Renal ischemia--reperfusion injury: an inescapable event affecting kidney transplantation outcome.
Ischemia--reperfusion (I-R) injury has been shown to be a common cause of late and irreversible complications during a variety of standard medical and surgical procedures. The pathogenesis of events which follow the I-R involves both injured endothelium and activated leukocytes and their interaction. In kidney transplantation, an I-R injury occurs in situations such as graft harvesting, cold storage and surgery. Clinical consequences of I-R injury have been considered to be delayed graft function and acute rejection in the short term and chronic rejection late after transplantation. Here we focused on current knowledge of pathophysiology of renal I-R injury in kidney transplantation and on possibilities of experimental therapy.


Immunology of brain tumors.
Brain tumors of different origin, but notably malignant gliomas, are characterized by their immunosuppressive properties which allow them to escape the host's immune surveillance. The activating immune cell ligands that are expressed by tumor cells, together with potentially immunogenic antigens, are overridden by numerous immune inhibitory signals, with TGF-3 as the master immunosuppressive molecule (Figure 4.1).The ongoing investigation of mechanisms of tumor-derived immunosuppression allows for an increasing understanding of brain tumor immunology. Targeting different mechanisms of tumor-derived immunosuppression, such as inhibition of TGF-[, may represent a promising strategy for future immunotherapeutic approaches.


Post-transplant interleukin-2 in patients with low-grade lymphoid neoplasms previously treated with fludarabine is limited by hematologic toxicity.
Given the favorable immunologic effects of IL-2 post transplant, we conducted a feasibility study examining rIL-2 1.0x106 IU/m2/day (SQ) beginning on D+14 post-transplant and continuing for 90 days in 12 patients with low-grade lymphoproliferative disorders. Prior to high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT), 11 patients underwent cytoreduction with fludarabine and cyclophosphamide (Flu/Cy); 11 were in complete remission (CR) and one was in partial remission at the time of HDCT. All 12 patients were in CR 90 days post-HDCT. At a median follow-up of 30 (range 3-44) months, seven patients (58%) remain in remission, four are alive with disease, and one has died of disease progression, resulting in an overall survival of 92%. Kaplan-Meier estimates of progression-free survival (PFS) for the group demonstrate a median of 31 (range 3-43) months. Five patients required rIL-2 cessation at 8-58 days after starting the therapy due to hematologic toxicity. These results are comparable to those achieved in other published bone marrow and peripheral blood stem cell transplantion (PBSCT) series without the addition of rIL-2. Furthermore, rIL-2 using this schedule following fludarabine-based cytoreduction was associated with excessive hematologic toxicity.


Adolescent mental health in China.
Adolescent Mental Health in China is the responsibility of the wider society and is supported by social, educational and health care resources. With limited facilities, China emphasizes community mental health care, with prevention and health promotion as priorities. Mental health is considered in the context of an orderly socialist society with stable family life supported by the state. Society is currently influenced by a mixture of Communist ideology, ancient tradition and newer Western approaches. Difficulties in reconciling these factors are affecting the attitudes and behaviour of China's youth.


Prevalence and persistence of cost-related medication non-adherence before and during the COVID-19 pandemic among medicare patients at high risk of hospitalization.
To study cost-related medication non-adherence (CRN) for a 30-month period before and during the COVID-19 pandemic using a sample of Medicare patients at high risk of hospitalization. A novel data set of quarterly surveys of CRN was used to evaluate CRN before and during the COVID-19 pandemic. Generalized Estimating Equation (GEE) analyses were conducted to evaluate the adjusted coefficients of change in CRN behaviors controlling for socio-demographic and health characteristics. Six hundred seventy-seven Medicare beneficiaries at high risk of hospitalization who were alive on January 1, 2020 and followed up through quarterly surveys on CRN for 30 months before and during the COVID-19 pandemic. Two metrics of prevalence and persistence of CRN and their adjusted coefficients in GEE with binomial family distribution and log link function controlling for socio-demographic and health characteristics. A total of 5,990 quarterly surveys were completed by the 677 patients during the 30-month study period. Among the 677 patients, 250 (37%) were men, 591 (87%) were African American, and 288 (42%) were Medicare-Medicaid dual eligible. The unadjusted prevalence of CRN before and during the COVID-19 pandemic was 31.1% and 25.7% respectively (p = 0.02 by Chi-squared test), and persistent CRN rates were 12.1% and 9.7% respectively (p = 0.17 by Chi-squared test). The adjusted odds ratio of CRN prevalence during the pandemic compared to the pre-pandemic level was 0.75 (p<0.01), and 0.74 (p = 0.03) for persistent CRN in GEE estimations. There are coherent evidence of a reversal of CRN rates during the COVID-19 pandemic among this high-need, high-cost resource utilization Medicare population. Patients' CRN behaviors may be responsive to exogenous impacts, and the behaviors changed in the same direction with similar magnitude in terms of prevalence (the extensive margin) and persistence (the intensive margin). More research is needed to advance the understanding of the driving forces behind patients' behavioral changes and to identify factors that may be informative for reducing CRN in the long run.


