and elemental composition matching, literature and database searching, and fragmentation rules elucidation. A total of 115 components, including 20 amino acids and derivatives, six nucleobases, nine nucleosides, 75 dipeptides, two tripeptides, and three other components, were tentatively identified. Among them, the targeted exploring method screened six nucleobases and nine nucleosides including modified nucleosides. To our best knowledge, this is the first time a report has been done on the presence of the 115 compounds in AFO. Profiling and characterisation compounds of AFO enriched its material basis, which would lay the foundation for improving potential medicinal and nutritional values and effecting comprehensive quality control of Fomes officinalis Ames.


Mechanical behavior and wall remodeling of blood vessels under axial twist.
Blood vessels are often subjected to axial torsion (or twist) due to body movement or surgery. However, there are few studies on blood vessel under twist. This review first summarizes the clinical observation on the twist of blood vessels and then presents what we know about the mechanical behaviors of blood vessel under twist, including the constitutive models. The state of art researches on the remodeling of blood vessels under twist via ex vivo organ culture, in vivo animal experiments, and mathematical model simulations are further discussed. It is our hope that this review will draw attention for further in-depth studies on the behavior and remodeling of blood vessels under twist.


From the Wild to the Cup: Tracking Footprints of the Tea Species in Time and Space.
Tea is one of the world's most popular beverages, known for its cultural significance and numerous health benefits. A clear understanding of the origin and history of domestication of the tea species is a fundamental pre-requisite for effective germplasm conservation and improvement. Though there is a general consensus about the center of origin of the tea plant, the evolutionary origin and expansion history of the species remain shrouded in controversy, with studies often reporting conflicting findings. This mini review provides a concise summary of the current state of knowledge regarding the origin, domestication, and dissemination of the species around the world. We note that tea was domesticated around 3000 B.C. either from non-tea wild relatives (probably Camellia grandibracteata and/or C. leptophylla) or intra-specifically from the wild Camellia sinensis var. assamica trees, and that the genetic origins of the various tea varieties may need further inquiry. Moreover, we found that lineage divergence within the tea family was apparently largely driven by a combination of orogenic, climatic, and human-related forces, a fact that could have important implications for conservation of the contemporary tea germplasm. Finally, we demonstrate the robustness of an integrative approach involving linguistics, historical records, and genetics to identify the center of origin of the tea species, and to infer its history of expansion. Throughout the review, we identify areas of debate, and highlight potential research gaps, which lay a foundation for future explorations of the topic.


The potential role of innate immunity in the pathogenesis of Hodgkin's lymphoma.
The innate immune system is our first line of defense against danger signals but in Hodgkin's lymphoma the role seems opposite, favoring malignant development. In this article we describe interactions between Hodgkin's and Reed-Sternberg cells and the cells of the innate immune system: eosinophils, mast cells, neutrophils, and macrophages. These cells clearly contribute to the pathogenesis of this disease and to the prognosis. Cytokines and chemokines released from the activated immune cells probably promote tumor cell growth and survival along with angiogenesis. Mast cells and eosinophils seem also to contribute to the fibrosis that is so characteristic for nodular sclerosis.


The polycomb group gene EMF2B is essential for maintenance of floral meristem determinacy in rice.
Polycomb Repressive Complex 2 (PRC2) represses the transcriptional activity of target genes through trimethylation of lysine 27 of histone H3. The functions of plant PRC2 have been chiefly described in Arabidopsis, but specific functions in other plant species, especially cereals, are still largely unknown. Here we characterize mutants in the rice EMF2B gene, an ortholog of the Arabidopsis EMBRYONIC FLOWER2 (EMF2) gene. Loss of EMF2B in rice results in complete sterility, and mutant flowers have severe floral organ defects and indeterminacy that resemble loss-of-function mutants in E-function floral organ specification genes. Transcriptome analysis identified the E-function genes OsMADS1, OsMADS6 and OsMADS34 as differentially expressed in the emf2b mutant compared with wild type. OsMADS1 and OsMADS6, known to be required for meristem determinacy in rice, have reduced expression in the emf2b mutant, whereas OsMADS34 which interacts genetically with OsMADS1 was ectopically expressed. Chromatin immunoprecipitation for H3K27me3 followed by quantitative (q)RT-PCR showed that all three genes are presumptive targets of PRC2 in the meristem. Therefore, in rice, and possibly other cereals, PRC2 appears to play a major role in floral meristem determinacy through modulation of the expression of E-function genes.


Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene.
Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v-gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v-gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesis.


Do platelets promote cardiac recovery after myocardial infarction: roles beyond occlusive ischemic damage.
Our understanding of platelet function has traditionally focused on their roles in physiological hemostasis and pathological thrombosis, with the latter being causative of vessel occlusion and subsequent ischemic damage to various tissues. In particular, numerous in vivo studies have implicated causative roles for platelets in the pathogenesis of ischemia-reperfusion (I/R) injury to the myocardium. However, platelets clearly have more complex pathophysiological roles, particularly as a result of the heterogeneous nature of biologically active cargo secreted from their granules or contained within released microparticles or exosomes. While some of these released mediators amplify platelet activation and thrombosis through autocrine or paracrine amplification pathways, they can also regulate diverse cellular functions within the localized microenvironment and recruit progenitor cells to the damage site to facilitate repair processes. Notably, there is evidence to support cardioprotective roles for platelet mediators during I/R injury. As such, it is becoming more widely appreciated that platelets fulfill a host of physiological and pathological roles beyond our basic understanding. Therefore, the purpose of this perspective is to consider whether platelets, through their released mediators, can assume a paradoxically beneficial role to promote cardiac recovery after I/R injury.


