Changes of reflexes in vasoconstrictor neurons supplying the cat hindlimb following chronic nerve lesions: a model for studying mechanisms of reflex sympathetic dystrophy?
The generic term 'reflex sympathetic dystrophy' describes a clinical syndrome which sometimes develops after traumata at the extremities with lesions of nerves or --more rarely--after other events. The syndrome consists of the following components: pain (hyperpathia, allodynia), trophic changes of skin and deep tissues, dysregulation of sweating and cutaneous blood flow of the extremity concerned. It is assumed that all symptoms are produced by abnormal sympathetic activity. Interruption of the sympathetic activity to the affected extremity abolishes most of the pain and may lead to remission of the trophic changes. The hypothesis is that the trauma with lesion of the primary afferent axons leads subsequently to an abnormal state of the primary afferent neurons and to distorted processing of information in the spinal cord. As a consequence of this abnormal central state the activity in the sympathetic (vasomotor and sudomotor) supply to the affected extremity is distorted. The results are pain, trophic changes and dysregulations of autonomic effector organs. In some yet unknown way a vicious circle between periphery and spinal cord is established (afferent leads to spinal cord leads to sympathetic leads to afferent). This hypothesis was the starting point for analysis of the reflex pattern in postganglionic vasoconstrictor neurons supplying the cat hindlimb after chronic nerve lesions performed in the same limb (cutting and ligating a skin nerve; suturing the central stump of a skin nerve to the peripheral stump of a muscle nerve). The results obtained show that the reciprocity of the reflex pattern which is normally observed between cutaneous and muscle vasoconstrictor neurons is lost in many animals. Cutaneous vasoconstrictor neurons are very similar to muscle vasoconstrictor neurons in their reactions to stimulation of arterial baroreceptors and chemoreceptors. If the same sequence of events also occurs in patients with reflex sympathetic dystrophy, it could explain the dysregulation of blood flow through skin and also the occurrence of trophic changes in the limb.


Heart failure is associated with increased risk of all-cause mortality after transvenous lead extraction: A systematic review and meta-analysis.
Transvenous lead extraction (TLE) is increasingly considered in cardiac implantable electronic device management. Heart failure (HF) might be associated with mortality risks after the TLE procedure. This study aims to assess mortality risk in HF patients undergoing TLE. We searched MEDLINE and Embase databases from inception to June 2022 to identify articles that included patients with and without HF who underwent TLE, which reported mortality in both groups. The pooled effect size was calculated with a random-effects model and 95% CI to compare post-TLE mortality between the two groups. Eleven studies were included in the analysis. Each left ventricular ejection fraction (LVEF) increased by 1% was associated with reduced mortality by 2% (HR = 0.98, 95% CI: 0.97-0.99, I 2 = 74.9%, p < .01). The presence of HF compared to those without HF was associated with higher mortality rates (OR: 3.04, 95% CI: 2.56-3.61, I 2 = 0.0%, p < .531). There was a significant increase in the mortality rates in patients with New York Heart Association (NYHA) function class III (OR: 2.29, 95% CI: 1.29-4.06, I 2 = 0.0%, p = .498) and NYHA IV (OR: 8.5, 95% CI: 2.98-24.3, I 2 = 0.0%, p = .997). Our study found that post-TLE mortality decreases by 2% as LVEF increases by 1%, also mortality is higher in patients with NYHA III and IV.


Delayed telogen replacement in a boy's scalp.
In case the shedding telogen hair is not replaced in time by a terminal anagen hair, an empty space results. To verify whether the phenomenon is present in prepubertal subjects. From July 1996 to May 1997, an 8-year-old boy was submitted monthly to the phototrichogram technique. Sixty hairs were monitored throughout the study. 52% of all studied hairs were terminal anagen hairs throughout the study and additionally 22% were in a regular hair cycle. Vellus hairs and empty spaces were observed in 18 and 8% of follicles, respectively. In 2% of hairs, vellus hairs and empty spaces were associated. Vellus hairs and empty spaces are present even in children. Without gonadal androgens and expression or induction of 5alpha-reductase in the prepubertal scalp, they are unlikely to herald androgenetic alopecia (AGA) but could reflect a physiological phenomenon of 'true resting' of a small proportion of scalp hair. Androgens may increase the phenomenon which may account in part for AGA development.


Immunorestorative properties of thymostimulin (TS) in patients with Hodgkin's disease in clinical remission.
Fifteen Hodgkin's disease patients (8 male, 7 female) aged 19-72 years, who had been in complete unmaintained remission for 1 year or more when the study was initiated, were given 50 mg thymostimulin (TS) IM daily for 60 consecutive days. When compared with 26-30 age- and sex-matched controls, as a group the patients' circulating ENR+, OKT+3, and OKT+4 cells were depressed (0.001 less than or equal to P less than or equal to 0.06), whereas their OKT+8 cell population was not. Low (greater than 1 SD or greater than 2 SD below mean in controls) or borderline (mean value of two subsequent tests greater than 1 SD below mean in controls) values of ENR+, OKT+3, and OKT+4 cells were seen in nine (group I) of the 15 patients tested, while the remaining six patients (group II) had normal T-cell proportions. Following TS treatment, the proportions of ENR+, OKT+3, and OKT+4 cells increased to normal in all group I patients. The T-cell levels, however, decreased to pretreatment values 60-70 days after completion of TS therapy. TS had no effect on the group II patients whose T-cell percentages had initially been normal. Spontaneous cell-mediated cytotoxicity (SCMC) was assessed in 11 patients, and irrespective of the baseline values, there was a significant enhancement (P less than 0.005) by day 15 of TS administration, which was maintained during treatment. SCMC, however, returned to pretreatment levels 60-70 days after TS was discontinued. The delayed skin test reactivity to DNCB was significantly depressed in all cases. Although TS restored the T-cell proportions, it failed to reverse DNCB reactivity from negative to positive in any of the patients tested. TS can thus restore defective T-cell frequencies and can enhance cytolytic functions that are potentially important in host immunosurveillance, but it apparently failed to improve the skin reactivity to neoantigen.


Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice.
Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2-8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8-15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2-4 and 8-10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411.


Permature death of Purkinje cells following low-level X-ray irradiation during embryonic development.
Rat embryos were exposed to 170 r of X-ray irradiation on day 15 or 18 of gestation, and sacrificed when they reached the postnatal age of 30 days. In the cerebella of these animals, normal-looking and atrophied Purkinje cells were studied and compared with those observed in the cerebellum of the normal animals. The normal animals did not show presence of any atrophied Purkinje cells, but the X-ray-irradiated animals showed a lesser number of Purkinje cells and many atrophied Purkinje cells. In the cerebellum of animals that were X-ray-irradiated on day 15 of gestation, the number of Purkinje cells was only 32% of those in the normal cerebellum, and in those that received X-ray irradiation on day 18 of embryogenesis there were about 95.5% as many Prukinje cells as in the normal cerebellum. But, in the cerebella of animals in the latter group there were two to three times more atrophied Purkinje cells than in the cerebella of animals in the former group. These findings are discussed in terms of lasting effects of low-level X-ray irradiation in the form of premature atrophy and death of the Purkinje cells.


Risk factor analysis of idiopathic pneumonia syndrome after allogeneic hematopoietic SCT in children.
Idiopathic pneumonia syndrome (IPS) is a critical complication following allogeneic hematopoietic SCT (HSCT); however, few reports have analyzed the risk factors for IPS in children. A total of 210 consecutive pediatric patients, including 131 boys and 79 girls, with various hematologic malignancies, aplastic anemia or solid tumors who underwent allogeneic HSCT were analyzed to clarify the incidence and risk factors for IPS. Patient and transplantation characteristics after allogeneic HSCT were compared between patients with and without IPS. Cumulative incidence rates of IPS 120 days after allogeneic HSCT were 6.7% (14/210). Of 14 patients with IPS, 11 (78.6%) died after developing IPS. The presence of prior HSCT was more frequent in patients with IPS (IPS group) than in those without IPS (non-IPS group; 35.7 vs 12.8%, respectively, P=0.018). The IPS group contained more patients with acute GVHD (grade II-IV) than the non-IPS group (50.0 vs 18.9%, respectively, P=0.006). The association of these two factors with IPS was further confirmed by multivariate analysis. We should be aware of these risk factors in patients who have undergone allogeneic HSCT.


Advances in adjuvant therapy of gastrointestinal stromal tumors.
The Gastrointestinal Stromal Tumor (GIST) is the most common sarcoma of the gastrointestinal tract. Major prognostic indices in the evaluation and management of GIST include the size, location and tumor mitotic rate. The discovery of the mutation in the tyrosine kinase receptor c-KIT (CD117) revolutionized the treatment of GIST in the early twenty-first century. Since the first case report of the success of the tyrosine kinase inhibitor (TKI) imatinib, in the treatment of a female patient with metastatic GIST, the paradigm of treatment of this tumor has evolved tremendously. The initial use in metastatic GISTs has progressed to use of the TKI in both the adjuvant and neoadjuvant settings. It is now standard of care for patients with complete resection of primary localized GIST, with high risk of recurrence, to have at least one year of adjuvant imatinib. Recent SSGVXIII study shows that patients benefit from extended duration of therapy.


Transporters in Drug Development: International Transporter Consortium Update on Emerging Transporters of Clinical Importance.
During its fourth transporter workshop in 2021, the International Transporter Consortium (ITC) provided updates on emerging clinically relevant transporters for drug development. Previously highlighted and new transporters were considered based on up-to-date clinical evidence of their importance in drug-drug interactions and potential for altered drug efficacy and safety, including drug-nutrient interactions leading to nutrient deficiencies. For the first time, folate transport pathways (PCFT, RFC, and FRα) were examined in-depth as a potential mechanism of drug-induced folate deficiency and related toxicities (e.g., neural tube defects and megaloblastic anemia). However, routine toxicology studies conducted in support of drug development appear sufficient to flag such folate deficiency toxicities, whereas prospective prediction from in vitro folate metabolism and transport inhibition is not well enough established to inform drug development. Previous suggestion of a retrospective study of intestinal OATP2B1 inhibition to explain unexpected decreases in drug exposure were updated. Furthermore, when the absorption of a new molecular entity is more rapid and extensive than can be explained by passive permeability, evaluation of the OATP2B1 transport may be considered. Emerging research on hepatic and renal OAT2 is summarized, but current understanding of the importance of OAT2 was deemed insufficient to justify specific consideration for drug development. Hepatic, renal, and intestinal MRPs (MRP2, MRP3, and MRP4) were revisited. MRPs may be considered when they are suspected to be the major determinant of drug disposition (e.g., direct glucuronide conjugates); MRP2 inhibition as a mechanistic explanation for drug-induced hyperbilirubinemia remains justified. There were no major changes in recommendations from previous ITC whitepapers.


