[Primary melanoma of the nasal and paranasal sinus mucosa].
The authors make short review on the one of most malignant neoplasms in human pathology--its incidence, ethiology, pathogenesis, clinical characteristics, diagnosis, treatment and prognostic features. We present a clinical case from our practice--a melanoma of the nasal cavity and paranasal sinuses--a rare localization. Melanocarcinomas of the mucous membranes of the nasal cavity and paranasal sinuses are almost uniformly fatal. Undoubtedly some of the contributory reasons for their grave prognosis are the delay in detection and in accurate histologic diagnosis, the frequent injudicious therapy, the difficulties in adequate operative removal. Melanomas o mucous membranes may arise in mucosa lined by either normally present, or metaplastic stratified squamous epithelium.


Potentiation of therapeutic effects of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride by 6-thioguanine in mouse tumor systems: comparison with other antimetabolites.
Antitumor activities of a combination chemotherapy with a water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), and a single dose of 6-thioguanine were studied using three obstinate murine tumor systems, i.e., Lewis lung carcinoma, B16 melanoma, and an advanced stage of L1210 leukemia systems. Therapeutically synergistic effect was observed either definitely against 1- or 2-day-old Lewis lung carcinoma and 6-day-old L1210 leukemia or moderately against 1-day-old B16 melanoma. Single intravenous treatment on day 7 after subcutaneous implantation of Lewis lung carcinoma, when the tumors had already metastasized to the lungs, produced a significant regression of tumor and a significant increment in survival time of tumor-bearing mice. In comparative studies, the combination of ACNU and 6-thioguanine showed a greater and a wider spectrum of antitumor activities against these tumors than those obtained by the combination with ACNU and a single dose of 5-fluorouracil, methotrexate, or 6-mercaptopurine. Increment in lethal toxicity for normal and tumor-bearing mice was not observed by the combination of ACNU and 6-thioguanine in contrast to definite increases in this toxicity by the combination of ACNU and 5-fluorouracil. The present experimental results may suggest the clinical utility of the combination chemotherapy with ACNU and 6-thioguanine in the treatment of several solid tumors as well as acute leukemias.


[Description of eggs and nymphs of Triatoma jurbergi Carcavallo, Galvão & Lent, 1998 through optical and scanning electron microscopy].
Eggs and nymphs of Triatoma jurbergi were described using optical microscopy and scanning electron microscopy. T. jurbergi is a wild species, found in State of Mato Grosso (15oS and 300 m.a.s.l), Brazil. Eggs showed the operculum and surface with pentagonal and hexagonal cells, with small fractures and punctuations randomly distributed. Differences were found in the five nymphal stages of T. jurbergi, that allow their to be distinguished from the similar species T. guazu. The diagnostic characters most useful for differentiation were the general color of the insect, abdomen shape and its length.


[Reality of respiratory symptoms in preschool-age children -result of a parental questionnaire-].
In Japan, incidence of respiratory symptoms in pre-school children is still unclear. A nationwide mail questionnaire survey on respiratory symptoms including symptom prevalence was conducted among mothers who had preschool-age children. Number of questionnaires sent was 1375, and valid responses was 1168 (valid response rate; 84.9%). In the last 12 months, 94.8% of children had runny nose and nasal congestion, followed by nonproductive cough (73.7%), wet cough (64.3%), and wheezing (19.2%). When classified according to age group, 56.1% of under 1-year-old infants had nonproductive cough, 40.4% had wet cough, 12.1% had wheezing, 84.3% had runny nose and nasal congestion, and 1- to 2-year-olds had an increased rate for all of these symptoms. The consultation rate for respiratory symptoms at the medical institution was as high as 91.9% in the children with nonproductive cough, and 94.0% with wheezing. Each respiratory symptom tends to decrease most in August and increase through the period of December to March. Peak times of symptom exacerbation were "just after falling asleep at night" for nonproductive cough and wet cough, "midnight" for wheezing, and "daytime" for runny nose and nasal congestion. Also, it was confirmed that the largest number of children have problems sleeping, and that most mothers also have problems sleeping due to having to take care of their child. This survey revealed the reality of respiratory symptoms of preschool-age children. The results suggest that respiratory symptoms are prevalent in children, and many of them have seasonal change and nocturnal exacerbation of symptoms.


Analysis of factors contributing to fertility decline in Korea.
With the successful Korean national family planning program and rapid socioeconomic advancement since 1962, the contraceptive prevalence rate has risen from 9% in 1964 to 79% in 1991, with the corresponding total fertility rate (TFR) going from 6.0 in 1960 to 1.6 in 1988, which is considerably below the replacement fertility rate. The main purpose of this study is, therefore, to identify the structural and causal factors that contributed to the fall in fertility over the last 3 decades, in an effort to formulate future population policy directions and strategies. The 2 methods used for the study were: the standardization approach to examine the structural factors on fertility decline, and the bongaarts model to measure the effects of the proximate variables in the fertility decline. The study indicated that the fall in the crude birth rate and the general fertility rate for the periods of 1960-70 and 1980-90 were largely influenced by the decline in marital fertility which was triggered by the national family planning program initiated in 1962. The analysis based on the bongaarts model revealed that the 3 principal factors which exercised a strong influence on the fertility decline were the rise in age at marriage, the increase in induced abortion, and the increase in contraceptive use, but the influence of induced abortion has been decreasing in recent years. In general, the study results suggest that the main concerns of the national family planning program should be shifted from the past quantitative approach with emphasis on fertility reduction to a qualitative approach which stresses maternal and child health and other public health programs.


Chemical composition of Silene morganae Freyn volatile oil.
The essential oil composition of flowering aerial parts of Iranian Silene morganae Freyn (Caryophyllaceae) was analysed for the first time using gas chromatography and gas chromatography-mass spectrometry. Thirty-one compounds consisting of 90.3% of the volatile oil were detected. The major constituents were benzaldehyde (11.6%), (Z)-3-hexenyl acetate (9.6%), (E)-β-ocimene (8.2%) and linalool (7.4%). Terpenoids (43.5%), particularly monoterpene hydrocarbons (24.2%), had the highest contribution in S. morganae Freyn flowering aerial parts oil.


Combined protective effects on interferon and interferon induction on herpes simplex and ectromelia virus infections in mice.
Mouse interferon or the induction of mouse interferon with polyriboinosinic acid-polyribocytidylic acid significantly protected mice against herpes simplex and ectromelia viral infections. When polyriboinosinic acid-polyribocytidylic acid was administered 24 h before herpes simplex or ectromelia viral infection and mouse interferon was administered shortly before and 24 h after infection, a combined protective effect against either herpes simplex or ectromelia viral infection in mice was evident. There was a significant decrease in the mortality rate with the combined treatment as compared either with the rate in group treated with interferon or polyriboinosinic acid-polyribocytidylic acid.


High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer.
To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC.


Toward more efficient CCSD(T) calculations of intermolecular interactions in model hydrogen-bonded and stacked dimers.
Interaction energies of the model H-bonded complexes, the formamide and formamidine dimers, as well as the stacked formaldehyde and ethylene dimers are calculated by the coupled cluster CCSD(T) method. These systems serve as a model for H-bonded and stacking interactions, typical in molecules participating in biological systems. We use the optimized virtual orbital space (OVOS) technique, by which the dimension of the space of virtual orbitals in coupled cluster CCSD(T) calculations can be significantly reduced. We demonstrate that when the space of virtual orbitals is reduced to 50% of the full space, which means reducing computational demands by 1 order of magnitude, the interaction energies for both H-bonded and stacked dimers are affected by no more than 0.1 kcal/mol. This error is much smaller than the error when interaction energies are calculated using limited basis sets.


Efficacy of Dexmedetomidine in two Different Doses as an Adjuvant to Lignocaine in Patients Scheduled for Surgeries under Axillary Block.
The effect of adding dexmedetomidine (α2-adrenoceptor agonist) to local anaesthetics in brachial plexus blocks has been evaluated, however there has been no consensus regarding the ideal dose of dexmedetomidine. Without ultrasound axillary block has been considered as the safest approach for brachial block. To evaluate the efficacy of two doses of dexmedetomidine (0.5 μg/kg and 1 μg/kg) as an adjuvant to lignocaine in patients undergoing forearm surgeries under axillary brachial plexus block. This prospective randomized controlled study was conducted on 104 adult patients, American Society of Anaesthesiologists (ASA) physical status 1 or 2. They were randomized and given following drug formulations, Group L (n=35) received 23 ml of 2% lignocaine with adrenaline + 7 ml of saline, Group LD0.5 (n=34) received 23 ml of 2% lignocaine with adrenaline + 0.5 μg/kg of dexmedetomidine diluted in saline to make a volume of 7 ml, Group LD1 (n=35) was given 23 ml of 2% lignocaine with adrenaline + 1 μg/kg of dexmedetomidine diluted in saline to make volume of 7 ml, the total volume of drug being 30 ml in each group and concentration of lignocaine 1.5%. The duration of postoperative analgesia and demand for rescue analgesia were the primary outcomes and block characteristics taken as secondary outcome. Sensory and motor block onset times were shorter in Group L than in group LD0.5, LD1 (p < 0.05). Sensory and motor blockade durations were longer in Group LD1, LD0.5 than Group L (p<0.01). Duration of analgesia was longer in Group LD1 than in group LD0.5 and least in Group L (p<0.05). Dexmedetomidine (0.5 μg/kg and 1 μg/kg) as an adjuvant in axillary brachial plexus increases the duration of postoperative analgesia and delays the requirement of first dose of analgesic in a dose dependent manner and 1 μg/kg seems to be the near ideal dose of dexmedetomidine as an adjuvant in axillary block.