Bcl2L12 mediates effects of protease-activated receptor-2 on the pathogenesis of Th2-dominated responses of patients with ulcerative colitis.
The immune dysregulation plays an important role in the pathogenesis of ulcerative colitis (UC). Bcl2 like protein-12 (Bcl2L12) and mast cells are involved in immune dysregulation of UC. This study aims to elucidate the role of Bcl2L12 in the contribution to the pathogenesis of T helper (Th)2-biased inflammation in UC patients. The results showed that Bcl2L12 was expressed by peripheral CD4+ T cells that was associated with Th2 polarization in UC patients. Bcl2L12 mediated the protease-activated receptor-2 (PAR2)-induced IL-4 expression in CD4+ cells. Activation of PAR2 increased expression of Bcl2L12 in CD4+ T cells. Bcl2L12 mRNA decayed spontaneously in CD4+ T cells after separated from UC patients which was prevented by activating PAR2. Bcl2L12 mediated the binding between GATA3 and the Il4 promoter in CD4+ T cells. Mice with Bcl2L12 deficiency failed to induce Th2-biased inflammation in the colon mucosa. We conclude that CD4+ T cells from UC patients expressed high levels of Bcl2L12; the latter plays an important role in the development of Th2-biased inflammation in the intestine. Bcl2L12 may be a novel therapeutic target in the treatment of Th2-biased inflammation.


Mapping of functional activity in the falcon visual system with [14C] 2-deoxyglucose.
[14C] 2-Deoxyglucose uptake was mapped in the brain of one awake falcon which had one eye covered during the experiment, with the aim of providing tentative data on the identification of this bird's visual centers. Most of the structures with increased [14C] 2-Deoxyglucose uptake receive information from the exposed eye. Labeling was rather symmetrical in the hyperstriatum which receives bilateral projections from the visual thalamic centers. The results are largely consistent with what is known about the visual pathways in pigeons and owls. The falcon's visual Wulst as detected by the [14C] 2-Deoxyglucose labeling, is proportionally larger than that found in the pigeon. This result is consistent with the marked representation of the binocular visual field in the falcon's Wulst.


Immunology of dermatophytosis. Experimental study.
By causing experimental lesions of dermatophytosis in rabbits inoculated and reinoculated with T. mentagrophytes var. granulosum and T. rubrum a study was carried out of the state of cellular immunity response, during infection, and also of the antigens responsible for the sensitization. Cellular immunity response was detected using the leucocyte migration test (L.M.T.) in the presence of antigenic compounds of the 'Keratinase' of Eleuterio et al.


T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis.
Alpha-mannosidosis (alpha-mannosidosis) is a lysosomal storage disease characterized by accumulation of oligosaccharides in various tissues leading to symptoms such as coarse facial features, dysostosis multiplex, hearing disabilities, mental developmental delay and skeletal involvement (dysostosis multiplex). Without treatment, the severe infantile onset form of this autosomal recessive disease leads to progressive neurodegeneration and sometimes to early death. Stem cell transplantation has been shown to be an effective treatment. In the five patients published so far, correction of skeletal abnormalities and improvement of neuropsychological capabilities have been observed. We report the first patient who received a T-cell-depleted peripheral blood stem cell transplantation (PBSCT) for alpha-mannosidosis. The diagnosis of alpha-mannosidosis was made at the age of 14 months. At the age of 24 months, he underwent PBSCT with T-cell depletion by CD34-positive selection from his HLA phenotypically identical mother. Conditioning was carried out with busulfan (20 mg/kg), cyclophosphamide (200 mg/kg), OKT3 and methylprednisolone. The patient is alive and well 27 months after PBSCT and has made significant developmental progress. The pattern of urinary oligosaccharides has returned to almost normal. CD34-positive-selected PBSCT is a feasible option to reduce risk for GVHD for these patients.


Modeling and optimization of red currants vacuum drying process by response surface methodology (RSM).
Fresh red currants were dried by vacuum drying process under different drying conditions. Box-Behnken experimental design with response surface methodology was used for optimization of drying process in terms of physical (moisture content, water activity, total color change, firmness and rehydratation power) and chemical (total phenols, total flavonoids, monomeric anthocyanins and ascorbic acid content and antioxidant activity) properties of dried samples. Temperature (48-78 °C), pressure (30-330 mbar) and drying time (8-16 h) were investigated as independent variables. Experimental results were fitted to a second-order polynomial model where regression analysis and analysis of variance were used to determine model fitness and optimal drying conditions. The optimal conditions of simultaneously optimized responses were temperature of 70.2 °C, pressure of 39 mbar and drying time of 8 h. It could be concluded that vacuum drying provides samples with good physico-chemical properties, similar to lyophilized sample and better than conventionally dried sample.


