Cumulative Inflammation and HbA1c Levels Correlate with Increased Intima-Media Thickness in Patients with Severe Hidradenitis Suppurativa.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has been associated with a greater risk of metabolic and cardiovascular comorbidities. The aim of this study is to assess cardiovascular risk by means of intima-media thickness (IMT), metabolic syndrome, and other potential biomarkers in patients with severe hidradenitis suppurativa who are candidates for biologic therapy and to explore potentially associated factors. A cross-sectional study was performed. Body mass index (BMI), carotid intima-media thickness (IMT), and blood tests, including glycemic and lipid profile, insulin, vitamin D, and inflammation markers were performed. Fifty patients were included in the study; the male/female ratio was 3:2. The mean age was 38 years, and the mean disease duration was 21.8 years. The mean carotid IMT was 651.39 μm. A positive association of IMT with disease duration, tobacco consumption, and HbA1c levels was observed. HbA1c correlated with the age of onset, hypertension, metabolic syndrome, and glucose levels. Vitamin D levels inversely correlated with the number of areas affected. In conclusion, patients with severe HS present a higher cardiovascular risk, but it is not distributed equally within the patients: Tobacco consumption, inadequate glycemic control, and disease duration could be useful clinical and biochemical markers to identify patients at higher risk.


Keeping Simon simple: examining the relationship between sequential modulations and feature repetitions with two stimuli, two locations and two responses.
The present study examined performance across three two-choice tasks that used the same two stimuli, the same two stimulus locations, and the same two responses to determine how task demands can alter the Simon Effect, its distribution across reaction time, and its sequential modulation. In two of the tasks, repetitions of stimulus features were not confounded with sequences of congruent and incongruent trials. This attribute allowed us to investigate the sequential modulation of the Simon Effect in a two-choice task while equalizing the occurrence of feature repetitions. All tasks showed a similar sequential modulation, suggesting that it is not driven by feature repetitions. Moreover, distributional analyses revealed that the advantage for congruent trials decreased as reaction time increased similarly following congruent and incongruent trials. Finally, a large increase in RT was observed when repeated responses were made to novel stimuli and when novel responses were made to repeated stimuli. This effect also showed a sequential modulation regardless of whether the stimulus repeated. The findings suggest that, even in two-choice tasks, response selection is mediated by complex, dynamic representations that encode abstract properties of the task rather than just simple features.


Chondrocalcinosis and other calcifications.
Less than 30 years ago, McCarty and others first described a syndrome which presented with gout-like attacks of arthritis but was due to CPPD crystals instead of urate crystals. They termed the condition "pseudogout." It was noted that this was often associated with chondrocalcinosis and it was commonly held that cartilage calcification had to be present if the diagnosis was to be suggested on the basis of the radiographic findings. Subsequently, a clinical and radiographic pattern has emerged in which the diagnosis of CPPD deposition disease can be suggested in the absence of chondrocalcinosis. This condition is termed pyrophosphate arthropathy and is differentiated from degenerative disease by the pattern and distribution of the joint disease. It is important to recognize CPPD deposition disease because of its association with other diseases, such as hemochromatosis and hyperparathyroidism. Although painful periarticular tendinous calcification (peritendinitis calcarea) resulting from the deposition of calcium HA crystals has long been recognized, it has only recently been discovered that intra-articular HA can be associated with an acute inflammatory synovitis. Additionally, patients are now being identified who have CPPD deposition at one anatomic location and HA deposition at another. Differentiation of these various types of crystal-induced arthropathies should lead to more effective therapy in the future.


Memory independence and memory interference in cognitive development.
Recent experiments have established the surprising fact that age improvements in reasoning are often dissociated from improvements in memory for determinative informational inputs. Fuzzy-trace theory explains this memory-independence effect on the grounds that reasoning operations do not directly access verbatim traces of critical background information but, rather, process gist that was retrieved and edited in parallel with the encoding of such information. This explanation also envisions 2 ways in which children's memory and reasoning might be mutually interfering: (a) memory-to-reasoning interference, a tendency to process verbatim traces of background inputs on both memory probes and reasoning problems that simultaneously improves memory performance and impairs reasoning, and (b) reasoning-to-memory interference, a tendency for reasoning activities that produce problem solutions to erase or reduce the distinctiveness of verbatim traces of background inputs. Both forms of interference were detected in studies of children's story inferences.


A case of tuberculous tenosynovitis in a patient with systemic lupus erythematosus.
A 52-year-old woman with systemic lupus erythematosus (SLE) was infected with tuberculosis (TB) on her forearm and hand, after 16 years of steroid therapy. Debridements and anti-TB therapy were performed successfully. Recently, the risk of significant morbidity from TB has been on the rise; this appears to be a complication of steroid therapy used to treat AIDS and some collagen vascular diseases. It is thought that steroid therapy causes an increased risk of TB. In this paper, we report our experience of this SLE patient who developed tuberculous tenosynovitis. We suggest that TB infection must be considered in the differential diagnosis whenever a patient presents with a chronic wrist or hand inflammation that is non-responsive to steroid treatment. Once TB infection is suspected, both histopathological and bacteriological examinations should be performed. Emergent treatment includes surgical debridement and the institution of early anti-TB therapy immediately after completing histopathological examination.


Prevalence and risk factors for early presentation of asthma among preschool children in Taiwan.
Traditional asthma prevalence surveys were based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which focuses on children aged 6-7 and 13-14. However, asthma-like symptoms usually commence in preschool aged children, in whom it is difficult to make a definite diagnosis of asthma. It is worth determining the prevalence rate of asthma or asthma-like symptoms and analyzing the risk factors for this phenomenon among preschool aged children. Children aged 3-6 years were recruited from kindergartens in Keelung City, northern Taiwan. The questionnaire used was based on the ISAAC phase III core and environmental questionnaires and included questions on asthma, rhino-conjunctivitis, and eczema, along with questions to elicit common and early presentations of asthma, as well as other demographic and environmental data. The questionnaires were delivered and completed by parents. 2395 questionnaires were delivered to parents with children at 50 kindergartens, of which 2170 questionnaires were returned (return rate 90.6%). 9.9% of these preschool children had physician-diagnosed asthma. However, 20.4% of them experienced asthma like symptoms while attending kindergarten. Both the physician-diagnosed asthma and asthma-like symptoms groups had more clinical symptoms in all seasons except summer, compared to children without asthma. It was significant that the asthma-like symptoms commenced after joining a kindergarten (p < 0.001), and 66.5% of the children started to experience the symptoms within one month of beginning kindergarten. Using antibiotics or antipyretics in young infancy and mothers having asthma were the risk factors for developing asthma and asthma-like symptoms (p < 0.001), but parental smoking was not contributory to asthma development in preschool children. More frequent use of antipyretics in a year had a higher risk for the development of asthma and asthma-like symptoms. Asthma and asthma-like symptoms were common in preschool children. Early infection of the respiratory tract and use of antibiotics were associated with presentation of symptoms. Attending a kindergarten is also a risk factor for early presentation of asthma among preschool children.


In vivo models of arterial thrombosis and thrombolysis.
This year approximately 1.5 million Americans will undergo a myocardial infarction (MI). Of those who make it to the hospital (approximately 1.2 million), only about 20% will receive thrombolytic therapy. Multiple factors contribute to this dismaying figure, but most of them are risk/benefit-related. Moreover, of those receiving lytic therapy, the coronary arteries of as many as one-third may not reopen, and of those that do undergo coronary thrombolysis, an unacceptable fraction will experience reocclusion acutely. Thus, despite significant progress, major challenges for antithrombotic and thrombolytic therapy remain. Promising results with aspirin provide some hope that the figures above can be altered favorably. Efforts are under way in industry and academia to develop drugs to accomplish one or more of the following: lower the incidence of MI, prevent the development of unstable angina or retard its progression to frank MI, increase the inclusion window for lytic therapy, raise the percentage of patients undergoing successful thrombolysis, and maintain coronary patency. During the period that thrombolytic agents have come into vogue important advances have been made in our understanding of platelet function, coagulation, and the endogenous fibrinolytic system. These have spurred the development of novel drugs, such as platelet fibrinogen receptor antagonists, plasminogen activators, and inhibitors of factor IIa (thrombin) and XIIIa. Evaluation of these agents for their antithrombotic or profibrinolytic activity requires relevant animal models of thrombosis. Despite appropriate concerns about their clinical relevance, these models bridge the wide gap between test tube assays of aggregation or coagulation and humans.


Endocrine testicular function in HIV-infected outpatients.
We investigated endocrine testicular function in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 27% decrease in plasma oestradiol, which was the only parameter that was weakly correlated with CD4 cell count (r = 0.312, p <0.05). Individual data showed a decreased plasma concentration of total and free testosterone in 35% and 26% of the subjects, respectively, but we could not demonstrate an increased frequency of hypogonadism going along with a progression of the stage of disease. There was no significant correlation between androgen, SHBG or FSH levels and duration of HIV-infection, BMI or CD4 cell count. Hypergonadotropic hypogonadism was associated with an euthyroid sick state in a 15% subgroup of patients reporting a decrease in libido. Plasma T3 was significantly correlated with testosterone (r = 0.419, p <0.01) and mean plasma T3 was significantly decreased in 8 subjects suffering from erectile impotence. Thus, hypogonadism occurs frequently in HIV-infected outpatients. Like euthyroid sickness it does not seem to be a predictor for progression of the disease but an indicator of actual state of health.


Risk factors for transmission in a COVID-19 cluster infection in a high school in the Republic of Korea.
This study aimed to examine the scale, characteristics, risk factors, and modes of transmission in a coronavirus disease 2019 (COVID-19) outbreak at a high school in Seoul, Republic of Korea. An epidemiological survey was conducted of 1,118 confirmed cases and close contacts from a COVID-19 outbreak at an educational facility starting on May 31, 2021. In-depth interviews, online questionnaires, flow evaluations, and CCTV analyses were used to devise infection prevention measures. Behavioral and spatial risk factors were identified, and statistical significance was tested. Among 3rd-year students, there were 33 confirmed COVID-19 cases (9.6%). Students who used a study room in the annex building showed a statistically significant 4.3-fold elevation in their relative risk for infection compared to those who did not use the study room. Moreover, CCTV facial recognition analysis confirmed that 17.8% of 3rd-year students did not wear masks and had the lowest percentage of mask-wearers by grade. The air epidemiological survey conducted in the study room in the annex, which met the 3 criteria for a closed space, confirmed that there was only 10% natural ventilation due to the poor ventilation system. To prevent and manage the spread of COVID-19 in educational facilities, advance measures that consider the size, operation, and resources of each school are crucial. In addition, various survey methodologies should be used in future studies to quickly analyze a wider range of data that can inform an evidence-based quarantine response.