Thymectomy for myasthenia gravis.
Thymectomy was performed on 31 patients with myasthenia gravis. Four of them had thymoma, 17 hyperplasia and 9 had normal thymic histology on microscopy. Discontinuation of anticholinergic medication together with tracheostomy, artificial ventilation and intensive observation were essential in the postoperative management. All the patients survived operation and were discharged from hospital. Sixty-eight per cent of the patients were in remission or improved after an average follow-up of 2.5 years. If the patients with thymoma were excluded, 74% were improved and, if only the patients with thymic hyperplasia were included in the series, 89% were improved after thymectomy. The severity of disease and duration of symptoms pre-operatively seemed to be of minor importance for the results of operation, since good results were obtained also in patients with a long history and in clinical classes III and IV. Two patients developed tracheal stenosis as a complication of intubation with a tracheostomy tube. Tracheal resection was performed in one of them and endobronchial removal of granulation tissue producing the stenosis in the other. Both recovered uneventfully. One patient, who was asymptomatic and without medication for myasthenia, died suddenly of acute cerebral bleeding 3 years after thymectomy.


Seroprevalence of Toxoplasma antibodies among individuals tested at hospitals and private laboratories in Beirut.
Toxoplasmosis is a zoonotic disease of worldwide distribution. Infection with Toxoplasma gondii can result in debilitating disease especially in the immunocompromized host and pregnant women. Determination of its seroprevalence and risk factors have been studied in many countries as a mean to understand its epidemiology and implement control measures. The scarcity of information on T. gondii infection in Lebanon warranted studying the toxoplasma antibody findings among individuals tested at different hospitals and private laboratories in Beirut in order to have an insight on its current seroprevalence in this country. This is a retrospective study targeting information related to IgG and IgM anti-T. gondii antibodies among females tested at different hospitals and private laboratories in Beirut. Toxoplasma antibody determination in the sera was done using different formats of semi-automated enzyme immunoassay techniques. The age of each tested individual was also recorded. The generated data was based on testing done at seven hospitals and seven private laboratories located in different areas of Beirut. The vast majority (around 96%) of the tested population were females with age ranging between 16 yrs and 40 yrs (i.e. mostly females at childbearing age). The seroprevalence of IgG anti-T. gondii antibodies determined on 1371 sera from hospital laboratories and 2145 sera from private laboratories were 55% and 67%, respectively. The IgM anti-T. gondii antibodies determined on 1352 sera from hospital laboratories and 2074 sera from private laboratories were 6.7% and 6.8%, respectively. Overall and among the 3516 and 3426 blood samples tested for toxoplasma IgG and IgM antibodies at all laboratories, the seropositivity was 62.2% and 6.8%, respectively. The toxoplasma IgG seropositivity showed significant (p<0.05) increasing correlation with advanced age, for example, from 9% at < or = 5 yrs to 78% at 46-50 yrs, and 94% at > or = 51 yrs. Based on this seroprevalence study, exposure to toxoplasm infection is considered high among the Lebanese population and it increases with advanced age. This current information reflects the endemicity of this disease and would help the medical and public health authorities to address policies for monitor and control aspects of the disease in Lebanon.


The brain in science education: what should everyone learn?
Dr. Jo Ellen Roseman and Mary Koppal, from the American Academy for the Advancement of Science (AAAS), discuss how brain science fits into national classroom curricula. While recommendations published by AAAS, the National Research Council, the Society for Neuroscience, and the College Board all include standards relating to the brain, what students actually learn in the classroom varies greatly from state to state.


Targeting Beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe.
Biomolecules containing the RGD peptide sequence are known to bind integrins with high affinity. Studies of hexa-and hepta-peptides labeled with a near-infrared fluorescent probe (cypate) showed that rearranging the glycine in a linear RGD peptide sequence to form the GRD analogue favored the uptake of the GRD compound by alphavbeta3 integrin receptor (ABIR)-positive A549 tumor cells and tissue. The internalization of the GRD compound in A549 cells and tumor uptake in mice were inhibited by ABIR-avid peptides, suggesting its recognition by this receptor. Further studies with functional blocking antibodies and beta3 knockout cells revealed that beta3 integrin mediates the internalization of the cypate-GRD peptide. Molecular modeling studies supported preferential interaction of the probe with the beta3 subunit of integrins relative to the alphav subunit. The results demonstrate that the cypate-GRD peptide targets beta3 integrin, thereby providing a strategy to monitor drug delivery and efficacy, and physiopathologic processes mediated by this protein.