[Status of immunologic reactivity and prospects of the implementation of occupational selection of workers at a microbiological plant].
The results of immunologic studies of different groups of workers engaged in the microbiologic synthesis production are presented. The study reveals a very important role of the immune system in the development of various forms of diseases. Differentiated shifts in various chains of cellular and humoral immunity have been identified in practically healthy people and in patients with occupational diseases both in acute condition and at the remittance stage. These shifts are specified by the form and stage of the disease, length of service at the given enterprise and individual immunity characteristics. By means of using immunograms it is possible to select patients with stable, adequate immune type enabling one to go on working at the industrial enterprise without any significant pathologic changes in the body.


Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities.
p53 is one of the most important tumor suppressor genes that is frequently mutated in human cancers. Generally, p53 functions as a transcription factor that is stabilized and activated by various genotoxic and cellular stress signals, such as DNA damage, hypoxia, oncogene activation and nutrient deprivation, consequently leading to cell cycle arrest, apoptosis, senescence and metabolic adaptation. p53 not only becomes functionally deficient in most cancers, but not infrequently mutant p53 also acquires dominant negative activity and oncogenic properties. p53 has remained an attractive target for cancer therapy. Strategies targeting p53 have been developed including gene therapy to restore p53 function, inhibition of p53-MDM2 interaction, restoration of mutant p53 to wild-type p53, targeting p53 family proteins, eliminating mutant p53, as well as p53-based vaccines. Some of these p53-targeted therapies have entered clinical trials. We discuss the therapeutic potential of p53, with particular focus on the therapeutic strategies to rescue p53 inactivation in human cancers. In addition, we discuss the challenges of p53-targeted therapy and new opportunities for the future.


Structure and function of the small (30K) subunit of calcium-activated neutral protease (CANP).
Calcium-activated neutral protease (CANP), a typical intracellular protease, is composed of a catalytic 80K subunit (80K) and a 30K subunit (30K) of unknown function. The structure of rabbit CANP 30K was examined to clarify its role in the enzyme function. It has a clear two-domain structure composed of 266 amino acid residues. The N-terminal domain presumably determines the location of CANP, whereas the C-terminal domain is a calmodulin-like Ca2+-binding domain and regulates CANP activity.


A retrospective study of the safety and efficacy of paclitaxel plus ramucirumab in patients with advanced or recurrent gastric cancer with ascites.
Ramucirumab has recently proved to be effective for advanced or recurrent gastric cancer (AGC). Ascites and peritoneal metastasis are among the most common complications of AGC. However, there are few data on the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites. The purpose of this retrospective study was to evaluate the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites. We retrospectively evaluated the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites in comparison with patients without ascites in a single institution from June 2015 to May 2016. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and differences evaluated using the Log-lank test. The differences in baseline characteristics and response rates of each ascites group were calculated for homogeneity by chi-square tests and for trends by Fisher's exact test. Eighty-three patients were analyzed in this study. Ascites was detected in 40 patients, 26 patients (31%) had small to moderate ascites and 14 (17%) had massive ascites. The proportion of patients who started with a reduced dose of paclitaxel was higher for patients with massive ascites than others. The frequencies of any grade 3 or 4 hematological toxicity were 51% in patients without ascites, 77% in patients with small to moderate ascites, and 71% in patients with massive ascites. The frequencies of common ramucirumab-related adverse events were also not significantly different among ascites groups, however one patient had a tumor hemorrhage, and one patient had a gastrointestinal perforation. PFS and OS were shorter in patients with massive ascites than in patients with small or moderate ascites or patients without ascites. The use of paclitaxel and ramucirumab in patients with AGC with large amounts of ascites was tolerable with adequate dose modification. However, we should pay attention to the risks of ramucirumab-related toxicity in patients with bleeding tumors or intestinal stenosis.


Reaction of the lateral periodontium of dogs' teeth to contaminated and noncontaminated perforations filled with mineral trioxide aggregate.
It has been shown that the mineral trioxide aggregate (MTA) used to seal lateral/furcal perforations stimulates the deposition of newly formed cementum. Nevertheless, when the site of the perforation is contaminated, the healing process might occur under less favorable conditions. This study evaluated the repair healing process of noncontaminated and contaminated lateral perforations filled with MTA and the effect of previously filling the contaminated perforations with a bactericidal agent. Thirty lateral root perforations were prepared in endodontically treated dog's teeth, thus forming 3 groups with 10 specimens each. In group 1 the perforations were immediately sealed with MTA. In group 2 the perforations were left open for 7 days and thereafter sealed with MTA. In group 3 the perforations were left open for 7 days, filled temporarily with a calcium hydroxide-based paste for 14 days, and then sealed with MTA. The animals were killed after 90 days, and the pieces were prepared for histomorphologic and histomicrobiologic evaluations. The statistical analysis showed that group 1 had significantly better repair than groups 2 (P < .05) and 3 (P < .05), which validates the superior results obtained when MTA was immediately used to seal root perforations. Groups 2 and 3 had statistically similar repair to each other (P > .05). There were a larger number of cases of complete or partial biologic seal in group 1 compared with the contaminated groups. It might be concluded that the lateral root perforations sealed with MTA after contamination presented worse repair than the noncontaminated, immediately sealed perforations. The temporary filling with a bactericidal agent (calcium hydroxide-based paste) did not improve the repair of perforations exposed to contamination, and the contaminated groups presented similar results to each other.


[Alterations of CD4+CXCR5+Tfh cells and its transcription regulatory factors in children with asthma].
To study the alterations of follicular T helper cells (CD4(+)CXCR5(+)Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA. Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4(+)CXCR5(+)Tfh cells on CD4(+)T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double -antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21. The proportion of CD4(+)CXCR5(+)Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4(+)CXCR5(+)Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05). The abnormal proportion of CD4(+)CXCR5(+)Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4(+)CXCR5(+)Tfh cells in children with acute asthma.


HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains.
Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination.


Structural insights into viral RNA capping and plasma membrane targeting by Chikungunya virus nonstructural protein 1.
Chikungunya virus (CHIKV) causes a debilitating arthralgic inflammatory disease in humans. The multifunctional CHIKV protein, nsP1, facilitates virus RNA replication and transcription by anchoring the viral replication complex (RC) to plasma membrane vesicles and synthesizing the viral RNA 5' cap-0. Here, we report a cryo-EM structure of CHIKV nsP1 at 2.38 Å resolution. Twelve copies of nsP1 form a crown-shaped ring structure with a 7.5-nm-wide channel for mediating communication and exchange between the viral RC and the host cell. The catalytic site for viral RNA capping is located in a tunnel that is shaped by neighboring nsP1 molecules. Two membrane-association loops target nsP1 to the inner leaflet of the plasma membrane via palmitoylation and hydrophobic and electrostatic interactions. Our study provides the structural basis of viral RNA capping and RC assembly mediated by nsP1 and guides the development of antivirals targeting these essential steps of virus infection.


Diotic and dichotic detection using multiplied-noise maskers.
Detection thresholds were measured with a multiplied-noise masker that was in phase in both ears and a sinusoidal signal which was either in phase or out of phase (NoSo and NoS pi conditions). The masker was generated by multiplying a low-pass noise with a sinusoidal carrier. The signal was a sinusoid with the same frequency as the carrier and a constant phase offset, theta, with respect to the carrier. By adjusting the phase offset, the stimulus properties were varied in such a way that only interaural time delays (theta = pi/2) or interaural intensity differences (theta = 0) were present within the NoS pi stimulus. Thresholds were measured at a center frequency of 4 kHz as a function of bandwidth for theta = pi/2 and for theta = 0. In a second experiment thresholds were measured for a bandwidth of 25 Hz as a function of the center frequency. The results show that narrow-band BMLDs at 4 kHz can amount to 30 dB for the theta = 0 condition. For this condition, narrow-band BMLDs are also reasonably constant across frequency, in contrast to results obtained with standard Gaussian-noise maskers. For theta = pi/2, BMLDs are restricted to the frequency region below 2 kHz provided that the masker is narrow band, but BMLDs of up to 15 dB are found at 4 kHz if the masker is 50 Hz or wider. The frequency dependence of the binaural thresholds seems to be best explained by assuming that the stimulus waveforms are compressed before binaural interaction.


Battery electric vehicles - implications for the driver interface.
The current study examines the human-machine interface of a battery electric vehicle (BEV) from a user-perspective, focussing on the evaluation of BEV-specific displays, the relevance of provided information and challenges for drivers due to the concept of electricity in a road vehicle. A sample of 40 users drove a BEV for 6 months. Data were gathered at three points of data collection. Participants perceived the BEV-specific displays as only moderately reliable and helpful for estimating the displayed parameters. This was even less the case after driving the BEV for 3 months. A taxonomy of user requirements was compiled revealing the need for improved and additional information, especially regarding energy consumption and efficiency. Drivers had difficulty understanding electrical units and the energy consumption of the BEV. On the background of general principles for display design, results provide implications how to display relevant information and how to facilitate drivers' understanding of energy consumption in BEVs. Practitioner Summary: Battery electric vehicle (BEV) displays need to incorporate new information. A taxonomy of user requirements was compiled revealing the need for improved and additional information in the BEV interface. Furthermore, drivers had trouble understanding electrical units and energy consumption; therefore, appropriate assistance is required. Design principles which are specifically important in the BEV context are discussed.