The HRD Decision-Which PARP Inhibitor to Use for Whom and When.
Rucaparib, a polyADPribose polymerase inhibitor (PARPi), was approved recently for use in women with high-grade serous ovarian cancer (HGSOC). It is now one of three approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome. Clin Cancer Res; 23(23); 7155-7. ©2017 AACRSee related article by Balasubramaniam et al., p. 7165.


[Metabolic status of acute myocardial infarction as a function of residual blood flow with and without revascularization].
In mongrel dogs anesthetized with Nembutal, the left anterior descending coronary artery was ligated for 2 h. The residual blood flow (RBF) was correlated with tissue levels of various myocardial metabolites after 1 and 24 h and 7 days of reperfusion. ATP and the sum of adeninnucleotides showed a better recovery with an increasing RBF. Initial increased value of creatine phosphate was followed by a decrease to subnormal values, which cannot be sufficiently explained. There was an accelerated overshoot beyond normal values in glycogen levels after 7 days with increasing RBF. After 7 days there was no recovery to normal values, and below a RBF of 5 ml/100 g/min metabolic recovery was poor.


Anxiety disorders and psychiatric referral in the general medical emergency room.
A retrospective chart review of patients seen in the medical emergency room between July 1983 and July 1984 indicated that only one third of the patients who received a final diagnosis that included anxiety were referred for psychiatric follow-up. This was in sharp contrast to the referral pattern from the ER of depressed or psychotic patients. In the present study, referred and nonreferred patients were compared on 17 variables to determine those factors that influenced decision to refer. Among the five factors that discriminated between the criterion groups were age, depression, and lack of concomitant medical findings.


Embryonic growth and mobilization of energy and material during incubation in the checkered keelback snake, Xenochrophis piscator.
We collected 20 checkered keelback snakes (Xenochrophis piscator) to study embryonic growth and mobilization of energy and material during incubation. Females laid eggs between late May and late June. The eggs were incubated at 27 degrees C (+/-0.3). One egg from each clutch was dissected at five-day intervals starting at oviposition. The mean incubation length at 27 degrees C was 48.9 days. We identified three phases of embryonic growth or yolk depletion in X. piscator. Phase 1, between oviposition and Day 20, was one of minimal transfer of energy and material from yolk to embryo. Phase 2, between Day 20 and Day 39-40, was characterized by increasingly rapid embryonic growth or yolk depletion. Phase 3, between Day 39-40 and hatching, was characterized by reduced embryonic growth or yolk depletion. Approximately 71% of dry mass, 53% of non-polar lipids and 66% of energy were transferred from the egg contents to the hatchling during incubation. Our data confirm that oviposition is not timed to coincide with the onset of rapid embryonic growth in oviparous squamate reptiles. The greater conversion efficiencies of energy and material from egg to hatchling in snakes can be attributed to their lower energetic costs of embryonic development and greater residual yolk sizes.


Preoperative Opioid Use Predicts Prolonged Postoperative Opioid Use and Inferior Patient Outcomes Following Anterior Cruciate Ligament Reconstruction.
(1) To determine patient factors associated with prolonged opioid use following anterior cruciate ligament reconstruction (ACLR) and (2) to evaluate the influence of preoperative opioid use on patient-reported outcomes. Patients who underwent ACLR and used opioids before the perioperative period, which was defined as the window 30 days before 15 days following the index surgery, were designated as preoperative opioid users. Patients who used opioids only in the perioperative period or post-operative period were designated as opioid-naïve. Predictors of opioid use at 6 and 12 months postoperatively and associations between preoperative opioid use and patient outcomes were assessed. After institutional review board approval, we identified 253 patients (225 opioid-naïve and 28 opioid users ) who underwent ACLR from 2014 to 2018 at a single institution and had one year follow up (median: 11.6 months; interquartile range [8.9-14.3]). Patients with a history of preoperative opioid use (odds ratio [OR] 3.63, P = .034), greater preoperative visual analog scale pain scores (OR 1.32, 95% CI 1.04-1.67; P = .003), and greater body mass index (OR 1.09, P = .018) were significantly more likely to be taking opioids at 6 months postoperatively. Patients with a perioperative opioid intake of greater than 513 oral morphine equivalents were significantly more likely to continue taking opioids at the 6 month (OR 3.17, P = .024) and the 1 year (OR 3.34, P = .048) postoperative time points. Patients with preoperative opioid use were significantly less likely to achieve the patient acceptable symptomatic state (PASS) on the International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score (KOOS) Sport, KOOS Joint Replacement, KOOS Pain, KOOS Symptoms, KOOS Quality of Life, and KOOS Activities of Daily Living. Preoperative opioid use, body mass index >30, and greater visual analog scale pain scores were predictors of continued opioid use at 6 months postoperatively. Preoperative opioid users were more likely to continue taking opioids, demonstrate significantly worse patient reported outcomes at baseline and 1-year postoperatively, and were less likely to achieve patient acceptable symptomatic state. Level III, Retrospective Cohort Study.


Compressible polyaniline-coated sodium alginate-cattail fiber foam for efficient and salt-resistant solar steam generation.
Solar steam generation has attracted widespread attention because of its ability to produce clean water through desalination and wastewater treatment without conventional energy consumption. In this work, a polyaniline (PANI)-coated sodium alginate (SA)/cattail fiber (CF) foam for photothermal evaporator is prepared via directional freezing and oxidative polymerization. The SA/CF foam displays desirable water pumping capability because of the lamellar sandwich structure interconnected by porous networks. More importantly, the directional porous network architecture ameliorates the mechanical and salt-resistant performances of the SA/CF foam. The as-prepared PANI@SA/CF foam shows inferior heat conductivity of 0.047 W m-1 K-1 and outstanding light absorption over 96% in solar window. A vapor evaporation rate of 2.04 kg m-2 h-1 under 1 sun illumination is achieved for the PANI@SA/CF evaporator. Furthermore, the PANI@SA/CF foam could be employed in solar-driven freshwater generation from seawater and wastewater with high ion and dye removal rates. The combination of water evaporation and cleaning capabilities of the PANI@SA/CF foam as photothermal materials provide a framework for the exploration of next-generation evaporators in seawater desalination and wastewater treatment applications.


[Measurement of biological tissue destruction time after exposure to eximer XeCl laser].
Relationship between atherosclerotic patch destruction time under UV light from a XeCl laser and energy density of 1.3-4.7 J/cm2 has been studied experimentally. As energy density increased, the destruction time, estimated on the basis of exploring product release by continuous-wave He-Ne laser, decrease from 40 to 3.5 microseconds.


The Laetiporus polyketide synthase LpaA produces a series of antifungal polyenes.
The conspicuous bright golden to orange-reddish coloration of species of the basidiomycete genus Laetiporus is a hallmark feature of their fruiting bodies, known among mushroom hunters as the "chicken of the woods". This report describes the identification of an eight-domain mono-modular highly reducing polyketide synthase as sole enzyme necessary for laetiporic acid biosynthesis. Heterologous pathway reconstitution in both Aspergillus nidulans and Aspergillus niger verified that LpaA functions as a multi-chain length polyene synthase, which produces a cocktail of laetiporic acids with a methyl-branched C26-C32 main chain. Laetiporic acids show a marked antifungal activity on Aspergillus protoplasts. Given the multiple products of a single biosynthesis enzyme, our work underscores the diversity-oriented character of basidiomycete natural product biosynthesis.


[Effects of pseudolaric acid B on apoptosis of bladder cancer cell 5637].
To investigate the apoptosis of bladder cancer cell 5637 induced by pseudolaric acid B in vitro and its mechanism. The cell proliferation was detected by MTT assay;the cell cycle was measured by flow cytometry; the cell apoptosis was observed by flow cytometry with Annexin V-FITC/PI double staining; the expressions of survivin protein and caspase-3 protein were detected by Western blot assay. It showed that pseudolaric acid B remarkably induced apoptosis of 5637 cell line. Moreover, pseudolaric acid B suppressed survivin and up-regulated caspase-3 expression. Pseudolaric acid B inhibits the proliferation and induces the apoptosis of 5637 cells. The molecular mechanism of pseudolaric acid B inducing the apoptosis of 5637 cells may be associated with its action of down-regulating the expression of survivin, and up-regulating the expression of caspase-3.


Neurotechnology: Bridging the dialogue between engineers, material scientists, clinicians, and ethicists.
This backstory is a conversation highlighting the importance of interdisciplinary collaboration for developing the field of neurotechnology and for its safe clinical translation and assessment of its societal impacts.


Clinical potentials of neuropeptide Y family of hormones.
Neuropeptide Y (NPY) family of hormones exhibits a wide spectrum of central and peripheral activities mediated by six G-protein coupled receptor subtypes denoted as Y1, Y2, Y3, Y4, Y5, and y6. Investigations to date have implicated NPY in the pathophysiology of a number of diseases including feeding disorders, seizures, anxiety, diabetes, hypertension, congestive heart failure and intestinal disorders. These observations suggest that long-acting, potent NPY receptor selective agonists and antagonists developed could be used to treat a variety of diseases. These possibilities are discussed in this paper.