Pulsatile stretch in coronary arteries elicits release of endothelium-derived hyperpolarizing factor: a modulator of arterial compliance.
To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has been demonstrated only in response to receptor-dependent Ca2+-elevating agonists. Since endothelial cells in situ are continuously subjected to rhythmic distension, we investigated the effect of rhythmic stretch on the release of EDHF from isolated porcine coronary arteries. In the combined presence of diclofenac and N(G)-nitro-L-arginine (L-NNA), sinusoidal pressure oscillations (from 40 to 50 mm Hg, 4 minutes, 1.5 Hz) led to simultaneous oscillations in the external diameter of coronary artery segments, the amplitude of which were decreased by iberiotoxin and apamin and also by endothelial denudation. In order to directly demonstrate the release of EDHF, the intraluminal solution from endothelium-intact coronary segments exposed to pulsatile stretch was applied to detector rat aortic smooth muscle cells, the membrane potential of which was continuously measured using the patch-clamp technique. The hyperpolarization of detector cells induced by the intraluminal solution was proportional to the amplitude of the pressure oscillations applied to the donor artery and was attenuated by either preincubation of donor arteries with 17-octadecynoic acid or application of either tetrabutylammonium or iberiotoxin to detector cells. In contrast to the bradykinin-induced release of EDHF, the EDHF synthesized in response to pulsatile stretch did not exhibit any tachyphylaxis. These findings demonstrate for the first time that the synthesis of EDHF in coronary arteries can be mechanically stimulated by rhythmic vessel wall distension and suggest that the continuous release of EDHF may contribute to the adjustment of an adequate vascular compliance and to the control of coronary blood flow.


Evaluation of exploration and risk assessment in pre-weaning mice using the novel cage test.
Exploration and risk behaviour (risk assessment/risk taking) are critical to enable mice to cope with novel situations and gain control over their environment. Evaluation of those behaviours would therefore be a useful part of early phenotypic characterization of genetically modified mice, allowing early detection of behavioural phenotypes that require special attention and/or are of scientific interest. This study aimed to evaluate exploration and risk behaviour in pre-weaning mice using the novel cage test, which consists in exploration of a novel, clean, Makrolon type III cage. The results of this test were compared with those obtained in more complex and established tests to which the same mice were subjected as adolescents and young adults. Mice of two inbred strains (129S6/Bkl, n=10; C57BL/6Bkl, n=10) and one hybrid (B6CBAF1/Bkl, n=10) were used for validation of the test. The animals were tested in the novel cage (at weaning), the open field test (at 5 weeks), and from 9 weeks of age in three other tests: the elevated plus-maze, the concentric square field and the rat exposure test. The novel cage test effectively detected strain differences in pre-weaning mice as regards exploration and risk behaviour and the results were largely consistent with those obtained in the established tests later in life. In all tests 129S6 displayed a low locomotion and high risk assessment, while C57BL/6 and B6CBAF1 showed high locomotion and exploration. In addition high levels of risk taking were observed in C57BL/6. The novel cage test is rapid, requires no special equipment and is as discriminatory as more complex tests in detecting strain/genotype differences. This suggests that the novel cage test is a valuable tool for evaluation of exploration, risk assessment and risk taking in juvenile mice.


Automatic calculation of the medial axis of foot outline and its flexion angles.
As one of the morphological characteristics of human foot, flexion angles of medial axis of foot outline have been proposed in order to improve shoe comfort. Foot outlines were easily obtained by a scriber, whereas calculation of the medial axis and its flexion angles from the foot outline had inter-operator errors and a lack of reproducibility. This is because foot outlines were inputted by a digitizer, and flexion points of the medial axis were determined by eye inspection. An automatic method of calculation was developed for the following purposes: (1) to decrease inter-operator errors caused by manual operation; (2) to improve the reproducibility of the medial axis and its flexion angles; and (3) to save time and trouble in processing a large amount of data. The flexion angle reproducibility of the present method was within 1 degree. The errors in the flexion angles determined by the present method are half those determined by the conventional method. The flexion angles of over 5000 foot outlines that were obtained in 1987 were calculated when the present method was developed. The mean posterior flexion angle of the adults was 8.4 degrees. Since the majority of Japanese feet are outflared, this characteristic should not be ignored in designing/modifying shoe lasts.


BBE02 disruption mutants of Borrelia burgdorferi B31 have a highly transformable, infectious phenotype.
We constructed highly transformable and infectious Borrelia burgdorferi B31 by inactivating BBE02, a putative restriction-modification gene on the linear plasmid lp25. The low-passage-number B31 clones 5A4 (containing all plasmids) and 5A18 (lp28-4(-) lp56(-)) were used for this study, and BBE02 was disrupted by homologous recombination. The transformation efficiency with the shuttle vector pBSV2C03::gntDeltakan was increased from <1 to approximately 10 colonies per mug of DNA for 5A4 and 5A4 BBE02::Kan(r) and from 14 to approximately 600 colonies per mug of DNA for 5A18 and 5A18 BBE02::Kan(r). lp25, which is required for infectivity in mice, was retained in BBE02 mutants transformed with pBSV2C03::gntDeltakan, but lp25 was not detected in transformants of the parental clones 5A4 and 5A18. BBE02 disruptants and pBSV2C03::gntDeltakan transformants of these clones remained infectious in C3H/HeN mice, and the 50% infective doses of the BBE02 disruptants were <10(2) organisms per mouse. The inactivation of BBE02 thus eliminates a transformation barrier for infectious B. burgdorferi B31 and will provide a valuable tool for studying the virulence factors of Lyme disease.


