Localization of the phosphorylations of polyomavirus large T antigen.
Polyomavirus large T antigen is phosphorylated on both serine and threonine residues at a ratio of approximately 6 to 1. This phosphorylation could be resolved into a series of nine Staphylococcus aureus V8 phosphopeptides. All of these were found in an N-terminal chymotryptic fragment with a molecular weight of 57,000. A C-terminal formic acid fragment of 50,000-molecular-weight lacked phosphate. Therefore, unlike simian virus 40 large T antigen, polyomavirus large T antigen has no significant C-terminal phosphorylation. Limited V8 and hydroxylamine cleavage showed that the phosphorylations can be localized to two different portions of the molecule. A significant fraction of the phosphate was localized in the N-terminal portion of the molecule before residue 183. Within this region V8 peptides 4, 8, and 9 represented phosphorylations that were more proximal, while peptides 1, 2, and 3 included more distal phosphorylations. None of these phosphorylations appeared analogous to those of simian virus 40 large T antigen. V8 phosphopeptides 5 and 7 were more distal and could be distinguished in biological experiments from the N-terminal phosphorylations. Formic acid mapping suggested that much, if not all, of this phosphorylation is located between residues 257 and 285.


Tinea pedis: clinical experience and efficacy of short treatment.
Tinea pedis is the commonest fungal infection in developed countries. Topical therapy is an accepted and successful method for the management of this condition. This has usually involved the application of an antifungal twice or 3 times a day for 3-4 weeks to achieve a cure rate of > or = 80%. Terbinafine, a new antifungal, has been shown in a number of studies to give equally good results when applied once or twice daily for 1-2 weeks. In one study, a cure rate of 78% was achieved in patients with tinea pedis after a single application of 1% terbinafine cream, demonstrating the high potency of this antifungal. Topical terbinafine has also been compared to clotrimazole for the treatment of tinea pedis. Terbinafine 1% cream applied twice daily for 1 week was significantly superior to a 4-week course of clotrimazole 1% cream for treating this common mycosis. Overall, the high efficacy of topical terbinafine in treating tinea pedis following such-short-duration therapy is undoubtedly due to its fungicidal mode of action.


Quality of Life and Symptom Burden 1 Month After Concussion in Children and Adolescents.
We conducted a prospective study of children and adolescents (n = 176; mean age = 13.0 ±2.7 years; 38% female) assessed acutely post-concussion and again 30 days later. We investigated the association between symptom burden and quality of life (QOL) outcomes, as well as the effect of age on QOL. We assessed QOL using patient-reported Pediatric Quality of Life Inventory 4.0, and symptoms using the Health and Behavior Inventory (HBI). Acute (<2 days post-injury) HBI ratings demonstrated a low correlation ( R2 = 0.08) with physical health QOL and a moderate correlation with psychosocial health QOL ( R2 = 0.21) 30 days post-concussion. HBI ratings 30 days post-concussion demonstrated a moderately high correlation with physical health QOL ( R2 = 0.35) and psychosocial health QOL ( R2 = 0.57). Age was not significantly associated with physical or psychosocial QOL ratings. Impairments in QOL following concussion may identify children and adolescents who need additional referral to address persistent symptoms at this time.


Feature selection for genetic sequence classification.
Most of the existing methods for genetic sequence classification are based on a computer search for homologies in nucleotide or amino acid sequences. The standard sequence alignment programs scale very poorly as the number of sequences increases or the degree of sequence identity is <30%. Some new computationally inexpensive methods based on nucleotide or amino acid compositional analysis have been proposed, but prediction results are still unsatisfactory and depend on the features chosen to represent the sequences. In this paper, a feature selection method based on the Gamma (or near-neighbour) test is proposed. If there is a continuous or smooth map from feature space to the classification target values, the Gamma test gives an estimate for the mean-squared error of the classification, despite the fact that one has no a priori knowledge of the smooth mapping. We can search a large space of possible feature combinations for a combination which gives a smallest estimated mean-squared error using a genetic algorithm. The method was used for feature selection and classification of the large subunits of rRNA according to RDP (Ribosomal Database Project) phylogenetic classes. The sequences were represented by dinucleotide frequency distribution. The nearest-neighbour criterion has been used to estimate the predictive accuracy of the classification based on the selected features. For examples discussed, we found that the classification according to the first nearest neighbour is correct for 80% of the test samples. If we consider the set of the 10 nearest neighbours, then 94% of the test samples are classified correctly. The principal novel component of this method is the Gamma test and this can be downloaded compiled for Unix Sun 4, Windows 95 and MS-DOS from http://www.cs.cf.ac.uk/ec/ firstname.lastname@example.com


Acute monensin toxicosis in sheep: light and electron microscopic changes.
Monensin was administered orally to 3 sheep at dosages of 12 (the LD50), 16, and 24 mg/kg of body weight, respectively. Clinical signs of monensin toxicosis were observed in the sheep in 24 to 36 hours of administration. Clinical signs included CNS depression, anorexia, diarrhea, and stiffness. Increased serum creatine phosphokinase and aspartate aminotransferase activities identified possible muscle damage. Sheep were euthanatized at 54 hours after dosing; at necropsy, there were skeletal muscle hemorrhages, pale myocardium, and pulmonary edema. Ultrastructural lesions were in the liver, diaphragm, and myocardium; diaphragm and myocardium were most severely affected. Mitochondrial swelling and cristolysis, swollen sarcoplasmic reticulum, and disruption of myofibrillar architecture were prominent. These ultrastructural changes are consistent with the hypothesis that monensin causes muscle cell necrosis due to its ionophorous properties and disruption of cellular Na+:Ca2+ balance. It is proposed that this upset of normal ionic processes allows increased intracellular calcium, which directly leads to the functional and structural mitochondrial changes observed.


Development of an instrument to measure patients' attitudes towards involuntary hospitalization.
To construct and assess the psychometric properties of an instrument to measure patients' attitudes towards involuntary hospitalization. This is a two phase study. In the first phase, based on comprehensive literature review, a twenty one item scale to measure patients' attitudes to involuntary admission was constructed. Forensic and inpatient Psychiatrists, patients' advocates and legal experts (n = 15) were invited to participate in the validation process of the written instrument, by formally rating each item of the instrument for its relevancy in measuring patients' attitudes to involuntary admission. In the second phase of the project, the instrument was administered to a sample of eighty consecutive patients, who were admitted involuntarily to an acute psychiatric unit of a teaching hospital. All patients completed the constructed attitudes towards involuntary admission scale, and the client satisfaction questionnaire. Responses from psychiatry and advocacy experts provided evidence for face and content validity for the constructed instrument. The internal consistency reliability of the instrument is 0.84 (Chronbach' alpha), factor analysis resulted in three correlated, and theoretically meaningful factors. There was evidence for content, convergent, and concurrent validity. A reliable twenty one item instrument scale to measure patients' attitudes to involuntary admission was developed. The developed instrument has high reliability, there is strong evidence for validity, and it takes ten minutes to complete.


Two-dimensional halide perovskites: synthesis, optoelectronic properties, stability, and applications.
Halide perovskites are promising materials for light-emitting and light-harvesting applications. In this context, two-dimensional perovskites such as nanoplatelets or Ruddlesden-Popper and Dion-Jacobson layered structures are important because of their structural flexibility, electronic confinement, and better stability. This review article brings forth an extensive overview of the recent developments of two-dimensional halide perovskites both in the colloidal and non-colloidal forms. We outline the strategy to synthesize and control the shape and discuss different crystalline phases and optoelectronic properties. We review the applications of two-dimensional perovskites in solar cells, light-emitting diodes, lasers, photodetectors, and photocatalysis. Besides, we also emphasize the moisture, thermal, and photostability of these materials in comparison to their three-dimensional analogs.


Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy.
Diabetic nephropathy (DN) is a complication of diabetes that is increasing in prevalence in China. Extracellular vesicles (EVs) carrying microRNAs (miRs) may represent a useful tool in the development of therapies for DN. Here, we report that EVs released by adipose-derived mesenchymal stem cells (ADSCs) during DN contain a microRNA, miR-26a-5p, that suppresses DN. Using bioinformatic analyses, we identified differentially expressed miRs in EVs from ADSCs and in DN and predicted downstream regulatory target genes. We isolated mesenchymal stem cells (MSCs) from adipose tissues and collected EVs from the ADSCs. We exposed mouse glomerular podocytes and MP5 cells to high glucose (HG), ADSC-derived EVs, miR-26a-5p inhibitor/antagomir, Toll-like receptor 4 (TLR4) plasmids, or the NF-κB pathway activator (phorbol-12-myristate-13-acetate, or PMA). We used the cell counting kit-8 (CCK-8) assay and flow cytometry to investigate the impact of miR-26a-5p on cell viability and apoptosis and validated the results of these assays with in vivo experiments in nude mice. We found that in DN, miR-26a-5p is expressed at very low levels, whereas TLR4 is highly expressed. Of note, EVs from ADSCs ameliorated the pathological symptoms of DN in diabetic mice and transferred miR-26a-5p to HG-induced MP5 cells, improving viability while suppressing the apoptosis of MP5 cells. We also found that miR-26a-5p protects HG-induced MP5 cells from injury by targeting TLR4, inactivating the NF-κB pathway, and downregulating vascular endothelial growth factor A (VEGFA). Moreover, ADSC-derived EVs transferred miR-26a-5p to mouse glomerular podocytes, which ameliorated DN pathology. These findings suggest that miR-26a-5p from ADSC-derived EVs protects against DN.