A Patient and Provider Research Agenda on Diabetes and Hypertension Management.
A demonstration project in Richmond, Virginia involved patients and other stakeholders in the creation of a research agenda on dietary and behavioral management of diabetes and hypertension. Given the impact of these diseases on morbidity and mortality, considerable research has been directed at the challenges patients face in chronic disease management. The continuing need to understand disparities and find evidence-based interventions to improve outcomes has been fruitful, but disparities and unmet needs persist. The Stakeholder Engagement in Question Development (SEED) method is a stakeholder engagement methodology that combines engagement with a review of available evidence to generate research questions that address current research gaps and are important to patients and other stakeholders. Using the SEED method, patients and other stakeholders participated in research question development through a combination of collaborative, participatory, and consultative engagement. Steps in the process included: (1) identifying the topic and recruiting participants; (2) conducting focus groups and interviews; (3) developing conceptual models; (4) developing research questions; and (5) prioritizing research questions. Stakeholders were involved in the SEED process from February to August 2015. Eighteen questions were prioritized for inclusion in the research agenda, covering diverse domains, from healthcare provision to social and environmental factors. Data analysis took place September to May 2016. During this time, researchers conducted a literature review to target research gaps. The stakeholder-prioritized, novel research questions developed through the SEED process can directly inform future research and guide the development of evidence that translates more directly to clinical practice.


Results of surgical therapy in patients with adenocarcinoma of the esophagus and cardia.
BACKGROUND: Adenocarcinoma of the esophagus and cardia is a challenging disease for the surgeon. Delay in diagnosis, nodal involvement, and incompleteness of resection have an adverse effect on long-term prognosis. Efforts are currently oriented to identify patients who may benefit from extensive resection.METHODS: Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In 6 patients (10.2%) cancer was discovered during endoscopic surveillance for Barrett's metaplasia. Overall, 147 patients (67%) underwent resection. An Ivor-Lewis approach was used in 121 patients; of these, 51 underwent an extended mediastinal lymph node dissection.RESULTS: Median cumulative survival was 25.9 +/- 3.1 months in patients undergoing resection, and 7 +/- 1.3 months in patients having palliation ( P < 0.01). Survival was significantly higher in patients with negative nodes than in those with lymph node metastases (54 +/- 12.9 versus 17 +/- 2.8 months; P < 0.01). Six of the 51 patients (11.8%) undergoing extended lym-phadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curvature, paracardial, peripancreatic, or lower mediastinal nodes. Three of these patients had recurrent disease within the first year of follow-up.CONCLUSIONS: Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. Endoscopic surveillance appears to be warranted in patients with Barrett's metaplasia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.


Prevalence of a photoparoxysmal response in the electroencephalograms of epileptics in the three main ethnic groups of Namibia.
This descriptive study consists of 1493 EEGs from patients with epilepsy referred to the State Hospital in Windhoek, over the years 1983-1988. Excluded were patients with febrile convulsions, acute symptomatic epilepsy and a history of alcoholism. A standardized procedure of intermittent photic stimulation (IPS) was performed. The three main population groups blacks, coloureds (people of mixed race) and whites, were adequately represented in the sample. Classical photoparoxysmal responses (PPR) occurred in 0.4, 4.2 and 5.2%, respectively. Climatic factors are not considered relevant in the elicitation of a PPR. It is postulated that different mutations occurred in the genes that were involved in the expression of the PPR in epileptic patients of different ethnic groups.


Atomic model of the E. coli membrane-bound protein translocation complex SecYEG.
The Sec complex forms the core of a conserved machinery transporting proteins across or into membranes. In Escherichia coli SecYEG is active as an oligomer, but the structure predicts that the protein-conducting channel is formed by the monomer. A homology model of the E.coli complex was built using the atomic structure of Methanococcus jannaschii SecYEbeta. Another structure of the membrane-bound dimer was then determined by fitting the homology model to an 8A map of SecYEG determined by electron microscopy. We found that the substrate-binding site of the dimer has opened slightly and the plug domain moved toward the outside. This new position retains the channel in a closed state. These differences partially reflect the movements that have been proposed to occur during channel gating. Further opening of the substrate-binding pocket to bind and release bound substrate and displacement of the plug during secretion, presumably rely on the action of the partner proteins. The contacts arising at the dimer interface in the environment of the lipid bilayer may have activated the assembly.


Effect of enzymatic degradation on the release kinetics of model drug from Pluronic F127/poly(lactic acid) nano-particles.
Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F127 block copolymer (PEO-PPO-PEO) to obtain amphiphilic PLA-F127-PLA block copolymers. The effect of enzymatic degradation on the release behaviors of hydrophobic model drug 9-(methylaminomethyl)anthracene (MAMA) from PLA-F127-PLA nano-particles with vesicular structure was studied by UV-Vis spectroscopy. It was observed that the release rate of MAMA from PLA-F127-PLA nano-particles with the enzymatic degradation varied with temperature due to the activity of the enzyme with temperature. However, the enzyme concentration has negligible effect on the release rates of MAMA.


Endo-rectal repair of rectocele.
Rectocele may cause colorectal symptoms particularly difficulty in evacuation. It is readily identified on clinical examination of the perineum but the pathophysiological abnormality can easily be defined by defaecography. Between 1984 and 1988 we have operated on 16 patients who presented with difficulty in evacuation associated with rectocele. We have used a simple endo-anal repair aimed to restore a firm recto-vaginal septum. Excellent functional results were obtained in 11 patients, 4 were considerably improved and one patient had a poor result.


Neuromuscular defects after infection with a beta coronavirus in mice.
COVID-19 affects primarily the lung. However, several other systemic alterations, including muscle weakness, fatigue and myalgia have been reported and may contribute to the disease outcome. We hypothesize that changes in the neuromuscular system may contribute to the latter symptoms observed in COVID-19 patients. Here, we showed that C57BL/6J mice inoculated intranasally with the murine betacoronavirus hepatitis coronavirus 3 (MHV-3), a model for studying COVID-19 in BSL-2 conditions that emulates severe COVID-19, developed robust motor alterations in muscle strength and locomotor activity. The latter changes were accompanied by degeneration and loss of motoneurons that were associated with the presence of virus-like particles inside the motoneuron. At the neuromuscular junction level, there were signs of atrophy and fragmentation in synaptic elements of MHV-3-infected mice. Furthermore, there was muscle atrophy and fiber type switch with alteration in myokines levels in muscles of MHV-3-infected mice. Collectively, our results show that acute infection with a betacoronavirus leads to robust motor impairment accompanied by neuromuscular system alteration.


Design, synthesis and structure-activity relationships of mangostin analogs as cytotoxic agents.
In order to better understand the structure-activity relationship of mangostin, a series of xanthone derivatives based on α-mangostin were designed and synthesized. All the compounds were evaluated for their cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) using MTT assays. Most of them showed cytotoxicity and most of all, compounds 1a and 2h showed the highest cytotoxic potency by HL-60 cancer cell lines with IC50 values of 5.96 μM and 6.90 μM respectively; compound 3e showed the highest cytotoxic potency against SMMC-7221 cancer cell line with IC50 values of 3.98 μM; compounds 2e and 2m showed lower cytotoxicity but higher selectivity than α-mangostin against HL-60 and SMMC-7221 cancer cell lines respectively. Structure-activity relationship analysis indicates that the maintenance of the isopentene group at C-8 is essential for the cytotoxic activity.


3D Printing in Medicine for Preoperative Surgical Planning: A Review.
The aim of this paper is to review the recent evolution of additive manufacturing (AM) within the medical field of preoperative surgical planning. The discussion begins with an overview of the different techniques, pointing out their advantages and disadvantages as well as an in-depth comparison of different characteristics of the printed parts. Then, the state-of-the-art with respect to preoperative surgical planning is presented. On the one hand, different surgical planning prototypes manufactured by several AM technologies are described. On the other hand, materials used for mimicking different living tissues are explored by focusing on the material properties: elastic modulus, hardness, etc. As a result, doctors can practice before performing surgery and thereby reduce the time needed for the operation. The subject of patient education is also introduced. A thorough review of the process that is required to obtain 3D printed surgical planning prototypes, which is based on different stages, is then carried out. Finally, the ethical issues associated with 3D printing in medicine are discussed, along with its future perspectives. Overall, this is important for improving the outcome of the surgery, since doctors will be able to visualize the affected organs and even to practice surgery before performing it.


Characterization of cytosolic glucocorticoid receptor of fetal rat epiphyseal chondrocytes.
The cytosolic glucocorticoid receptor of 21st gestational day rat epiphyseal chondrocytes has been evaluated. The receptor, a single class of glucocorticoid binding component approached saturation, utilizing [3H]triamcinolone acetonide ([3H]TA) as the radiolabeled ligand, at approximately 1.8-2.0 x 10(-8) M. The dissociation constant (Kd) reflected high-affinity binding, equaling 4.0 +/- 1.43 x 10(-9) M (n = 7) for [3H]TA. The concentration of receptor estimated from Scatchard analysis was approximately 250 fmol/mg cytosolic protein and when calculated on a sites/cell basis equalled 5800 sites/cell. The relative binding affinities of steroid for receptor were found to be triamcinolone acetonide greater than corticosterone greater than hydrocortisone greater than progesterone greater than medroxyprogesterone acetate much greater than 17 alpha-hydroxyprogesterone much greater than testosterone greater than 17 beta-estradiol. Cytosolic preparations activated in vitro by warming (25 degrees C for 20 min) were shown to exhibit an increased affinity for DNA-cellulose. 46% of the total specifically bound activated ligand-receptor complex was bound to DNA-cellulose. Cytosol maintained at 0-4 degrees C in the presence of 10 mM molybdate or activated in vitro in the presence of molybdate, bound to DNA-cellulose at 8 and 10% respectively. DEAE-Sephadex elution profiles of the nonactivated receptor were indicative of a single binding moiety which eluted from the columns at 0.4 M KCl. Elution profiles of activated receptor were suggestive of an activation induced receptor lability. The 0.4 M KCl peak was diminished, while a concomitant increase in the 0.2 M KCl peak was only modestly discernible. Evaluation of endogenous proteolytic activity in chondrocyte cytosol using [methyl-14C]casein as substrate show a temperature-dependent proteolytic activity with a pH optimum of 5.9-6.65. The proteolytic activity was susceptible to heat inactivation and was inhibitable, by 20 mM EDTA. The sedimentation coefficient of the nonactivated receptor was 9.3s (n = 6) on sucrose density gradients and exhibited steroid specificity and a resistance to activation induced molecular alterations when incubated in the presence of 10 mM molybdate. Receptor activation in vitro, in the absence of molybdate induced an increased receptor susceptibility to proteolytic attack and/or enhanced ligand receptor dissociation as evidenced by a diminution of the 9.3s binding form without a concomitant increase in 5s or 3s receptor fragments.