[Adenicarcinoma in an ileostomy 41 years after proctocolectomy due to familial adenomatous polyposis].
This casestory describes a complication 41 years after a proctocolectomy due to familial adenomatous polyposis. Due to a granuloma the patient experienced problems in bandaging his ileostomy. The granuloma was excised, and a histologic examination revealed an adenocarcinoma. A small bowel resection was performed and 30 cm of the ileum was removed along with 3 cm of surrounding peristomal tissue. The patient did not wish to move the ileostomy, and a peristomal hernia occured. The recommendation is to excise the stoma including a tube of the surrounding tissue and to move the new stoma to another location, thereby reducing the risk of stomal hernia.


A comparative approach to recombinantly produce the plant enzyme horseradish peroxidase in Escherichia coli.
Horseradish peroxidase (HRP) is used in various biotechnological and medical applications. Since its isolation from plant provides several disadvantages, the bacterium Escherichia coli was tested as recombinant expression host in former studies. However, neither production from refolded inclusion bodies nor active enzyme expression in the periplasm exceeded final titres of 10mg per litre cultivation broth. Thus, the traditional way of production of HRP from plant still prevails. In this study, we revisited the recombinant production of HRP in E. coli and investigated and compared both strategies, (a) the production of HRP as inclusion bodies (IBs) and subsequent refolding and (b) the production of active HRP in the periplasm. In fact, we were able to produce HRP in E. coli either way. We obtained a refolding yield of 10% from IBs giving a final titre of 100mgL-1 cultivation broth, and were able to produce 48mg active HRP per litre cultivation broth in the periplasm. In terms of biochemical properties, soluble HRP showed a highly reduced catalytic activity and stability which probably results from the fusion partner DsbA used in this study. Refolded HRP showed similar substrate affinity, an 11-fold reduced catalytic efficiency and 2-fold reduced thermal stability compared to plant HRP. In conclusion, we developed a toolbox for HRP engineering and production. We propose to engineer HRP by directed evolution or semi-rational protein design, express HRP in the periplasm of E. coli allowing straight forward screening for improved variants, and finally produce these variants as IB in high amounts, which are then refolded.


The main protease 3CLpro of the SARS-CoV-2 virus: how to turn an enemy into a helper.
Despite the long history of use and the knowledge of the genetics and biochemistry of E. coli, problems are still possible in obtaining a soluble form of recombinant proteins in this system. Although, soluble protein can be obtained both in the cytoplasm and in the periplasm of the bacterial cell. The latter is a priority strategy for obtaining soluble proteins. The fusion protein technology followed by detachment of the fusion protein with proteases is used to transfer the target protein into the periplasmic space of E. coli. We have continued for the first time to use the main viral protease 3CL of the SARS-CoV-2 virus for this purpose. We obtained a recombinant 3CL protease and studied its complex catalytic properties. The authenticity of the resulting recombinant enzyme, were confirmed by specific activity analysis and activity suppression by the known low-molecular-weight inhibitors. The catalytic efficiency of 3CL (0.17 ± 0.02 µM-1-s-1) was shown to be one order of magnitude higher than that of the widely used tobacco etch virus protease (0.013 ± 0.003 µM-1-s-1). The application of the 3CL gene in genetically engineered constructs provided efficient specific proteolysis of fusion proteins, which we demonstrated using the receptor-binding domain of SARS-CoV-2 spike protein and GST fusion protein. The solubility and immunochemical properties of RBD were preserved. It is very important that in work we have shown that 3CL protease works effectively directly in E. coli cells when co-expressed with the target fusion protein, as well as when expressed as part of a chimeric protein containing the target protein, fusion partner, and 3CL itself. The results obtained in the work allow expanding the repertoire of specific proteases for researchers and biotechnologists.


Exposure to blue light during lunch break: effects on autonomic arousal and behavioral alertness.
Exposures to melanopsin-stimulating (melanopic) component-rich blue light enhance arousal level. We examined their effects in office workers. Eight healthy university office workers were exposed to blue and orange lights for 30 min during lunch break on different days. We compared the effects of light color on autonomic arousal level assessed by heart rate variability (HRV) and behavioral alertness by psychomotor vigilance tests (PVT). Heart rate was higher and high-frequency (HF, 0.150.45 Hz) power of HRV was lower during exposure to the blue light than to orange light. No significant difference with light color was observed, however, in any HRV indices during PVT or in PVT performance after light exposure. Exposure to blue light during lunch break, compared with that to orange light, enhances autonomic arousal during exposure, but has no sustained effect on autonomic arousal or behavioral alertness after exposure.