Valued Outcomes in the Cancer Experience (VOICE)™: Development and validation of a multidimensional measure of perceived control.
Enhancing cancer patients' sense of control can positively impact psychological well-being. We developed and assessed the psychometric properties of Valued Outcomes in the Cancer Experience (VOICE)TM, a measure of patients' perceived control over key personal priorities within their cancer experience. VOICE construction and testing were completed in three phases with separate participant samples: (1) item generation and initial item pool testing (N = 459), (2) scale refinement (N = 623), and (3) confirmatory validation (N = 515). A 21-item measure was developed that captures cancer patients' sense of control in seven key domains: (1) Purpose and Meaning, (2) Functional Capacity, (3) Longevity, (4) Quality Care, (5) Illness Knowledge, (6) Social Support, and (7) Financial Capability. VOICE demonstrated adequate internal consistency (full-scale α = 0.93; factor α = 0.67-0.89) and adequate to strong convergent and discriminatory validity. VOICE measures cancer patients' perceived control across a diverse range of personal priorities, creating a platform for elevating patient perspectives and identifying pathways to enhance patient well-being. VOICE is positioned to guide understanding of the patient experience and aid the development and evaluation of supportive care interventions to enhance well-being.


Transcription Pattern of Neurotrophic Factors and Their Receptors in Adult Zebrafish Spinal Cord.
In vertebrates, neurotrophins and their receptors play a fundamental role in the central and peripheral nervous systems. Several studies reported that each neurotrophin/receptor signalling pathway can perform various functions during axon development, neuronal growth, and plasticity. Previous investigations in some fish species have identified neurotrophins and their receptors in the spinal cord under physiological conditions and after injuries, highlighting their potential role during regeneration. In our study, for the first time, we used an excellent animal model, the zebrafish (Danio rerio), to compare the mRNA localization patterns of neurotrophins and receptors in the spinal cord. We quantified the levels of mRNA using qPCR, and identified the transcription pattern of each neurotrophin/receptor pathway via in situ hybridization. Our data show that ngf/trka are the most transcribed members in the adult zebrafish spinal cord.


The little prince: psychotherapy of a boy with borderline personality structure.
The author describes the history and treatment of a nine-year-old boy who had presented autistic features of withdrawal and bizarre behavior until the age of four and was later diagnosed as suffering from a minimal brain dysfunction. Treatment was recommended because of enuresis, violent arguments, especially with mother, odd interests, fears, dangerous accident-proneness and inability to tolerate physical closeness, and was continued for two years. The therapy dealt initially with apparently typical oedipal conflicts, but interpretations were followed by rage reactions and the emergence of primitive defenses: projection, grandiosity, idealization and depreciation. The therapist was forced into physically controlling the patient's rage, challenging the narcissistic reality distortion and vigorously interpreting the negative transference. Support of the family was secured by monthly joint therapy sessions. Psychotherapy helped the family to resolve a deadlock created by the patient's rages, and helped the patient to progress from a borderline personality organization, with predominance of narcissism and primitive defenses, into a more advanced organization, centered upon masculine identification.


Influence of social and behavioural characteristics of users on their evaluation of subjective loudness and acoustic comfort in shopping malls.
A large-scale subjective survey was conducted in six shopping malls in Harbin City, China, to determine the influence of social and behavioural characteristics of users on their evaluation of subjective loudness and acoustic comfort. The analysis of social characteristics shows that evaluation of subjective loudness is influenced by income and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Meanwhile, evaluation of acoustic comfort evaluation is influenced by income, education level, and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.60 (p<0.05 or p<0.01). The effect of gender and age on evaluation of subjective loudness and acoustic comfort is statistically insignificant. The effects of occupation are mainly caused by the differences in income and education level, in which the effects of income are greater than that of education level. In terms of behavioural characteristics, evaluation of subjective loudness is influenced by the reason for visit, frequency of visit, and length of stay, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Evaluation of acoustic comfort is influenced by the reason for visit to the site, the frequency of visit, length of stay, and also season of visit, with correlation coefficients of 0.10 to 0.30 (p<0.05 or p<0.01). In particular, users who are waiting for someone show lower evaluation of acoustic comfort, whereas users who go to shopping malls more than once a month show higher evaluation of acoustic comfort. On the contrary, the influence of the period of visit and the accompanying persons are found insignificant.


Predicting Planned Suicide Attempts With the Columbia-Suicide Severity Rating Scale: A Subanalysis of the 2013 Korea National Suicide Survey on Emergency Department Visitors.
Identifying predictors of planned suicide attempts (PSA) is critical because these are associated with grave consequences. Using data of suicide attempters visiting emergency departments, we investigated whether the Columbia-Suicide Severity Rating Scale (C-SSRS) subscales, by retrospectively evaluating ideation before an attempt, could predict the occurrence of PSA versus unplanned suicide attempts using logistic regression analyses. The severity subscale was used as a continuous (model A) and a categorical (model B) variable. In model A, higher scores on each subscale were associated with increased risk of PSA. In model B, the highest score on the severity subscale and a higher intensity subscale score predicted PSA. The severity and intensity subscales had areas under receiver operating curves of 0.712 and 0.688 with optimum cutoff points of 4/5 and 15/16, respectively. In addition, being aged 30 to 49 and 50 to 69 years, being male, interpersonal stress, and depressive and adjustment disorders increased PSA risk. The C-SSRS subscales, along with sociodemographic and clinical risk factors, can predict PSA.


How I treat classical Hodgkin lymphoma in patients infected with human immunodeficiency virus.
HIV-associated classical Hodgkin lymphoma (HIV-cHL) is an important complication of HIV disease in the era of effective combination antiretroviral therapy (cART). Generally, newly diagnosed HIV-cHL should be managed with curative intent. With modern HIV therapeutics, HIV-cHL treatment outcomes are largely comparable to those of the background population with cHL (non-HIV-cHL). To achieve these outcomes, particular attention must be given to managing HIV. This management includes understanding HIV as a comorbid condition with a spectrum of impact that is unique to each patient. Meticulous attention to drug-drug interactions is required to avoid toxicity and pharmacokinetic effects that can undermine cure. Relapsed and refractory HIV-cHL poses additional therapeutic challenges. The standard management in this setting should also be based on that for non-HIV-cHL, and includes the use of salvage chemotherapy followed by autologous stem cell transplant in chemosensitive disease. The role of allogeneic hematopoietic stem cell transplant is less clear but may be useful in select cases. Newer agents with activity in cHL are being tested as part of primary and salvage therapy and are also highly relevant for HIV-cHL.


Differential diagnosis of adductor spasmodic dysphonia and muscle tension dysphonia using phonatory break analysis.
Muscle tension dysphonia (MTD) can masquerade as adductor spasmodic dysphonia (ADSD) leading to diagnostic confusion. Intraword phonatory breaks have been offered as the sine qua non of ADSD, however, little is known regarding the presence of phonatory breaks in MTD. This investigation assessed the diagnostic worth of acoustic analysis of phonatory breaks as a possible objective test to distinguish ADSD from MTD. Case-control comparison. Voice samples from patients with confirmed ADSD (n = 41) and MTD (n = 59) were analyzed acoustically to determine the presence, frequency, and duration of phonatory breaks -- defined as complete interruption of phonation within a word. Estimates of sensitivity, specificity, positive and negative predictive value, and likelihood ratios were calculated to determine the precision and worth of phonatory break analysis as a clinical diagnostic test. 1) Individuals with ADSD showed a significantly higher number of phonatory breaks as compared with MTD. 2) All measures of diagnostic precision varied according to both duration and frequency of phonatory breaks, with separation of males and females leading to different diagnostic test performance results. The results suggest that phonatory break analysis offers promise as an objective test to distinguish ADSD from MTD, with respectable diagnostic precision, especially among men. Automation of the acoustic analysis procedure should be explored.


The effects of ischemia and reperfusion on mucosal respiratory function, adenosine triphosphate, electrolyte, and water content in the ascending colon of ponies.
The purpose of this study was to examine the effects of ischemia and reperfusion on the biochemical integrity of equine colonic mucosa to assess the relative roles of ischemic- and reperfusion-induced damage. Two hours of no-flow ischemia experimentally induced by 720 degrees counterclockwise ascending colon volvulus followed by 2 hours reperfusion after derotation. Ten ponies. Ascending colon biopsies were obtained every hour for measurement of mucosal adenosine triphosphate (ATP), water, sodium, and potassium content. Additional samples were homogenized for assay of mitochondrial respiratory function. ATP content diminished 92% after ischemia and recovered to only 44% of control levels (P < .001 versus controls) after 2 hours reperfusion. Reperfusion increased mucosal water and decreased sodium and potassium content for the duration of the experiment. Both NADH-(pyruvate) and FADH-linked (succinate) respiration decreased after ischemia and did not recover during reperfusion indicating electron transport chain dysfunction. Two hours ischemia induced severe metabolic dysfunction in equine colon mucosa which persisted throughout reperfusion. Unequivocal evidence of injury specific to reperfusion was not observed in this study suggesting that much of the damage observed during reperfusion may be a continuation of injury induced during the ischemic period and not specific to reperfusion per se. This study suggests that greater efforts to metabolically support ischemically injured mucosa may be an important aspect of obtaining improved survival of horses affected by ascending colon volvulus (ACV).


Differential contribution of two Ppd-1 homoeoalleles to early-flowering phenotype in Nepalese and Japanese varieties of common wheat.
Wheat landraces carry abundant genetic variation in heading and flowering times. Here, we studied flowering-related traits of two Nepalese varieties, KU-4770 and KU-180 and a Japanese wheat cultivar, Shiroganekomugi (SGK). These three wheat varieties showed similar flowering time in a common garden experiment. In total, five significant quantitative trait loci (QTLs) for three examined traits, the heading, flowering and maturation times, were detected using an F2 population of SGK/KU-4770. The QTLs were found at the Ppd-1 loci on chromosomes 2B and 2D and the 2B QTL was also confirmed in another F2 population of SGK/KU-180. The Ppd-D1 allele from SGK and the Ppd-B1 alleles from the two Nepalese varieties might be causal for early-flowering phenotype. The SGK Ppd-D1 allele contained a 2-kb deletion in the 5' upstream region, indicating a photoperiod-insensitive Ppd-D1a allele. Real-time PCR analysis estimating the Ppd-B1 copy number revealed that the two Nepalese varieties included two intact Ppd-B1 copies, putatively resulting in photoperiod insensitivity and an early-flowering phenotype. The two photoperiod-insensitive Ppd-1 homoeoalleles could independently contribute to segregation of early-flowering individuals in the two F2 populations. Therefore, wheat landraces are genetic resources for discovery of alleles useful for improving wheat heading or flowering times.