Automated nuclei segmentation of malignant using level sets.
Segmentation of objects from a noisy and complex image is still a challenging task that needs to be addressed. This article proposed a new method to detect and segment nuclei to determine whether they are malignant or not (determination of the region of interest, noise removal, enhance the image, candidate detection is employed on the centroid transform to evaluate the centroid of each object, the level set [LS] is applied to segment the nuclei). The proposed method consists of three main stages: preprocessing, seed detection, and segmentation. Preprocessing stage involves the preparation of the image conditions to ensure that they meet the segmentation requirements. Seed detection detects the seed point to be used in the segmentation stage, which refers to the process of segmenting the nuclei using the LS method. In this research work, 58 H&E breast cancer images from the UCSB Bio-Segmentation Benchmark dataset are evaluated. The proposed method reveals the high performance and accuracy in comparison to the techniques reported in literature. The experimental results are also harmonized with the ground truth images.


Congenital aphallia associated with congenital urethrorectal fistula: A rare case report.
Aphallia is an extremely rare congenital malformation of unknown cause, with few reports in the literature. It is usually associated with other urogenital and gastrointestinal anomalies and is believed to be a result of either the absence of a genital tubercle or chromosome polymorphism. Herein, we describe an extremely rare case of congenital aphallia with congenital urethrorectal fistula and describe our treatment for this patient. An 8-year-old boy was brought to our hospital by his parents because of congenital absence of the penis. The child was male per karyotype and had excess heterochromatin on chromosome 9 (46 XY with 9 qh+). No urethral orifice was identified, and urine passed rectally since birth; thus, urinary tract outlet obstruction led to urine reflux from the anus to the epididymis for a long time. The boy had to be placed on prophylactic antibiotics because he developed urinary tract infection and epididymitis almost every day. Congenital aphallia (46 XY normal male karyotype) associated with congenital urethroretal fistula. We performed urethral exteriorization via perineal urethroplasty and urethrorectal fistula repair. The parents approved for phallic reconstruction when the boy reached puberty. A new external urethral orifice was created on the lower scrotum. The urinary reflux was corrected, and the epididymitis symptoms disappeared. The urethral fistula was then closed. At 8 months follow up, the patient was no longer on antibiotics and had no symptoms of urinary tract infection or epididymitis. Compatible treatment should be adopted to address urinary tract drainage and infection. Management requires a stepwise approach to address needs as they arise. Neophalloplasty should be performed by an experienced team in early adolescence.


Clinical Characteristics and Etiology of Bilateral Vestibular Loss in a Cohort from Central Illinois.
Previous series of bilateral vestibular loss (BVL) identified numerous etiologies, but surprisingly, a cause in a significant number of cases remains unknown. In an effort to understand possible etiology and management strategies, a global effort is currently in progress. Here, I contribute my 10-year experience with both acute and chronic BVL during the 2007-2017 decade. This is a retrospective review of the charts and EMR of patients diagnosed with BVL in the last 10 years. Following Institutional IRB approval, we identified 57 patients with a diagnosis of BVL and utilized the current diagnostic criteria listed by the Barany society (1). The inclusion criteria included patients with BVL of any cause, within an age span older than 18 and a neuro-otologic examination supporting the clinical impression of BVL. During the current decade 2007-2017, I identified two broad categories of BVL (acute and chronic) in 57 patients; only 41 of them had records available. The etiology includes: idiopathic: n = 9, Wernicke's encephalopathy n = 11, superficial siderosis n = 3, paraneoplastic syndrome: n = 3, bilateral vestibular neuritis (recurrent AVS lasting days without cochlear symptoms) n = 3, simultaneous ototoxicity of aminoglycoside and chemotherapy toxicity n = 2, MELAS n = 2, Meniere's disease treated with intra-tympanic streptomycin in one ear n = 1, acute phenytoin intoxication: n = 1, combined chronic unilateral tumor-related vestibulopathy and new contralateral vestibular neuritis (this patient presented with Betcherew's phenomenon) n = 1, bilateral AICA stroke n = 1, mixed spinocerebellar ataxia type 3, n = 2 and CANVAS n = 2. This cohort included a 28% overall incidence of acute and subacute BVL; among them, 65% improved with intervention. In the thiamine deficiency group, specifically, the vestibular function improved in 80% of the patients. Even though acute, subacute, or chronic showed slightly asymmetric horizontal-VOR gain loss, it never did cause spontaneous, primary straight gaze horizontal nystagmus. n = 39/41 patients had abnormal manual HIT, n = 26/41 BVL patients tested with video head impulse immediately after manual testing showed decreased VOR gain, including two with covert saccades. Two thiamine patients with positive bedside pretreatment manual HIT, tested after treatment with high-dose thiamine showed improved VOR. In acute thiamine deficiency, the horizontal VOR was abnormal and the vertical was either normal or mildly decreased. This series favored a neurologic cause of BVL. Finally, 20% of the chronic cases were idiopathic.


Unprecedented Development of Ultrahigh Expansion Injection-Molded Polypropylene Foams by Introducing Hydrophobic-Modified Cellulose Nanofibers.
Herein, an ultrahigh 18-fold expansion of isotactic polypropylene (iPP)/cellulose nanofiber (CNF) nanocomposite foams was achieved for the first time using a core-back foam injection molding technique. It was found that CNFs were well dispersed and aligned along the cell wall in the core-back direction. Interestingly, the formations of a hybrid shish-kebab of CNFs and classic shish-kebab of PP were simultaneously achieved in the PP/CNF composites. Finally, we proposed that the combination of local strong melt strength, probably resulting from the strong alignment of CNFs and subsequent formation of hybrid shish-kebab structures, and weak melt strength in the unreinforced PP melt might be the driving force for remarkably enhancing the PP foamability.


Acceptor or donor (diaryl B or N) substituted octupolar truxene: synthesis, structure, and charge-transfer-enhanced fluorescence.
Two diaryl B- and N-substituted truxene charge-transfer compounds B3 and N3 have been synthesized. The fluorescence intensities of several nonfunctionalized truxene compounds are 1 order of magnitude weaker than that of B3 and N3. To reveal the structure-property correlations, the X-ray structures of B3 and N3 and their precursors 3 and 4 have been determined. The extended molecular dimension, the especially shortened B-C bond, and the improved planarity of B3 can serve as direct structural evidence for the charge transfer.


Implementing an Inclusive, Multidisciplinary Supportive Care Model to Provide Integrated Care to Breast and Gynaecological Cancer Survivors: A Case Study at an Asian Ambulatory Cancer Centre.
Supportive care models considering inclusivity and community services to improve integrated care for cancer survivors are limited. In this case study, we described the implementation of a multidisciplinary care model employing routine distress screening and embedded integrated care pathways to integrate care across disciplines and care sectors, while remaining inclusive of the multi-ethnic and multilingual population in Singapore. We reported implementation outcomes after 18 months of implementation. We reviewed the model's process indicators from September 2019 to February 2021 at the largest public ambulatory cancer centre. Outcomes assessed included penetration, fidelity to screening protocol, and feasibility in three aspects - inclusiveness of different ethnic and language groups, responsiveness to survivors reporting high distress, and types of community service referrals. We elucidated opportunities to promote access to community services and inclusivity. Integration of community services from tertiary settings should be systematic through mutually beneficial educational and outreach initiatives, complemented by their inclusion in integrated care pathways to encourage systematic referrals and care coordination. A hybrid approach to service delivery is crucial in ensuring inclusivity while providing flexibility towards external changes such as the COVID-19 pandemic. Future work should explore using telehealth to bolster inclusiveness and advance community care integration.


A stepwise approach to justify phase III randomized clinical trials and enhance the likelihood of a positive result.
Multiple time-consuming, expensive, and negative phase III clinical trials involving many thousands of patients have been undertaken in critical care and continue to be funded. The vast majority of these clinical trials are negative. Furthermore, phase III studies frequently fail to achieve their planned recruitment target. Often such studies are based on small pilot studies with inadequate phase II trial data and limited mechanistic data to provide a sound scientific rationale. The body of research required to justify undertaking a phase III trial in the critically ill population has not been defined adequately. In particular, guidance on the design of phase II studies for evaluating treatments in the critically ill population is needed. Research to inform critical care practice will progress more efficiently and effectively if this can be achieved. The following article presents a template on the minimum evidence required to justify phase III clinical trials in the critically ill population.


Degradation of alkyl ethers, aralkyl ethers, and dibenzyl ether by Rhodococcus sp. strain DEE5151, isolated from diethyl ether-containing enrichment cultures.
Twenty strains isolated from sewage sludge were found to degrade various ethers, including alkyl ethers, aralkyl ethers, and dibenzyl ether. In Rhodococcus strain DEE5151, induction of ether degradation needed substrates exhibiting at least one unsubstituted Calpha-methylene moiety as the main structural prerequisite. The cleavage reaction observed with anisole, phenetole, and dibenzyl ether indicates that the initial oxidation occurs at such respective Calpha positions. Diethyl ether-induced strain DEE5151 degraded dibenzyl ether via intermediately accumulated benzoic acid. Phenetole seems to be subject also to another ether-cleaving enzyme. Other strains of this group showed different enzymatic activities towards the substrate classes investigated.


Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid.
The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.


A patient with mosaic neurofibromatosis type 2 presenting with early onset meningioma.
A female patient was found to have meningioma when she was 3 years and 11 months old and subtotal excision was performed. The residual tumour recurred 3 months after the first excision, and again 11 months after the second one. She was also found to have subcutaneous neurofibroma. However, her clinical features did not fulfil the diagnostic criteria for neurofibromatosis type 2 (NF2), and her family history was unremarkable. Considering that primary meningioma is extremely rare in the paediatric population, the diagnosis of NF2 was considered. It was thought that this might have an impact on her subsequent management. Genetic testing on blood DNA for NF2 was arranged, and the results confirmed that she had mosaic deletion of the promoter to exon 16 of NF2. With uncertainty of whether NF2 mutations are also present in other tissues, vigilant follow-up for other NF2-related complications would be required in the future.


Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer.
It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.


Considerations of 201T1 as a myocardial radionuclide imaging agent in man.
Recent reports have suggested the use of intravenous 201T1 (thallium-201) for myocardial imaging with the gamma scintillation camera. In order to better appreciate the possible utility of this agent in humans we examined its distribution and kinetics in 13 patients and in six mongrel dogs, three with experimental coronary artery occlusion. In addition, 201T1 was compared to 86Rb (rubidium-86) in 84 rats. In the rat heart, the concentration of 201T1 was 30% higher than that of 86Rb ten minutes after injection. Moreover, myocardium-to-blood ratios for 201T1 averaged 51:1, but only 32:1 for 86Rb ten minutes after administration. In the dog heart, the distribution of 201T1 paralleled that of radioiodinated (131I) albumin particles injected into the left atrium and, thus, appears to be related to regional blood flow. Its concentration in ischemic regions decreased to 32.3% of the normally perfused myocardium. In the patients with a recent or old myocardial infarction, areas of decreased 201T1 uptake were easily identified and corresponded in location to that by ECG. Repeat scans 24 hours after the initial injection showed a significant retention of 201T1 by the myocardium. 201T1 blood levels in humans 15 minutes after injection were low (averaging 1.06% +/- 0.41% SD of the total dose per liter) and these levels decreased with a biological half-life of 3.1 +/- 0.7 days. Twenty-four hour urinary excretion rates ranged from 0.6 to 6.5% of the total dose and appeared related to urinary flow and the concentation of 201T1 in blood. Because of the higher target to background ratios, 201T1 compares favorably with radioactive rubidium. 201T1 in diagnostic doses remained without detectable adverse effects and appears promising as an agent for visualizing abnormal regional myocardial perfusion in patients with coronary artery disease.


Effects of high glucose on proliferation and function of circulating fibrocytes: Involvement of CXCR4/SDF‑1 axis.
The present study aimed to further investigate the effects of high glucose on the function of circulating fibrocytes and its underlying mechanisms. The total peripheral blood mononuclear cells were obtained from normal glucose tolerance patients and type 2 diabetic mellitus patients. Circulating fibrocytes were stimulated with different glucose concentrations for different time periods (24, 48 and 72 h). Cell proliferation was determined by Cell Counting Kit‑8 assay. The expression of connective tissue growth factor (CTGF) was detected by western blotting. The expression of COL‑I was detected by flow cytometry. The apoptotic bodies of cells were detected by fluorescence microscopy after Hoechst33258 staining. The invasive and migration abilities of fibrocytes were detected by Transwell chamber assay. Secretion of stromal cell‑derived factor 1 (SDF‑1) was measured by ELISA. The circulating fibrocytes showed a typical spindle‑shape and were double‑positive for cluster of differentiation 45 (green) and COL‑I (red). Compared with the 5.5 mmol/l glucose group, a high glucose concentration significantly promoted the proliferation of circulating fibrocytes and showed the most significant effects at 30 mmol/l after treatment for 48 h. AMD3100 showed no effects on the proliferation of circulating fibrocytes. Flow cytometry revealed that 30 mmol/l glucose significantly promoted the expression of COL‑I vs. 5.5 mmol/l glucose group (P<0.01), while AMD3100 reversed this (P<0.05). Hoechst33258 staining showed no differences in the apoptotic bodies between experimental groups (P>0.05). Western blotting revealed that the expression of CTGF was decreased significantly by AMD3100 pretreatment (P<0.01). Transwell chamber assay showed that 30 mmol/l glucose significantly promoted the invasive and transfer abilities (P<0.01) of fibrocytes when compared with the 5.5 mmol/l glucose group. While AMD3100 reversed the cell migratory effects induced by high glucose (P<0.01). In addition, the secretion of SDF‑1 stimulated by 30 mmol/l glucose DMEM showed no differences compared with 5.5 mmol/l glucose DMEM (P>0.05). High glucose stimulated the expressions of CTGF and COL‑I, and promoted migration of circulating fibrocytes via the CXC chemokine receptor 4/SDF‑1 axis.


Detection and classification of paraproteins by capillary immunofixation/subtraction.
A selection of 58 specimens with a monoclonal component identified by immunoelectrophoresis and/or immunofixation was analyzed with the immunosubtraction procedure on the Paragon 2000 capillary electrophoresis system. The capillary system detected 93% of the paraproteins and, using immunosubtraction, correctly identified 91% of the paraproteins. Paraproteins that were detected by immunofixation and/or immunoelectrophoresis but not by capillary electrophoresis were also missed by agarose electrophoresis and cellulose acetate electrophoresis. Cellulose acetate electrophoresis was the least sensitive method for detection of paraproteins. Only 74% of the monoclonal components were detected by this technique, whereas 86% were revealed by agarose electrophoresis. In addition to monoclonal paraproteins, we also studied biclonal paraproteins and oligoclonal banding. Capillary electrophoresis and immunosubtraction correctly detected and identified three specimens containing biclonal paraproteins. In one specimen, capillary zone electrophoresis detected only one band, whereas agarose gel electrophoresis detected two bands. The sensitivity for detection and identification of oligoclonal banding by capillary electrophoresis was inferior to immunofixation.


Sonographically guided percutaneous needle biopsy of soft tissue masses with histopathologic correlation.
The purpose of this study was to evaluate the accuracy of sonographically guided percutaneous core biopsy of soft tissue masses. We retrospectively reviewed the medical records of patients who underwent sonographically guided biopsy of soft tissue masses at our institution during a 50-month period. Core biopsy histopathologic results were compared with surgical or clinical follow-up. One hundred eighty-three patients, 76 male and 107 female, with a mean age of 48.5 years were included in the study. Thirteen patients had more than 1 biopsy, and the total number of biopsies performed was 196. Five patients were lost to follow-up. Biopsy results were diagnostically accurate in 174 (91%) cases. Thirteen biopsies were inconclusive. No complications occurred. The overall sensitivity, specificity, positive predictive value, and accuracy in separating malignant from benign lesions were 97%, 99%, 99%, and 98%, respectively. Sonographically guided core needle biopsy is an accurate and safe means to obtain tissue samples for the histopathologic diagnosis of soft tissue masses. It obviates the need for open biopsy and should be performed routinely for treatment planning.


Assessment of risk of late rectal bleeding for patients with prostate cancer started on anticoagulation before or after radiation treatment.
To evaluate the risk of late rectal bleeding and its association with the timing and type of anticoagulation use in patients receiving dose-escalated radiation therapy (RT) (≥ 7,560 cGy) for prostate cancer. Between 2003-2010, 465 patients were treated at our Institution with dose-escalated RT and included in this analysis. Patients were placed into the following categories: no anticoagulation use, aspirin during RT, clopidogrel/warfarin during RT, aspirin after completion of RT, clopidogrel/warfarin after completion of RT. The overall bleeding rate was 7.5%. For those on aspirin during RT, the 4-year freedom from rectal bleeding (FFBS) rate was 91%, compared to 94.7% for patients who were never on anticoagulation (p=0.16). For those on warfarin/clopidogrel during RT the 4-year FFBS rate was 78.2%, compared to 94.7% in those never on anticoagulation (p<0.001). On multivariate analysis, use of warfarin/clopidogrel during radiation treatment were strongly associated with an increased risk of rectal bleeding (multivariate HR=4.84, 95% CI=1.84-12.68, p=0.001). However, initiation of anticoagulation after completion of radiation treatment did not significantly increase the risk of rectal bleeding (multivariate HR=0.78, 95% CI=0.21-2.91, p=0.71). The use of clopidogrel or warfarin during radiation is associated with significantly increased risk of rectal bleeding. However, initiation of these medications after completion of radiation does not appear to impact such risk.


Ab initio molecular dynamics study of the mechanism of proton recombination with a weak base.
Despite its fundamental nature, many of the microscopic features of acid–base recombination remain poorly understood. In this work, we use ab initio molecular dynamics simulations to study the recombination of the proton with a weak base, the carbonate ion CO3(2–). Our simulations elucidate the network structure around CO3(2–) that provides a distribution of pathways over which recombination can occur. We observe that the penultimate neutralization step involves a correlated behavior of the transferred protons that is mediated by the water wires decorating the carbonate. These concerted proton transfers are coupled to collective compressions of these water wires. We show further that these processes are dynamically coupled to the reorganization of the water molecules hydrating the CO3(2–) ion. The insights from these simulations help to bridge the structural and dynamical complexity of the microscopic mechanisms with those of phenomenological models invoked by experiments in this field.


SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential.
Mice that are deficient in suppressor of cytokine signaling-1 (SOCS-1) succumb to neonatal mortality that is associated with extensive cellular infiltration of many tissues. T cells seem to be necessary for disease, which can be alleviated largely by neutralizing interferon-gamma. Examining T cell receptor (TCR) specificity shows that even monospecific T cells can mediate disease in SOCS-1-deficient mice, although disease onset is substantially faster with a polyclonal T cell repertoire. A major phenotype of SOCS-1-/- mice is the accumulation of CD44(high)CD8+ peripheral T cells. We show that SOCS-1-deficient CD8, but not CD4, T cells proliferate when transferred into normal (T cell-sufficient) mice, and that this is dependent on two signals: interleukin (IL)-15 and self-ligands that are usually only capable of stimulating homeostatic expansion in T cell-deficient mice. Our findings reveal that SOCS-1 normally down-regulates the capacity of IL-15 to drive activation and proliferation of naive CD8 T cells receiving TCR survival signals from self-ligands. We show that such dysregulated proliferation impairs the deletion of a highly autoreactive subset of CD8 T cells, and increases their potential for autoimmunity. Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell-mediated disease of SOCS-1-/- mice.


Sema3A drastically suppresses tumor growth in oral cancer Xenograft model of mice.
Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Interestingly, the axonal sprouting inhibitor semaphorin 3A (Sema3A), a potent suppressor of tumor angiogenesis in various cancer models, is lowly expressed in human oral cancer. Thus, we hypothesized that overexpression of Sema3A in human oral cancer cells may have potential therapeutic effects. The LentiSema3A-EGFP was first constructed and transduced to the tongue squamous cell carcinoma cell line SSC-9. Angiogenesis assay was performed with endothelial cell tube formation assay and chorioallantoic membrane (CAM) assay. Tumor xenografts model was used to evaluate the effect of Sema3a on the tumor growth. Finally, western blot was performed to study the mechanisms of inhibiting angiogenesis by Sema3A. In vitro and in vivo approaches revealed that Sema3A significantly inhibited tube formation of endothelial cells and reduced angiogenesis in CAM assay. In addition, overexpression of Sema3A in the tongue squamous cell carcinoma cell line SSC-9 resulted in significantly reduced angiogenesis and drastically suppressed tumor growth in mice. Mechanistically, Sema3A inhibited the phosphorylation of VEGFR2, as well as Src and FAK, downstream of the VEGF/VEGFR2 pathway. Our results demonstrated that overexpression of Sema3A in oral cancer cells drastically suppressed tumor growth by inhibiting angiogenesis. Our findings provide a basis for the development of novel therapeutics in the management of oral cancer.


Long-term follow-up of Tako-Tsubo-like syndrome: a retrospective study of 22 cases.
To assess the late outcome of the Tako-Tsubo like syndrome in a community hospital in northern Italy. We reviewed 2233 patients who were admitted from 2001 to 2006 with diagnosis of acute coronary syndrome. Twenty-two patients (1%) presenting clinical and instrumental characteristics of Tako-Tsubo like syndrome were included in the study and prospectively underwent clinical and echocardiographic follow-up. All patients were women; aged 76 +/- 7 years; 82% experienced a stress before the acute episode; 50% reported chest pain and dyspnoea also days before. Mean troponin peak value was 3.6 +/- 3.3 microg/l. Mean acute echocardiographic ejection fraction was 40 +/- 7%. Eighteen percent of them presented major in-hospital complications. At a mean follow-up time of 27 +/- 19 months, 2 patients (9%) died because of ischemic stroke and renal failure, respectively, 14 (63%) were asymptomatic, 1 (5%) declared a paroxysmal episode of atrial fibrillation, and 5 (23%) still lamented dyspnoea or atypical chest pain. In all patients, typical apical ballooning disappeared and an increase in mean ejection fraction to 60 +/- 4% was observed. After complications are promptly recognized and treated in the acute phase, prognosis of Tako-Tsubo like syndrome appears to be good at long-term follow-up, with a complete recovery of normal left ventricular function.


Physiological studies of methane- and methanol-oxidizing bacteria: immunological comparison of a primary alcohol dehydrogenase from Methylococcus capsulatus and Pseudomonas sp. M27.
A primary alcohol dehydrogenase was purified from cell extracts of two apparently unrelated microorganisms, namely, Pseudomonas sp. M27 and Methylococcus capsulatus. Rabbit antiserum prepared against the purified enzyme from M. capsulatus revealed distinctive antigenic determinants by quantitative and gel precipitin reactions. Rabbit antiserum to M27 enzyme detected both distinctive and shared antigenic determinants. Certain methane- and methanol-oxidizing bacteria were grouped on the basis of serological cross-reacting enzyme specificities.


Evolutionary studies of the bHLH transcription factors belonging to MBW complex: their role in seed development.
The MBW complex consist of proteins belonging to three major families (MYB, bHLH and WDR) involved in various processes throughout plant development: epidermal cell development, mucilage secretory cells and flavonoid biosynthesis. Recently, it has been reported that TT8, encoding a bHLH transcription factor, is involved in the biosynthesis of flavonoids in the seed coat and it also plays a role in bypassing the postzygotic barrier resulting from an unbalance in genetic loads of the parental lines. Here, we focus on the functional evolution, in seed development, of the bHLH proteins that are part of the MBW complex, complemented with a literature review. Phylogenetic analyses performed across seed plants and expression analyses in the reproductive tissues of four selected angiosperms (Arabidopsis thaliana, Brassica napus, Capsella rubella and Solanum lycopersicum) allow us to hypothesize on the evolution of its functions. TT8 expression in the innermost layer of the seed coat is conserved in the selected angiosperms. However, except for Arabidopsis, TT8 is also expressed in ovules, carpels and fruits. The homologues belonging to the sister clade of TT8, EGL3/GL3, involved in trichome development, are expressed in the outermost layer of the seed coat, suggesting potential roles in mucilage. The ancestral function of these genes appears to be flavonoid biosynthesis, and the conservation of TT8 expression patterns in the innermost layer of the seed coat in angiosperms suggests that their function in postzygotic barriers might also be conserved. Moreover, the literature review and the results of the present study suggest a sophisticated association, linking the mechanisms of action of these genes to the cross-communication activity between the different tissues of the seed. Thus, it provides avenues to study the mechanisms of action of TT8 in the postzygotic triploid block, which is crucial because it impacts seed development in unbalanced crosses.


Adverse cardiovascular events associated with biodegradable polymer drug-eluting stents and durable polymer everolimus-eluting stents: A systematic review and meta-analysis of 10 randomized controlled trials.
Controversies have been observed among network meta-analyses comparing biodegradable polymer drug-eluting stents (BP-DES) with durable polymer drug-eluting stents (DP-DES). We aimed to compare the adverse cardiovascular events associated with BP-DES and durable polymer everolimus-eluting stents (DP-EES) using a large number of patients obtained from randomized controlled trials (RCTs). Electronic databases were searched for randomized trials comparing BP-DES with DP-EES. Adverse cardiovascular outcomes observed between 6 months and 3 years were considered as the clinical endpoints in this analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software. All authors had full access to the data, and they have read and agreed to the manuscript as written. Ten trials involving a total number of 13,218 patients (7451 patients treated by BP-DES and 5767 patients treated by DP-EES) were included. No significant difference was observed when analyzing mortality and myocardial infarction between BP-DES and DP-EES with OR 1.08, 95% CI 0.87-1.34, P = .47 and OR 1.04, 95% CI 0.84-1.28, P = .72 respectively. Target vessel revascularization, target lesion revascularization, major adverse cardiac events, and stroke were also not significantly different with OR 1.11, 95% CI 0.92-1.33, P = .28; OR 1.11, 95% CI 0.94-1.33, P = .22; OR 1.12, 95% CI 0.99-1.27; P = .07; and OR 1.13, 95% CI 0.69-1.84; P = .62 respectively. In addition, total stent thrombosis (ST) was similarly reported between BP-DES and DP-EES with OR 0.85, 95% CI 0.59-1.21; P = .37. However, even if BP-DES were associated with a higher rate of definite ST with OR 1.69, 95% CI 0.92-3.08, P = .09 and DP-EES were associated with a higher rate of probable ST with OR 0.67, 95% CI 0.38-1.17, P = .16, these results were not statistically significant. Between 6 months and 3 years, BP-DES were similar in terms of cardiovascular outcomes compared to DP-EES. However, further long-term follow-up research is recommended.