Repeated injections of PEG-PE liposomes generate anti-PEG antibodies.
Liposomes containing the polyethylene glycol (PEG) derivative of phosphatidyl ethanolamine (PE) have recently been found to be promising drug carriers, as they facilitate controlled and target-oriented release of therapeutics. They also reduce the side effects of many drugs. Here, we present the results of a study on antiliposomal properties of rabbit sera obtained after weekly injections of small liposomes containing 20% PEG-PE. The effect was analysed as the level of induced carboxyfluorescein release from these liposomes in vitro. The incubation of liposomes with rabbit serum taken after the injections induced the release of carboxyfluorescein at a higher level than was seen for incubation with untreated animal's serum. The strongest effect was observed for serum obtained after the second injection, i.e. during the second week of the study. The effect was much smaller after the serum samples were preheated at 56 degrees C. The binding of serum proteins by PEGylated liposomes was analysed via gel filtration and via the immunoblot technique using goat anti-rabbit IgG; this revealed that the serum protein which bound to the liposomes in vitro had a molecular weight of 55 kD and reacted with the anti-IgG antibody. Competition with PEG or lipids indicate that this IgG has an anti-PEG activity. We therefore assume that these antibodies are responsible for the activation of complement and leakage induction of PEG-liposomes. Such antibodies could be responsible for increased phagocytosis by RES macrophages (in particular liver macrophages) and decreased circulation time.


Contralateral papillary thyroid cancer at completion thyroidectomy has no impact on recurrence or survival after radioiodine treatment.
This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients. We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI. Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI. The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.


Amiodarone-Associated Optic Neuropathy: Clinical Review.
Amiodarone, an antiarrhythmic agent, has been associated with visual loss secondary to optic neuropathy. The reported mean duration of amiodarone use before visual loss is about 9 months. Patients receiving amiodarone have a 2-fold increased risk of developing optic neuropathy, especially in males and possibly in patients with longer duration of treatment. Amiodarone-associated optic neuropathy is characterised by an insidious onset, slow progression, bilateral simultaneous visual loss, and protracted disc swelling. After discontinuing amiodarone use, visual acuity and visual field deficits tend to improve or stabilise in most patients, with about 20% of the patients getting worse.


Studies on lipid peroxidation and non-enzymatic antioxidant status as indices of oxidative stress in patients with chronic myeloid leukaemia.
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder of the haematopoietic cell. Free radicals can be important causative agents of a number of human diseases, including cancer and leukaemia. Thus, antioxidants, which control the oxidative stress state, represent a major line of defense for regulating the overall true state of health. The relationship between non-enzymatic antioxidant status and the levels of well-known markers of oxidative stress that are measured as lipid peroxides reflects better health indices. The aim of this study was to evaluate the plasma levels of lipid peroxidation products and non-enzymatic antioxidant status as indices of oxidative stress, disease progression and early responses to chemotherapeutic agents in chronic myeloid leukaemia patients. The study included 128 CML patients and 50 age- and gender-matched healthy control volunteers. Indices of oxidative stress were evaluated as lipid peroxidation and non-enzymatic antioxidant status using the spectrophotometric method. There was a significant increase in the plasma levels of lipid peroxidation products in CML patients as compared to the healthy volunteers. The plasma levels of lipid peroxidation products continued to rise significantly as the disease progressed. The non-enzymatic antioxidant status was found to be significantly decreased in CML patients as compared to the healthy participants. The plasma levels of non-enzymatic antioxidant status continued to decrease significantly during the disease progression. It can be concluded that plasma lipid peroxidation and non-enzymatic antioxidant status reflect oxidative stress in CML patients, and may be used as indices for oxidative stress, disease progression and early responses to different therapeutic modalities.


Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.
Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models. Here, we report the stepwise optimization of the tool compound EED226 toward the potent and selective EED inhibitor MAK683 (compound 22) and its subsequent preclinical characterization. Based on a balanced PK/PD profile, efficacy, and mitigated risk of forming reactive metabolites, MAK683 has been selected for clinical development.


Molybdenum-Catalyzed Ammonia Formation Using Simple Monodentate and Bidentate Phosphines as Auxiliary Ligands.
We have found molybdenum-catalyzed ammonia formation using simple and commercially available monodentate and bidentate phosphines as auxiliary ligands with a simple and convenient procedure. Molybdenum complexes generated in situ from [MoI3(THF)3] and the corresponding phosphines such as PMePh2 and 1,5-bis(diphenylphosphino)pentane worked effectively toward ammonia formation.


Chromosomal integration of HHV-6A during non-productive viral infection.
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two different species of betaherpesviruses that integrate into sub-telomeric ends of human chromosomes, for which different prevalence rates of integration have been reported. It has been demonstrated that integrated viral genome is stable and is fully retained. However, study of chromosomally integrated viral genome in individuals carrying inherited HHV-6 (iciHHV-6) showed unexpected number of viral DR copies. Hence, we created an in vitro infection model and studied retention of full or partial viral genome over a period of time. We observed an exceptional event where cells retained viral direct repeats (DRs) alone in the absence of the full viral genome. Finally, we found evidence for non-telomeric integration of HHV-6A DR in both cultured cells and in an iciHHV-6 individual. Our results shed light on several novel features of HHV-6A chromosomal integration and provide valuable information for future screening techniques.