Locking of tunneled hemodialysis catheters with gentamicin and heparin.
Catheter-related infection (CRI) is a major cause of morbidity and mortality in patients receiving hemodialysis. Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis, and to reduce the incidence of sepsis. We have studied the use of gentamicin locking of catheters (in combination with standard heparin rather than previously reported citrate) to reduce CRI rates. Furthermore, we have investigated the effects of this strategy on epoetin requirements and vascular access function. Fifty patients were studied. Patients were randomized to catheter-restricted filling with either standard heparin (5000 IU/mL) alone, or gentamicin and heparin (5 mg/mL). Epoetin requirements and hemoglobin response were monitored over the study period. The gentamicin-locked group suffered only one infective episode (0.3/1000 catheter days) compared to 10 episodes in six patients in the heparin alone group (4/1000 catheter days, P= 0.02). The isolated organisms were equally split between Staphylococcal species and coliforms. There were no statistically significant differences in delivered dialysis dose (Kt/V) or QA between the two groups. Use of antibiotic locking was associated with both a higher mean hemoglobin (10.1 +/-0.14 g/dL vs. 9.2 +/- 0.17 g/dL in the heparin group, P= 0.003) and a lower mean epoetin dose (9000 +/- 734 IU/week vs. 10790 +/-615 IU/week in the heparin group, P= 0.04). The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates, and is associated with beneficial effects on epoetin requirements.


The Effect of Sodium Bicarbonate Injection on the Physico-Chemical Quality of Post-Harvest Trout.
The muscle hardness of fish is an important parameter associated with meat quality, and the post-mortem decrease in the pH of fish tissue pH affects its physical properties. We hypothesized that maintaining a high pH in fish tissue after death would prevent protein denaturation and consequent textural deterioration. This study aimed to determine the effectiveness of sodium bicarbonate (SBC) injections in preventing tissue softening caused by low pH after death in trout. We injected varying molar concentrations of SBC in rainbow trout (Oncorhynchus mykiss; 0 M, 0.5 M, 0.75 M, and 1 M) after harvest, and the product quality was assessed at 0, 24, 48, 72, and 96 h of ice storage. Quality was evaluated using proximate analyses for color, pH, water holding capacity (WHC), texture profile, and rigor index. The 0 M group had the lowest pH, and the 0.75 M group had the highest pH at all time points during storage. We observed improved tissue texture during storage in fish treated with 0.75 and 1 M SBC. The texture profile analysis showed higher hardness, frangibility, and stickiness in the tail than in the other regions. These varying results can be explained by significant differences between parts of the fish and sampling point selection. We also observed the highest pH and WHC values in the groups injected with 0.75 and 1 M SBC during storage.


[Two cases of advanced gastric cancer, successfully treated with TS-1/CDDP combination chemotherapy--case report].
We reported 2 cases with advanced gastric cancer, successfully treated with TS-1 and CDDP. Case 1 had Type 3 gastric cancer with left supra-clavicular (Virchow) and para-aortic lymph node metastases. Those distant node metastases completely disappeared after two courses of neoadjuvant chemotherapy (NAC) consisting of TS-1/ CDDP, and radical surgery for cure was conducted. The second case had Type 3 carcinoma with peritoneal dissemination. The primary lesion significantly decreased after four courses of the combination chemotherapy. The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed.


Physiocochemical properties of "spun glass" hair.
The amount of protein solubilized with a Trisurea-mercaptoethanol buffer was markedly reduced in a patient with"spun glass" hair but normal in 3 other patients with similar appearing hair. Polyacrylamide gel electrophoresis showed that it was mainly the matrix component that was solubilized. X-ray diffraction and stress strain tests on the "spun glass" hair proved normal, as was the amino acid analysis. The cause of the insolubility has not been established.


Transdifferentiation of ocular tissues in larval Xenopus laevis.
Transdifferentiation phenomena offer a useful opportunity to study experimentally the mechanisms on which cell phenotypic stability depends. The capacities of vertebrate eye tissues to reprogram cell differentiation are well known in avian and mammalian embryos, and in larval and adult newt. From research into the capacity of anuran eye tissues to reprogram differentiation into a new pathway, considerable data have accumulated concerning the transdifferentiative capacities of eye tissues in larval Xenopus laevis. This work reviews the data concerning the transdifferentiative phenomena of eye tissues in that species and, based on these, aims to establish the extent of our knowledge about the mechanism controlling these processes. In larval Xenopus laevis the outer cornea can regenerate a lens by a lens-transdifferentiation process triggered and substained by a factor(s), probably of a protein nature, produced by the neural retina. In a normal eye phenotypic stability of the outer cornea is guaranteed by the presence of the inner cornea and lens, which prevent the spread of retinal factor(s). The stimulus for lens transdifferentiation of the outer cornea can be supplied by other tissues as well, but this capacity is not widely distributed. The iris and retinal pigmented epithelium can transdifferentiate into neural retina if isolated from the surrounding tissues and implanted in the vitreous chamber. As for lens transdifferentiation of the outer cornea, retinal transdifferentiation of the iris can be stimulated by certain nonocular tissues as well.


Influence of tomato waste composts on dry matter and heavy metals content in cucumber and summer squash seedlings.
Huge quantities of agricultural waste are available annually in Saudi Arabia, which are not well exploited, leading to large environmental pollution and health problems. The use of different proportions of tomato waste compost (TWC) mixed with commercial peat-moss as a natural, economical, cheap and environmentally friendly fertilizer for fertilizing vegetables is very important, therefore, this study is concerned with investigating and evaluating the dry matter content (DM) and the accumulated heavy metal contents (HMs) in the root and leaf seedlings tissues of cucumber and summer squash plants as a result of using this fertilizer. Five ratios of mixtures (vermiculite: peat moss: TWC by weight) used in the experiment, and the TWC in the mixture represents 0, 5, 10, 15 and 20% (by wieght). The results indicated that, the DM contents in the root and leaf tissues were relatively close between cucumber and summer squash seedlings. However, they were higher in the root than in leaf tissues, particularly under 20% TWC. A TWC application ratio of 20% reduced concentrations of the most HMs in the two vegetable species seedlings due to high EC and pH levels. The amounts of HMs in vegetable species were not high, which proves the that transfer of HMs from the TWC substrate to the seedlings is determined chiefly by metal bioavailability and by a vegetable species. DM, mineral and nutritional quality of vegetable seedlings showed that substrates containing 5% and 10% TWC appeared to be the most suitable growing medium for economic vegetable seedlings; and it is recommended for use in the nursery production. Implications: The idea of this research revolves around the use of different proportions of tomato waste compost in fertilizing cucumber and summer squash seedlings and investigate the effect of this compost on dry matter (DM) and heavy metal (HMs) contents in the root and leaf tissues of the seedlings, and fruit quality of cucumber and summer squash plants.


THE MINIMUM CLINICALLY IMPORTANT DIFFERENCE ON THE VISA-A AND LEFS FOR PATIENTS WITH INSERTIONAL ACHILLES TENDINOPATHY.
Cohort study of subjects with insertional Achilles tendinopathy (IAT). The purpose of this study was to establish the minimum clinically important difference (MCID) on the Victorian Institute of Sport Assessment - Achilles Questionnaire (VISA-A) and the Lower Extremity Functional Scale (LEFS) for patients with IAT. The VISA-A and LEFS are two measures commonly utilized for patients with IAT. Previous authors have estimated the MCID for the VISA-A, but a MCID has not been formally established. The MCID for the LEFS has been established for patients with lower extremity conditions in general, but it is not clear if this MCID is applicable to patients with IAT. Fifteen subjects participating in a randomized controlled trial studying the effectiveness of intervention for IAT over a 12-week period were included in this study. Subjects completed the VISA-A and LEFS forms at baseline and 12 weeks after the initiation of treatment. All subjects also completed a 15-point global rating of change (GROC) questionnaire at 12 weeks after the initiation of treatment. Subjects were classified as improved or stable based on their GROC scores. The area under the curve (AUC) for the VISA-A was 0.97 and a MCID of 6.5 points was identified. The AUC for the LEFS was 0.97 and a MCID of 12 points was identified. The VISA-A and LEFS are both useful outcome measures to assess response in patients with IAT. 3.


Screening of Indian Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes): A UPC2-SQD-MS Approach.
Oriental medicinal mushroom Ganoderma lucidum has been widely used for the promotion of health and longevity owing to its various bioactive constituents. Therefore, comprehending metabolomics of different G. lucidum parts could be of paramount importance for investigating their pharmacological properties. Ultra-performance convergence chromatography (UPC2) along with mass spectrometry (MS) is an emerging technique that has not yet been applied for metabolite profiling of G. lucidum. This study has been undertaken to establish metabolomics of the aqueous extracts of mycelium (GLM), fruiting body (GLF), and their mixture (GLMF) using ultra-performance convergence chromatography single quadrupole mass spectrometry (UPC2-SQD-MS). Aqueous extracts of G. lucidum prepared using an accelerated solvent extraction technique have been characterized for their mycochemical activities in terms of total flavonoid content, 1,1-diphenyl-2-picryl-hydrazyl scavenging activity, and ferric ion reducing antioxidant power. The UPC2-SQD-MS technique has been used for the first time for metabolite profiling of G. lucidum on a Princeton Diol column (4.6 × 250 mm; 5 µm) using supercritical CO2 (solvent) and 20 mM ammonium acetate in methanol (co-solvent). In the present study, UPC2-SQD-MS was found to be a rapid, efficient, and high-throughput analytical technique, whose coupling to principal component analysis (PCA) and phytochemical evaluation could be used as a powerful tool for elucidating metabolite diversity between mycelium and fruiting body of G. lucidum. PCA showed a clear distinction in the metabolite compositions of the samples. Mycochemical studies revealed that overall GLF possessed better antioxidant properties among the aqueous extracts of G. lucidum.