Effective decrease of photoelectric emission threshold from gold plated surfaces.
Many applications require charge neutralization of isolated test bodies, and this has been successfully done using photoelectric emission from surfaces which are electrically benign (gold) or superconducting (niobium). Gold surfaces nominally have a high work function (∼5.1 eV) which should require deep UV photons for photoemission. In practice, it has been found that it can be achieved with somewhat lower energy photons with indicative work functions of (4.1-4.3 eV). A detailed working understanding of the process is lacking, and this work reports on a study of the photoelectric emission properties of 4.6 × 4.6 cm2 gold plated surfaces, representative of those used in typical satellite applications with a film thickness of 800 nm, and measured surface roughnesses between 7 and 340 nm. Various UV sources with photon energies from 4.8 to 6.2 eV and power outputs from 1 nW to 1000 nW illuminated ∼0.3 cm2 of the central surface region at angles of incidence from 0° to 60°. Final extrinsic quantum yields in the range 10 ppm-44 ppm were reliably obtained during 8 campaigns, covering a period of ∼3 years but with intermediate long-term variations lasting several weeks and, in some cases, bake-out procedures at up to 200 °C. Experimental results were obtained in a vacuum system with a baseline pressure of ∼10-7 mbar at room temperature. A working model, designed to allow accurate simulation of any experimental configuration, is proposed.


Homocysteine plasma concentration levels for the prediction of preeclampsia in women with chronic hypertension.
The purpose of this study was to evaluate prospectively midtrimester homocysteine concentration levels for the prediction of superimposed preeclampsia in women with chronic hypertension. Between March 1, 2000, and February 1, 2002, pregnancies that were complicated by chronic hypertension that required medication had homocysteine, vitamin B(12), and folate concentrations measured between 16 and 20 weeks of gestation. All women received folate supplementation. An upper limit threshold for increased homocysteine was defined as the mean value plus 2 SDs. Fifty-seven women were enrolled. Mean homocysteine concentration levels were 5.1+/-1.7 micromo/L for the 16 women who had preeclampsia compared with 4.7+/-1.3 micromo/L for the 41 women without preeclampsia (P=.56). Two of 16 women with preeclampsia (13%) had concentration levels that exceeded the 95th percentile (6.9 micromo/L) compared with 2 of 41 women (5%) without preeclampsia (P=.31). The sensitivity and specificity were 13% (95% CI, 1.6-38.3) and 95.1% (95% CI, 83.5-99.4), respectively. Second-trimester homocysteine concentration levels were not helpful in the prediction of preeclampsia in chronically hypertensive women.


Equine coronary artery responds to 5-hydroxytryptamine with relaxation in vitro.
Isolated equine coronary arteries responded to 5-hydroxytryptamine (5-HT) with relaxations in both endothelium-dependent and endothelium-independent mechanisms. Experiments were designed to characterize the 5-HT receptor subtype mediating these relaxations. Both 5-HT and alpha-methyl-5-HT (alpha-Me-5-HT; 5-HT2 agonist) produced concentration-dependent relaxations in equine coronary arteries precontracted with a thromboxane A2 derivative (ONO11113). The degree of the maximal relaxation induced by alpha-Me-5-HT was about one-half of that induced by 5-HT. In the coronary arteries without endothelium, alpha-Me-5-HT produced no relaxation, but 5-HT caused relaxation, which was inhibited by a 5-HT1 antagonist (methysergide, mianserin and methiothepin), but was inhibited neither by ketanserin (5-HT2 antagonist) nor by MDL72222 (5-HT3 antagonist). In the coronary arteries with endothelium, however, the relaxation induced by alpha-Me-5-HT was inhibited by ketanserin, L-nitro-arginine (NO synthase inhibitor) and methylene blue (soluble guanylate cyclase inhibitor). These results suggest that the relaxation induced by 5-HT in equine coronary arteries depends mainly on the stimulation of both 5-HT1 receptor subtype on smooth muscle cells directly, and 5-HT2 receptor subtype on endothelial cells indirectly by liberating endothelium-derived NO.


[Effect of the complex treatment conducted in the rehabilitation center in the city of Loznitsa on oral glucose tolerance and insulin secretion in patients with morbid obesity].
In the rehabilitation center Loznitsa the influence of the comprehensive treatment on the oral glucose tolerance test and insulin secretion was studied in patients with high-degree obesity. A flat blood sugar and insulin curve by oral glucose tolerance test was found without manifested hyperglycemia and hyperinsulinemia. One month treatment leads to a decrease of the basal insulinemia on the background of which the stimulating effect of glucose loading is more clearly expressed up to the 120th minute but without increase of the absolute values above the reference ranges.


Epitopes of Escherichia coli alpha-hemolysin: identification of monoclonal antibodies that prevent hemolysis.
The antigenic regions of Escherichia coli alpha-hemolysin were determined by antibody binding to cyanogen bromide (CnBr) fragments of this protein under denatured conditions. Alpha-hemolysin was isolated from filtered culture supernatants of a recombinant strain by a combination of trichloroacetic acid precipitation and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Alpha-hemolysin was used to (i) produce polyclonal rabbit antisera and murine monoclonal immunoglobulin G (IgG) antibodies and (ii) generate CnBr fragments. Rabbit IgG and 13 murine IgG monoclonal antibodies (MAbs) were elicited to alpha-hemolysin as determined by enzyme-linked immunosorbent and immunoprecipitation assays. Antibodies bound to three specific CnBr fragments of alpha-hemolysin in Western blots (immuno-blots) from sodium dodecyl sulfate-polyacrylamide gels: CnBrII (encompassing residues [R] 2 to 160), CnBrV (R 425 to 892), and CnBrVI (R 893 to 1023). Five MAbs bound to CnBrII, seven MAbs bound to CnBrV, and one MAb bound to CnBrVI. These specific CnBr fragments are predicted to be hydrophilic and charged. There was no antibody binding to the highly hydrophobic CnBrIII (R 161 to 416). Similar binding patterns were observed when rabbit polyclonal anti-alpha-hemolysin IgG was used. Polyclonal antibodies to alpha-hemolysin readily inhibited hemolysis and its neutralization capacity was 4- to 64-fold more potent than neutralizing MAbs. The five MAbs that bind to CnBrII possessed hemolytic neutralizing activity to various degrees. In contrast, only three of seven MAbs that bind to CnBrV fragment exhibited neutralization capacity to various degrees; the MAb to CnBrVI did not exhibit this capacity. Based on these data, we predict that denatured alpha-hemolysin and its CnBrII and CnBrV fragments might be worthwhile immunoprophylactic candidates for the prevention of hemolysin-mediated E. coli tissue injury.


Relationship Between Glycerolipids and Photosynthetic Components During Recovery of Thylakoid Membranes From Nitrogen Starvation-Induced Attenuation in Synechocystis sp. PCC 6803.
Thylakoid membranes, the site of photochemical and electron transport reactions of oxygenic photosynthesis, are composed of a myriad of proteins, cofactors including pigments, and glycerolipids. In the non-diazotrophic cyanobacterium Synechocystis sp. PCC 6803, the size and function of thylakoid membranes are reduced under nitrogen (N) starvation but are quickly recovered after N addition to the starved cells. To understand how the functionality of thylakoid membranes is adjusted in response to N status in Synechocystis sp. PCC 6803, we examined changes in thylakoid components and the photosynthetic activity during the N starvation and recovery processes. In N-starved cells, phycobilisome content, photosystem II protein levels and the photosynthetic activity substantially decreased as compared with those in N-sufficient cells. Although the content of chlorophyll (Chl) a, total protein and total glycerolipid also decreased under the N-starved condition based on OD730 reflecting cell density, when based on culture volume, the Chl a and total protein content remained almost constant and total glycerolipid content even increased during N starvation, suggesting that cellular levels of these components decrease under the N-starved condition mainly through dilution due to cell growth. With N addition, the photosynthetic activity quickly recovered, followed by full restoration of photosynthetic pigment and protein levels. The content of phosphatidylglycerol (PG), an essential lipid constituent of both photosystems, increased faster than that of Chl a, whereas the content of glycolipids, the main constituents of the thylakoid lipid bilayer, gradually recovered after N addition. The data indicate differential regulation of PG and glycolipids during the construction of the photosynthetic machinery and regeneration of thylakoid membranes. Of note, addition of PG to the growth medium slightly accelerated the Chl a accumulation in wild-type cells during the recovery process. Because PG is required for the biosynthesis of Chl a and the formation of functional photosystem complexes, rapid PG biosynthesis in response to N acquisition may be required for the rapid formation of the photosynthetic machinery during thylakoid regeneration.


Chlorpromazine Increases the Expression of Polysialic Acid (PolySia) in Human Neuroblastoma Cells and Mouse Prefrontal Cortex.
The neural cell adhesion molecule (NCAM) is modified by polysialic acid (polySia or PSA) in embryonic brains. In adult brains, polySia modification of NCAM is only observed in restricted areas where neural plasticity, remodeling of neural connections, or neural generation is ongoing although the amount of NCAM remains unchanged. Impairments of the polySia-expression and several single nucleotide polymorphisms (SNPs) of the polysialyltransferase (polyST) ST8SIA2 gene are reported to be associated with schizophrenia and bipolar disorder. Chlorpromazine (CPZ) is well-known as an agent for treating schizophrenia, and our hypothesis is that CPZ may affect the polySia expression or the gene expression of polySTs or NCAM. To test this hypothesis, we analyzed the effects of CPZ on the expression of polySia-NCAM on human neuroblastoma cell line, IMR-32 cells, by immunochemical and chemical methods. Interestingly, the cell surface expression of polySia, especially those with lower chain lengths, was significantly increased on the CPZ-treated cells, while mRNAs for polySTs and NCAM, and the amounts of total polySia-NCAM remained unchanged. The addition of brefeldin A, an inhibitor of endocytosis, suppressed the CPZ-induced cell surface polySia expression. In addition, polySia-NCAM was also observed in the vesicle compartment inside the cell. All these data suggest that the level of cell surface expression of polySia in IMR-32 is highly regulated and that CPZ changes the rate of the recycling of polySia-NCAM, leading to the up-regulation of polySia-NCAM on the cell surface. We also analyzed the effect of CPZ on polySia-expression in various brain regions in adult mice and found that CPZ only influenced the total amounts of polySia-NCAM in prefrontal cortex. These results suggest a brain-region-specific effect of CPZ on the expression of total polySia in mouse brain. Collectively, anti-schizophrenia agent CPZ consistently up-regulates the expression polySia at both cellular and animal levels.