[Pancreatic hypersecretion in pancreatitis].
Extensive data on clinical and experimental pathology of pancreatic function are reviewed. In literature there is much controversy on the presence of hyperenzymatic secretion on the mechanism of hypersecretion and therapeutic policy for pancreatitis with hypersecretion. Fifty patients with chronic pancreatitis were evaluated functionally. Experimental study of progressing pancreatitis showed enhanced protein biosynthesis in the initial disease. Protein spectra were shifted. It is stated that hypersecretion can be either primary or secondary depending on the cause of pancreatic inflammation which is thought to initiate pancreatic hypersecretion as such.


[Medroxyprogesterone acetate therapy against antiangiogenesis of transplanted ovarian cancer in nude mice].
To investigate the effects of medroxyprogesterone acetate (MPA) on angiogenesis and growth of transplanted human ovarian cancer cells in nude mice. Ovarian cancer cell line COCI derived from human ovarian serous adenocarcinoma was transplanted into 30 nude mice, which were then randomized equally into 3 groups consisting of two treatment groups (in which MPA was administered at 60 and 120 mg/kg, respectively, twice a week for 4 weeks) and a control group. Six weeks later, the body mass of the nude mice was recorded and the morphology of tumor cells observed by electron microscope. The microvascular density (MVD) was examined by immunohistochemical staining with anti-human factor VIII antibody. Compared with the control group, the growth inhibitory rate in the two treatment groups were 23.76% and 43.80%, respectively, corresponding to the doses of 60 and 120 mg/kg. MVD of 60 mg/kg MPA group (3.64+/-0.02) and 120 mg/kg MPA group (2.11+/-0.12) was lower than that of the control group (5.14+/-0.74) (P<0.05 and P<0.01, respectively), and there was also significant difference between the two treatment groups (P<0.01). The morphological changes including compaction and margination of the nuclear chromatin, apoptotic bodies, and cell necrosis were significantly increased in the two treatment groups. MPA can inhibit the angiogenesis and growth of transplanted human ovarian cancer cells in nude mice in a dose-dependent manner, and its anticancer effect may involve induction of cell apoptosis as the result of its effect against angiogenesis.


Repair of the adult temporomandibular joint meniscus with an autogenous dermal graft.
A surgical procedure for the successful repair of the temporomandibular joint meniscus is described. Twenty-three patients have been treated by this procedure, with both objective and subjective improvement. The procedure is accomplished with minimal technical difficulty and minimal cosmetic defect.


The function of the primordial germ cell in extragonadal tissues.
The identity of the germ cell tumours of the pineal and the thymus with those of the testis and ovary suggests that the widely disseminated primordial germ cells might subserve some special function in these sanctuaries. It is proposed that thymic localization might be required for the conveyance of genetic haematological and immunological information and that the pineal-diencephalic localization could programme neuroophthalmic tissues prior to the development of the blood-brain barrier. The latter speculation was tested by producing allergic encephalomyelitis in thymectomized, bursectomized and thymobursectomized chickens. It was found that although thymectomy and, to a lesser extent, bursectomy decreased the severity of the experimental encephalomyelitis the combined procedure resulted in more severe inflammatory lesions. This may be due to release of suppressed intraneural immunological mechanisms in the somatically impaired bird.


Mitochondrial NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase is essential for embryonic development.
Folate-dependent enzymes are compartmentalized between the cytoplasm and mitochondria of eukaryotes. The role of mitochondrial folate-dependent metabolism and the extent of its contribution to cytoplasmic processes are areas of active investigation. NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) catalyzes the interconversion of 5,10-methylenetetrahydrofolate and 10-formyltetrahydrofolate in mitochondria of mammalian cells, but its metabolic role is not yet clear. Its expression in embryonic tissues but not in most adult tissues as well as its stringent transcriptional regulation led us to postulate that it may play a role in embryonic development. To investigate the metabolic role of NMDMC, we used a knockout approach to delete the nmdmc gene in mice. Heterozygous mice appear healthy, but homozygous NMDMC knockout mice die in utero. At embryonic day 12.5 (E12.5), homozygous null embryos exhibit no obvious developmental defects but are smaller and pale and die soon thereafter. Mutant fetal livers contain fewer nucleated cells and lack the characteristic redness of wild-type or heterozygous livers. The frequencies of CFU-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) from fetal livers of E12.5 null mutants were not reduced compared with those of wild-type or heterozygous embryos. It has been assumed that initiation of protein synthesis in mitochondria requires a formylated methionyl-tRNA(fmet). One role postulated for NMDMC is to provide 10-formyltetrahydrofolate as a formyl group donor for the synthesis of this formylmethionyl-tRNA(fmet). To determine if the loss of NMDMC impairs protein synthesis and thus could be a cause of embryonic lethality, mitochondrial translation products were examined in cells in culture. Mitochondrial protein synthesis was unaffected in NMDMC-null mutant cell lines compared with the wild type. These results show that NMDMC is not required to support initiation of protein synthesis in mitochondria in isolated cells but instead demonstrate an essential role for mitochondrial folate metabolism during embryonic development.