[Compassionate nursing care: the experience of italian nurses].
In international nursing literature compassion and compassionate care has acquired a considerable importance and it's considered to be a growing phenomenon. The approach to the application of compassionate care to patients is clearly not well-defined in Italian nursing. The aim of this study is to define what compassionate care is through the analysis of Italian nurses' experiences. The research is based on a qualitative method. Content analysis was used to analyze the transcript data. The research has been carried out by creating three focus groups, for a total of 15 nurses. All the participants expressed their opinions freely. The outcomes of the analysis can be grouped in four areas: definition of compassion and compassionate care; categorisation of patients; provision of care; and formation and training in compassionate care. The survey has shown contrasting opinions, negative opinions such as feelings of rejections and positive opinions such as love, charity, empathy and support. The last one (support) in particular has highlighted the importance of involving the patient's relatives in providing compassionate care. It is difficult to define exactly the meaning of compassion and compassionate care.This study has contributed to extend and deep the current knowledge in regard of the concept of compas-sionate care applied to assistance entities. Further research is needed in the field of compassionate care to strength the effectiveness of assistance provided by nurses.


Enhanced bioavailability and safety of curcumagalactomannosides as a dietary ingredient.
In spite of the various bioavailable formulations of curcumin for pharma and dietary supplement applications, food grade formulations suitable as a dietary ingredient, and capable of providing significant levels of plasma curcumin, are limited. The present contribution describes the safety and oral bioavailability of a novel water soluble formulation of curcumin, curcumagalactomannosides (CGM), when used as a dietary ingredient in selected food items. CGM was prepared using a food grade hydrocolloid (galactomannans) derived from the kitchen spice fenugreek (Trigonella foenum graccum), without using any synthetic excipients. The safety of the formulation was assessed through acute and subchronic toxicity studies on Wistar rats and genotoxicity studies. The efficacy of CGM as a bioavailable dietary ingredient was assessed by successfully preparing various food items and by measuring the post-blood plasma curcumin levels at various time intervals after the consumption of food items. High performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) and electrospray ionization tandem mass spectrometer (ESI-MS/MS) was employed for the quantification of plasma curcuminoids. It was observed that CGM is safe and suitable for further development and clinical studies, with a no observable adverse effect level (NOAEL) up to 2.0 g kg⁻¹ per day b.wt. CGM was found to offer seven to ten times higher bioavailability of curcumin in humans, when incorporated into various food/beverage items at 100 mg CGM per serving size, as compared to the standard unformulated curcumin.


Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study.
Mood stabilizers appear to be more potent in treating mania than depression. The anticonvulsant lamotrigine has been shown to be effective for bipolar depression. This study examines putative antidepressive properties of lamotrigine in a mainly unipolar routine clinical patient population. Forty patients with a depressive episode (DSM-IV criteria) requiring psychiatric intervention received lamotrigine or placebo using a fixed dose escalation scheme with a target dose of 200 mg/day for 9 weeks. Additionally, all patients were treated with paroxetine. Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) ratings were used to monitor therapeutic efficacy. Adjunctive treatment with lamotrigine did not result in a significant difference in HAM-D total score at the endpoint of the study when compared with paroxetine alone. However, lamotrigine demonstrated significant efficacy on core depressive symptoms as reflected by HAM-D items 1 (depressed mood; p = .0019), 2 (guilt feelings; p = .0011), and 7 (work and interest; p = .049) and the CGI-Severity of Illness scale (p < .0001). Patients receiving lamotrigine had fewer days on treatment with benzodiazepines and fewer withdrawals for treatment failure. Lamotrigine appeared to accelerate the onset of action of the antidepressant. Two patients on lamotrigine treatment developed neutropenia, and 1 developed a benign rash. There was no detectable pharmacokinetic interaction between lamotrigine and paroxetine. Lamotrigine might have antidepressive properties in unipolar patients and may accelerate onset of action when given in combination with typical antidepressants.


Semi-automated measurement of true chord length distributions and moments by video microscopy and image analysis.
The distribution of the lengths of airspace chords in pulmonary parenchyma characterizes many architectural features of the alveoli and alveolar ducts. Laborious to obtain manually, the distributions and density functions may be acquired semi-automatically by video microscopy, digitization and image processing. The accuracy of the estimation is influenced by the microscopical methods and also by the techniques used (i) to convert the digitized greyscale picture to a two-valued image, (ii) to collect the chord lengths and (iii) to compensate for finite field widths. The last problem arises because some chords are completely visible within a field while others are only partially seen, since one of the two air-tissue boundaries lies outside the field of view. This error systematically biases the observed distribution. This paper contains solutions to hardware, software and analytic problems encountered while developing the capability to measure airspace chord length density functions semi-automatically. Formulas for estimating the true chord length density function from samples of observed chord lengths are presented. Also given are formulas for the estimation of the first and second moments of the true chord length distribution from the means of observed chord lengths. These techniques of image preparation and analysis should be suitable for characterizing particle, grain or cell size distributions, especially where many profiles fall partially outside the field of view.


Congenital pulmonary lymphangiectasia: an unusual presentation of nonimmune hydrops in a preterm infant.
Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung. CPL can present antenatally as nonimmune hydrops with pleural effusions, which are frequently associated with polyhydraminos. CPL presents in the neonatal period with severe respiratory distress and can be complicated by chylothorax. Diagnosis is difficult, as radiographic findings are nonspecific. Lung biopsy is indicated in some severe cases to diagnose CPL. The majority of infants with this condition rarely survive the neonatal period and are often diagnosed at autopsy. The final diagnosis is confirmed histologically by lung biopsy or at postmortem. We report a rare case of CPL in a preterm female infant presenting with severe nonimmune Hydrops fetalis who survived the neonatal period, and report clinical follow-up to early childhood.


Evidence for recent positive selection at the human AIM1 locus in a European population.
Two missense polymorphisms (E272K and L374F) of the AIM1 locus, encoding a melanocyte differentiation antigen, were shown to have a clear association with human ethnicities. These two nonpathogenic single nucleotide polymorphisms (SNPs) may be associated with human pigmentation variation. In this study, we investigated sequence variation in the coding region and exon-flanking sequence and found low genetic variation only in subjects of European descent. All four statistical tests applied to the 7.55-kb region surrounding the L374F polymorphism detected statistically significant deviations from selective neutrality in Europeans. In addition, haplotype analysis revealed that one haplotype carrying 374F was overrepresented in this population, and the low rate of variation, with some features of selective sweeps, was shown to be statistically significant. These results suggest that positive selection recently has been acting or has acted on at least this region of the melanogenic gene and that an advantageous haplotype spread rapidly in Europe.


Insights into porphyrin chemistry provided by the microperoxidases, the haempeptides derived from cytochrome c.
The water-soluble haem-containing peptides obtained by proteolytic digestion of cytochrome c, the microperoxidases, have been used to explore aspects of the chemistry of iron porphyrins, and as mimics for some reactions catalysed by the haemoproteins, including the reactions catalysed by the peroxidases and the cytochromes P450. The preparation of the microperoxidases, their physical and chemical properties including their electronic structure, the kinetics and thermodynamics of their reactions with ligands, electrochemical studies and examples of their uses as haemoproteins mimics, is reviewed.


How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.
Orthopoxviruses are complex, large-genome DNA viruses that have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV) was originally characterized during outbreaks among captive primates in the late 1950's. Human disease (mpox) has been observed since the 1970's and inter-human spread has largely been associated with non-sexual, close physical contact in endemic areas of west and central Africa. In May 2022, a focus of Clade IIb MPXV transmission was detected, spreading largely by sexual contact through international networks of gay, bisexual, and other men who have sex with men. Despite decades of preparedness for the potential biothreat risk posed by smallpox, the outbreak grew in both size and geographic scope, testing the strength of smallpox preparedness tools and public health science alike. In this article we consider what was known about mpox prior to the 2022 outbreak, what we have learned about mpox and Clade IIb virus during the outbreak, and what outbreak response actions and continued research are needed to ensure the global public health community is equipped to detect and halt the further spread of this disease threat. We focus on how epidemiologic characterization and investigation together with laboratory studies have advanced our understanding of the transmission and pathogenesis of mpox, and describe what work remains to be done to optimize diagnostics, therapeutics, and vaccines. Persistent health inequities challenge our capacity to fully eliminate circulation of the 2022 outbreak strain of MPXV currently in the United States.


A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana.
To better understand the diversity of small silencing RNAs expressed in plants, we employed high-throughput pyrosequencing to obtain 887,000 reads corresponding to Arabidopsis thaliana small RNAs. They represented 340,000 unique sequences, a substantially greater diversity than previously obtained in any species. Most of the small RNAs had the properties of heterochromatic small interfering RNAs (siRNAs) associated with DNA silencing in that they were preferentially 24 nucleotides long and mapped to intergenic regions. Their density was greatest in the proximal and distal pericentromeric regions, with only a slightly preferential propensity to match repetitive elements. Also present were 38 newly identified microRNAs (miRNAs) and dozens of other plausible candidates. One miRNA mapped within an intron of DICER-LIKE 1 (DCL1), suggesting a second homeostatic autoregulatory mechanism for DCL1 expression; another defined the phase for siRNAs deriving from a newly identified trans-acting siRNA gene (TAS4); and two depended on DCL4 rather than DCL1 for their accumulation, indicating a second pathway for miRNA biogenesis in plants. More generally, our results revealed the existence of a layer of miRNA-based control beyond that found previously that is evolutionarily much more fluid, employing many newly emergent and diverse miRNAs, each expressed in specialized tissues or at low levels under standard growth conditions.