Cuticular Architecture of Hassalstrongylus epsilon (Nematoda: Trichostrongyloidea).
Hassalstrongylus epsilon is a small nematode, whose adult forms are found among the intestinal microvilli of the water rat Nectomys squamipes, Brants 1827 (Rodentia: Muridae). The external appearance of the cuticle, which presents transversal striations and longitudinal ridges, is described using scanning electron microscopy. Transmission electron microscopy of thin sections and replicas of quick-frozen, freeze-fractured, deep-etched and rotatory shadowed samples showed the presence in the cuticle of struts that arise from the fluid median layer, extending outward to the epicuticle. The cuticle showed the presence of five layers: epicuticle, cortical, fibril-rich, fluid median and fibrous. The cuticle layers were made of an assemblage of fibers that create compartments, which were larger in the fluid region than in the fibril-rich median layer.


[Complete anterolateral dislocation of the talus].
A 22-year-old woman suffered an anterolateral dislocation of the talus in a horse-riding accident. Immediately after admission, closed reduction was performed, and then a low knee cast was used for 12 weeks of immobilisation with partial weight bearing (10 kg). Nine months later, the patient had achieved nearly free range of motion of the ankle without pain (dorsal-plantar 10-0-30 degrees ). There were no radiological signs of osteoarthritis or talus bone necrosis. Immediate closed reduction led to an excellent outcome.


Long-term external radiation exposure of inhabitants in the western Bryansk region of Russia as a consequence of the Chernobyl accident.
The western Bryansk region in south-western Russia was highly contaminated with 137Cs and 134Cs due to the Chernobyl accident in 1986. In 1990, a joint Nordic-Russian project was initiated in order to make measurements and estimates of the absorbed doses to selected groups of inhabitants in this area. The participating individuals were living in small villages with contamination levels between 0.9 and 2.7 MBq m(-2). Only some villages had been decontaminated. Both school-children and adults participated in the study and the number of persons was between 100 and 130 each year, residing in 5 villages. Every year in September-October, from 1990 to 1998. we performed individual measurements of external absorbed doses, assessed with thermoluminescent (TL) dosemeters (LiF). The mean effective dose per year from external irradiation due to the Chernobyl accident of the inhabitants in the villages ranged between 0.8 and 2.9 mSv during the study period and decreased with an apparent half-time of 3.7-8.2 years, depending on village and group. The highest individual doses within one village were, on average higher by a factor of 3 than the mean value for that village. Under the conservative assumption of a decrease rate in the external effective dose of 2% per year after 1998, individuals in the most highly exposed village are assumed to receive a life-time effective dose of about 75 mSv (between 1986 and 2056) from external exposure to caesium radionuclides. The mean value for the villages under study was estimated to be around 65 mSv using the assumed rate of decrease.


Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times.
An increased incidence of thrombosis has been reported in patients with a prolonged activated partial thromboplastin time (APTT) due to a lupus anticoagulant (LA), which is an antibody to negatively charged phospholipids. The antiphospholipid antibodies can be quantitated in an enzyme-linked immunoabsorbent assay (ELISA) that utilizes cardiolipin as the antigen. With the development of the ELISA, two major areas of controversy have arisen. First, the correlation between assay results for LA and for the ELISA has varied widely among laboratories. Second, some investigators have described a correlation between high levels of anticardiolipin antibodies (ACA) and thrombotic disorders, whereas others have found no association between ACA levels and thrombosis in a general population of medical patients. To explore these issues further, the present study determined the sensitivity and specificity of an LA assay for detecting ACA in medical patients with a prolonged APTT. The association between the isotype and titer of ACA and thrombosis was examined in those patients positive for LA. Plasma samples from 70 medical patients with a prolonged APTT by routine screening studies were tested for the presence of LA by dilution of phospholipid in an APTT system and for IgM and IgG ACA according to a standardized ELISA. Clinical records were reviewed for a history of thrombotic events by an investigator who had no knowledge of the laboratory results. The ACA assay gave positive results in 47 patients, 44 of whom also tested positive for LA. Thus, the sensitivity for the LA assay for detecting ACA was 94% (confidence interval, 82% to 99%). The result of the LA assay was negative in 20 of 23 patients who were ACA-negative. The specificity of the LA assay was 87% (confidence interval, 67% to 98%). Twelve of the 47 patients (26%) had a history of venous or arterial thrombosis. Of these patients, 75% tested in the high-positive range for IgG or IgM ACA, or both. Of the 35 patients without thrombosis, only 14% were in this range. Patients with thrombosis had either underlying systemic lupus erythematosus, lymphoma, or no apparent etiology for LA. There was no history of thrombosis in patients with LA associated with infection or medication. A test for LA in medical patients with a prolonged APTT can be sensitive and specific for ACA. Determination of ACA levels in patients who have LA that is not induced by medication or infection may define those patients at increased risk for thrombosis.


Core binding factor in the early avian embryo: cloning of Cbfbeta and combinatorial expression patterns with Runx1.
We have isolated the avian ortholog for CBFbeta, the common non-DNA binding subunit of the core binding factor (CBF) that has important regulatory roles in major developmental pathways. CBFbeta forms heterodimers with the DNA-binding Runx proteins and increases their affinity for DNA and their protein stability. Here, we describe the Cbfbeta expression pattern during the first 4 days of chick embryo development, with a special interest in the developing hematopoietic system. We have compared its expression pattern to that of Runx1, which is crucial for the generation of definitive hematopoietic cells, and to other hematopoietic- or endothelial-specific markers (c-Myb, Pu.1, CD45, c-Ets-1 and VE-Cadherin). Initially, Cbfbeta is widely expressed in the early mesoderm in both the yolk sac and the embryo proper, but later its expression becomes restricted to specific organs or cell types. We have found that Cbfbeta expression overlaps with Runx1 in the hematopoietic system and neural tube. The somitic and mesonephric structures, however, express Cbfbeta in the absence of detectable Runx1. Finally, Cbfbeta and Runx1 display multiple combinatorial patterns in the endoderm and in specific nerves or ganglia. Taken together, we show that Cbfbeta exhibits a dynamic expression pattern that varies according to the organ, cell type or developmental stage. By revealing multiple combinatorial patterns between Cbfbeta and Runx1, these data provide new insights into the role of CBF during early development.


Oscillatory CO2 evolution in glycolysing yeast extracts.
The rate of formation of carbon dioxide in cytoplasmic yeast extracts in an open system with continuous infusion of glucose was measured by membrane inlet mass spectrometry during glycolytic oscillations. The rate of CO2 production rose in the first third of each cycle to a maximum of about 100 mumol per ml yeast extract per hour and subsequently diminished to a final level of about 50 mumol per h. Measurements of the NADH light absorption under the same conditions revealed oscillations of relaxation type. The phase of high CO2 production could be related to the phase of the high NADH level, giving evidence that the flux in glycolysis is increased during the phase of high NADH concentration. Only half of the amount of injected glucose was metabolized to CO2 during the sustained oscillation, although free glucose did not accumulate.


European multicenter survey on the laparoscopic treatment of gastroesophageal reflux in patients aged less than 12 months with supraesophageal symptoms.
This multicenter survey includes neonates and infants who underwent surgery for primary gastroesophageal reflux (GER) who presented with supraesophageal symptoms of unknown origin with a minimum of 12 months postoperative follow-up. A total of 726 patients underwent GER surgery in 10 European Centers in the period 1998-2002. Respiratory symptoms were present in 204 patients (28%); 135 patients (17%) had surgery under 1 year of age, and 46 of them (6.3%) because of respiratory symptoms. Surgery was performed without any previous medical treatment in 10 cases (21%). The type of procedure included 37 complete 360 degrees wraps (80%) (Nissen, 12, and Rossetti, 25) and nine partial wraps (20%) (Thal five, Lortat Jacob one, Toupet one, others two). Gastrostomy was associated in 17 cases (37%) (6 PEG and 11 modified Stamm). No gastric emptying procedures were recorded. No major intraoperative complications were reported. Six patients developed complications (13%) and a redo operation was performed in three (6.5%). Respiratory outcome after antireflux surgery was good in 35 patients (76%) and fair with significantly improved respiratory symptoms in 11 (24%). This multicenter survey underlines that GER has to be suspected and aggressively treated in infants with difficult-to-treat supraesophageal symptoms, and also in high-risk cases, in order to prevent major complications.


Editorial: 'Engineering the Tumor Immune Microenvironment' Special Issue.
Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy [...].


Locomotor activity in mice during chronic treatment with caffeine and withdrawal.
Chronic ingestion of caffeine by mice caused a marked reduction in locomotor exploratory activity. At least 4 days of withdrawal were required to restore activity to normal levels. Stimulatory effects of injected caffeine were lower in chronically treated mice and the biphasic dose-response (stimulatory followed by depressant) curve for injected caffeine was left shifted. Seven days of withdrawal were required before the dose-response curve to caffeine was identical to that of control mice. The depressant effects of a potent xanthine phosphodiesterase inhibitor, 1,3-dipropyl-7-methylxanthine, were blunted in caffeine-treated mice. The depressant effects of A1- and A2-selective adenosine analogs were enhanced after chronic caffeine. There was little or no effect of chronic caffeine on the stimulatory effects of dopaminergic agents (amphetamine, caffeine), while both depressant and stimulatory effects of cholinergic agents (nicotine, oxotremorine, scopolamine) were reduced. The results indicate that chronic caffeine affects functions of adenosine and cholinergic receptors related to regulation of locomotor exploratory activity.