Phylogenetic Status of Two Undescribed Zygomycete Species from Korea: Actinomucor elegans and Mucor minutus.
During a survey of fungal diversity of the order Mucorales, three zygomycete isolates, CNUFC-YR113-1, CNUFC-KNU16-7, and CNUFC-BS1-1 were isolated from freshwater and soil samples in Korea. The strains were analyzed both morphologically and phylogenetically based on internal transcribed spacer and 28S rDNA gene sequences. Based on their morphology and phylogeny, the CNUFC-YR113-1 and CNUFC-KNU16-7 isolates were identified as Actinomucor elegans, and CNUFC-BS1-1 was identified as Mucor minutus. To the best of our knowledge, the species A. elegans and M. minutus, belonging to an undiscovered taxon, have not been previously described in Korea.


Intramuscular compartment pressure measurement in chronic exertional compartment syndrome: new and improved diagnostic criteria.
Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that subsides with rest. Diagnosis is usually confirmed by intramuscular compartment pressure (IMCP) measurement. Controversy exists regarding the accuracy of existing diagnostic criteria. (1) To compare dynamic IMCP measurement and anthropometric factors between patients with CECS and asymptomatic controls and (2) to establish the diagnostic utility of dynamic IMCP measurement. Cohort study (diagnosis); Level of evidence, 2. A total of 40 men aged 21 to 40 years were included in the study: 20 with symptoms of CECS of the anterior compartment and 20 asymptomatic controls. Diagnoses other than CECS were excluded with rigorous inclusion criteria and magnetic resonance imaging. The IMCP was measured continuously before, during, and after participants exercised on a treadmill, wearing identical footwear and carrying a 15-kg load. Pain experienced by study subjects increased incrementally as the study progressed (P < .001). Pain levels experienced by the case group during each phase of the exercise were significantly different (P = .021). Subjects had higher IMCP immediately upon standing at rest compared with controls (23.8 mm Hg [controls] vs 35.5 mm Hg [subjects]; P = .006). This relationship persisted throughout the exercise protocol, with the greatest difference corresponding to the period of maximal tolerable pain (68.7 mm Hg [controls] vs 114 mm Hg [subjects]; P < .001). Sensitivity and specificity were consistently higher than the existing criteria with improved diagnostic value (sensitivity = 63%, specificity = 95%; likelihood ratio = 12.5 [95% CI, 3.2-49]). Anterior compartment IMCP is elevated immediately upon standing at rest in subjects with CECS. In patients with symptoms consistent with CECS, diagnostic utility of IMCP measurement is improved when measured continuously during exercise. A cutoff of 105 mm Hg in phase 2 provides better diagnostic accuracy than do the Pedowitz criteria of 30 mm Hg and 20 mm Hg at 1 and 5 minutes after exercise, respectively.


Theoretical description of Coulomb balls: fluid phase.
A theoretical description for the radial density profile of a finite number of identical charged particles confined in a harmonic trap is developed for application over a wide range of Coulomb coupling (or, equivalently, temperatures) and particle numbers. A simple mean-field approximation neglecting correlations yields a density profile which is monotonically decreasing with radius for all temperatures, in contrast to molecular dynamics simulations and experiments showing shell structure at lower temperatures. A more complete theoretical description including charge correlations is developed here by an extension of the hypernetted chain approximation, developed for bulk fluids, to the confined charges. The results reproduce all of the qualitative features observed in molecular dynamics simulations and experiments. These predictions are then tested quantitatively by comparison with benchmark Monte Carlo simulations. Quantitative accuracy of the theory is obtained by correcting the hypernetted chain approximation with a representation for the associated bridge functions.


[Effects of induced deletion of repeats in binding domain of the VLDL receptor on its ligand-binding capacity].
The ligand-binding domain of the very low-density lipoprotein receptor (VLDL-R) contains eight cysteine-rich repeat sequences that have been postulated as ligand-binding sites. This is obviously different from that of low-density lipoprotein receptor (LDL-R) that includes seven similar repeats. To make clear the contribution of these repeats to ligand-binding and to explore the reason of both receptors' ligand-binding characteristic, the VLDL-R recombinants lacking different repeat(s) were constructed by oligonucleotide-directed mutagenesis and transfected into ldl-A7 cell. Ligand-binding results showed that repeat 1 and repeat 2 were the most important in binding with apoE-rich lipoprotein(VLDL and beta-VLDL). Repeat 3 and repeat 6 also important for binding VLDL. The results also showed that VLDL-R lacking LBR7 retained partly LDL-R ligand-binding properties. It suggests that LBR7 in VLDL-R may responsible for both receptors' ligand-binding properties differences.


Inhibition of proteasome activity in Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells.
The anomalous fruit extract of Gleditsia sinensis (GSE) was shown to possess anticancer potential on various solid tumour and leukaemia cell lines in vitro. We have recently demonstrated that the mitochondrial-dependent apoptotic pathway including mitochondrial membrane potential depolarization, changes in the level of reactive oxygen species and activation of caspase 3 were recruited in GSE-induced apoptosis. Whether receptor-dependent APO-1/Fas apoptotic pathway is also involved remains uncertain. Using two solid tumour cell lines, the HepG2 hepatoblastoma carcinoma cells and MDA-MB231 breast cancer cells, we demonstrated that the Fas ligand and Fas receptor protein levels did not have significant variation after GSE incubation. Caspase 8 activity increased only weakly when compared with that of caspase 3. The chrymotrypsin-like activity of proteasome was partially inhibited up to 30-40% when compared with the untreated control. Taken together, we believe that GSE- mediated apoptosis on HepG2 and MDA-MB231 carcinoma cells is mainly dictated by the mitochondrial-dependent pathway while inhibition of proteasome activity may also be involved in GSE-induced apoptosis.