Supraclavicular vs. Infraclavicular Brachial Plexus Nerve Blocks: Clinical, Pharmacological, and Anatomical Considerations.
Peripheral nerve blocks (PNB) have become standard of care for enhanced recovery pathways after surgery. For brachial plexus delivery of anesthesia, both supraclavicular (SC) and infraclavicular (IC) approaches have been shown to require less supplemental anesthesia, are performed more rapidly, have quicker onset time, and have lower rates of complications than other approaches (axillary, interscalene, etc.). Ultrasound-guidance is commonly utilized to improve outcomes, limit the need for deep sedation or general anesthesia, and reduce procedural complications. Given the SC and IC approaches are the most common approaches for brachial plexus blocks, the differences between the two have been critically evaluated in the present manuscript. Various studies have demonstrated slight favorability towards the IC approach from the standpoint of complications and safety. Two prospective RCTs found a higher incidence of complications in the SC approach - particularly Horner syndrome. The IC method appears to support a greater block distribution as well. Overall, both SC and IC brachial plexus nerve block approaches are the most effective and safe approaches, particularly under ultrasound-guidance. Given the success of the supraclavicular and infraclavicular blocks, these techniques are an important skill set for the anesthesiologist for intraoperative anesthesia and postoperative analgesia.


Thymidylate synthase gene variations: predictive and prognostic markers.
Since its introduction more than 50 years ago by Heidelberger et al., the fluoropyrimidine 5-fluorouracil (5-FU) has remained the mainstay of therapeutic regimens used in the treatment of colorectal cancer and other human malignancies, with single-agent response rates of 20% to 25% in advanced disease stage. Pharmacogenomics has emerged as a useful tool to address interindividual gene variations by analyzing the interplay of host and tumor genotype and drug efficacy and toxicity. Having a reliable panel of prognostic and predictive markers will be critical in selecting an individualized and tailored chemotherapy regimen based on the particular tumor and host genotype. Although conflicting results have been reported, higher thymidylate synthase (TS) protein and mRNA expression levels in tumors have generally been associated with poor clinical outcome in patients treated with 5-FU-based chemotherapy regimens. However, the cause of the variability in TS expression still remains not fully understood, although several germ-line polymorphisms seem to affect the expression of TS, some of which have been found to have an effect on prognosis and the probability of response to 5-FU-based chemotherapy. This review will provide an update on pharmacogenomic studies of TS that were aimed at elucidating their role as prognostic and predictive markers.


Fatal strokes in patients with rhino-orbito-cerebral mucormycosis and associated vasculopathy.
Within a 10-y period, fatal strokes occurred during parenteral administration of amphotericin B and surgical debridement of paranasal sinuses in 6 pathologically verified cases of rhino-orbito-cerebral mucormycosis (ROCM). All patients had unnoticed type-2 diabetes mellitus without ketoacidosis. They presented with unilateral orbital cellulitis and cavernous sinus syndrome. Fatal malignant cerebral infarctions occurred in the carotid system in 5 patients, and in the basilar artery or its major branches in 2 patients. Accelerated thrombotic occlusion of the cavernous portion of the carotid artery or the basilar artery was likely to be due to mucormycosis associated-vasculopathy and diabetic vasculopathy. One patient died of massive subarachnoid hemorrhage following rupture of the mycotic aneurysm. Despite parenteral administration of amphotericin B, fatal outcome of ROCM in patients with unnoticed diabetes mellitus occurs due to mucormycosis-associated malignant strokes. To improve outcome, a combination of early radical debridement, ocular exenteration, parenteral and local administration of amphotericin B, and decompression craniotomy should be considered.


Mitochondrial multiorgan disorder syndrome score generated from definite mitochondrial disorders.
Mitochondrial disorders (MIDs) frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or evolve into MIMODS during the course. This study aimed to find which organs and/or tissues are most frequently affected by MIMODS, which are the most frequent abnormalities within an affected organ, whether there are typical MIMODS patterns, and to generate an MIMODS score to assess the diagnostic probability for an MID. This is a retrospective evaluation of clinical, biochemical, and genetic investigations of adult patients with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women, aged 29-82 years were included in this study. The diagnosis was based on genetic testing (n=21), on biochemical investigations (n=17), or on both (n=2). The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS was diagnosed in 97% of patients. The organs most frequently affected were the muscle (97%), central nervous system (CNS; 72%), endocrine glands (69%), heart (58%), intestines (55%), and peripheral nerves (50%). The most frequent CNS abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and atrophy. The most frequent endocrine abnormalities included thyroid dysfunction, short stature, and diabetes. The most frequent cardiac abnormalities included arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most frequent MIMODS patterns were encephalomyopathy, encephalo-myo-endocrinopathy, and encepalo-myo-endocrino-cardiopathy. The mean ± 2SD MIMODS score was 35.97±27.6 (range =11-71). An MIMODS score >10 was regarded as indicative of an MID. Adult MIDs manifest as MIMODS in the vast majority of the cases. The organs most frequently affected in MIMODS are muscles, CNS, endocrine glands, and heart. An MIMODS score >10 suggests an MID.


HEp-2 cell adherence patterns, serotyping, and DNA analysis of Escherichia coli isolates from eight patients with AIDS and chronic diarrhea.
Three morphologic patterns of interaction between bacteria and enterocytes have been observed in colonic biopsy specimens from AIDS patients with chronic diarrhea in the United States. The DNA encoding virulence factors and the HEp-2 cell adherence patterns of Escherichia coli strains isolated from the stools of eight symptomatic AIDS patients were compared with those of five control strains with known adherence patterns. One clinical isolate from a patient with attaching-and-effacing enteropathy displayed the localized adherence attaching-and-effacing pattern typical of enteropathogenic E. coli on HEp-2 cells, five isolates displayed the "stacked-brick" aggregative adherence pattern typical of enteroaggregative E. coli strains, and one isolate showed the pattern characteristic of diffusely adherent E. coli. One patient's isolate displayed features of all three patterns. No clinical isolate hybridized with standard probes for enteropathogenic, enteroaggregative, diffusely adherent, enterotoxigenic, and enteroinvasive E. coli strains. Thus, isolates from symptomatic AIDS patients in the United States can display the same interactive patterns with HEp-2 cells as the agents of pediatric or traveler's diarrhea, but lack their typical virulence factors.


Control of intraocular inflammation associated with cataract surgery.
Major advances in cataract extraction techniques and instrumentation have occurred over the past decade. Smaller incisions, more efficient phacoemulsifiers, and decreased surgical times are a few of the changes that have helped to alleviate postoperative inflammation, but postoperative inflammation continues to be a cause of patient discomfort; delayed recovery; and, in some cases, suboptimal visual results secondary to cystoid macular edema. This article reviews the most recent literature regarding the control of intraocular inflammation associated with cataract surgery.


Long-term behavioural consequences of infant feeding: the limits of observational studies.
Observational (non-experimental) studies of the association between infant feeding and subsequent child or adult behaviour are prone to residual confounding by subtle differences in psychological attributes and interactional styles of mothers who breast feed vs. those who formula-feed. We followed up 13,889 6.5-year-old Belarusian children who participated in a large cluster-randomised trial of a breast-feeding promotion intervention. Behaviour was evaluated using the Strengths and Difficulties Questionnaire (SDQ), completed independently by the children's parents and teachers. We compared the results of experimental (intention-to-treat, ITT) and observational analyses (based on feeding actually received), both adjusted for clustering. Observational analyses were additionally adjusted for geographical region, urban vs. rural residence, child's sex, age at follow-up, birthweight, and maternal and paternal education. No differences between the randomised experimental vs. control groups were observed in ITT analyses. In contrast, small but statistically significant associations with weaning prior to 3 months were observed for parent and teacher SDQ scores on total difficulties, conduct problems and hyperactivity, even after multivariable adjustment. The absence of associations based on ITT analyses, in contrast with the significant associations based on observed breast-feeding duration, strongly suggests that the latter are biased by residual confounding.


The relevance of non-linear mathematics (chaos theory) to the treatment of cancer, the role of the immune response and the potential for vaccines.
Non-linear mathematics or 'chaos' theory was first applied in the prediction of complex systems such as the weather. Chaotic systems exhibit not only apparently random unpredictability, but also a degree of determinism, in that randomness remains confined within specific parameters. Biological systems manifest many of the features of chaotic systems, including the inherent repetition of self, fractal structure, and the existence of strange attractors. In this article, the interaction between a tumour and the immune system is examined with regard to the capacity for immunotherapy to influence these two complex systems beneficially. It is postulated that judicious immunization may lead to profound changes in the stability of this interaction, in the favour of the immune system's ability to recognize tumour cells.


Baccalaureate nursing education curricula in the People's Republic of China: status, issues and reforms.
This article examines baccalaureate nursing education curricula in the People's Republic of China. Three 5-year curricula and one 4-year curriculum were content analyzed and contrasted. Findings of this study suggested that: (i) the biomedical model dominated the three 5-year traditional curricula; (ii) political-ideological content permeated all four curricula; and (iii) the reformed curriculum at Peking Union Medical College was a genuine effort toward building a new nursing curriculum model that intended to differentiate nursing education from medical education. In addition, major themes of recent curriculum reforms were highlighted. Recommendations were suggested to improve the outcomes of future curriculum endeavors. Explicit as well as implicit comparisons with an ideal-typical American generic baccalaureate nursing curriculum were made when appropriate.