Whom to Engage in Patient-Engaged Research? Reflection on Selection.
Engaging patients in research has come to be viewed as a vital component of high-quality research, and funders now regard engaging patients and other stakeholders as a core criterion for funding decisions. In response, numerous empirical and conceptual papers have emerged to guide the process of engagement. However, as Emily Largent and colleagues rightly note, the inquiry of whom to engage has received less attention. While several teams have suggested that the selection of patients for engagement is an important consideration, researchers generally have little guidance on how to undertake this process. To that end, Largent and colleagues offer an important contribution to the literature. I agree with their argument regarding the centrality of critically examining which patients to engage in research and with their recommendations to maximize the positive goals of patient engagement. However, three issues warrant further consideration.


Morphological and chemical variation of Stemona tuberosa from southern China - Evidence for heterogeneity of this medicinal plant species.
The occurrence of bioactive alkaloids and tocopherols was studied in 15 different provenances of Stemona tuberosa Lour. collected in southern China, to examine chemical variation of individuals that show notable differences in flower characteristics. Morphological variations stimulated examination of chemical characteristics of these individuals. Methanolic root extracts of 15 individuals of S. tuberosa were comparatively assessed with HPLC-UV-DAD/ELSD. Five of seven compounds were co-chromatographically identified. Two compounds were isolated and their structure elucidated using NMR and MS. Amounts of alkaloids and tocopherols were determined using HPLC-UV-DAD/ELSD with the external standard method. Five alkaloids, tuberostemonine (1), tuberostemonine A (2), neotuberostemonine (3), tuberostemonine N (4), stemoninine (5) and two 3,4-dehydrotocopherol derivatives were identified. Within S. tuberosa alkaloid accumulation tends either towards tuberostemonine (1) or stemoninine (5). All individuals show a notable co-occurrence of compounds 1 or 5 and 3,4-dehydro-δ-tocopherol (6). These results coincide with differences in flower morphology of S. tuberosa. Stemona tuberosa, as defined in the Flora of China, shows a remarkable variation in flower morphology and additionally in the accumulation of alkaloids. The obtained data show the need for future species delimitation to either species or subspecies level.


Place and modalities of laparoscopy in surgical management of suspected adnexal masses.
Only benign adnexal masses are suitable for treatment by operative laparoscopy. Ovarian cancer must always be managed by midline laparotomy. In our experience the preoperative workup (clinical examination, study of past history, trans vaginal ultrasonography, doppler, tumoral markers etc.) together with the diagnostic phase of laparoscopy provide a sensitivity value of 100%, a positive predictive value of 50% and a negative predictive value of 100% for diagnosis of malignancy. Provided a strict selection, laparoscopy is reliable both for the diagnosis and the management of benign ovarian masses.


Evidence of SARS-CoV-2 Related Coronaviruses Circulating in Sunda pangolins (Manis javanica) Confiscated From the Illegal Wildlife Trade in Viet Nam.
Despite the discovery of several closely related viruses in bats, the direct evolutionary progenitor of SARS-CoV-2 has not yet been identified. In this study, we investigated potential animal sources of SARS-related coronaviruses using archived specimens from Sunda pangolins (Manis javanica) and Chinese pangolins (Manis pentadactyla) confiscated from the illegal wildlife trade, and from common palm civets (Paradoxurus hermaphroditus) raised on wildlife farms in Viet Nam. A total of 696 pangolin and civet specimens were screened for the presence of viral RNA from five zoonotic viral families and from Sarbecoviruses using primers specifically designed for pangolin coronaviruses. We also performed a curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, to illustrate the global pangolin supply chain in the context of Viet Nam where the trade confiscated pangolins were sampled for this study. All specimens from pangolins and civets sampled along the wildlife supply chains between February 2017 and July 2018, in Viet Nam and tested with conventional PCR assays designed to detect flavivirus, paramyxovirus, filovirus, coronavirus, and orthomyxovirus RNA were negative. Civet samples were also negative for Sarbecoviruses, but 12 specimens from seven live pangolins confiscated in Hung Yen province, northern Viet Nam, in 2018 were positive for Sarbecoviruses. Our phylogenetic trees based on two fragments of the RdRp gene revealed that the Sarbecoviruses identified in these pangolins were closely related to pangolin coronaviruses detected in pangolins confiscated from the illegal wildlife trade in Yunnan and Guangxi provinces, China. Our curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, reflected what is known about pangolin trafficking globally. Pangolins confiscated in Viet Nam were largely in transit, moving toward downstream consumers in China. Confiscations included pangolin scales sourced originally from Africa (and African species of pangolins), or pangolin carcasses and live pangolins native to Southeast Asia (predominately the Sunda pangolin) sourced from neighboring range countries and moving through Viet Nam toward provinces bordering China.


In Their Own Words: The Challenges Experienced by Certified Nursing Assistants and Administrators During the COVID-19 Pandemic.
This qualitative study aimed to provide an in-depth understanding of the challenges experienced by certified nursing assistants and administrators during the unprecedented COVID-19 crisis. We conducted 6 administrator interviews and 10 remote focus groups with day and evening CNAs at 5 nursing homes (N = 56) in downstate New York. Content analysis was conducted, and emerging themes were identified across sites and roles. Results showed numerous challenges for both CNAs and administrators including many that were personal. These personal challenges included feeling helpless, anxious, or fearful; experience of COVID illness; and balancing high concurrent demands of work and family. There were also many operational challenges such as a lack of COVID testing capacity, information, and consistent guidance and support, staffing and equipment. Understanding these challenges can facilitate goals to promote future safety, skill refinement, and enhanced resilience in the workforce.


Analysis of anaerobic digester mixing: comparison of long shafted paddle mixing vs gas mixing.
The anaerobic digestion (AD) process is influenced by a variety of operation parameters, such as sludge rheology, mixing, temperature, solid retention time (SRT), hydraulic retention time (HRT) and solids concentration. The optimum in the mixing lies somewhere between no-mixing and continuous mixing, as the lack or excessive mixing can lead to poor AD performance instead. A three-dimensional computational fluid dynamics steady/unsteady model, incorporating the rheological properties of the sludge, was developed and applied to quantify mixing in a full-scale anaerobic digester. Mechanical and gas mixing solutions were taken into account, keeping constant the daily energy consumption. Results, consisting of velocity magnitude and patterns, dead zone formation and turbulence levels were discussed. Compared to the mechanical mixing, gas mixing had lower percentage of dead zones (about 5% against 50%), larger maximum velocity (about 3 m/s against 1 m/s) as well as larger turbulent kinetic energy levels (0.24 m2/s2 against 0.001 m2/s2).


Reversible manipulation of telomerase expression and telomere length. Implications for the ionizing radiation response and replicative senescence of human cells.
Most human cells do not express telomerase and irreversibly arrest proliferation after a finite number of divisions (replicative senescence). Several lines of evidence suggest that replicative senescence is caused by short dysfunctional telomeres, which arise when DNA is replicated in the absence of adequate telomerase activity. We describe a method to reversibly bypass replicative senescence and generate mass cultures that have different average telomere lengths. A retrovirus carrying hTERT flanked by excision sites for Cre recombinase rendered normal human fibroblasts telomerase-positive and replicatively immortal. Superinfection with retroviruses carrying wild-type or mutant forms of TIN2, a negative regulator of telomere length, created telomerase-positive, immortal populations with varying average telomere lengths. Subsequent infection with a Cre-expressing retrovirus abolished telomerase activity, creating mortal cells with varying telomere lengths. Using these cell populations, we show that, after hTERT excision, cells senesce with shorter telomeres than parental cells. Moreover, long telomeres, but not telomerase, protected cells from the loss of division potential caused by ionizing radiation. Finally, although telomerase-negative cells with short telomeres senesced after fewer doublings than those with long telomeres, telomere length per se did not correlate with senescence. Our results support a role for telomere structure, rather than length, in replicative senescence.


Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.
A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.


Correlation Between Hyperhomocysteinemia and Outcomes of Patients With Acute Myocardial Infarction.
Overwhelming clinical and epidemiological studies have identified elevated plasma total homocysteine (Hcy) as new important risk factor for atherosclerotic vascular disease. But the relationship between outcome and hyperhomocysteinemia in patients with acute myocardial infarction (AMI) has been rarely reported. This study aimed to evaluate the association between hyperhomocysteinemia and short-term outcomes of patients with AMI. Eight hundred five patients were divided into high Hcy level group (group H: N = 457) and low Hcy level group (group L: N = 348) according to the plasma Hcy levels of 15 mmol/L. The comparisons were made between 2 groups in the following aspects: sex, hypertension, diabetes, hyperlipidemia, the time for symptom from onset to percutaneous coronary intervention, homoccyteine, creatine phosphokinase isoenzyme (creatine kinase myocardial band), and the incidence of 30-day adverse events. The incidences of heart failure, cardiac rupture, death, and the total adverse cardiovascular events were statistically significantly higher in group H than in group L. But the incidence of postoperative angina pectoris and reinfarction was similar between groups. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to the age and the level of Hcy. An elevated plasma total Hcy level in patients with AMI experienced pemutaneous coronary intervention may be related to the short-term outcomes. An elevated high plasma Hcy level also seems to be an independent predictor of 30-day cardiovascular events in patients with AMI.


Resin bonding to enamel and dentin with one-component UDMA/HEMA adhesives.
The aim of this study was to investigate the potential of UDMA/HEMA mixtures as priming and sealing components of dental adhesives. The monomers were mixed in weight ratios 100/0, 80/20, 60/40, 50/50, 40/60, 20/80, 10/90, and 0/100, light activated, and dissolved in acetone at equal parts. The 60/40 UDMA/HEMA mixture served as a reference which was modified with 5, 10, 20, and 30 parts 4-MET relative to the mass of the basic monomer mixture. Shear bond strengths (24 h) of resin composite cylinders, bonded with the adhesive monomers on human enamel and dentin, were determined following a total etch technique with phosphoric acid and application of the adhesives in 2 coats on moist tooth surfaces. Average bond strength to enamel was 32 MPa with no difference between the adhesives. On dentin, significantly different bond strengths were found between UDMA (12.9 MPA) and HEMA (19.4 MPa), whereas all binary mixtures' bond strengths were not significantly different (mean 16.2 MPa). Addition of 5 to 20 wt% 4-MET resulted in a significantly increased mean shear bond strength of 22.3 MPa on dentin. At 10%, a maximum mean strength of 25.4 MPa was recorded. It is concluded that mixtures of commonly used polymerizable monomers, characterized by hydrophilic moieties and dissolved in acetone, are promising candidates for effective resin bonding to enamel and dentin, provided application by the moist bonding technique.