Saturation-Tolerant Prescribed Control for a Class of MIMO Nonlinear Systems.
This article proposes a saturation-tolerant prescribed control (SPC) for a class of multiinput and multioutput (MIMO) nonlinear systems simultaneously considering user-specified performance, unmeasurable system states, and actuator faults. To simplify the control design and decrease the conservatism, tunnel prescribed performance (TPP) is proposed not only with concise form but also smaller overshoot performance. By introducing non-negative modified signals into TPP as saturation-tolerant prescribed performance (SPP), we propose SPC to guarantee tracking errors not to violate SPP constraints despite the existence of saturation and actuator faults. Namely, SPP possesses the ability of enlarging or recovering the performance boundaries flexibly when saturations occur or disappear with the help of these non-negative signals. A novel auxiliary system is then constructed for these signals, which bridges the associations between input saturation errors and performance constraints. Considering nonlinearities and uncertainties in systems, a fuzzy state observer is utilized to approximate the unmeasurable system states under saturations and unknown actuator faults. Dynamic surface control is employed to avoid tedious computations incurred by the backstepping procedures. Furthermore, the closed-loop state errors are guaranteed to a small neighborhood around the equilibrium in finite time and evolved within SPP constraints although input saturations and actuator faults occur. Finally, comparative simulations are presented to demonstrate the feasibility and effectiveness of the proposed control scheme.


Umbilical cord blood stem cells--an ethical source for regenerative medicine.
Never before in the history of human kind have we tried to keep a tissue preserved for the entire life of a human. This, however, is what is proposed with umbilical cord blood banking. The media often report on the latest 'Stem Cell' breakthrough in 'Regenerative Medicine'. Between human embryonic stem cells, adult stem cells and umbilical cord blood stem cells, it is hard to decipher what all these have done and will do for patients. Cord blood is collected after birth with no harm to mother or baby and contains stem cells with an incredible potential to form tissues including neural, liver and pancreatic tissues in a laboratory. In less than 20 years, cord blood has become the biggest real success story in stem cells, with nearly 10,000 patients treated, from blood and immune transplants, through to more controversial interventions, such as Type 1 diabetes. With ongoing clinical trials and research predicting new avenues, the future seems assured for this stem cell source. What does this predict, however, for cord blood banking? More importantly, what does it justify?


Wnt3a regulates survival, expansion, and maintenance of neural progenitors derived from human embryonic stem cells.
Many reports describe the efficient derivation and expansion of neural progenitors (NP) from human embryonic stem cells (hESC). However, little is known about the signaling factors found within the neurosphere microenvironment that regulate NP maintenance and differentiation. We show that Wnt ligand and receptor transcripts are endogenously upregulated within neurospheres derived from noggin-primed hESC. In addition, neurosphere formation and size were significantly greater in the presence of exogenous Wnt3a compared to control conditions. Inhibition of endogenous Wnt signaling resulted in a significant reduction in the efficiency of neurosphere formation and overall size, due to effects on both NP proliferation and apoptosis. These findings demonstrate a requirement of Wnt signaling for maintenance, proliferation, and survival of NP when cultured in neurosphere conditions.


Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation.
Mammalian spermatozoa acquire their fertilizing ability in the female reproductive tract (sperm capacitation). On the other hand, seminal vesicle secretion, which is a major component of seminal plasma, inhibits the initiation of sperm capacitation (capacitation inhibition) and reduces the fertility of the capacitated spermatozoa (decapacitation). There are seven major proteins involved in murine seminal vesicle secretion (SVS1-7), and we have previously shown that SVS2 acts as both a capacitation inhibitor and a decapacitation factor, and is indispensable for in vivo fertilization. However, the effects of SVSs other than SVS2 on the sperm have not been elucidated. Since mouse Svs2-Svs6 genes evolved by gene duplication belong to the same gene family, it is possible that SVSs other than SVS2 also have some effects on sperm capacitation. In this study, we examined the effects of SVS3 and SVS4 on sperm capacitation. Our results showed that both SVS3 and SVS4 are able to bind to spermatozoa, but SVS3 alone showed no effects on sperm capacitation. On the other hand, SVS4 acted as a capacitation inhibitor, although it did not show decapacitation abilities. Interestingly, SVS3 showed an affinity for SVS2 and it facilitated the effects of SVS2. Interaction of SVS2 and spermatozoa is mediated by the ganglioside GM1 in the sperm membrane; however, both SVS3 and SVS4 had weaker affinities for GM1 than SVS2. Therefore, we suggest that separate processes may cause capacitation inhibition and decapacitation, and SVS3 and SVS4 act on sperm capacitation cooperatively with SVS2.