DSM-IV and new diagnostic categories: holding the line on proliferation.
The authors discuss aspects of the decision-making process for including "new" diagnostic categories in DSM-IV. They detail the different kinds of new categories proposed for inclusion in DSM-IV and discuss the risks and benefits of incorporating them. The authors comment on whether new diagnostic categories should be included in official nosologies as a stimulus for research or as a culmination of research. They also highlight problems with "sunsetting" diagnoses. The criteria for change in DSM-IV--a way to deal with the expanding array of proposals for additional diagnostic entities--are discussed. The authors also offer a series of specific examples of the different kinds of new categories being considered for inclusion in DSM-IV.


Teaching nurses psychological support of patients with wounds.
Concerns about lack of professional empathy with psychological aspects of wound care provided the springboard for this study. Forty-three qualified nurses who regularly care for patients with wounds recorded in research diaries how they supported patients holistically before and after attending a counselling skills workshop. Thirty-nine nurses then attended focus groups to share their experiences. Participants represented varied practice settings, with 581 patient situations recorded in the diaries. Data analysis identified four themes: reflection sharpens the focus on practice; complex situations; emotional labour; and knowing the patient. While patients' feelings were identified in the first diary period, and reflection sharpened the focus on practice, patients' psychological needs were not attended to fully. Following the workshop there was a major shift in the understanding and provision of psychological support for patients with wounds by some of the nurses. Others were unable or unwilling to embrace counselling skills into care. This highlights the need to address nurses' attitudes and beliefs that might interfere with psychological support for patients with wounds.


Effects and consequences of caring for persons with heart failure: (ECCUPENIC study) a nested case-control study.
Primary: To report a research protocol to analyse the relationship between the degree of heart failure and the health-related quality of life of patients and their family caregivers. Secondary: To identify the characteristics of heart failure patients and their caregivers and the association between these characteristics and hospital admissions. Moreover, to conduct a longitudinal analysis of the relationship between patients' and that of their family caregivers. As heart failure progresses, it reduces the patient's quality of life and progressive functional deterioration requires hospital admission and the provision of healthcare resources. The availability of a family caregiver is a key element in addressing and managing this healthcare problem and some research results have associated this factor with the prognosis for heart failure. Multicentre cohort nested case-control study. Exploratory analysis: Descriptive statistics, measures of central tendency and dispersion or percentages. Bivariate analysis: Using Student's t-test and chi-square test, anova and non-parametric tests. Survival analysis: Kaplan-Meier curves. Multivariate analysis: Cox's proportional hazards model. All calculations performed with an alpha level of 0·05. Lack of family support for patients with HF or greater duration of care is associated with more hospitalizations and increased depression among caregivers. Further longitudinal studies with a large population sample are required.


Use of tissue plasminogen activator to revive blebs following intraocular surgery.
Tissue plasminogen activator (tPA) is a serine protease with thrombolytic-fibrinolytic activity. In the anterior segment of the eye, it has been used to lyse blood and fibrin clots immediately following trabeculectomy. To review our experience using tPA to revive previously functional but newly failing blebs following secondary surgical procedures (cataract extraction or penetrating keratoplasty). A retrospective medical record review of all eyes receiving tPA to revive a failing bleb after a later anterior segment surgery was performed. Blebs were functional for at least 9 months before tPA, 12.5 microg, was injected into the anterior chamber. Eyes had longer than 6 months of follow-up after tPA use. Six eyes that had undergone phacoemulsification and 1 that had undergone penetrating keratoplasty were identified. Before the secondary surgery, blebs had been in place for 20.4 +/- 9.3 months, with an intraocular pressure of 10.7 +/- 3.6 mm Hg. New bleb failure in these eyes was observed following phacoemulsification or penetrating keratoplasty between postoperative days 4 and 14, with the intraocular pressure increasing to 27.7 +/- 9.5 mm Hg. One day after tPA use, the intraocular pressure had decreased to 11.0 +/- 3.7 mm Hg (P =.002). In 5 of the 7 patients, the bleb height improved following tPA use. The final intraocular pressure was 10.7 +/- 3.6 mm Hg at a follow-up of 13.4 +/- 6.4 months. (All data are given as mean +/- SD.) Tissue plasminogen activator can be a useful adjunct for reviving newly failing blebs after other anterior segment surgery.


Low-level laser effect on neurosensory recovery after sagittal ramus osteotomy.
This study examined the potential benefit of perioperative and short-term postoperative low-level laser (LLL) therapy on objective and subjective neurosensory recovery after bilateral sagittal split osteotomy surgery. Six consecutive patients undergoing bilateral sagittal split osteotomy procedures were enrolled in this prospective study. A complete preoperative clinical neurosensory test, consisting of brush stroke directional discrimination, 2-point discrimination, contact detection, pin prick nociception, and thermal discrimination, was performed on each patient; and a subjective assessment of neurosensory function was made by using a visual analog scale (VAS). The protocol for LLL treatments consisted of real LLL (4 x 6 J per treatment) along the distribution of the inferior alveolar nerve at 4 sites, for a total of 7 treatments, delivered immediately before surgery; at 6 and 24 hours after surgery; and on postoperative days 2, 3, 4, and 7. The clinical neurosensory test and VAS were completed just before each of the treatment sessions and on days 14 and 28, by one examiner. When the results of the patients treated with LLL were compared with published values for neurosensory recovery after orthognathic surgery, there was a significant acceleration in the time course, as well as in the magnitude, of neurosensory return. Brush stroke directional discrimination approached normal values by 14 days, whereas 2-point discrimination and contact detection showed significant improvement at 14 days and returned to near-normal values by 2 months. The results of thermal discrimination and pin prick nociception revealed few neurosensory deficits; however, those patients who were affected showed a slower recovery trend and remained neurosensory-deficient for up to 2 months. The VAS analysis revealed a rapidly progressive improvement in subjective assessment, showing a 50% deficit at 2 days and only a 15% subjective deficit at 2 months. This study demonstrates that neurosensory recovery after bilateral sagittal split osteotomy procedures can be significantly improved, both in terms of time course and magnitude of return of function, with the adjunctive use of LLL therapy.


Regulation of 5-Aminolevulinic Acid (ALA) Synthesis in Developing Chloroplasts : III. Evidence for Functional Heterogeneity of the ALA Pool.
Gabaculine and 4-amino-5-hexynoic acid (AHA) up to 3.0 millimolar concentration strongly inhibited 5-aminolevulinic acid (ALA) synthesis in developing cucumber (Cucumis sativus L. var Beit Alpha) chloroplasts, while they hardly affected protochlorophyllide (Pchlide) synthesis. Exogenous protoheme up to 1.0 micromolar had a similar effect. Exogenous glutathione also exhibited a strong inhibitory effect on ALA synthesis in organello but hardly inhibited Pchlide synthesis. Pchlide synthesis in organello was highly sensitive to inhibition by levulinic acid, both in the presence and in the absence of gabaculine, indicating that the Pchlide was indeed formed from precursor(s) before the ALA dehydratase step. The synthesis of Pchlide in the presence of saturating concentrations of glutamate was stimulated by exogenous ALA, confirming that Pchlide synthesis was limited at the formation of ALA. The gabaculine inhibition of ALA accumulation occurred whether levulinic acid or 4,6-dioxohepatonic acid was used in the ALA assay system. ALA overproduction was also observed in the absence of added glutamate and was noticeable after 10-minute incubation. These observations suggest that although Pchlide synthesis in organello is limited by ALA formation, it does not utilize all the ALA that is made in the in organello assay system. Gabaculine, AHA, and probably also protoheme, inhibit preferentially the formation of that portion of ALA that is not destined for Pchlide. A model proposing a heterogenous ALA pool is described.


Effect of nitrous oxide-oxygen inhalation with scavenging on behavioral and physiological parameters during routine pediatric dental treatment.
The purpose of this study was to determine the influence of 40% nitrous oxide/60% oxygen inhalation with scavenging on the behavioral and physiological parameters during routine pediatric dental procedures. Twenty-two subjects, aged 60-116 months, were randomized into a double blind, cross-over study design and administered alternately either 40% nitrous oxide/60% oxygen or 100% oxygen during two sequential restorative appointments. All subjects were monitored continuously for respiratory rate, pulse rate, and hemoglobin oxygen saturation using a combined capnograph and pulse oximeter. The subject's breath sound and behavior were recorded every minute along with vital signs. When compared to 100% oxygen inhalation, 40% nitrous oxide/60% oxygen inhalation produced significant reductions in adverse patient behavior, respiratory rate, and pulse rate, but did not affect percent hemoglobin oxygen saturation. Nitrous oxide inhalation had no effect on breath sound revealed by auscultation or on the occurrence of the apnea alarm displayed by the capnograph. This study demonstrated that the administration of 40% nitrous oxide/60% oxygen delivered via a scavenging nasal hood significantly improved patient behavior and altered physiological parameters commonly monitored during conscious sedation.


Implant science of artificial organ: design for success.
Although many artificial organs have come to be used clinically, there still remain many problems such as thrombus formation, calcification, infection, malfunction, etc., that sometimes expose the patient to danger. One of the causes of these damages is that we do not know the true mechanisms of these phenomena. In other words, the design criteria of implant devices have not yet been established under scientific basis. It is very important that we artificial organ researchers and manufacturers establish the implant science of artificial organs. In this paper, mention is made of the kinds of factors we should consider for the design of artificial organs and how we should approach them scientifically. Also introduced is our approach method for an implantable total artificial heart.