Oxatomide protects Trichinella spiralis infected mice from lethal anaphylaxis.
Infection with Trichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active anti-allergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice. The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.


Model-free metacognition.
Extensive work has been done on the metacognitive capacities of humans, as well as to investigate metacognitive processes in nonhuman animals. What we propose here, however, is that there are two very different forms that metacognition can take: either model-based (implicating at least a simplified model of the thinker's own mind), or model-free (representing some mental state or process in oneself in the absence of any such model). The focus of all work on human metacognitive judgments has been on the model-based variety, as have been most attempts to discover metacognition in animals. We first review recent studies suggesting that there are no resources shared between human metacognitive judgments and the sorts of behavioral tests employed with animals, implying that the latter fail to provide evidence of even simplified forms of model-based metacognition. Thereafter the question of model-free metacognition in animals is pursued. Negative verdicts are rendered on a pair of possible claims of this sort. But two positive answers are defended. One is that epistemic emotions like curiosity and interest, as well as the signals involved in failed memory searches, implicate representations whose content is, unknown. The other is that decisions to deploy attentional / mental effort (which many animals besides humans can do) depend on appraisals of an analog-magnitude signal representing the extent to which executive resources are engaged.


Synthesis of Oxazoles by Tandem Cycloisomerization/Allylic Alkylation of Propargyl Amides with Allylic Alcohols: Zn(OTf)2 as π Acid and σ Acid Catalyst.
A Zn(OTf)2-catalyzed tandem cycloisomerization/allylic alkylation of N-(propargyl)arylamides and allylic alcohols to produce oxazole derivatives has been successfully developed. The zinc catalyst served as π acid and also σ acid in this reaction. The target allylic oxazoles have been transformed into multisubstituted diene structures, which are potential aggregation-induced emission active optical materials.


AIDS: methodological problems in studying its prevention and spread.
This paper outlines some problems in conducting AIDS research in developing countries, discusses the impact of the socio-cultural setting on study efforts, and emphasizes the need for adopting methodological approaches that are highly sensitive to the environment. The importance of seeing AIDS as a disease that affects humans not merely biologically, but also socially--in terms of their conceptions of sexual behavior and their belief systems of disease, illness and sickness--is considered. The potential of scientists to disregard this facet in the study of AIDS is stressed. The imperatives for interdisciplinary collaboration between the medical and social scientists are examined to argue that without combining research agendas, significant variables will be ignored in the search for ways to control AIDS. Special attention is given to the limitations of several methods that are employed by medical and social science researchers, including research designs, sampling, data collection and analysis, to suggest that with AIDS research these may be difficult to operationalize. The ethical implications of some of these are weighed. The interaction of economic and political conditions of the context with research activity is explored. Suggestions are given which take cognizance of the fact that it is human beings and Third World conditions, as well as the complexities of HIV and AIDS, that make AIDS research so problematic.


Minimally invasive cosmetic dentistry: alignment, bleaching and bonding (ABB).
This article will outline how combining existing techniques in a new and unique manner can potentially redefine the traditional approach to smile design planning and execution. Alignment, tooth whitening and edge bonding with new highly polishable nano-hybrid composites can make cosmetic dentistry far simpler and less invasive. Patients' perceptions of their end smile result can change dramatically if they are allowed to see their teeth improve gradually. This technique will highlight a choice of pathways available in cosmetic dentistry making it much less invasive for the patient and less risky for dentists.


Hydrolysis of substance P and bradykinin by black widow spider venom gland extract.
Black widow spider venom gland extract was found to contain significant peptidase activity. Aliquots of the venom gland extract incubated at 37 degrees inactivated substance P (SP) and bradykinin but not angiotensin II or the enkephalins. The peptide inactivation was proportional to the duration of the incubation and the amount of extract used. Analysis of the peptides on high pressure liquid chromatography demonstrated that the loss in biological activity of SP and bradykinin in the longitudinal muscle of the guinea pig ileum was correlated with cleavage of the peptides into several fragments. Kinetic studies revealed that SP was initially split into two fragments but that these products underwent further degradation into smaller peptides. The optimal pH for the peptidase activity was 6.5. At 0 degree the enzymatic activity was undetectable, and it was irreversibly destroyed by incubation at 100 degrees for 5 min or by pretreatment of the extract with 100 microM diisopropyl fluorophosphate. In addition, the gland extract preparation hydrolyzed artificial substrates designed to detect trypsin or chymotrypsin-like activity.


The peptide molecular links between the central nervous and the immune systems.
The central nervous system (CNS) and the immune system were for many years considered as two autonomous systems. Now, the reciprocal connections between them are generally recognized and very well documented. The links are realized mainly by various immuno- and neuropeptides. In the review the influence of the following immunopeptides on CNS is presented: tuftsin, thymulin, thymopoietin and thymopentin, thymosins, and thymic humoral factor. On the other side, the activity in the immune system of such neuropeptides as substance P, neurotensin, some neurokinins, enkephalins, and endorphins is discussed.


Preoperative selective internal carotid artery dural branch embolisation for petroclival meningiomas.
We assessed the clinical value of preoperative embolisation of the dural branches of the internal carotid artery (ICA) in cases of petroclival meningioma was evaluated. We carried out preoperative selective embolisation on seven consecutive patients with large petroclival meningiomas, using nonbraided 2 F steam-shaped microcatheters and shapeable hydrophilic microguide-wires to enter the dural branches of the ICA. The embolisations were performed using digital subtraction fluoroscopy with 150-250 microm polyvinyl alcohol particles. The tumours were resected a few days after embolisation. We reviewed angiographic findings before and after endovascular devascularisation, blood loss during tumour resection and clinical outcome. All endovascular procedures were technically successful, and postembolisation angiography showed disappearance of or marked decrease in tumour stain in all cases. Intraoperative bleeding was easily controlled, and intraoperative blood loss was low.


Secondary Metabolomic Analysis and In Vitro Bioactivity Evaluation of Stems Provide a Comprehensive Comparison between Dendrobium chrysotoxum and Dendrobium thyrsiflorum.
The stems of Dendrobium chrysotoxum (DC) are commonly used as health-promoting foods due to their excellent biological activities. However, the stems of D. thyrsiflorum (DT) are often used to meet the scarcity of DC in production because of their highly similar morphology. However, the related metabolomic and bioactive information on the stems of DC and DT are largely deficient. Here, secondary metabolites of DC and DT stems were identified using an ultra-performance liquid chromatography-electrospray ionization-mass spectrometry, and their health-promoting functions were evaluated using several in vitro arrays. A total of 490 metabolites were identified in two stems, and 274 were significantly different. We screened out 10 key metabolites to discriminate the two species, and 36 metabolites were determined as health-promoting constituents. In summary, DT stems with higher extract yield, higher total phenolics and flavonoids, and stronger in vitro antioxidant activities demonstrated considerable potential in food and health fields.


Video Modeling and Observational Learning to Teach Gaming Access to Students with ASD.
The purpose of this study was to evaluate both video modeling and observational learning to teach age-appropriate recreation and leisure skills (i.e., accessing video games) to students with autism spectrum disorder. Effects of video modeling were evaluated via a multiple probe design across participants and criteria for mastery were based on these results. Secondary measures were collected on observational learning across participants and behaviors. Participants included 4 children with autism, ages 8-11, who were served in self-contained special education classrooms. Results indicated a functional relation between video modeling and increased independence in gaming; observational learning occurred for at least some steps across students. Results, implications for practitioners, limitations, and ideas for future research are discussed.


Development of a filtration-based SERS mapping platform for specific screening of Salmonella enterica serovar Enteritidis.
The presence of Salmonella in natural freshwater and drinking water is a leading cause of intestinal illness all over the world; thus, the detection of Salmonella in water is of great importance to public health. The objective of this study is to develop a rapid screening method for the detection of Salmonella enterica serovar Enteritidis in water involving surface-enhanced Raman spectroscopy (SERS), aptamers, and filtration. SERS offers a great alternative to traditional methods of pathogen detection, with a simplified detection assay and shortened detection time. The specific capturing and labeling of Salmonella Enteritidis are realized by a specific single-stranded DNA aptamer, which is modified with an additional chain of adenine and fluorescein (FAM) and used as presence/absence indicator of Salmonella Enteritidis. By incorporating a vacuum filtration system, bacterial cells recognized by the specific aptamer are concentrated onto a membrane. With additional filtration of gold nanoparticles, the aptamer signals were captured and used to construct a SERS mapping indicating the presence and absence of target bacterial strains with potential quantitative capability. The specificity of the method was validated by using other strains of bacteria such as Escherichia coli and Listeria monocytogenes. The sensitivity of the method goes down to 103 CFU/mL for 1 mL of sample with a total detection and analyzing time within 3 h. This study demonstrates the capability of the filtration-based SERS platform for detecting Salmonella Enteritidis in various aqueous matrices such as distilled water and rinsing water from fresh produce with high selectivity and sensitivity. Graphical abstract.


Critical period and pathways of water borne nitrogen loss from a rice paddy in northeast China.
Rice paddy nitrogen (N) loss is a great concern leading to a high risk of receiving water pollution. Various models have been applied as practical tools for simulation of the nutrient loss amount, and pathways or yield change affected by management factors in previous studies. However, N loss features of rice paddies in northern regions have received less attention and few model simulation studies have combined crop yield and N loss to simultaneously meet the needs of yield maintenance and environmental protection. To consider benefits to local farmers and to assess the paddy N loss features and factors in northeast China, rice yields and water borne N losses in 2013-2017 were simulated using the APSIM-Oryza model applied to Xingkai Lake Farm. Different from subtropical regions, high field ridges and lower rainfall limit local paddy overflow occurrence except after unexpected storms after irrigation in dry years or serial rainfall events, which result in subsurface N loss during stages of tillering (Ti) to flowering (Fl) which comprise the dominant pathway accounting for 50.03-69.99% of the total water borne N loss. The correlation analysis results also indicate irrigation and the applied N amount more significantly affect local paddy N loss than does precipitation. In each year, stimulated by an increase in the applied N amount, increasing rice yield (symbolizing crop growth status) indicated N loss implicitly rose. But under similar applied N amount range, inter-annual N loss results showed weaker growth status result in a higher N loss. Based on local N loss features, nutrient conservation practices including planting density increase or side strip application, and net N loss reduction practices including intermittent or recycling irrigation are recommended to limit nutrient loss from a paddy field which would be helpful for optimization of local nutrient conservation and surrounding water environment protection.