Are corticosteroid-binding globulin and sex hormone-binding globulin hormones?
Because it no longer seemed reasonable to us that the sole function of the steroid-binding proteins in plasma was to serve as a buffer reservoir for steroid hormones, we conducted experiments which sought out other possibilities. Both CBG and SHBG bind to cell membranes, and this interaction partakes of the general characteristics of peptide hormone-membrane receptor systems. Additionally, human CBG has the ability to cause an increase in the activity of membrane-bound adenylate cyclase in MCF-7 cells, and this, in turn, results in an increase in cellular cAMP content. Thus, CBG appears to be a protein hormone. As a first consideration, one might presume that because CBG's half-life is measured in days, it would be counted among the hormones which, for the most part, are tonic in their effects, e.g., thyroid hormone. However, two important considerations tend to believe this presumption: (1) CBG which is unoccupied by steroid is not hormonally active (Figure 5): (2) Depending upon the time of day, circulating CBG is approximately 0-60% occupied in normal humans. These observations result in a circumstance in which a substantial portion of circulating CBG is available for activation by bursts of cortisol secretion. It seems prudent to speculate that, because steroids are essential for CBG's activity, the hormonal role of CBG may be entwined with, or complementary to the steroids which it binds. Finally, we should comment on the impact that our model of CBG as a hormone has on the view that only unbound steroid can be hormonally active. First, it should be stated that we have not addressed this question experimentally. Although there is evidence that CBG may be required for cortisol action, we feel that an obligate role for it is not documented adequately. At this time, we believe that CBG's hormonal role is compatible with a hypothesis that encompasses the view that unbound steroid hormones can diffuse into cells in some tissues and that both free and bound steroid can enter cells in others. Obviously, the final word on these important topics, as always, awaits the proper experiments.


An immunophenotypic study of the inflammatory cell populations in colon adenomas and carcinomas.
There is increasing interest in the host immunologic response to colon carcinoma as immunotherapeutic techniques are being developed. We studied the inflammatory cells in 27 specimens of normal mucosa, 16 hyperplastic polyps, 21 tubular adenomas, 19 tubulovillous adenomas, 12 villous adenomas, and 17 invasive carcinomas using immunohistochemical techniques in paraffin-embedded tissue. UCHL-1-positive T-cells predominated in the lamina propria of all specimens. In polyps and carcinomas, reactive lymphoid follicles composed of L26-positive B-cells, and UCHL-1-positive T-cells were a prominent feature and UCHL-1-positive cells were increased in the epithelial compartment. Cells bearing surface immunoglobulins were widely distributed in all specimens, with IgA predominating. There was a relative increase in IgG-positive cells in the carcinomas. KP1-positive macrophages, S-100-positive dendritic cells, and HLA-DR-positive cells were oriented toward the lumenal surface in normal mucosa and hyperplastic polyps, suggesting a diffuse antigen presenting system. Macrophages and dendritic cells were increased and dispersed in the neoplasms. HLA-DR expression was increased in the neoplasms, mainly in the stromal cells. We conclude that there is an activated immune response in adenomas and carcinomas of the colon compared to normal mucosa. This is represented by expansion and reorganization of both the T- and B-cell compartments and the macrophage-cell systems.


RAS mutations in thyroid cancer.
In recent years, our understanding of the genetic alterations underlying thyroid oncogenesis has greatly expanded. The use of molecular markers, including RAS, in the management of thyroid carcinoma is also increasing. This review summarizes the current literature surrounding RAS and discusses its potential as a diagnostic and prognostic indicator in the management of thyroid cancer.


Comparison of visual quality after SMILE correction of low-to-moderate myopia in different optical zones.
To compare the effects of different optical zones for small-incision lenticule extraction (SMILE) on postoperative visual quality in low-to-moderate myopia. This retrospective case-control study involved patients who underwent SMILE using two optical-zone diameters: 6.5 mm (50 patients, 100 eyes) and 6.8 mm (50 patients, 100 eyes). Uncorrected visual acuity (UCVA), best corrected visual acuity, spherical equivalent (SE), corneal higher-order aberrations (HOAs), and subjective visual-quality questionnaire scores were assessed. Postoperatively, UCVA and SE did not differ between the two groups (P > 0.05). In both groups, corneal HOAs, spherical aberration, and coma significantly increased at 1 and 3 months postoperatively (P < 0.05), while trefoil was unchanged after surgery (P > 0.05). Corneal HOAs, spherical aberration, and coma significantly differed between the groups at 1 and 3 months (P < 0.05), while trefoil did not (P > 0.05). Visual-quality scores were higher in the 6.8 mm group than in the 6.5 mm group at 1 month (P = 0.058), but not at 3 months (P > 0.05). In both groups, subjective scores significantly decreased at 1 month (P < 0.05) and gradually returned to the preoperative level at 3 months (P > 0.05). The subjective visual-quality scores were negatively and positively correlated with pupillary and optical-zone diameter, respectively (P < 0.05 for both). Objective visual-quality indicators (HOAs, spherical aberration, and coma) were negatively correlated with optical-zone diameter (P < 0.05) but not pupillary diameter (P > 0.05). SMILE in different optical zones effectively corrected low-to-moderate myopia. The larger the optical-zone diameter, the better the early postoperative visual quality.


Novel Tetrazole Derivatives Targeting Tubulin Endowed with Antiproliferative Activity against Glioblastoma Cells.
Increasing awareness of the structure of microtubules has made tubulin a relevant target for the research of novel chemotherapies. Furthermore, the particularly high sensitivity of glioblastoma multiforme (GBM) cells to microtubule disruption could open new doors in the search for new anti-GBM treatments. However, the difficulties in developing potent anti-tubulin drugs endowed with improved pharmacokinetic properties necessitates the expansion of medicinal chemistry campaigns. The application of an ensemble pharmacophore screening methodology helped to optimize this process, leading to the development of a new tetrazole-based tubulin inhibitor. Considering this scaffold, we have synthesized a new family of tetrazole derivatives that achieved remarkable antimitotic effects against a broad panel of cancer cells, especially against GBM cells, showing high selectivity in comparison with non-tumor cells. The compounds also exerted high aqueous solubility and were demonstrated to not be substrates of efflux pumps, thus overcoming the main limitations that are usually associated with tubulin binding agents. Tubulin polymerization assays, immunofluorescence experiments, and flow cytometry studies demonstrated that the compounds target tubulin and arrest cells at the G2/M phase followed by induction of apoptosis. The docking experiments agreed with the proposed interactions at the colchicine site and explained the structure-activity relationships.


Simulation of a sudden drop-off in distal dense core vesicle concentration in Drosophila type II motoneuron terminals.
Recent experimental observations have shown evidence of an unexpected sudden drop-off in the dense core vesicles (DCVs) content at the ends of certain types of axon endings. This article seeks to determine whether these observations may be explained without modifying the parameters characterizing the ability of distal en passant boutons to capture and accumulate DCVs. We developed a mathematical model that is based on the conservation of captured and transiting DCVs in boutons. The model consists of 77 ordinary differential equations and is solved using a standard Matlab solver. We hypothesize that the drop in DCV content in distal boutons is due to an insufficient supply of anterogradely moving DCVs coming from the soma. As anterogradely moving DCVs are captured (and eventually destroyed) in more proximal boutons on their way to the end of the terminal, the fluxes of anterogradely moving DCVs between the boutons become increasingly smaller, and the most distal boutons are left without DCVs. We tested this hypothesis by modifying the flux of DCVs entering the terminal and found that the number of most distal boutons left unfilled increases if the DCV flux entering the terminal is decreased. The number of anterogradely moving DCVs in the axon can be increased either by the release of a portion of captured DCVs into the anterograde component or by an increase of the anterograde DCV flux into the terminal. This increase could lead to having enough anterogradely moving DCVs such that they could reach the most distal bouton and then turn around by changing molecular motors that propel them. The model suggests that this could result in an increased concentration of resident DCVs in distal boutons beginning with bouton 2 (the most distal is bouton 1). This is because in distal boutons, DCVs have a larger chance to be captured from the transiting state as they pass the boutons moving anterogradely and then again as they pass the same boutons moving retrogradely.


Repolymerizability of native thin filaments of rabbit skeletal muscle.
The repolymerizability of native thin filaments of rabbit skeletal muscle was examined under various conditions. The native thin filaments usually did not repolymerize after depolymerization, but it was found that the process was only inhibited at the nucleation step of the G-F transformation of actin. The inhibited state was released by the addition of sonicated F-actin fragments as seeds or by direct sonication. An attempt to isolate the actin moiety from native thin filaments showed that the isolated actin was very similar to Straub-type G-actin2 in its polymerizability. However, a protein factor which inhibits the polymerization of G-actin was obtained by ammonium sulfate fractionation of the depolymerized native thin filaments. Thus, the apparent lack of repolymerizability of native thin filaments was found to be due to the action of this factor on the polymerization of G-actin.