From the Cover: Coagulation-Driven Hepatic Fibrosis Requires Protease Activated Receptor-1 (PAR-1) in a Mouse Model of TCDD-Elicited Steatohepatitis.
Emerging evidence supports a role for environmental chemical exposure in the pathology of non-alcoholic fatty liver disease (NAFLD), a disease process tightly linked to increased activity of the blood coagulation cascade. Exposure of C57BL/6 mice to the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) recapitulates features of the NAFLD spectrum, including steatosis, hepatic injury, inflammation, and fibrosis. We assessed coagulation cascade activation, and determined the role of the thrombin receptor protease activated receptor-1 (PAR-1) in experimental TCDD-elicited NAFLD. Chronic exposure to TCDD (30 µg/kg every 4 days for 28 days) was associated with intrahepatic coagulation, indicated by increased plasma thrombin-antithrombin levels and hepatic fibrin(ogen) deposition. PAR-1 deficiency diminished TCDD-elicited body weight loss and relative liver weight was reduced in TCDD-exposed PAR-1-/- mice compared with TCDD-exposed wild-type mice. PAR-1 deficiency did not affect TCDD-induced hepatic steatosis or hepatocellular injury, as indicated by serum alanine aminotransferase activity. Despite a lack of effect on these 2 features of NAFLD pathology, PAR-1 deficiency was associated with a reduction in hepatic inflammation evident in liver histopathology, and reflected by a reduction in serum levels of the proinflammatory cytokine interleukin-6. Moreover, TCDD-driven hepatic collagen deposition was markedly reduced in PAR-1-deficient mice. These results indicate that experimental TCDD-elicited steatohepatitis is associated with coagulation cascade activation and PAR-1-driven hepatic inflammation and fibrosis.


An atomic-level strategy for unraveling gold nanocatalysis from the perspective of Au(n)(SR)m nanoclusters.
An atomic-level strategy is devised to gain insight into the origin of nanogold catalysis by using atomically monodisperse Au(n)(SR)(m) nanoclusters as well-defined catalysts for styrene oxidation. The Au(n)(SR)(m) nanoclusters are emerging as a new class of gold nanocatalyst to overcome the polydispersity of conventional nanoparticle catalysts. The unique atom-packing structure and electronic properties of Au(n)(SR)(m) nanoclusters (<2 nm) are rationalized to be responsible for their extraordinary catalytic activity observed in styrene oxidation. An interesting finding is that quantum size effects of Au(n)(SR)(m) nanoclusters, rather than the higher specific surface area, play a major role in gold-catalyzed selective oxidation of styrene. For example, Au(25)(SR)(18) nanoclusters (≈1 nm) are found to be particularly efficient in activating O(2), which is a key step in styrene oxidation, and hence, the ultrasmall Au(25) catalyst exhibits higher activity than do larger sizes. This atomic-level strategy has allowed us to obtain an important insight into some fundamental aspects of nanogold catalysis in styrene oxidation. The ultrasmall yet robust Au(n)(SR)(m) nanoclusters are particularly promising for studying the mechanistic aspects of nanogold catalysis and for future design of better catalysts with high activity and selectivity for certain chemical processes.


Single-Fraction Celiac Plexus Radiosurgery: A Preliminary Proof-of-Concept Phase 2 Clinical Trial.
Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate this pain. We performed a single-arm prospective clinical trial (ClinicalTrials.gov identifier: NCT02356406). Eligible and evaluable patients had celiac pain of at least 5 out of 10 on the Numerical Rating Scale, completed treatment per protocol, and had at least 1 posttreatment visit. The entire retroperitoneal celiac plexus was irradiated with a single 25-Gy fraction. The primary endpoint was change in the Numerical Rating Scale 3 weeks posttreatment. Toxic effects and pain interference (as measured with the Brief Pain Inventory) were secondary endpoints. For our study, 31 patients signed consent, and, of these, 18 patients were treated and evaluable. Median age was 68 years (range, 51-79); 89% of the patients had pancreatic cancer; the median Eastern Cooperative Oncology Group performance status was 1; and the median interval from initial diagnosis to treatment was 9 months (range, 1-36), and, in this interval, patients received a median of 1 systemic treatment line (range, 0-3). Acute toxicity was limited to grade 1 to 2. Three weeks after treatment, 16 patients (84%) reported decreased celiac pain, with median pain level falling from 6 out of 10 (interquartile range [IQR], 5.0-7.5) at baseline to 3 out of 10 (IQR, 1.0-4.3); six weeks after treatment, the Numerical Rating Scale number fell further to 2.8 out of 10 (IQR, 0-3.3; both P < .005 vs baseline), including 4 patients who reported complete eradication of their celiac pain. Total daily morphine milligram equivalents decreased from 59 pretreatment to 50 at 3 weeks, and from 50 to 45 at 6 weeks. Significant improvement was seen in pain-interference scores. Celiac plexus radiosurgery appears to alleviate cancer-related pain. An international multicenter phase 2 trial is currently accruing.


Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis.
A protein analysis using mass spectrometry revealed the existence of serum proteins with significant quantitative changes after the administration of infliximab. Among these proteins, regenerating gene (REG) 1α appears to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, the present study was conducted to examine the mechanism of REG1α in RA disease progression. Serum samples were collected from RA patients and normal healthy controls. REG1α expression was evaluated by ELISA, RT-PCR, and indirect immunofluorescence microscopy. The functions of REG1α on synovial fibroblasts with regard to apoptosis, receptor activator of NF-κB ligand (RANKL) expression, and cellar proliferation were evaluated using siRNA to inhibit the intrinsic REG1α mRNA expression. The serum concentrations of REG1α in RA patients were higher than in normal healthy controls. The high expression of REG1α was also observed in the synovial tissue of RA patients compared to those of osteoarthropathy patients. In addition, tumor necrosis factor-α (TNF-α) upregulated REG1α expression in the synovial fibroblasts cell line (MH7A). Inhibition of REG1α expression suppressed the induction of RANKL expression by TNF-α. Furthermore, exogenous recombinant REG1α protein inhibited apoptosis and promoted cell proliferation in MH7A cells. These effects were abolished in the REG1α-siRNA MH7A cells. The present data suggest that TNF-α induces aberrant REG1α expression and that REG1α plays an important role in aberrant cell proliferation and RANKL expression of synovial fibroblasts, ultimately resulting in pannus formation. Restoration of normal physiological REG1α expression may contribute to disease amelioration.


The stress-buffering role of alcohol consumption: the importance of symptom dimension.
This paper examines the possibility of the existence of stress-buffering properties of alcohol consumption suggested by a recent study in which life events were related to depressive symptoms for abstainers and heavy drinkers but not for moderate drinkers. Survey data on affective and somatic symptoms from 364 urban and 333 rural Florida residents indicated some support for the buffering argument. Moderate and heavy drinkers manifested significantly lower levels of symptoms than did abstainers only with regard to somatic symptoms. Life event-drinking pattern interactions did not reach statistical significance, although trends consistent with the buffering hypothesis were obtained with the somatic symptom measure. Implications of the data are explored.


Interrelationships between Skin Structure, Function, and Microbiome of Pregnant Females and Their Newborns: Study Protocol for a Prospective Cohort Study.
Pregnancy leads to several skin changes, but evidence about structural and functional skin changes is scarce. Findings on skin structure and function in children in their first year reveal rapid skin maturation, but evidence indicates that in particular, water holding and transport mechanisms are different from adults. Important questions include whether maternal cutaneous properties predict infant skin condition, and if so, how. This is especially relevant for the skin's microbiome because it closely interacts with the host and is assumed to play a role in many skin diseases. Therefore, the study objective is to explore characteristics of skin and hair of pregnant women and their newborns during pregnancy and in the first six months after delivery and their associations. The study has an observational longitudinal design. We are recruiting pregnant females between 18 and 45 years using advertisement campaigns in waiting areas of gynecologists and hospital's outpatient services. A final sample size of n = 100 women is the target. We perform noninvasive, standardized skin, hair, and skin microbiome measurements. We establish the baseline visit during pregnancy until at the latest four weeks before delivery. We schedule follow-up visits four weeks and six months after birth for mothers and their newborns. We will calculate descriptive statistical methods using frequencies and associations over time depending on scale levels of the measurements. Discussion. The majority of previous studies that have investigated infants' skin microbiome and its associations used cross-sectional designs and focused on selected characteristics in small samples. In our longitudinal study, we will characterize a broad range of individual and environmental characteristics of mothers and their newborns to evaluate interrelationships with skin parameters and their changes over time. Considering the combination of these multiple variables and levels will allow for a deeper understanding of the complex interrelationship of the newborn's skin maturation. This trial is registered with ClinicalTrials.gov (Identifier: NCT04759924).


Inferring genome trees by using a filter to eliminate phylogenetically discordant sequences and a distance matrix based on mean normalized BLASTP scores.
Darwin's paradigm holds that the diversity of present-day organisms has arisen via a process of genetic descent with modification, as on a bifurcating tree. Evidence is accumulating that genes are sometimes transferred not along lineages but rather across lineages. To the extent that this is so, Darwin's paradigm can apply only imperfectly to genomes, potentially complicating or perhaps undermining attempts to reconstruct historical relationships among genomes (i.e., a genome tree). Whether most genes in a genome have arisen via treelike (vertical) descent or by lateral transfer across lineages can be tested if enough complete genome sequences are used. We define a phylogenetically discordant sequence (PDS) as an open reading frame (ORF) that exhibits patterns of similarity relationships statistically distinguishable from those of most other ORFs in the same genome. PDSs represent between 6.0 and 16.8% (mean, 10.8%) of the analyzable ORFs in the genomes of 28 bacteria, eight archaea, and one eukaryote (Saccharomyces cerevisiae). In this study we developed and assessed a distance-based approach, based on mean pairwise sequence similarity, for generating genome trees. Exclusion of PDSs improved bootstrap support for basal nodes but altered few topological features, indicating that there is little systematic bias among PDSs. Many but not all features of the genome tree from which PDSs were excluded are consistent with the 16S rRNA tree.


Characterization of acanthamoeba isolates from dust of a public hospital in Curitiba, Paraná, Brazil.
Occurrence of Acanthamoeba in the hospital environment may represent a health risk for patients, since these organisms can cause severe opportunistic illness, such as keratitis, and also can harbor pathogenic agents. We analyzed the dust from some environments of a public hospital in Curitiba, Parana State, Brazil. Two distinct populations of Acanthamoeba were isolated in five locations and morphologically classified as group I and group II according to Pussard and Pons. Isolates were identified as Acanthamoeba by PCR using primers to amplify a region of 18S rDNA, which showed variation in the product length among the isolates. A cloned culture of group II showed greater growth at 37 degrees C and in media with 0.1, 0.5, and 1.0 M mannitol, which are the physiological characteristics of pathogenic Acanthamoeba. Monitoring the presence of Acanthamoeba in hospital units, as well as evaluating the pathogenicity of the isolates, can be an approach to alert the health professionals to improve the disinfection procedures and minimize the risks of treating this problematic disease caused by this protozoan.