An unbalanced (6q;13q) translocation in a male with clinical features of Ehlers-Danlos type II syndrome.
Ehlers-Danlos syndrome has been divided into several different types according to the variety and severity of clinical manifestations, and may follow autosomal dominant, autosomal recessive, or X linked patterns of inheritance. Only rarely have chromosome anomalies been seen in patients manifesting phenotypic features of the syndrome and most are considered insignificant. However, one case report involved a balanced t(9;17)(q34;q11) in a female with the clinical features of Ehlers-Danlos type I and IV syndromes and, as noted by McKusick: "It is possible, furthermore, that certain very rare syndromes that are transmitted in a Mendelian manner are the result of small chromosome aberrations, such as deletion or inversion, affecting the action of several genes". We present a 14 year old male with features of Ehlers-Danlos type II syndrome and an unbalanced (6q;13q) translocation.


Nature of albumin exported from the frog oocyte following microinjection of mouse liver mRNA.
Microinjections of mouse liver mRNA into Xenopus laevis oocytes induced efficient export of a polypeptide with an apparent Mr or 68,000 which was immunoprecipitable with anti-mouse albumin antibody. Analysis of the anti-albumin precipitate of the exported protein by two-dimensional gel electrophoresis showed that the electrophoretic behavior precisely coincided with that of authentic mouse serum albumin. This result indicates that the Xenopus oocyte may perform secretory processes similar or identical to those occurring in liver cells with respect to the processing of albumin.


The contact activation mechanism in human plasma: activation induced by dextran sulfate.
Incubation of normal human plasma with dextran sulfate for 7 min at 4 degrees C generates kallikrein amidolytic activity. No kallikrein activity is generated in factor XII or prekallikrein-deficient plasma and only small amounts (8%) in high molecular weight (HMW) kininogen-deficient plasma. Addition of specific antisera directed against prekallikrein or HMW kininogen to normal plasma blocked the generation of kallikrein activity by dextran sulfate. Thus, factor XII, prekallikrein, and HMW kininogen are essential components for optimal activation of prekallikrein. The role of limited proteolysis in the activation of prekallikrein induced by dextran sulfate was studied by adding 125I-prekallikrein to plasma. The generation of kallikrein activity paralleled the proteolytic cleavage of prekallikrein as judged on SDS gels in the presence of reducing agents. The same cleavage fragments were observed as obtained by activation of purified prekallikrein by beta-factor-XIIa. Addition of 131I-HMW kininogen and 125I-factor XII or 131I-HMW kininogen and 125I-prekallikrein to normal plasma followed by activation with dextran sulfate and analysis on SDS gels indicated that the observed cleavage of prekallikrein and HMW kininogen is fast compared to the observed cleavage of factor XII, which is much slower and less extensive. During the first minutes of incubation of normal plasma with dextran sulfate, mainly alpha-factor-XIIa is formed. During prolonged incubation, beta-factor-XIIa is also formed.


Ooplast transfer of triploid pronucleus zygote improve reconstructed human-goat embryonic development.
Poor development of the interspecies somatic cell nuclear transfer (iSCNT) embryos was due to nuclear-mitochondrial incompatibility. In humans, it has been known that ooplast transfer (OT) could support normal fertilization, the development of embryos and prevents the transmission of mtDNA disease. To investigate whether OT could support development of the iSCNT embryos, the ooplast of Triploid Pronucleus (3PN) zygote which would be discarded in IVF lab was transferred into the enucleated goat oocytes to construct humanized iSCNT embryos in our study. The results showed the 3PN-OT could significantly improve the early development of humanized iSCNT embryos. The percentage of blastocyst development of OT group was also higher than that of the control group. Interestingly, the morphology of some OT-iSCNT blastocysts was similar to normal human blastocysts in vitro fertilization, while the morphology of iSCNT blastocysts from control group was similar to goat blastocysts. Importantly, the pluripotent marker Oct4 of the OT-iSCNT blastocyst was expressed stronger than that of the control group. These results suggested that 3PN-OT could improve the developmental potency of human iSCNT embryos and would facilitate establishing ESCs from iSCNT blastocysts.


Automated medical knowledge acquisition: a study of consistency.
Knowledge bases are more representative of the population of medical experts if they are constructed by a group of individuals, rather than one practitioner. However, one runs into problems with consistency when information is elicited from a group without a consistent format and terminology. This study examines the consistency of relatively unconstrained computer-elicited medical knowledge using the computer program, KSSO. The results of this study show that the group of ten general internists were somewhat consistent in the diagnoses they listed for a patient presenting with chest pain. They were much less consistent in the findings they listed to differentiate between the diagnoses they had listed. The mean number of subjects listing each diagnosis was 3.3 +/- 2.7 while the mean for findings was 2.0 +/- 1.5. The implications of these data are discussed.


Organization of a cloned repetitive DNA fragment in mosquito genomes (Diptera: Culicidae).
The structure and genomic organization of a cloned 5.2-kb repetitive DNA fragment, H-85, isolated from the Aedes albopictus genome have been examined. In situ hybridization of the 3H-labeled H-85 DNA to the meiotic and mitotic chromosome preparations of Ae. albopictus shows that the sequences homologous to H-85 DNA are dispersed throughout the length of all three pairs of chromosomes. A similar pattern of in situ hybridization appears in Aedes seatoi, Aedes flavopictus, and Aedes aegypti. The study shows that the arrangement of sequences in the cloned 5.2-kb fragment is rare in the Ae. albopictus genome. Dot-blot hybridization reveals that the sequences homologous to H-85 DNA are present in 12 species of mosquitoes examined, belonging to six genera in subfamilies Culicinae ad Anophelinae. The H-85 sequences are also present in the genome of Mochlonyx velutinus of the nematocerous family Chaoboridae, earlier proposed as the ancestor of the mosquito family Culicidae. Although the sequences homologous to H-85 DNA are present in different species of mosquitoes, they have diverged in their structure and organization. The cloned 5.2-kb fragment is composed of elements of different and independently evolving repetitive DNA families.


An X-ray-based method for the determination of the contrast agent propagation in 3-D vessel structures.
A method for the determination of the contrast-agent propagation in vessel trees is presented. A standard three-dimensional (3-D) rotational angiography procedure is performed to reconstruct the morphology of the contrast-filled vessel tree in a 3-D volume. An additional fluoroscopy projection series acquired with a fixed projection angle delivers the temporal information of the bolus propagating. The mapping of the propagation information from the two-dimensional projections to the 3-D image data set is the topic of this paper. A symbolic tree structure is built up that represents the vessel tree including bifurcations. Neighborhood relations between vessel pieces are given in three dimensions. This facilitates filtering procedures and plausibility controls of the resulting time dependent 3-D data set. The presented method proved to be accurate with phantom data and gives novel insight in the feeding structure of arterio-venous malformations and aneurysms.


Roles of Histone Acetylation Modifiers and Other Epigenetic Regulators in Vascular Calcification.
Vascular calcification (VC) is characterized by calcium deposition inside arteries and is closely associated with the morbidity and mortality of atherosclerosis, chronic kidney disease, diabetes, and other cardiovascular diseases (CVDs). VC is now widely known to be an active process occurring in vascular smooth muscle cells (VSMCs) involving multiple mechanisms and factors. These mechanisms share features with the process of bone formation, since the phenotype switching from the contractile to the osteochondrogenic phenotype also occurs in VSMCs during VC. In addition, VC can be regulated by epigenetic factors, including DNA methylation, histone modification, and noncoding RNAs. Although VC is commonly observed in patients with chronic kidney disease and CVD, specific drugs for VC have not been developed. Thus, discovering novel therapeutic targets may be necessary. In this review, we summarize the current experimental evidence regarding the role of epigenetic regulators including histone deacetylases and propose the therapeutic implication of these regulators in the treatment of VC.


[Development of a novel artificial gene delivery system multifunctional envelope-type nano device for gene therapy].
For efficient gene delivery to the nucleus, nonviral vectors need to overcome several barriers such as the plasma membrane, endosomal membrane, and nuclear membrane. To overcome these obstacles, it is necessary to equip the delivery system with various functional devices. However, it is difficult to package all such functional devices into a single system to exert each of their functions at the appropriate time and at the correct location. Thus our group proposed a new packaging concept, "programmed packaging." A multifunctional envelope-type nano device (MEND) was developed for use as an efficient nonviral system for the delivery of plasmid DNA (pDNA), oligodeoxynucleotide (ODN), and siRNA using octaarginine (R8) as an internalizing ligand based on the programmed packaging. The R8-modified MEND (R8-MEND) encapsulating pDNA showed significantly high transfection activity comparable to that of adenovirus, and the uptake pathway of R8-MEND was macropinocytosis, which can avoid lysosomal degradation. R8-MEND successfully delivered gene to hair follicles after in vivo topical application to mouse skin. Moreover, R8-MEND encapsulating anti-luciferase ODN using protamine showed a 90% antisense effect, and R8-MEND encapsulating siRNA condensed with stearylated R8 significantly silenced luciferase activity. Our group thus succeeded in the development of R8-MEND based on programmed packaging, and MEND is a promising new delivery system for pDNA and functional nucleic acids.