Opioid Legislation in Patients With Inflammatory Bowel Disease: A State-wide Retrospective Cohort Study.
Indiana State opioid prescription legislation has been shown to decrease overall opioid prescriptions. However, this effect has not been studied in specific diseases associated with chronic pain such as inflammatory bowel disease (IBD). We aimed to determine the effect of state opioid prescription legislation on opioid prescribing patterns in IBD. A retrospective cohort analysis using an interrupted time-series from December 15, 2010 to July 1, 2018, with 2 time periods separated by Title 844 of the Indiana Administrative Code, in a statewide health care system capturing the majority of the state's population including all adult patients with IBD. The primary outcome was opioid prescription rate per person-year. In total, 9436 patients met inclusion criteria. After legislation, the total number of opioid orders per patient-year continued to increase (0.543, 95% CI, 0.528-0.558, to 0.663, 95% CI, 0.654-0.672), with fewer scripts from the emergency department (0.113, 95% CI, 0.106-0.120, to 0.092, 95% CI, 0.088-0.095) and more from outpatient providers (0.303, 95% CI, 0.292-0.314 to 0.432, 95% CI, 0.424-0.439). There were increases in biologic (0.206, 95% CI, 0.197-0.215 to 0.517, 95% CI, 0.509-0.525) and steroid (0.182, 95% CI, 0.173-0.190 to 0.237, 95% CI, 0.232-0.243) prescriptions per person-year following legislation. Factors associated with heavy opioid use included chronic steroids (odds ratio, 5.030; 95% CI, 4.176-6.054), history of IBD-related surgery (odds ratio, 2.807; 95% CI, 2.367-3.323) and current smoking (odds ratio, 2.650; 95% CI, 2.223-3.158). Despite legislation and the increased use of disease-modifying drugs, statewide opioid prescriptions continued to increase. The increase in opiate use, high steroid use, and significant health care utilization suggests poor underlying disease control.


Hospitals' Adoption of Mobile-Based Personal Health Record Systems and Patients' Characteristics: A Cross-Sectional Study Analyzing National Healthcare Big Data.
Insufficient information exists on the associations between hospitals' adoption of mobile-based personal health record (mPHR) systems and patients' characteristics. This study explored the associations between patients' characteristics and hospitals' adoption of mPHR systems in Korea. This cross-sectional study used 316 hospitals with 100 or more beds as the unit of analysis. Previously collected data on mPHR adoption from May 1 to June 30, 2020 were analyzed. National health insurance claims data for 2019 were also used to analyze patients' characteristics. The dependent variable was mPHR system adoption (0 vs 1) and the main independent variables were the number of patients, age distribution, and proportions of patients with cancer, diabetes, and hypertension among inpatients and outpatients. The number of inpatients was significantly associated with mPHR adoption (adjusted odds ratio [aOR]: 1.174; 1.117-1.233, P < .001), as was the number of outpatients (aOR: 1.041; 1.028-1.054, P < .001). The proportion of inpatients aged 31 to 60 years to those aged 31 years and older was also associated with hospital mPHR adoption (aOR: 1.053; 1.022-1.085, P = .001). mPHR system adoption was significantly associated with the proportion of inpatients (aOR: 1.089; 1.012-1.172, P = .024) and outpatients (aOR: 1.138; 1.026-1.263, P = .015) with cancer and outpatients (aOR: 1.271; 1.101-1.466, P = .001) with hypertension. Although mPHR systems are useful for the management of chronic diseases such as diabetes and hypertension, the number of patients, younger age distribution, and the proportion of cancer patients were closely associated with hospitals' introduction of mPHR systems.


The structural model of pain, cognitive strategies, and negative emotions in functional gastrointestinal disorders.
Patients with functional gastrointestinal disorders (FGIDs) may use specific coping strategies. We intend to provide a mediating role of the relationship between pain (intensity and acceptance), cognitive emotion regulation strategies, and negative emotions in patients with FGIDs. Participants were 176 inpatients, all experiencing significant FGIDs symptomatology as confirmed by gastroenterologists. Patients completed data on cognitive emotion regulation questionnaire, short form of depression, anxiety, stress scale, chronic pain acceptance questionnaire-revised, and pain intensity scale. Data were analyzed using structural equation modeling method. The pain intensity had significantly direct effect on cognitive emotion regulation strategies and indirect effect on negative emotions. Besides, the mediating role of negative emotions in the relationship between the strategies and pain acceptance were supported, whereas indirect relationships between pain intensity and acceptance through cognitive strategies were not confirmed. The results of the study emphasize the role of pain intensity in the development of negative emotions through cognitive strategies and the role of the strategies in pain acceptance through negative emotions. In fact, cognitive strategies to be related to pain and emotions.


Mother-male bond, but not paternity, influences male-infant affiliation in wild crested macaques.
In promiscuous primates, interactions between adult males and infants have rarely been investigated. However, recent evidence suggests that male affiliation towards infants has an influence on several aspects of the infants' life. Furthermore, affiliations may be associated with male reproductive strategy. In this study, we examined which social factors influenced male-infant affiliation initiated by either male or infant, in wild crested macaques (Macaca nigra). We combined behavioral data and genetic paternity analysis from 30 infants living in three wild groups in Tangkoko Reserve, Indonesia. Our results indicate that adult males and infants do not interact at random, but rather form preferential associations. The social factors with the highest influence on infant-initiated interactions were male rank and male association with the infant's mother. While infants initiated affiliations with males more often in the absence of their mothers, adult males initiated more affiliations with infants when their mothers were present. Furthermore, males initiated affiliations more often when they were in the same group at the time the infant was conceived, when they held a high dominance rank, or when they had a close relationship with the mother. Interestingly, paternity did not affect male-infant affiliation despite being highly skewed in this species. Overall, our results suggest that adult males potentially associate with an infant to secure future mating with the mother. Infants are more likely to associate with a male to receive better support, suggesting a strategy to increase the chance of infant survival in a primate society with high infant mortality. We explore social relationships between males and infants in a promiscuous primate, the wild crested macaque. Our novel approach addresses the nature of affiliations both from males' and infants' perspectives. The results show that males and infants form preferential associations. Male-female affiliation, but not paternity, was a significant predictor of interactions initiated both by males and infants. Males initiated more interactions towards infants when the mother was in proximity, while infants initiated more interactions in her absence. Finally, high-ranking males were more likely to initiate interactions towards infants. We demonstrated that paternity is not a good predictor of male-infant affiliations, even in a species with a high reproductive skew and a relatively high confidence of paternity. Our paper is one of the first to show that infants are active agents in establishing and maintaining preferential relationships with males.


Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration.
To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization.


Firearm deaths by law enforcement.
The use of deadly force during law enforcement is a matter that compels public scrutiny. There were 42 gunshot deaths caused by police over a 4-year period in New York City. The decedents' average age was 31 years and ranged from 17 to 64 years. There were 41 males and one female; and 26 Black, nine Hispanic, and seven White decedents. Ethanol and/or drugs of abuse were detected in 78% (31/40) of the decedents. The vast majority of shootings occurred with the police responding to a crime and 90% of the decedents were armed (26 handguns, six knives, one axe, one metal pipe, and one toy gun). Vehicles were used as weapons in two incidents. A total of 177 bullets struck the 42 decedents. Fourteen decedents sustained single gunshot wounds (GSWs), and the remainder had multiple GSWs ranging from 2 to 21. In the majority of the cases in this study, the number of GSWs of the body was three or fewer. Thirteen decedents had at least one GSW of the back or buttocks, accounting for 25 of the total 177 wounds, and four of the 13 had GSWs of only the back. With the exception of the upper extremities, GSWs of all locations were more likely to penetrate than perforate. Although these deaths may be high profile, the certification is typically straightforward and the cause (i.e., GSW) and manner of death (homicide) are readily apparent. Although police shootings in which the decedent was unarmed and/or sustained numerous GSWs are widely reported by the lay press, these types of shootings were not typical in our study.


Ovarian artery: angiographic appearance, embolization and relevance to uterine fibroid embolization.
To describe the angiographic appearance of the ovarian artery and its main variations that may be relevant to uterine fibroid embolization. The flush aortograms of 294 women who had been treated by uterine artery embolization for fibroids were reviewed. Significant arterial supply to the fibroid, and the origin and diameter of identified ovarian arteries were recorded. In patients with additional embolization of the ovarian artery, the follow-up evaluation also included hormonal levels and Doppler imaging of the ovaries. A total of 75 ovarian arteries were identified in 59 women (bilaterally in 16 women and unilaterally in 43 women). All ovarian arteries originated from the aorta below the level of the renal arteries with a characteristic tortuous course. Fifteen women had at least one enlarged ovarian artery supplying the fibroids. Fourteen women (14/15, 93%) presented at least one of the following factors: prior pelvic surgery, tubo-ovarian pathology or large fundal fibroids. We advocate the use of flush aortography in women with prior tubo-ovarian pathology or surgery or in cases of large fundal fibroids. In the case of an ovarian artery supply to the fibroids, superselective catheterization and embolization of the ovarian artery should be considered.


Characterization of transduction by bacteriophage T1: time of production and density of transducing particles.
The transducing activity of two different kinds of premature lysates of T1-infected cells have been compared to normal lysates. The results show that T1-transducing particles are made early in the maturation period. The average density of T1-transducing particles is slightly greater than the density of plaque-forming T1.


The Na(+)-K(+)-ATPase beta 1 subunit is associated with the HK alpha 2 protein in the rat kidney.
The Na-K-ATPase beta 1 subunit acts as the beta subunit for the HK alpha 2 protein in the rat kidney. The colonic H(+)-K(+)-ATPase is a member of the P-type ATPases, and has been shown to contribute to potassium transport by the mammalian kidney and colon. The P-type ATPases often consist of an alpha subunit that contains the catalytic site and a beta subunit that participates in regulation of enzyme activity and targeting of the enzyme to the plasma membrane. The cDNA of the alpha subunit (HK alpha 2) has been cloned and the HK alpha 2 protein has been isolated from the rat kidney and colon. However, a unique beta subunit for the colonic H(+)-K(+)-ATPase has not been described. To determine if one of the known beta subunits present in the kidney might act as the beta subunit for the colonic H(+)-K(+)-ATPase, microsomes enriched in the colonic H(+)-K(+)-ATPase were isolated using an HK alpha 2-specific antibody (AS 31.7) and the Minimac magnetic separation system. Immunoblots of rat kidney microsomal protein isolated with antibody AS 31.7 were probed with antibodies directed against the gastric HK beta subunit, Na(+)-K(+)-ATPase alpha 1, and Na(+)-K(+)-ATPase beta 1 subunits. A band of the appropriate size was detected with Na(+)-K(+)-ATPase beta 1-specific antibodies, but not those directed against HK beta 1. These data suggest that Na(+)-K(+)-ATPase beta 1 could be the beta subunit for the colonic H(+)-K(+)-ATPase in the kidney.