Frequent epigenetic inactivation of Myocardin in human nasopharyngeal carcinoma.
Epigenetic silencing of tumor suppressor genes plays an important role in nasopharyngeal carcinoma (NPC) tumorigenesis. In the present study, we explore a novel target gene of epigenetic silencing in NPC, Myocardin, which is inactivated by promoter hypermethylation. Transcriptional expression levels of Myocardin were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Methylation status was addressed by methylation-specific PCR and bisulfite genomic sequencing. Myocardin mRNA expression was inactivated in 4 of 5 NPC cell lines. Myocardin was aberrantly methylated in 4 of 5 NPC cell lines (80%) and in 48 of 65 NPC primary tumors (73.8%, but not in any of the 12 normal nasopharyngeal tissues tested. Myocardin expression could be reactivated in NPC cells after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC). Epigenetic inactivation of Myocardin is a frequent and tumor-specific event in NPC. Our findings suggest that Myocardin is a candidate tumor suppressor gene in NPC.


Properties and cytotoxicity of water soluble Na2O-CaO-P2O5 glasses.
Various compositions of Na2OCaO-P2O5 glasses are prepared to estimate glass formation, dissolution properties and cytotoxicity. In the wide composition range of 40 mol% of P2O5 or more, clear glass samples were obtained. The estimated glass forming region was consistent with other ternary phosphate glass systems. The glass transition temperatures and crystallization temperatures decreased with increasing P2O5 content and increased with CaO content. Dissolution properties in distilled water and simulated body fluid (SBF) were measured. In distilled water, CaO free glasses showed extremely fast dissolution. The dissolution rate decreased with increasing CaO content and decreasing P2O5 content. This composition effect results from cross-link formation between the non-bridging oxygens of two different chains by Ca2+ ions which improves the phosphate network strength. In SBF, the dissolution rate followed a similar trend, but glass dissolution was suppressed. This suppression occurred due to the existence of soluble species of glass such as Na+, Ca2+ and HPO(2-)4. The cytotoxicity decreased with increasing CaO content and with decreasing PO2.5 content. This was the result of a change in pH and ion concentration in the medium.


Prevalence of neutralising antibodies to Berne virus in animals and humans in Vellore, South India. Brief report.
In Southern India the prevalence of neutralising antibody to Berne virus was high in sera obtained from cattle (49%), horses (38%), and sheep (36%). Neutralising antibody was not detected in sera from humans and monkeys.


Expression studies of neuronatin in prenatal and postnatal rat pituitary.
The pituitary gland, an indispensable endocrine organ that synthesizes and secretes pituitary hormones, develops with the support of many factors. Among them, neuronatin (NNAT), which was discovered in the neonatal mouse brain as a factor involved in neural development, has subsequently been revealed to be coded by an abundantly expressing gene in the pituitary gland but its role remains elusive. We analyze the expression profile of Nnat and the localization of its product during rat pituitary development. The level of Nnat expression was high during the embryonic period but remarkably decreased after birth. Immunohistochemistry demonstrated that NNAT appeared in the SOX2-positive stem/progenitor cells in the developing pituitary primordium on rat embryonic day 11.5 (E11.5) and later in the majority of SOX2/PROP1 double-positive cells on E13.5. Thereafter, during pituitary embryonic development, Nnat expression was observed in some stem/progenitor cells, proliferating cells and terminally differentiating cells. In postnatal pituitaries, NNAT-positive cells decreased in number, with most coexpressing Sox2 or Pit1, suggesting a similar role for NNAT to that during the embryonic period. NNAT was widely localized in mitochondria, peroxisomes and lysosomes, in addition to the endoplasmic reticulum but not in the Golgi. The present study thus demonstrated the variability in expression of NNAT-positive cells in rat embryonic and postnatal pituitaries and the intracellular localization of NNAT. Further investigations to obtain functional evidence for NNAT are a prerequisite.


Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease.
An obstacle to developing new treatment strategies for Alzheimer's disease (AD) has been the inadequate translation of findings in current AD transgenic rodent models to the prediction of clinical outcomes. By contrast, nonhuman primates (NHPs) share a close neurobiology with humans in virtually all aspects relevant to developing a translational AD model. The present investigation used African green monkeys (AGMs) to refine an inducible NHP model of AD based on the administration of amyloid-beta oligomers (AβOs), a key upstream initiator of AD pathology. AβOs or vehicle were repeatedly delivered over 4 weeks to age-matched young adult AGMs by intracerebroventricular (ICV) or intrathecal (IT) injections. Induction of AD-like pathology was assessed in subregions of the medial temporal lobe (MTL) by quantitative immunohistochemistry (IHC) using the AT8 antibody to detect hyperphosphorylated tau. Hippocampal volume was measured by magnetic resonance imaging (MRI) scans prior to, and after, intrathecal injections. IT administration of AβOs in young adult AGMs revealed an elevation of tau phosphorylation in the MTL cortical memory circuit compared with controls. The largest increases were detected in the entorhinal cortex that persisted for at least 12 weeks after dosing. MRI scans showed a reduction in hippocampal volume following AβO injections. Repeated IT delivery of AβOs in young adult AGMs led to an accelerated AD-like neuropathology in MTL, similar to human AD, supporting the value of this translational model to de-risk the clinical trial of diagnostic and therapeutic strategies.


Design and fast-fabrication of a system for functional electrical stimulation in upper limb of people with tetraplegia.
Proof of concept. Standard Functional Electrical Stimulation (FES) systems can enhance motor learning in people with tetraplegia and are widely delivered by self-adhesive electrodes. Their limitations are dexterity, specific knowledge to place the electrodes on muscles, need to fix electrodes when they lose the gel layer, and time. We designed a new FES system, using an existing protocol of drinking-like movements, to the upper limb of a person with tetraplegia C5 that fits in any anthropometry and can be easily produced. Furthermore, we tested the system to assess its effectiveness and users' perception during FES rehabilitation. São Carlos, SP, Brazil. A shell was designed with parametric design and fast-fabrication methods, and a stimulation unit and a smartphone application were developed. Questionnaires assessed the perceptions of a patient and a physiotherapist, about the usability of the new system in relation to standard FES. Kinematic data of drinking-like movements were collected from the patient wearing both systems and compared with data from an aged-matched control subject. The results are a personalized shell and an intuitive FES system, overcoming the limitations of standard FES. The new system suggested better wrist-flexion control shown by the mean angles (-18.93°), then the other system (-59.35°), and compared with the control (-10.97°). Fast-fabrication with parametric design offers a promising alternative for personalizing FES systems, with potential for home use. Further studies are required including randomized clinical trials.


Seafood freshness determination through vapour phase Fourier transform infrared spectroscopy.
A new vapour-phase manifold has been developed to determine trimethylamine (TMA) in fish and cephalopod samples by Fourier transform infrared (FT-IR) spectroscopy. Samples were treated off-line for 1h with trichloroacetic acid (TCA), filtered and washed. The obtained extracts were aspirated and alkalinized with NaOH 2.0M, in an on-line system. TMA was separated from the solution in a gas phase separator and then transported by means of a nitrogen carrier into a home made 10 cm pathlength IR gas cell, where the corresponding FT-IR spectra were acquired by accumulating 30 scans per spectrum with 2 cm(-1) nominal resolution. The method was applied to the determination of TMA in natural samples providing concentration values statistically comparables with those obtained by a head space gas chromatography (HS-GC) reference procedure. The sample throughput by FT-IR is increased by a factor of 6 as compared with HS-GC.


Limits on the tightness of coupling in active transport.
Control of the coupled reaction sequence in active transport depends on systematic changes in the properties of the carrier protein as the reaction proceeds. These changes would have to be brought about by specific interactions with the substrate, the binding forces being used to stabilize either (i) a carrier state with altered properties or (ii) the transition state in a carrier transformation. In the first case the tightness of coupling (the ratio of the coupled rate to slippage) will at first rise with the increment in binding energy in the altered state but will approach an upper limit when overly strong binding forces retard substrate dissociation in a subsequent step in the coupled reaction sequence. Primary and secondary active transport are subject to this limitation because the coupling mechanism necessarily involves intermediates in which the substrate is strongly bound. Exchange-only transport is not necessarily subject to the same limitation because the mechanism can involve only a substrate-catalyzed change in carrier state. The available data, although scant, agree with these conclusions.


Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission.
Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002-2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1-15.5) and 3.3 (1.5-18.0), respectively. Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts.


Leadership among Women Working to Eradicate Female Genital Mutilation: The Impact of Environmental Change in Transcultural Moments.
The study of cultural moments can identify the level of acceptance of female genital mutilation and the visibility of the involved health problems in a globalized world. To describe the transcultural process through which immigrant women who have experienced female genital mutilation become leaders against this practice. Descriptive research with cross-cultural principles and a qualitative approach. A semi-structured interview was the chosen technique for data collection. A total of 18 women participated in the preliminary observation and analysis unit, and only 8 women (38.8%) were ideologically against female genital mutilation (FGM). The selected women had undergone FGM and were fully prepared to discuss it. Staying in a different country and the associated social relations reduce cultural pressure and promote critical thinking. Cultural moments reflect the different situations that affect the perception and practice of female genital mutilation. Health problems associated with female genital mutilation (sexual, reproductive, and psychological) become visible at transcultural moments. Environmental country change affects the cultural pressure that sustains this practice in individual minds, institutions, structures, and bodies. These changes produce transcultural moments. The practice of female genital mutilation constitutes a significant segment of gender-based violence.