Disrupted Brain Network in Progressive Mild Cognitive Impairment Measured by Eigenvector Centrality Mapping is Linked to Cognition and Cerebrospinal Fluid Biomarkers.
Mild cognitive impairment (MCI) is a heterogeneous condition associated with a high risk of progressing to Alzheimer's disease (AD). Although functional brain network alterations have been observed in progressive MCI (pMCI), the underlying pathological mechanisms of network alterations remain unclear. In the present study, we evaluated neuropsychological, imaging, and cerebrospinal fluid (CSF) data at baseline across a cohort of: 21 pMCI patients, 33 stable MCI (sMCI) patients, and 29 normal controls. Fast eigenvector centrality mapping (fECM) based on resting-state functional MRI (rsfMRI) was used to investigate brain network organization differences among these groups, and we further assessed its relation to cognition and AD-related pathology. Our results demonstrated that pMCI had decreased eigenvector centrality (EC) in left temporal pole and parahippocampal gyrus, and increased EC in left middle frontal gyrus compared to sMCI. In addition, compared to normal controls, patients with pMCI showed decreased EC in right hippocampus and bilateral parahippocampal gyrus, and sMCI had decreased EC in right middle frontal gyrus and superior parietal lobule. Correlation analysis showed that EC in the left temporal pole was related to Wechsler Memory Scale-Revised Logical Memory (WMS-LM) delay score (r = 0.467, p = 0.044) and total tau (t-tau) level in CSF (r = -0.509, p = 0.026) in pMCI. Our findings implicate EC changes of different brain network nodes in the prognosis of pMCI and sMCI. Importantly, the association between decreased EC of brain network node and pathological changes may provide a deeper understanding of the underlying pathophysiology of pMCI.


Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus.
All classes of antidepressants increase hippocampal cell proliferation and neurogenesis, which contributes, in part, to the behavioral actions of these treatments. Among antidepressant treatments, electroconvulsive seizure (ECS) is the most robust stimulator of hippocampal cell proliferation and the most efficacious treatment for depression, but the cellular mechanisms underlying the actions of ECS are unknown. To address this question, we investigated the effect of ECS on proliferation of neural stem-like and/or progenitor cells in the subgranular zone of rat dentate gyrus. We define the neural differentiation cascade from stem-like cells to early neural progenitors (also referred to as quiescent and amplifying neural progenitors, respectively) by coexpression of selective cellular and mitotic activity markers. We find that at an early mitotic phase ECS increases the proliferation of quiescent progenitors and then at a later phase increases the proliferation of amplifying progenitors. We further demonstrate that vascular endothelial growth factor (VEGF) signaling is necessary for ECS induction of quiescent neural progenitor cell proliferation and is sufficient to produce this effect. These findings demonstrate that ECS and subsequent induction of VEGF stimulates the proliferation of neural stem-like cells and neural progenitor cells, thereby accounting for the superior neurogenic actions of ECS compared with chemical antidepressants.


Intestinal permeability, atopic eczema and oral disodium cromoglycate.
A dual sugar (lactulose-mannitol) absorption test was performed in 19 patients with atopic eczema before and after a 21 day elimination-diet. Moreover L/M test was carried out in 20 controls. The mean value of lactulose-mannitol urinary ratio (L/M) was 0.015 (+/- 0.018 SD) in the group of patients and 0.012 (+/- 0.011 SD) in the control group (p = 0.49). The mean clinical score improved significantly after elimination diet (41,6 +/- 12.9 SD before the diet, 21.7 +/- 10.4 SD after the diet, p less than 0.001) but no significant modification of intestinal permeability was recorded (L/M = 0.015 +/- 0.018 SD before the diet and 0.21 +/- 0.022 SD after the diet, p = 0.38). Using a double blind approach we were not able to demonstrate any significant effect of disodium cromoglycate on the clinical score and intestinal permeability. The connections between food allergy, intestinal permeability and atopic dermatitis have not been understood, but disodium cromoglycate doesn't seem to play a significant role in the treatment of atopic dermatitis nor in the modification of intestinal permeability.


Removal of organic micropollutants in waste stabilisation ponds: A review.
As climate change and water scarcity continue to be of concern, reuse of treated wastewater is an important water management strategy in many parts of the world, particularly in developing countries and remote communities. Many countries, especially in remote regional areas, use waste stabilisation ponds (WSPs) to treat domestic wastewater for a variety of end uses, including using the treated wastewater for irrigation of public spaces (e.g. parks and ovals) or for crop irrigation. Thus, it is vital that the resulting effluent meets the required quality for beneficial reuse. In this paper, both the performance of WSPs in the removal of organic micropollutants, and the mechanisms of removal, are reviewed. The performance of WSPs in the removal of organic micropollutants was found to be highly variable and influenced by many factors, such as the type and configuration of the ponds, the operational parameters of the treatment plant, the wastewater quality, environmental factors (e.g. sunlight, temperature, redox conditions and pH) and the characteristics of the pollutant. The removal of organic micropollutants from WSPs has been attributed to biodegradation, photodegradation and sorption processes, the majority of which occur in the initial treatment stages (e.g. in the anaerobic or facultative ponds). Out of the many hundreds of organic micropollutants identified in wastewater, only a limited number (40) have been studied in WSPs, with the majority of these pollutants being pharmaceuticals, personal care products and endocrine disrupting compounds. Thus, future research on the fate of organic micropollutants in WSPs should encompass a broader range of micropollutants and include emerging organic pollutants, such as illicit drugs and perfluorinated compounds. Further research is also needed on the formation and toxicity of transformation products from organic micropollutants in WSPs, since the transformation products of some organic micropollutants can be more toxic than the parent compound. Combining other wastewater treatment processes with WSPs for removal of recalcitrant organic micropollutants should also be considered.


The Safety of Pegylated Liposomal Doxorubicin Plus Irinotecan in Recurrent Ovarian Cancer Patients: A Phase I Trial.
The study was designed to evaluate the safety of combined chemotherapy with pegylated liposomal doxorubicin (PLD) and irinotecan (CPT-11) in patients with recurrent ovarian cancer. Six patients with platinum-resistant and taxane-pretreated ovarian cancer were enrolled in the study based on the traditional 3-plus-3 design. PLD was administered intravenously on day 1 and CPT-11 on days 1 and 8 of each 28-day course. Initial doses were 30 mg/m(2) PLD and 50 mg/m(2) CPT-11. Hematotoxicity was the principal toxicity (1 patient developed grade 3 neutropenia and 2 developed grade 3 leukocytopenia); hand-foot syndrome was not observed. Furthermore, 1 patient achieved complete response, whereas 2 patients achieved partial response. The combined PLD and CPT-11 regimen was well-tolerated indicating its potential clinical benefit for ovarian cancer patients.


Discovery and Optimization of a Novel Macrocyclic Amidinourea Series Active as Acidic Mammalian Chitinase Inhibitors.
Our research group has been involved for a long time in the development of macrocyclic amidinoureas (MCAs) as antifungal agents. The mechanistic investigation drove us to perform an in silico target fishing study, which allowed the identification of chitinases as one of their putative targets, with 1a showing a submicromolar inhibition of Trichoderma viride chitinase. In this work, we investigated the possibility to further inhibit the corresponding human enzymes, acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1), involved in several chronic inflammatory lung diseases. Thus, we first validated the inhibitory activity of 1a against AMCase and CHIT1 and then designed and synthesized new derivatives aimed at improving the potency and selectivity against AMCase. Among them, compound 3f emerged for its activity profile along with its promising in vitro ADME properties. We also gained a good understanding of the key interactions with the target enzyme through in silico studies.


[The biorhythmological types of work capacity and the late prognosis for patients who have had a myocardial infarct].
The authors analyze postmyocardial infarction 10-year survival and frequency of repeated cardiac accidents (fatal and nonfatal MI and sudden cardiac death). Biorhythmological types of mental and muscular performance were involved in long-term MI prognosis. Of 412 males who had their first myocardial infarction at the age under 59, 10-year prognosis was poor for those with early pattern of efficient work vs good prognosis in those who work most efficiently in the evening. The differences in the long-term prognosis of acute myocardial infarction related to performance biorhythm were observed both for subjects performing muscular and mental work.


Geometry of Proximal Humerus Locking Plates.
Proximal humerus fractures are commonly treated with open reduction and internal fixation with periarticular locking plates. This study compared the geometry of proximal humerus locking plate's screw distribution, amount of bone-screw interface, and the volume the screws occupy within the humeral head, as well as how leaving the screws short of the articular surface affects these measures. Locking plates from 7 manufacturers were applied to foam humerus models. The entry and exit hole of each screw trajectory was digitized using a 3-dimensional motion tracking system. A trajectory for each screw was modeled, as well as the volume enclosed by the screw trajectories. The following outcome metrics were calculated: the bone-screw interface, the volume enclosed by the screws, and the effect of leaving the screws short of the articular surface. Biomet had the most bone-screw interface (7259 mm), whereas Zimmer had the least (3982 mm). The original Synthes plate had the largest screw volume, occupying 31.5% of the humeral head, whereas Smith & Nephew and Zimmer had the lowest volumes, occupying 21.2% and 12.6%, respectively. Leaving the screws 15 mm short of the articular surface resulted in the most reduction in volume for the Depuy plate (50%) and the least reduction for the new version of the Synthes plate (29%). Many different manufactured periarticular locking plates exist to stabilize a proximal humeral fracture. Clinicians need to be familiar with the different plate configurations, screw lengths, and trajectories, which affect potential biomechanical performance and can optimize fracture site maintenance.


Stenosing tenosynovitis of the flexor hallucis longus tendon at the sesamoid area.
The author presents a case of stenosing tenosynovitis of the flexor hallucis longus tendon at the sesamoid area of the great toe following injury of the hallux. Although stenosing tenosynovitis of the flexor hallucis longus tendon is not rare, occurring frequently in ballet dancers, its entrapment at the sesamoid area was rarely described in the literature. Early recognition of this condition is very important for successful treatment. This patient did not respond to nonoperative treatment and surgical tenolysis was very successful for relief of the symptoms.