Sensitivity of anticancer drugs in Saos-2 cells transfected with mutant p53 varied with mutation point.
A human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53 gene, and clones of Saos-2 cells, which were transfected with wild type p53 or mutant p53 genes (123A, 143A, 175H and 273H), were observed for their surviving fraction after treatment with the commonly used anticancer drugs, cisplatin (CDDP), nimustine (ACNU), adriamicin (ADR) and bleomicin (BLM). The transfectants of the mutant 143A, 175H and 273H were significantly more resistant to CDDP than the transfectant of pOPI3 (expression plasmid only). The transfectants of the wild type p53 and mutant 123A were significantly more sensitive to ACNU than the transfectant of pOPI3. The transfectant of mutant 123A was more sensitive to ADR than the transfectant of pOPI3. There was no significant difference in sensitivity to BLM between Saos-2 and all kinds of transfectants. Thus the sensitivity of the cells to anticancer drugs varied with the mutation point of the p53 gene.


Application of minority stress and the interpersonal theory of suicide in bisexual+ versus gay/lesbian young adults.
Sexual minority young adults are at increased risk for suicidal ideation (SI) compared with heterosexual young adults. Though several frameworks exist to explain the development of suicide risk, including the Interpersonal Theory of Suicide (IPTS) and the Minority Stress Model, few studies have examined these frameworks simultaneously. This study examines these frameworks longitudinally among sexual minority young adults. A total of 792 sexual minority young adults (50% bisexual+, 50% gay/lesbian) completed an online survey at baseline, one-month follow-up, and two-month follow-up assessing constructs related to IPTS, the minority stress model, and SI. Over half of our sample (52.9%) reported any SI at baseline. In the full sample, all types of minority stress at baseline were significantly associated with SI at two-month follow-up via perceived burdensomeness (PB) and thwarted belongingness (TB) at one-month follow-up. In the bisexual+ subsample, all bisexual-specific minority stressors at baseline were significantly associated with SI at two-month follow-up via PB at one-month follow-up; internalized binegativity was also associated with SI via TB. However, effects became non-significant when controlling for previous levels of the mediators and outcome variables. Both minority stress and IPTS are relevant for understanding suicide risk among sexual minority young adults.


Repulsive inter-layer coupling induces anti-phase synchronization.
We present numerical results for the synchronization phenomena in a bilayer network of repulsively coupled 2D lattices of van der Pol oscillators. We consider the cases when the network layers have either different or the same types of intra-layer coupling topology. When the layers are uncoupled, the lattice of van der Pol oscillators with a repulsive interaction typically demonstrates a labyrinth-like pattern, while the lattice with attractively coupled van der Pol oscillators shows a regular spiral wave structure. We reveal for the first time that repulsive inter-layer coupling leads to anti-phase synchronization of spatiotemporal structures for all considered combinations of intra-layer coupling. As a synchronization measure, we use the correlation coefficient between the symmetrical pairs of network nodes, which is always close to -1 in the case of anti-phase synchronization. We also study how the form of synchronous structures depends on the intra-layer coupling strengths when the repulsive inter-layer coupling is varied.


Participation of a persistent sodium current and calcium-activated nonspecific cationic current to burst generation in trigeminal principal sensory neurons.
The properties of neurons participating in masticatory rhythmogenesis are not clearly understood. Neurons within the dorsal trigeminal principal sensory nucleus (dPrV) are potential candidates as components of the masticatory central pattern generator (CPG). The present study examines in detail the ionic mechanisms controlling burst generation in dPrV neurons in rat (postnatal day 8-12) brain stem slices using whole cell and perforated patch-clamp methods. Nominal extracellular Ca(2+) concentration transformed tonic discharge in response to a maintained step pulse of current into rhythmical bursting in 38% of nonbursting neurons. This change in discharge mode was suppressed by riluzole, a persistent Na(+) current (INaP) antagonist. Veratridine, which suppresses the Na(+) channel inactivation mechanism, induced rhythmical bursting in nonbursting neurons in normal artificial cerebrospinal fluid, suggesting that INaP contributes to burst generation. Nominal extracellular Ca(2+) exposed a prominent afterdepolarizing potential (ADP) following a single spike induced by a 3-ms current pulse, which was suppressed, but not completely blocked, by riluzole. Application of BAPTA, a Ca(2+) chelator, intracellularly, or flufenamic acid, a Ca(2+)-activated nonspecific cationic channel (ICAN) antagonist, extracellularly to the bath, suppressed rhythmical bursting and the postspike ADP. Application of drugs to alter Ca(2+) release from endoplasmic reticulum also suppressed bursting. Finally, voltage-clamp methods demonstrated that nominal Ca(2+) facilitated INaP and induced ICAN. These data demonstrate for the first time that the previously observed induction in dPrV neurons of rhythmical bursting in nominal Ca(2+) is mediated by enhancement of INaP and onset of ICAN, which are dependent on intracellular Ca(2+).


Identification of a novel subtype of feline immunodeficiency virus in a population of naturally infected felines in the Brazilian Federal District.
The feline immunodeficiency virus (FIV) is a retrovirus that is found worldwide, and it can be assigned to six subtypes (A, B, C, D, E, and a putative subtype F) based on sequencing analysis of the env and gag genes. Subtypes A and B are the most common worldwide. In Brazil, several authors have isolated only subtype B, and its prevalence differs markedly among investigated populations. Blood samples from 200 domestic felines from the Federal District in Brazil were analyzed by PCR. Samples that tested positive for FIV were then cloned, sequenced, and analyzed phylogenetically and statistically. The results represent the first description of FIV infection in the Central Region of Brazil and suggest that only 2 % of felines in this region are positive for the virus. In addition, the analysis showed that one out of the four positive samples that we detected could not be assigned to any of the six classical subtypes. This sample was taken as a putative novel subtype of the FIV virus. The remaining three positive samples were assigned to subtype B, with differences existing among these samples.


Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair.
Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2), on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks.


Continuous ambulatory peritoneal dialysis is effective for patients with severe congestive heart failure.
Although the use of continuous ambulatory peritoneal dialysis (CAPD) to treat refractory heart failure is not new, in combination with current medical treatment it improves patients'symptoms as well as their cardiac function. We started 16 patients (13 men with a mean age of 66.3 +/- 2.8 years, and 3 women with a mean age of 72 +/- 4.2 years) on CAPD. All patients were symptomatic with congestive heart failure. Mean left ventricular ejection fraction (LVEF) before the start of CAPD was 31% +/- 3%. Introduction to CAPD was associated with a significant improvement in LVEF (to 44% +/- 6%, p < 0.05) and in blood pressure control at 1 year. Also at 1 year, 87% of patients were classified as New York Heart Association grade I or II (maximum possible grade is grade III). These results suggest that CAPD is a treatment of choice for patients suffering from a combination of congestive heart failure and chronic renal insufficiency.


In Search of the Ultimate Benzene Sensor: The EtQxBox Solution.
In this work we report a comprehensive study leading to the fabrication of a prototype sensor for environmental benzene monitoring. The required high selectivity and ppb-level sensitivity are obtained by coupling a silicon-integrated concentration unit containing the specifically designed EtQxBox cavitand to a miniaturized PID detector. In the resulting stand-alone sensor, the EtQxBox receptor acts at the same time as highly sensitive preconcentrator for BTEX and GC-like separation phase, allowing for the selective desorption of benzene over TEX. The binding energies of the complexes between EtQxBox and BTX are calculated through molecular mechanics calculations. The examination of the corresponding crystal structures confirms the trend determined by computational studies, with the number of C-H···N and CH···π interactions increasing from 6 to 9 along the series from benzene to o-xylene. The analytical performances of EtQxBox are experimentally tested via SPME, using the cavitand as fiber coating for BTEX monitoring in air. The cavitand EFs are noticeably higher than those obtained by using the commercial CAR-DVB-PDMS. The LOD and LOQ are calculated in the ng/m3 range, outperforming the commercial available systems in BTEX adsorption. The desired selective desorption of benzene is achieved by applying a smart temperature program on the EtQxBox mesh, which starts releasing benzene at lower temperatures than TEX, as predicted by the calculated binding energies. The sensor performances are experimentally validated and ppbv level sensitivity toward the carcinogenic target aromatic benzene was demonstrated, as required for environmental benzene exposure monitoring in industrial applications and outdoor environment.


Tai Chi Chuan can improve balance and reduce fear of falling in community dwelling older adults: a randomized control trial.
Fear of falling and balance impairment are prevalent in older adults and cause major morbidities for this population. The aim of this study was to evaluate the effect of Tai Chi Chuan on balance and fear of falling in community-dwelling older adults. This study was a single-blind randomized control trial. Sixty older adults were randomly allocated into two groups using a 4-cell random block design. The participants of intervention group were trained in Tai Chi Chuan for eight weeks, twice a week, and 55 min in each session. Balance and fear of falling were assessed by Timed Up and Go (TUG) test, Tinetti test and Falls Efficacy Scale International in baseline and after 8 weeks. After eight weeks of intervention, the mean scores of the TUG and Tinetti scales in the intervention group were improved significantly compared to the baseline and the control group (P<0.001). Moreover, the intervention group showed a significant reduction in fear of falling scores (P<0.001), while those in the control group remained unchanged. Tai Chi Chuan effectively improves the balance and fear of falling and could be considered as a practical and useful method for fall prevention in community-dwelling older adults.