Challenges in the Management of Care of Brain-Dead Patients in the Donation Process: A Qualitative Content Analysis.
In care of brain-dead patients, nurses face several challenges. It is important to determine the context behind these challenges since they affect the performance of nurses and the organ donation process. To identify factors affecting the emergence of challenges related to the management of brain-dead patients by nurses in the donation process. In this qualitative conventional content analysis, data were collected by performing 28 semi-structured and in-depth interviews with nurses working in the ICUs. Purposive sampling started from March 2014 until saturation, which was reached in June 2016. Data analysis occurred simultaneously with data collection. Qualitative analysis of contents provided from interviews led to the extraction of themes that showed the experience of nurses about the challenges of caring for brain-dead patients in the donation process. These themes included "doubt and conflict in accepting the situation" and "defects in an effective and targeted care system." In the end, the main theme of "inconsistency and incompatibility of care management" was abstracted. According to the results of the study, factors involved in the emergence of challenges for nurses in care management included defects in education or managerial problems, which increased tension for nurses.


Initial age of unlicensed motorcycling experience for a cohort of high school students.
The aim of this study is to use retrospective data to examine the initial age of unlicensed motorcycling experience for a cohort of senior high school students in Taiwan. The life-table method was applied to estimate the probability of unlicensed motorcycling at different age intervals below the minimum licensing age. The results indicated that an increase in the prevalence of unlicensed teenage motorcycling began at 10 years of age and peaked in the ages between 16 and 17 years. Only 38% of students had no motorcycle riding experience when they reached the minimum licensing age of 18 years. Gender and parental attitude were the factors that had a significant influence on the initial motorcycling age. In addition, we observed a significant difference between licensed and unlicensed students in the following areas: parental attitude, proportion of students using borrowed motorcycles, and riding and accident frequency. The results reveal a number of important implications, such as the promotion of alternative modes of transport, increased parental monitoring, and penalty enhancement, that may help to suppress the tendency of teenagers' unlicensed motorcycling.


[Prehospitale analgesia in adults].
After securing vital function, treatment of pain is an important aspect in emergency medical care. Irrespective of the underlying disease or injury, pain is an important warning symptom of the body and the most common reason for an emergency alert notification. A patient assesses quality of care and success of prehospital care using the criteria of the extent of pain relief he experiences. Since mild pain does not usually lead to an emergency alert, the criteria apply mainly to treatment of severe and very severe pain. Pain perception varies from individual to individual. Accordingly, assessment of pain intensity is the very first step in pain therapy. The Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst pain imaginable) is suitable for pain assessment in adult emergency patients. Above a grade of 4, therapeutic intervention should be initiated with the goal of reducing pain to reach a value of <4, or at least to achieve a reduction by 3 points. The choice of analgesics that can be meaningfully used in pre-hospital emergency medicine is limited. The emergency physician should be aware of available drugs and administration routes.


Evaluation of clinical outcomes with alvimopan in clinical practice: a national matched-cohort study in patients undergoing bowel resection.
To evaluate in-hospital clinical outcomes after open and laparoscopic bowel resection (BR) with or without alvimopan treatment. Delayed return of gastrointestinal function after BR may be associated with greater postoperative morbidity and increased hospital length of stay (LOS). In clinical trials, alvimopan--a peripherally acting μ-opioid receptor antagonist--accelerated gastrointestinal recovery after open BR. A retrospective matched-cohort study (NCT01150760) was conducted using a national inpatient database. Each alvimopan patient was exact matched (surgical procedure, surgeon specialty) and propensity score matched (baseline characteristics) to a nonalvimopan BR patient. Outcomes included gastrointestinal and other morbidity (cardiovascular, pulmonary, infection, cerebrovascular, thromboembolic); mortality; readmission rate; and intensive care unit (ICU) stay (intent-to-treat [ITT] population). Postoperative LOS and estimated cost were also compared (modified ITT population). Each cohort included 3525 ITT patients with similar baseline characteristics. Gastrointestinal (29.8% vs 35.7%) and other morbidity (cardiovascular [19.4% vs 24.0%], pulmonary [7.3% vs 10.5%], infectious [9.6% vs 11.8%], thromboembolic [1.2% vs 2.1%]), mortality (0.4% vs 1.0%), and mean ICU stay (0.3 vs 0.6 days) were lower in the alvimopan group (P ≤ 0.003 for each). Postoperative LOS and estimated direct cost were lower for all alvimopan patients and after laparoscopic and open BR (LOS: -1.1, -0.8, and -1.8 days respectively; cost: -$2345, -$1382, and -$3218, respectively; P ≤ 0.0008 for each). On average, alvimopan-treated patients had a lower incidence of mortality and most incidents of morbidities. Length of stay, ICU use, and estimated cost were also lower with comparable readmissions. These results in patients outside the clinical trial setting include laparoscopic colectomy and demonstrate a potential association between acceleration of gastrointestinal recovery and improved early postoperative outcomes.


Intra-abdominal adiposity and individual components of the metabolic syndrome in adolescence: sex differences and underlying mechanisms.
To investigate the association between intra-abdominal adiposity and individual components of the metabolic syndrome (MS) in adolescent males and females. Cross-sectional study of a population-based cohort. Saguenay Youth Study, Quebec, Canada. A total of 324 adolescents, aged 12 to 18 years. Measures were compared between males and females with "high" or "low" intra-abdominal fat (IAF). Intra-abdominal fat was quantified with magnetic resonance imaging. Primary outcome measures were blood pressure (BP) and fasting serum glucose, insulin, lipids, and C-reactive protein levels. Secondary mechanistic measures were cardiovascular variability indexes of autonomic nervous system function, pubertal development, and serum levels of cortisol, leptin, and sex hormones. The MS was completely absent in adolescents with low IAF and was present in 13.8% of males and 8.3% of females with high IAF. Excess IAF was associated with a higher homeostasis model assessment index (0.5 [95% confidence interval (CI), 0.3 to 0.8]; P < .001) and triglycerides level (17.7 mg/dL [to convert to millimoles per liter, multiply by 0.0113] [95% CI, 9.7 to 25.7 mg/dL]; P < .001), lower high-density lipoprotein cholesterol level (-3.9 mg/dL [to convert to millimoles per liter, multiply by 0.0259] [95% CI, -6.2 to -1.5 mg/dL]; P = .003), and higher C-reactive protein level (0.03 mg/L [to convert to nanomoles per liter, multiply by 9.524] [95% CI, 0.01 to 0.05 mg/L]; P = .003). High IAF was associated with elevations of BP and sympathetic activity in males only (higher systolic BP, 6 mm Hg [95% CI, 1 to 11 mm Hg]; P = .02 and low-frequency power of diastolic BP, 629 mm Hg2 [95% CI, 37 to 1222 mm Hg2]; P = .04). Our results suggest that, already in adolescence, accumulation of IAF may promote development of the MS, affecting the metabolic and inflammatory components similarly in both sexes but influencing BP adversely only in males. The latter may be attributed, in part, to the augmentation of sympathetic activity also seen only in males.


[Expression of proteolytic enzymes of metastatic tumor cells and the effects of some influencing factors].
To elucidate the types of proteolytic enzymes the dendritic cell sarcoma (DCS) cell expressed in vitro and the effects of modulating factors. The proteolytic spots of DCS cells were examined, with ten different proteinase inhibitors, various antibodies and matrix. Aprotinin, EDTA-Na2 and pepstatin could inhibit the proteolysis of DCS cells respectively. Anti-ubiquitin antibody and anti-DCS antibody (1:200-1:100) showed no obvious inhibitory effects. DCS cells spread out fairly well but with no proteolysis. Under the conditions of our experiments the DCS cells had serine proteinase, metalloproteinase and aspartate proteinase activities. Antiubiquitin antibodies and anti-DCS antibodies showed no obvious influence on the proteolysis of DCS cells. DCS cells displayed different proteolysis status on different matrix.


Perinatal outcome of macrosomic infants born to diabetic versus non-diabetic mothers.
To assess the incidence and perinatal complications of macrosomic infants born to diabetic and non-diabetic mothers. A six-year retrospective study of newborns at our hospital. A total of 996 macrosomic newborns were found. Maternal characteristics, mode of delivery, and perinatal outcomes were studied. Of 18005 newborns, 996 were macrosomic infants (5.53%). Of these, 103 (10.3%) were born to diabetic mothers. Diabetic mothers had higher parity (1.89 vs. 1.35; P<0.000), cesarean section rate (52.4 vs. 31.1%; P<0.05), and resuscitation rate (5.8 vs. 1.8%; P<0.006; RR: 2.9; 95% CI: 1.42-5.9), and greater need for hospitalization (19.4 vs. 9.6%; p<0.002; RR: 2; 95% CI: 1.3-3.2) and intensive care (5.8 vs. 0.7%; P<0.000; RR: 5.3; 95% CI: 2.8-10) mostly for hypoglycemia (7.8 vs. 1%; P<0.000; RR: 5; 95% CI: 2.8-8.3), jaundice (8.7 vs. 2.1%; P<0.000; RR: 3.1; 95% CI: 1.9-5.9), respiratory distress (4.9 vs. 1.3%; P<0.009; RR: 2.9; 95% CI: 1.4-6.7), and asphyxia (2.9 vs. 0.4%; P<0.005; RR: 4.3; 95% CI: 1.8-11.1). No differences were found in birth trauma. Macrosomic infants born to diabetic mothers have an increased risk of hospital admission in the neonatal period for hypoglycemia, jaundice, respiratory distress, and asphyxia, and a greater need of intensive care. Obstetric trauma rates were similar in both groups.


Studies on the synthesis of valienamine and 1-epi-valienamine starting from D-glucose or L-sorbose.
Two synthetic routes to a carbocyclic precursor to valienamine are reported, starting from either D-glucose or L-sorbose and using ring-closing metathesis as a key step. A low-yielding synthesis of 1-epi-valienamine is reported. Results from an abortive third possible route to valienamine based on an early introduction of nitrogen are discussed.