Weak polyelectrolyte complexation driven by associative charging.
Weak polyelectrolytes are relevant for a wide range of fields; in particular, they have been investigated as "smart" materials for chemical separations and drug delivery. The charges on weak polyelectrolytes are dynamic, causing polymer chains to adopt different equilibrium conformations even with relatively small changes to the surrounding environment. Currently, there exists no comprehensive picture of this behavior, particularly where polymer-polymer interactions have the potential to affect charging properties significantly. In this study, we elucidate the novel interplay between weak polyelectrolyte charging and complexation behavior through coupled molecular dynamics and Monte Carlo simulations. Specifically, we investigate a model of two equal-length and oppositely charging polymer chains in an implicit salt solution represented through Debye-Hückel interactions. The charging tendency of each chain, along with the salt concentration, is varied to determine the existence and extent of cooperativity in charging and complexation. Strong cooperation in the charging of these chains is observed at large Debye lengths, corresponding to low salt concentrations, while at lower Debye lengths (higher salt concentrations), the chains behave in apparent isolation. When the electrostatic coupling is long-ranged, we find that a highly charged chain strongly promotes the charging of its partner chain, even if the environment is unfavorable for an isolated version of that partner chain. Evidence of this phenomenon is supported by a drop in the potential energy of the system, which does not occur at the lower Debye lengths where both potential energies and charge fractions converge for all partner chain charging tendencies. The discovery of this cooperation will be helpful in developing "smart" drug delivery mechanisms by allowing for better predictions for the dissociation point of delivery complexes.


A case of everolimus-associated chylothorax in a cardiac transplant recipient.
We herein report a case of putative everolimus-associated chylothorax in a cardiac transplant recipient. A 17-year-old Japanese boy with dilated cardiomyopathy and severe cardiac failure requiring left ventricular assist support was determined to be a cardiac transplant candidate in 1992. He underwent overseas heart transplantation in Houston, Texas in October 1992. He was subsequently treated with immunosuppression therapy: Cyclosporine (CSA), azathioprine, and prednisolone (PRD). After several acute rejection episodes requiring steroid therapy, intravascular ultrasonography revealed a moderate degree of transplant coronary arterial vasculopathy (TCAV) with 50% stenosis in 2003. He underwent coronary stenting twice; the immunosuppressive regimen was converted to CSA, mycophenolate mofetil, everolimus (EVL), and PRD in 2006. TCAV has not progressed since then. In October 2008, chest x-ray showed bilateral pleural effusion. As we thought that the pleural effusion was caused by cardiac dysfunction due to moderate mitral regurgitation and TCAV as well as renal impairment, he was treated with diuretics and digoxin. However, the pleural effusion progressed gradually associated with exertional dyspnea and moderate edema of his lower legs. Chest computed tomography showed massive bilateral pleural effusions without evidence of malignancy in 2011. A pleural tap in 2011 revealed chylothorax. Although mammalian target of rapamycin inhibitors were major drugs for lymphoangioleimyomatosis, we believed that the chylothorax was associated with EVL. EVL was discontinued in March 2011: the chylothorax spontaneously resolved in November 2011.


[The role of the mouthguard in preventing sports-related oral-facial and dental traumas.].
Sports play a significant role in all nations worldwide. More and more people involve in sports so that the incidence of the oral-facial and dental traumas with accidents ascends. The treatment cost is considerable, and the sporters' lives will be influenced by these traumas. This paper examines the status and the reasons of the oral-facial and dental traumas. It reviews not only the principle and the types of the mouthguard but also the evidence of the mouthguard in preventing sports-related traumas. Prevention is thought to be the key element in minimizing traumas that occur in sports, the using of mouthguard is considered essential.


In vitro muscle contracture investigations on the malignant hyperthermia like episodes in myotonia congenita.
A common form of congenital myotonia, myotonia congenita (MC), is caused by mutations in the skeletal muscle Cl(-) channel gene type 1 (CLCN1). Due to the reduced Cl(-) conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during general anaesthesia. The clinical symptoms resemble malignant hyperthermia (MH), which may lead to mistreatment of the patient. Muscle specimens of ADR mice (an animal model of MC) as well as of human individuals were used and exposed to potent ryanodine receptor type 1 (RyR1) activators and increasing K(+) concentration. Muscle force was monitored by a standardized diagnostic method for MH, the so-called in vitro contracture test. Neither muscle of ADR mice nor MC muscle (murine and human myotonic muscle) showed pathological contractures after exposure to the potent RyR1 agonists caffeine and halothane. Increasing concentrations of K(+) had a dose-dependent preventive effect on myotonic stiffness. We conclude that the adverse anaesthetic MH-like episodes observed in MC patients do not primarily originate from an altered Ca(2+) release in skeletal muscle. In MC muscle, this hypermetabolism is facilitated by a (pharmacologically induced) sustained depolarization due to an instable membrane potential. The in vitro results suggest that these patients benefit from tight K(+) monitoring because of the membrane potential stabilizing effect of K(+) .


Paracrine signaling through MYCN enhances tumor-vascular interactions in neuroblastoma.
Neuroblastoma, a tumor of peripheral neural crest origin, numbers among the most common childhood cancers. Both amplification of the proto-oncogene MYCN and increased neoangiogenesis mark high-risk disease. Because angiogenesis is regulated by phosphatidylinositol 3-kinase (PI3K), we tested a clinical PI3K inhibitor, NVP-BEZ235, in MYCN-dependent neuroblastoma. NVP-BEZ235 decreased angiogenesis and improved survival in both primary human (highly pretreated recurrent MYCN-amplified orthotopic xenograft) and transgenic mouse models for MYCN-driven neuroblastoma. Using both gain- and loss-of-function approaches, we demonstrated that the antiangiogenic efficacy of NVP-BEZ235 depended critically on MYCN in vitro and in vivo. Thus, clinical PI3K/mammalian target of rapamycin inhibitors drove degradation of MYCN in tumor cells, with secondary paracrine blockade of angiogenesis. Our data demonstrated significantly improved survival in treated animals and suggest that NVP-BEZ235 should be tested in children with high-risk, MYCN-amplified neuroblastoma.


[Degradation of Azlocillin and Mezlocillin / I. Behaviour in biological material and buffer (author's transl)].
The degradation of 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido] penicillanic acid Na-salt (azlocillin, Securopen) and 6-[(R)-2-[3-methylsulfonyl-2-oxoimidazolidine-1-carboxamido]-2-phenyl-acetamido ] penicillanic acid Na-salt (mezlocillin, Baypen), two chemically related acylureido penicillins, was tested in biological material (plasma and urine) and borate buffer at 37 degrees C over the time period of at least 6 h. In fresh human urine (pH 5.0) no degradation could be observed. In freshly prepared human plasma (pH 7.6) degradation was independent of the initial concentration and amounted to no more than 5%. No difference could be noted between the degradation in plasma or buffer, respectively, indicating that direct aminolysis did not play an important role in the degradation process. The extent of degradation could be demonstrated to be pH-dependent. After 8 h incubation at pH 9.0 azlocillin concentration was decreased to 70% and mezlocillin concentration to 50%, respectively, of the initial concentration. Since urinary pH values up to 8.5 are reported the urinary recovery of the substance could be influenced by alkaline pH.


Fragmentation, circadian amplitude, and fractal pattern of daily-living physical activity in people with multiple sclerosis: Is there relevant information beyond the total amount of physical activity?
Physical activity is lower in people with multiple sclerosis (pwMS) compared to healthy controls. Previous work focused on studying activity levels or activity volume, but studies of daily-living rest-activity fragmentation patterns, circadian rhythms, and fractal regulation in pwMS are limited. Based on findings in other cohorts, one could suggest that these aspects of daily-living physical activity will provide additional information about the health and well-being of pwMS. Therefore, here, we aimed to (1) identify which fragmentation, fractal, and circadian amplitude measures differ between pwMS and healthy controls, (2) evaluate the relationship between fragmentation, fractal, and circadian amplitude measures and disease severity, and (3) begin to evaluate the added value of those measures, as compared to more conventional measures of physical activity (e.g., mean signal vector magnitude (SVM). A global measure of the overall volume of physical activity). 132 people with relapsing-remitting MS (47±11 yrs, 69.7% female, Expanded Disability Status Scale, EDSS, median (IQR): 3 (2-4)) and 90 healthy controls (46±11 yrs, 47.8% female) were asked to wear a 3D accelerometer on their lower back for 7 days. Rest-activity fragmentation, circadian amplitude, fractal regulation, and mean SVM metrics were extracted. PwMS and healthy controls were compared using independent samples t-tests and linear regression, including comparisons adjusted for mean SVM to control for the effect of physical activity volume. Spearman correlations between measures and logistic regressions were used to identify the clinical condition based on the measures that differed significantly after adjusting for SVM. All analyses included adjustments for demographic and clinical parameters (e.g., age, sex). Multiple measures of activity fragmentation significantly differed between pwMS and healthy controls, reflecting a more fragmented active behavior in pwMS. PwMS had a lower circadian rhythm amplitude, indicating a smaller amplitude in the circadian changes of daily activity, and weaker temporal correlations as based on the fractal analysis. When taking into account physical activity volume, one circadian amplitude measure and one fractal measure remained significantly different in pwMS and controls. Fragmentation measures and circadian amplitude measures were significantly associated with disability level as measured by the EDSS; the association with circadian amplitude remained significant, even after adjusting for the mean SVM. The physical activity patterns of pwMS differ from those of healthy individuals in rest-activity fragmentation, the amplitude of the circadian rhythm, and fractal regulation. Measures describing these aspects of activity provide information that is not captured in the total volume of physical activity and could, perhaps, augment the monitoring of disease progression and evaluation of the response to interventions.