Psychometric properties of the Iranian version of the Copenhagen Burnout Inventory.
Background: The Copenhagen Burnout Inventory (CBI) is a commonly used tool for evaluation of job burnout in three (personal, work-related and client-related) domains. The aims of this study were to translate and investigate the psychometric properties of the Iranian (Persian) CBI. Methods: A total of 750 employees of different occupations (from educational centres, healthcare, industrial settings, and social services) participated in this descriptive methodological study. A forward-backward procedure was applied and content validity was evaluated by a panel of10 experts. Exploratory and confirmatory factor analyses were used for construct validity. The internal consistency (using Cronbach's alpha), test-retest reliability (using intraclass correlation coefficient - ICC), and feasibility (using ceiling and floor effect) were also assessed for this tool. Results: Content validity of the Persian CBI was established. Three-factor structure of the PersianCBI was supported by the factor analysis, and this confirmed the construct validity of the instrument. The internal consistency (Cronbach's alpha ranged from 0.82 to 0.90) and test-retest reliability (ICC ranged from 0.85 to 0.95) were excellent and there was no ceiling or floor effect. Conclusion: The Persian CBI is a valid and reliable measurement tool for burnout in the Iranian context.


Enteral access in mechanically ventilated patients.
The early institution of enteral nutrition is now accepted as the preferred route of feeding in critically ill patients with a functioning gastrointestinal tract. It is particularly important to establish early enteral nutrition in mechanically ventilated patients because of the metabolic demands associated with mechanical ventilation. The options for enteral access in mechanically ventilated patients are reviewed, with an emphasis on those techniques that may be performed at the bedside. The advantages, disadvantages, and complications of the different techniques will be considered.


DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex.
DJ-1 gene mutations have been found to cause early-onset Parkinson's disease. We report a family from southern Italy with three brothers affected by early-onset parkinsonism, dementia, and amyotrophic lateral sclerosis. Molecular analysis of the DJ-1 gene in two living patients showed a novel homozygous mutation in exon 7 (E163K) and a new homozygous mutation (g.168_185dup) in the promoter region of the gene. Both mutations cosegregated with the disease and were detected in a heterozygous state in the patients' mother and their healthy siblings. Our findings expand the spectrum of clinical presentations associated with mutations in DJ-1 gene.


Fc gamma receptor biology and systemic lupus erythematosus.
The maintenance of immune homeostasis and the regulation of pro-inflammatory responses that underlie autoimmune pathology require a coordinated interplay between cytokines, cellular receptors and downstream signaling pathways. The family of fragment crystallizable receptors for immunoglobulin G (IgG) (Fc gammaR) represents a good example of how controlling the simultaneous triggering of activatory and/or inhibitory receptors results in a balanced immune response. Fc gammaRs play a crucial role in linking the antibody-mediated recognition of pathogens, allergens or auto-antigens to the cellular arm of the immune response. In this review, we detail how dysfunction in Fc gammaR pathways is linked to the development of the autoimmune disease, systemic lupus erythematosus.


Role of Thy-1,2+ cells in hemopoiesis regulation during hypoxia.
We studied the role of Thy-1,2+ cells in the regulation of hemopoiesis during oxygen deficiency of different genesis. These cells of the hemopoiesis-inducing microenvironment play an important role in the compensatory and adaptive reactions of the blood system to hypoxia. Thy-1,2+ cells directly or indirectly (via interaction with adherent myelokaryocytes) stimulated hemopoietic precursors. The effect of these cells on committed erythroid precursors was most pronounced.


RNA force field with accuracy comparable to state-of-the-art protein force fields.
Molecular dynamics (MD) simulation has become a powerful tool for characterizing at an atomic level of detail the conformational changes undergone by proteins. The application of such simulations to RNA structures, however, has proven more challenging, due in large part to the fact that the physical models ("force fields") available for MD simulations of RNA molecules are substantially less accurate in many respects than those currently available for proteins. Here, we introduce an extensive revision of a widely used RNA force field in which the parameters have been modified, based on quantum mechanical calculations and existing experimental information, to more accurately reflect the fundamental forces that stabilize RNA structures. We evaluate these revised parameters through long-timescale MD simulations of a set of RNA molecules that covers a wide range of structural complexity, including single-stranded RNAs, RNA duplexes, RNA hairpins, and riboswitches. The structural and thermodynamic properties measured in these simulations exhibited dramatically improved agreement with experimentally determined values. Based on the comparisons we performed, this RNA force field appears to achieve a level of accuracy comparable to that of state-of-the-art protein force fields, thus significantly advancing the utility of MD simulation as a tool for elucidating the structural dynamics and function of RNA molecules and RNA-containing biological assemblies.


Synthesis, structure, and magnetic properties of a Mn(21) single-molecule magnet.
The reaction of [Mn(3)O(O(2)CMe)(6)(py)(3)](ClO(4)) (1; 3Mn(III)) with [Mn(10)O(4)(OH)(2)(O(2)CMe)(8)(hmp)(8)](ClO(4))(4) (2; 10Mn(III)) in MeCN affords the new mixed-valent complex [Mn(21)O(14)(OH)(2)(O(2)CMe)(16)(hmp)(8)(pic)(2)(py)(H(2)O)](ClO(4))(4) (3; 3Mn(II)-18Mn(III); hmp(-) is the anion of 2-(hydroxymethyl)pyridine), with an average Mn oxidation state of +2.85. Complex 3.7MeCN crystallizes in the triclinic space group P. The structure consists of a low symmetry [Mn(21)(micro(4)-O)(4)(micro(3)-O)(12)(micro-O)(16)] core, with peripheral ligation provided by 16 MeCO(2)(-), 8 hmp(-), and 2 pic(-) groups and one molecule each of water and pyridine. The magnetic properties of 3 were investigated by both dc and ac magnetic susceptibility measurements. Fitting of dc magnetization data collected in the 0.1-0.8 T and 1.8-4.0 K ranges gave S = (17)/(2), D approximately -0.086 cm(-)(1), and g approximately 1.8, where S is the molecular spin of the Mn(21) complex and D is the axial zero-field splitting parameter. ac susceptibility studies in the 10-997 Hz frequency range reveal the presence of a frequency-dependent out-of-phase ac magnetic susceptibility (chi(M)' ') signal consistent with slow magnetization relaxation rates. Fitting of dc magnetization decay versus time data to the Arrhenius equation gave a value of the effective barrier to relaxation (U(eff)) of 13.2 K. Magnetization versus applied dc field sweeps exhibited hysteresis. Thus, complex 3 is a new member of the small but growing family of single-molecule magnets.


Circadian sleep regulation in the absence of light perception: chronic non-24-hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule.
Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free-running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule.


Emotion-relevant impulsivity predicts sustained anger and aggression after remission in bipolar I disorder.
Recent evidence suggests that anger and aggression are of concern even during remission for persons with bipolar I disorder, although there is substantial variability in the degree of anger and aggression across individuals. Little research is available to examine psychological models of anger and aggression for those with remitted bipolar disorder, and that was the goal of this study. Participants were 58 persons diagnosed with bipolar I disorder using the Structured Clinical Interview for DSM-IV, who were followed with monthly symptom severity interviews until they achieved remission, and then assessed using the Aggression-Short Form. We examined traditional predictors of clinical parameters and trauma exposure, and then considered three trait domains that have been shown to be elevated in bipolar disorder and have also been linked to aggression outside of bipolar disorder: emotion-relevant impulsivity, approach motivation, and dominance-related constructs. Emotion-relevant impulsivity was related to anger, hostility, verbal aggression, and physical aggression, even after controlling for clinical variables. Findings extend the importance of emotion-relevant impulsivity to another important clinical outcome and suggest the promise of using psychological models to understand the factors driving aggression and anger problems that persist into remission among persons with bipolar disorder.


Comparative study of short term results in two multidrug regimens in multibacillary leprosy.
Thirty lepromatous and Borderline lepromatous leprosy patients were treated with multidrug therapy in an open trial. Fifteen of them received the standard WHO multidrug regimen ie., rifampicin 600 mg and clofazimine 300 mg monthly, supervised, and dapsone 100 mg daily and clofazimine 100 mg on alternate days as self administered; the other 15 received a modified multidrug therapy regimen comprising of rifampicin 600 mg, clofazimine 100 mg and dapsone 100 mg daily for 21 days as suggested by the Indian Association of Leprologists, followed by the standard WHO regimen. The observation period was six months. Clinical, bacteriological, histological and immunological parameters were studied. The fall in morphological index was much faster in patients receiving modified multidrug therapy regimen compared to those receiving the standard WHO regimen. Otherwise, there was no difference between the two groups of patients. Five patients developed type I (upgrading) reaction with one developing ulnar nerve paralysis. No untoward effects of drugs were noted in the study subjects except for darkening of skin colour of all the patients.