Enantioselective DNA binding of iron(II) complexes of methyl-substituted phenanthroline.
The enantioselective binding of [Fe(4,7-dmp)(3)](2+) (dmp: 4,7-dimethyl-1,10-phenantroline) and [Fe(3,4,7,8-tmp)(3)](2+) (tmp: 3,4,7,8-tetramethyl-1,10-phenanthroline) to calf-thymus DNA (ct-DNA) has been systematically studied by monitoring the circular dichroism (CD) spectral profile of the iron(II) complexes in the absence and presence of ct-DNA. The effect of salt concentration and temperature on the degree of enantioselectivity of the ct-DNA binding of the iron(II) complexes, i.e. the molar ratio of Delta- to Lambda-enantiomer in the solution or vice versa has been rigorously evaluated. It is noticeable that Delta-[Fe(4,7-dmp)(3)](2+) and Lambda-[Fe(3,4,7,8-tmp)(3)](2+) are preferentially bound to ct-DNA as reflected in their opposite CD spectral profiles. The preferential binding of the Lambda-enantiomer of [Fe(3,4,7,8-tmp)(3)](2+) to ct-DNA compared to that of the Delta-enantiomer is associated with the bulkiness of the ancillary ligands due to substitution of four hydrogen atoms in 1,10-phenanthroline for four methyl groups. The determination of enantiomeric inversion constant (K(inv)) at various salt concentrations has revealed that the degree of enantioselectivity is salt concentration dependent, indicating that electrostatic interaction is involved in the enantioselective binding of the iron(II) complexes to ct-DNA. Although [Fe(4,7-dmp)(3)](2+) and [Fe(3,4,7,8-tmp)(3)](2+) exhibit an opposite pattern in the CD spectra, the degree of their enantioselectivity (K(inv)) is not different from each other significantly. A thermodynamic study on the enantioselective binding of [Fe(4,7-dmp)(3)](2+) to ct-DNA using the van't Hoff plot of In K(inv) versus 1/T has demonstrated that the enthalpy change (Delta H degrees ) in the inversion process from the Lambda- to Delta-enantiomer of [Fe(4,7-dmp)(3)](2+) ct-DNA is positive, indicating that the process is endothermic and thus entropically driven.


Direct methods: the identification of conditions which simplify the generation of inconsistent quadrupoles.
An algorithm is implemented to determine the form and phase shift for inconsistent type II quadrupoles for any space group having glide or screw-axis translations which are not a consequence of lattice centering. Cumulatively there are only six different Miller index restrictions and nine different phase shift forms common to all space groups of orthorhombic or lower symmetry. A similar analysis has been performed for a newly discovered type III class of quadrupoles. The configuration of the phase connections among the four triples of the type III quadrupole is different from the common configuration previously described for both normal (type I) and inconsistent (type II) quadrupoles. A knowledge of these constraint conditions for type II and III quadrupoles greatly simplifies a procedure for generating these relationships.


Gene replacement therapy in two Golgi-retained CMT1X mutants before and after the onset of demyelinating neuropathy.
X-linked Charcot-Marie-Tooth disease type 1 (CMT1X) is a demyelinating neuropathy resulting from loss-of-function mutations affecting the GJB1/connexin 32 (Cx32) gene. We previously showed functional and morphological improvement in Gjb1-null mice following AAV9-mediated delivery of human Cx32 driven by the myelin protein zero (Mpz) promoter in Schwann cells. However, CMT1X mutants may interfere with virally delivered wild-type (WT) Cx32. To confirm the efficacy of this vector also in the presence of CMT1X mutants, we delivered AAV9-Mpz-GJB1 by lumbar intrathecal injection in R75W/Gjb1-null and N175D/Gjb1-null transgenic lines expressing Golgi-retained mutations, before and after the onset of the neuropathy. Widespread expression of virally delivered Cx32 was demonstrated in both genotypes. Re-establishment of WT Cx32 function resulted in improved muscle strength and increased sciatic nerve motor conduction velocities in all treated groups from both mutant lines when treated before as well as after the onset of the neuropathy. Furthermore, morphological analysis showed improvement of myelination and reduction of inflammation in lumbar motor roots and peripheral nerves. In conclusion, this study provides proof of principle for a clinically translatable gene therapy approach to treat CMT1X before and after the onset of the neuropathy, even in the presence of endogenously expressed Golgi-retained Cx32 mutants.


Temporal Changes in Transcription Factor Expression Associated with the Differentiation State of Cerebellar Neural Stem/Progenitor Cells During Development.
During central nervous development, multi-potent neural stem/progenitor cells located in the ventricular/subventricular zones are temporally regulated to mostly produce neurons during early developmental stages and to produce glia during later developmental stages. After birth, the rodent cerebellum undergoes further dramatic development. It is also known that neural stem/progenitor cells are present in the white matter (WM) of the postnatal cerebellum until around P10, although the fate of these cells has yet to be determined. In the present study, it was revealed that primary neurospheres generated from cerebellar neural stem/progenitor cells at postnatal day 3 (P3) mainly differentiated into astrocytes and oligodendrocytes. In contrast, primary neurospheres generated from cerebellar neural stem/progenitor cells at P8 almost exclusively differentiated into astrocytes, but not oligodendrocytes. These results suggest that the differentiation potential of primary neurospheres changes depending on the timing of neural stem/progenitor cell isolation from the cerebellum. To identify the candidate transcription factors involved in regulating this temporal change, we utilized DNA microarray analysis to compare global gene-expression profiles of primary neurospheres generated from neural stem/progenitor cells isolated from either P3 or P8 cerebellum. The expression of zfp711, zfp618, barx1 and hoxb3 was higher in neurospheres generated from P3 cerebellum than from P8 by real-time quantitative PCR. Several precursor cells were found to express zfp618, barx1 or hoxb3 in the WM of the cerebellum at P3, but these transcription factors were absent from the WM of the P8 cerebellum.


Optimizing brain tissue contrast with EPI: a simulated annealing approach.
A new magnetization preparation and image acquisition scheme was developed to obtain high-resolution brain images with optimal tissue contrast. The pulse sequence was derived from an optimization process using simulated annealing, without prior assumptions with regard to the number of radiofrequency (RF) pulses and flip angles. The resulting scheme combined two inversion pulses with the acquisition of three images with varying contrast. The combination of the three images allowed separation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) based on T1, contrast. It also enabled the correction of small errors in the initial T1 estimates in postprocessing. The use of three-dimensional (3D) sensitivity-encoded (SENSE) echo-planar imaging (EPI) for image acquisition made it possible to achieve a 1.15(3) mm3 isotropic resolution within a scan time of 10 min 21 s. The cortical GM signal-to-noise ratio (SNR) in the calculated GM-only image varied between 30 and 100. The novel technique was evaluated in combination with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on human subjects, and provided for excellent coregistration of anatomical and functional data.


Interactions of intermediate filaments with cell structures.
Intermediate filaments (IF) are unique components of the cytoskeleton of most eukaryotic cells. Also the nuclear lamins are now recognized to be IF-like proteins, providing the nucleus with a putative skeleton for chromatin attachment. Immunofluorescence and whole-mount electron microscopic studies reveal that IF form a cytoplasmic network that surrounds the nucleus and extends to cell surface, as 'mechanical integrators of cellular space'. It seems however unlikely that IF in the cell accomplish a merely structural role, considering the diversity of IF proteins and the complex regulation of their gene expression. In this work we primarily present electron microscopic data that points to the presence of interactions between IF and several cellular components, namely the nucleus, plasma membrane, other cytoskeletal elements, cytoplasmic organelles and ribonucleoproteins. Although the functional significance of such interactions remains to be demonstrated, assumptions like involvement of IF in information transfer or cytoskeleton-dependent control of gene expression represent attractive hypothesis for future research.


Chlorella vulgaris supplementation effects on performances, oxidative stress and antioxidant genes expression in liver and ovaries of New Zealand White rabbits.
Oxidative stress is an exclusive biochemical complication affecting reproduction; hence, dietary antioxidant supplementation for its attenuation is a required nutrition - reproduction improvement strategy. On this background, Chlorella vulgaris (a natural antioxidant) was supplemented to grower female rabbits to maturity. The rabbits were thirty-five in number randomly distributed into five experimental groups in a completely randomized design. Control group was fed only basal feed while treatment groups were fed diets containing 40 %, 60 %, 80 % and 100 % Chlorella vulgaris biomass as T1, T2, T3 and T4 respectively at 500 mg per animal body weight (kg) along with the basal feed daily. Performance records were obtained, blood was collected, and at the end uterus, ovaries and liver were removed from sacrificed animals for analysis. Serum, uterus and liver oxidative stress status were determined while RNA isolated from liver and ovaries samples were used for antioxidant genes expression analysis. Oxidative stress status and antioxidant enzymes activities were determined using chemical assays while antioxidant gene expression levels were determined using real-time quantitative PCR system. There was significant difference in feed intake (p < 0.014), final body weights (p < 0.008), empty carcass weights (p < 0.001) and commercial carcass weights (p < 0.001) of the rabbits as results of the microalgae supplementation. There was also significant difference in malondialdehyde (MDA) concentrations (p < 0.050), total antioxidant capacity (TAC) (p < 0.050) and protein carbonyl (PCO) concentrations (p < 0.050) due to the supplementation of the microalgae; in addition, supplementation of the microalgae significantly improved activities of superoxide dismutase (SOD) (p < 0.050), catalase (CAT) (p < 0.050) and reduced glutathione (GSH) concentration (p < 0.050). Furthermore, there was significant difference in relative expression of primary antioxidant genes sod1 (p < 0.050) and gpx1 (p < 0.050); however, there was no significant difference in relative expression of bre (p > 0.050) and ucp1 (p > 0.050). The study concluded from the outcomes stated above that supplementation of microalgae Chlorella vulgaris improved performances of rabbits through attenuation of oxidative stress, enhancement of antioxidant enzymes activities as well as up-regulation of primary antioxidant genes. Hence, it was recommended as dietary supplement for protection against oxidative stress and improved productivity in rabbits and other food producing mammalian species. In addition, further studies into assessment of its effects on expression of transcripts and immune modulation genes in rabbits and other animals is warranted as future studies in order to established its potential as beneficial nutraceutical for animals and human.