Spondylodiscitis and bacteremia due to Staphylococcus hyicus in an immunocompetent man.
Staphylococcus hyicus is a coagulase-variable Staphylococcus spp. well-known by veterinarians since it is the major agent of a severe cutaneous infection in piglets called exudative epidermitis. In other species the symptoms of infection are quite different. Human cases are uncommon but seem to occur more frequently after repeated contacts with farm animals. We report the case of a 58-year-old man suffering from debilitating subacute lumbar pain, in whom diagnosis of infectious spondylodiscitis was based on spine MRI and positive microbiological results. A strain of S. hyicus was surprisingly isolated from blood cultures and bone biopsy. Identification was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, Bruker, USA), and the patient was successfully cured with a six-week course of anti-staphylococcal antibiotic regimen. The prevalence of S. hyicus in human clinical samples is very low, but may be underestimated. This pathogen may enter the bloodstream through a skin injury, and then induce various pyogenic manifestations in people working with farm animals. S. hyicus exfoliative toxins, responsible for dermatological lesions in piglets, seem unable to damage the human epidermis, explaining the absence of cutaneous blisters in the previously reported cases. Precise data about its pathogenicity in humans and the adequate therapy are lacking.


[Lumbar epidural and foraminal injections: update].
A fluoroscopy-guided lumbar spine injection procedure may be complicated by immediate paralysis. Twelve cases (five recent and seven published) that occurred between 2002 and 2008 were reviewed (history of lumbar surgery, route of injection, image-guidance, injection of contrast, type of steroid, level of paraplegia, MR imaging features). MRI showed cord ischemia from arterial origin. The high number of patients with prior lumbar spine surgery suggests that the presence of scar tissue could increase the risk of paraplegia. A transforaminal approach was used in all patients without history of lumbar surgery while transforaminal, interlaminar and juxta-zygapophyseal approaches were used in patients with prior lumbar surgery. The high number of cases in France could be explained by the exclusive use of prednisolone acetate which has a higher rate of macro-aggregate formation that could lead to embolization in medullary arteries.


Vitamin D Compounds Are Bactericidal against Streptococcus mutans and Target the Bacitracin-Associated Efflux System.
Vitamin D analogs were identified as compounds that induced lysis of planktonic cultures of Streptococcus mutans in a high-throughput screen of FDA-approved drugs. Previous studies have demonstrated that certain derivatives of vitamin D possess lytic activity against other bacteria, though the mechanism has not yet been established. Through the use of a combinatorial approach, the vitamin D derivative doxercalciferol was shown to act synergistically with bacitracin, a polypeptide-type drug that is known to interfere with cell wall synthesis, suggesting that doxercalciferol may act in a bacitracin-related pathway. Innate resistance to bacitracin is attributed to efflux by a conserved ABC-type transporter, which in S. mutans is encoded by the mbrABCD operon. S. mutans possesses two characterized mechanisms of resistance to bacitracin, the ABC transporter, S. mutans bacitracin resistance (Mbr) cassette, consisting of MbrABCD, and the rhamnose-glucose polysaccharide (Rgp) system, RgpABCDEFGHI. Loss of function of the transporter in ΔmbrA and ΔmbrD mutants exacerbated the effect of the combination of doxercalciferol and bacitracin. Despite conservation of a transporter homologous to mbrABCD, the combination of doxercalciferol and bacitracin appeared to be synergistic only in streptococcal species. We conclude that vitamin D derivatives possess lytic activity against S. mutans and act through a mechanism dependent on the bacitracin resistance mechanism of MbrABCD.


Prevalence of human papillomavirus infection among prostitutes in Calcutta.
We investigated the presence of human papilloma virus (HPV) 16/18 and herpes simplex virus-1,-2 (HSV-1,-2) infections in buccal mucosal cells of prostitutes of Calcutta, India, by in situ DNA hybridization and immunocytochemical technique. In some of them, we also examined the prevalence of viral infections in uterine cervical cells. The women were also tested for venereal disease research laboratory antigen (VDRL) positivity. Oral infections with HSV-1, -2 and HPV 16/18 were detected in 24.6%, 11.6%, and 29%, respectively. Similar cervical infections were found in 0%, 44%, and 62.9% of the cases studied. HPV coinfection was significantly higher (p < 0.01) in both the oral and cervical cells that had HSV infection. The cervical HPV infections were not markedly higher among the VDRL-positive prostitutes (p > 0.05). The HPV or HSV infection rates showed no remarkable variation between the two age groups of the prostitutes studied (p > 0.05). Cytological abnormalities were more pronounced in the cervix of women having concurrent infection with HPV and HSV-2 rather than in the presence of infection with either of the two. This preliminary investigation, the first of its kind in India, requires a larger study to understand the significance of the association of different sexually transmitted agents including HPV (apart from HIV) as risk factors for pathologic lesions.


Inaccuracy of Forefoot Axial Radiographs in Determining the Coronal Plane Angle of Sesamoid Rotation in Adult Hallux Valgus Deformity: A Study Using Weightbearing Computed Tomography.
Hallux abducto valgus is a triplane deformity with recent attention given to the significance of correcting the coronal plane component. This study explored the accuracy of the forefoot axial (FFA) study as a standard radiographic assessment method compared with weightbearing computed tomography (CT). Twelve feet with hallux abducto valgus from 12 individuals were included in this study. Three images of the affected foot were taken: FFA radiograph and weightbearing CT with the foot in maximum pronation (pronated CT) and maximum supination (supinated CT). Five investigators determined the sesamoid rotation angles (SRAs) from each of the images. The measurements from a single investigator were used to compare the SRA means from each of the image types, and those from all five investigators were used to determine reliability. The mean ± SD SRA was 22.1° ± 7.6° for pronated CT, 10.5° ± 5.0° for supinated CT, and 12.2° ± 9.4° for FFA images. The mean SRA from the pronated CT was significantly greater than the supinated CT (P < .001) and FFA (P < .005) SRAs. There were no significant differences in mean SRA between the FFA and supinated CT images (P > .99). Results indicated high reliability in measurements among investigators. Using weightbearing CT, these findings indicate that the sesamoids significantly alter their position in the coronal plane, as determined by the SRA, with changes in weightbearing subtalar joint position. Moreover, the affected foot positioning required for determining the SRA from the FFA radiograph seems to significantly underestimate the true SRA. Thus, use of this image in surgical hallux abducto valgus planning is called into question.


The development of a professional role orientation inventory.
This paper describes the development and testing of the Professional Role Orientation Inventory, a 40-item Likert-type instrument designed to assess a dentist's perception of his or her professional role. The test includes four 10-item scales representing four attitudinal dimensions: Authority, Responsibility, Agency, and Autonomy. The study describes differences between and among groups of professionals and dental students who took the test. Responses to the various scales suggest that practitioners do have different conceptualizations of their professional role, though these conceptions vary somewhat from the various models of professionalism described in the literature.


Silencing of hsa_circ_0004771 inhibits proliferation and induces apoptosis in breast cancer through activation of miR-653 by targeting ZEB2 signaling pathway.
Background: Circular RNAs (circRNAs) have been reported as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) implicating in the initiation and progression of breast cancer. However, the functions of circRNAs in breast cancer have not been completely clarified. In the present study, we aimed to identify differentially expressed circRNAs in breast cancer tumor tissues, and their roles and downstream targets were investigated in the progression of breast cancer. Methods: High-throughput circRNA sequencing was performed to detect the differentially expressed circRNAs. The CCK-8 and flow cytometry were performed to measure the cell viability and apoptosis in breast cancer cells. Gene and protein expression were assayed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Results: hsa_circ_0004771 and Zinc finger E-box binding homeobox 2 (ZEB2) expression levels were up-regulated and positively correlated in breast cancer tumor tissues. In addition, the expression levels of miR-653 were reduced in breast cancer tumor tissues. We also found that hsa_circ_0004771 functioned as a sponge of miR-653 to inhibit its expression. miR-653 as a post-transcriptional regulator down-regulated the expression of ZEB2 by binding to its 3'-UTR. Interestingly, a significant inverse correlation was observed between miR-653 and hsa_circ_0004771 or ZEB2 expression in breast cancer tumor tissues. Knockdown of hsa_circ_0004771 and ZEB2 served as equally authentic of miR-653 mimics to induce growth inhibition and apoptosis in breast cancer cells. Conclusion: Hsa_circ_0004771/miR-653/ZEB2 regulatory feedback revealed a new molecular mechanism in the pathogenesis of breast cancer, which might provide novel therapeutic targets for the treatment of breast cancer.


The discriminability of local surface structure.
The ability of observers to discriminate depth and orientation differences between separated local regions on object surfaces was examined. The objects were defined by many optical sources of information simultaneously, including shading, texture, motion, and binocular disparity. Despite the full-cue nature of the displays, the observers' performance was relatively poor, with Weber fractions ranging from 10% to 40%. The Weber fractions were considerably lower for discriminations of surface-orientation differences than for similar discriminations of depth differences. The ability of observers to discriminate surface-orientation differences was approximately invariant over the separation of the regions in the projected image. In contrast, the ability to discriminate depth differences was highly influenced by the amount of image separation. This qualitative difference between the perception of depth intervals and surface-orientation differences suggests that knowledge of depths and orientations may be represented separately within the human visual system.


Recurrent cardiac myxoma: why it occurs. A case report with literature review.
Two years after surgical removal of a right atrial myxoma, recurrences were found in both atria: multiple tumors in the right atrium and one tumor in the left atrium. All were subsequently removed. There was no further recurrence during the following 3 years. We report on an unusual case which, to our knowledge, is the first time that such a case appears in the literature. We also discuss the clinical symptoms, diagnostic aspects, as well as details of a literature review regarding recurring myxoma. We think the recurrence in our case was due to totipotent multicentricity of the tumor. Previous studies showed that the recurrence might be due to the following reasons: inadequate resection, or multifocal pattern behaviour of a benign myxoma, either in the same or in a different location as the primary tumor. Familial disposition may also play a role in recurrent development. The abnormal DNA ploidy pattern of myxoma patients showed a high recurrence.


Cross-trait prediction accuracy of summary statistics in genome-wide association studies.
In the era of big data, univariate models have widely been used as a workhorse tool for quickly producing marginal estimators; and this is true even when in a high-dimensional dense setting, in which many features are "true," but weak signals. Genome-wide association studies (GWAS) epitomize this type of setting. Although the GWAS marginal estimator is popular, it has long been criticized for ignoring the correlation structure of genetic variants (i.e., the linkage disequilibrium [LD] pattern). In this paper, we study the effects of LD pattern on the GWAS marginal estimator and investigate whether or not additionally accounting for the LD can improve the prediction accuracy of complex traits. We consider a general high-dimensional dense setting for GWAS and study a class of ridge-type estimators, including the popular marginal estimator and the best linear unbiased prediction (BLUP) estimator as two special cases. We show that the performance of GWAS marginal estimator depends on the LD pattern through the first three moments of its eigenvalue distribution. Furthermore, we uncover that the relative performance of GWAS marginal and BLUP estimators highly depends on the ratio of GWAS sample size over the number of genetic variants. Particularly, our finding reveals that the marginal estimator can easily become near-optimal within this class when the sample size is relatively small, even though it ignores the LD pattern. On the other hand, BLUP estimator has substantially better performance than the marginal estimator as the sample size increases toward the number of genetic variants, which is typically in millions. Therefore, adjusting for the LD (such as in the BLUP) is most needed when GWAS sample size is large. We illustrate the importance of our results by using the simulated data and real GWAS.


Hyperconnectivity between the posterior cingulate and middle frontal and temporal gyrus in depression: Based on functional connectivity meta-analyses.
Disrupted whole-brain resting-state functional connectivity (RSFC) of the posterior cingulate (PCC) has been highlighted to associate with cognitive and affective dysfunction in major depressive disorder (MDD). However, prior findings showed certain inconsistency about the RSFC of the PCC in MDD. This study aims to investigate the aberrant RSFC of the PCC in MDD using anisotropic effect-size version of seed-based d mapping (AES-SDM). Web of Science and PubMed were searched for studies investigating PCC-based RSFC in MDD. A total of 17 studies, involving 804 patients and 724 healthy controls (HCs), fit our selection criteria. Additionally, to seek for the link between functional and structural differences, we did a meta-analysis on the studies in conjunction with voxel-based morphology (VBM) analysis. The PCC showed higher RSFC with the left middle temporal gyrus (MTG) and the right middle frontal gyrus (MFG), and lower RSFC with the left superior frontal gyrus (SFG) and the left precuneus in patients with MDD than HCs. Moreover, the meta-regression analysis revealed a negative correlation between the FC alteration of the right MFG with the PCC and depression severity. Notably, the left MTG and the left MFG demonstrated gray matter deviations in conjunction analysis. Our results indicated that the aberrant RSFC between the PCC and brain regions sub-serving cognitive control and emotional regulation in patients with MDD. And such functional alterations may have structural basis. These findings may underlie the mechanisms of deficits in cognitive control and emotional regulation of MDD.


T-DNA insertional mutagenesis for activation tagging in rice.
We have developed a new T-DNA vector, pGA2715, which can be used for promoter trapping and activation tagging of rice (Oryza sativa) genes. The binary vector contains the promoterless beta-glucuronidase (GUS) reporter gene next to the right border. In addition, the multimerized transcriptional enhancers from the cauliflower mosaic virus 35S promoter are located next to the left border. A total of 13,450 T-DNA insertional lines have been generated using pGA2715. Histochemical GUS assays have revealed that the GUS-staining frequency from those lines is about twice as high as that from lines transformed with the binary vector pGA2707, which lacks the enhancer element. This result suggests that the enhancer sequence present in the T-DNA improves the GUS-tagging efficiency. Reverse transcriptase-PCR analysis of a subset of randomly selected pGA2715 lines shows that expression of the genes immediately adjacent to the inserted enhancer is increased significantly. Therefore, the large population of T-DNA-tagged lines transformed with pGA2715 could be used to screen for promoter activity using the gus reporter, as well as for creating gain-of-function mutants.


Ex vivo IFN-gamma secretion by circulating CD8 T lymphocytes: implications of a novel approach for T cell monitoring in infectious and malignant diseases.
To elucidate the functional heterogeneity of Ag-specific T lymphocyte populations, we combined labeling of lymphocytes with MHC/peptide tetramers and a cell surface affinity matrix for IFN-gamma. Magnetic cell sorting of IFN-gamma-positive lymphocytes allowed the selective enrichment and identification of live Ag-specific cytokine-secreting cells by flow cytometry. Naive, memory, and effector Ag-specific populations were evaluated in healthy HLA-A2 individuals. Significant fractions of influenza- and CMV-specific cells secreted IFN-gamma upon challenge with cognate peptide, consistent with an effector/memory status. The sensitivity of the approach allowed the detection of significant numbers of CMV-specific IFN-gamma-secreting cells ex vivo (i.e., without Ag stimulation). This was not apparent when using previously described assays, namely, ELISPOT or intracellular IFN-gamma staining (cytospot). CD8+ T cells specific for the melamoma-associated Ag Melan-A/MART-1 did not produce IFN-gamma upon challenge with cognate peptide, reminiscent with their naive functional state in healthy individuals. In contrast, CD45RA(low) Melan-A/MART-1 tumor-specific cells from three of three melanoma patients presented levels of activity similar to those found for influenza- or CMV virus-specific lymphocytes, compatible with a functional differentiation into competent effector/memory T lymphocytes in vivo. Notably, a sizable fraction of Melan-A/MART-1-specific cells from a patient secreted IFN-gamma ex vivo following peptide-based vaccination. Thus, the high sensitivity of the assay provides a valuable tool to monitor effector T cell responses in different clinical situations.


Toughening of Poly(lactic acid) and Thermoplastic Cassava Starch Reactive Blends Using Graphene Nanoplatelets.
Poly(lactic acid) (PLA) was reactively blended with thermoplastic cassava starch (TPCS) and functionalized with commercial graphene (GRH) nanoplatelets in a twin-screw extruder, and films were produced by cast-film extrusion. Reactive compatibilization between PLA and TPCS phases was reached by introducing maleic anhydride and a peroxide radical during the reactive blending extrusion process. Films with improved elongation at break and toughness for neat PLA and PLA-g-TPCS reactive blends were obtained by an addition of GRH nanoplatelets. Toughness of the PLA-g-TPCS-GRH was improved by ~900% and ~500% when compared to neat PLA and PLA-g-TPCS, respectively. Crack bridging was established as the primary mechanism responsible for the improvement in the mechanical properties of PLA and PLA-g-TPCS in the presence of the nanofiller due to the high aspect ratio of GRH. Scanning electron microscopy images showed a non-uniform distribution of GRH nanoplatelets in the matrix. Transmittance of the reactive blend films decreased due to the TPCS phase. Values obtained for the reactive blends showed ~20% transmittance. PLA-GRH and PLA-g-TPCS-GRH showed a reduction of the oxygen permeability coefficient with respect to PLA of around 35% and 50%, respectively. Thermal properties, molecular structure, surface roughness, XRD pattern, electrical resistivity, and color of the films were also evaluated. Biobased and compostable reactive blend films of PLA-g-TPCS compounded with GRH nanoplatelets could be suitable for food packaging and agricultural applications.


A New Electrochemical Sensor for Direct Detection of Purine Antimetabolites and DNA Degradation.
The development of a reliable electrochemical sensor using a hybrid nanocomposite consisting of ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate) functionalized graphene oxide (GrO-IL) and gold nanoparticles (AuNPs) stabilized by chitosan (Chit) was described. The new sensor, labelled as GrO-IL-AuNPs-Chit/CSE, exhibited an improved electrocatalytic response to cancer drugs such as purine antimetabolites (6-thioguanine, 6-mercaptopurine, and azathioprine) in a wide concentration range with a low detection limit (20-40 nmol·L-1, S/N = 3), and satisfactory recoveries (97.1-103.0%). The sensor has been also successfully used for cyclic voltammetric study of a salmon sperm double-stranded DNA degradation and DNA-6-mercaptopurine interaction in aqueous solutions (pH 7.4).


Tactile vibration thresholds after acute poisonings with organophosphate insecticides.
This study evaluated the association between acute poisoning with organophosphate pesticides (OPs) and quantitative tactile vibration thresholds. Thresholds of the dominant index fingers and big toes of 56 men hospitalized for acute poisoning with OPs were measured at hospital discharge (1-24 days after poisoning) and around seven weeks later (24-176 days after poisoning), and compared with those of controls. Thresholds of the big toes of men with severe intentional poisonings due to neuropathic OPs (metamidophos and chlorpyrifos) increased between the first and second examinations. Threshold impairment was not detected in the index finger regardless of poisoning agent or severity. The development of threshold impairment as a consequence of severe intentional poisonings with neuropathic OPs is consistent with other reports indicating that only severe OP poisonings produce sensory peripheral nerve effects.


Phytochemistry, pharmacology and ethnomedicinal uses of Ficus thonningii (Blume Moraceae): a review.
The common wild fig, Ficus thonningii, is extensively used in African ethnomedicine for treating a number of disease conditions which include diarrhoea, urinary tract infections, diabetes mellitus, gonorrhoea, respiratory infections, and mental illnesses. This review aims to present a logical analysis of the nutritional, phytochemical and pharmacological properties of F. thonningii in relation to its therapeutic applications. A bibliographic analysis of the uses, phytochemical constituents and phytophamacological properties of Ficus thonningii was carried out using published papers, medicinal plant databases and various ethnobotanical and ethnopharmacological books. Ficus thonningii contains various bioactive compounds which include alkaloids, terpenoids, flavonoids, tannins and active proteins, all of which contribute to its curative properties. In vitro and in vivo pharmacological studies revealed that F. thonningii possesses antimicrobial, antidiarrhoeal, antihelmintic, antioxidant, anti-inflammatory and analgesic properties. Acute and sub-chronic toxicity studies have shown that Ficus thonningii is non-toxic if administered orally in low doses. Scientific research has validated the ethnomedicinal claims that Ficus thonningii is useful in disease management. However, there is need to continue identifying, isolating and quantifying the active principles and possibly determine the mechanisms underlying its curative properties.