Impaired metabolic profile is a predictor of capillary rarefaction in a population of hypertensive and normotensive individuals.
Capillary rarefaction is typically encountered in essential hypertension, yet identification of factors interfering with this phenomenon remains substantially underinvestigated. We examined whether components of metabolic profile (dyslipidemia, insulin resistance), inflammatory (high-sensitivity C-reactive protein, high-sensitivity C-reactive protein), and angiogenic (vascular endothelial growth factor) factors are implicated in this phenomenon in a population of newly diagnosed, never-treated hypertensive patients and normotensive controls. Nailfold capillary density was estimated with nailfold capillaroscopy using specifically designed software. A total of 159 individuals, 93 hypertensives, and 66 normotensives were included. Nailfold capillary density was lower among hypertensives compared to normotensives (146.4 ± 31.0 vs. 155.4 ± 26.9, respectively; P = .047). In the total population, capillary density significantly correlated with high-density lipoprotein (HDL) (r = 0.232; P = .003), HDL/low-density lipoprotein ratio (r = 0.175; P = .025), age (r = 0.236; P = .003), but neither with vascular endothelial growth factor or high-sensitivity C-reactive protein. An inverse association was found with body mass index (r = -0.174; P = .029), insulin levels (r = -0.200; P = .018), and homeostasis model assessment-insulin resistance (r = -0.223; P = .009). In the separate analysis for the hypertensive population, sex (P = .014) and homeostasis model assessment-insulin resistance (P = .011) were identified as significant predictors of capillary rarefaction after adjustment for other factors. On the contrary, only HDL levels (P = .036) predicted capillary density in the multiple regression model for the normotensive population. Different aspects of impaired metabolic profile, that is, insulin resistance and low HDL levels, but not angiogenic or inflammatory markers, appear to be independently associated with capillary rarefaction in hypertensive and normotensive individuals.


Effectiveness of simulation in teaching immunization in nursing: a randomized clinical trial.
to evaluate the effectiveness of the clinical simulation on the cognitive performance of nursing students in adult immunization scenarios in the context of Primary Health Care. a controlled and randomized pre-test and post-test clinical trial applied to random intervention and control groups. 34 undergraduate nursing students were selected and divided into two groups: classes with active participation of students and skills training (control); and classes with active participation of students, skills training, and clinical simulation (intervention). the students in the intervention group performed better than those in the control group in the four assessments of cognitive performance, with statistical significance in the assessments of immediate (p=0.031) and late (1-20 days) (p=0.031) knowledge. from the simulation, students learn more in the short and medium terms. The information learned is retained for longer and the students are better prepared for the professional practice. Universal Trial Number: u1111-1195-2580.


Clinical and molecular spectrum of P/Q type calcium channel Cav2.1 in epileptic patients.
Epilepsy is a neurological disorder characterized by the potential to induce seizure and accompanied by cognitive, psychological, and social consequences. CACNA1A gene is a voltage-gated P/Q-type Cav2.1 channel that is broadly expressed in the central nervous system, and the pathogenic variants within this gene may be associated with the epileptic phenotype. In the present study, we collected clinical and molecular data related to epileptic patients with CACNA1A pathogenic variants and investigated possible meaningful relationship between age at onset, neurodevelopmental disorders, type of seizures, brain imaging abnormalities, genotype, and protein domains. In our retrospective literature studies, from among 890 articles reviewed, a total of 90 individuals were related to epilepsy phenotype. Our findings showed that about 90 percent of patients have shown the first symptoms in childhood and teenage years and different types of neurodevelopmental disorders, such as intellectual disability, developmental arrest, and behavioral disorders, have been common findings for these patients. Further, a wide range of abnormalities have been observed in their brain imaging, and generalized seizures have been the most type of seizures in these patients. However, our data showed no specific genotype-phenotype correlation in epileptic patients with CACNA1A pathogenic alterations. Our study focused on epileptic phenotype in patients with CACNA1A pathogenic variants and showed a wide range of clinical and molecular heterogeneity with no specific genotype-phenotype correlation. It seems that incomplete penetrance, de-novo variants, and modifier genes are obstacles in predicting the clinical outcome.


A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) is a human neurodegenerative disease characterized by the invasion of autoreactive T cells from the periphery into the CNS. Application of pan-histone deacetylase inhibitors (HDACi) ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model for MS, suggesting that HDACi might be a potential therapeutic strategy for MS. However, the function of individual HDAC members in the pathogenesis of EAE is not known. In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4+ T cells to differentiate into Th17 cells. RNA sequencing revealed STAT1 as a prominent upstream regulator of differentially expressed genes in activated HDAC1-cKO CD4+ T cells and this was accompanied by a strong increase in phosphorylated STAT1 (pSTAT1). This suggests that HDAC1 controls STAT1 activity in activated CD4+ T cells. Increased pSTAT1 levels correlated with a reduced expression of the chemokine receptors Ccr4 and Ccr6, which are important for the migration of T cells into the CNS. Finally, EAE susceptibility was restored in WT:HDAC1-cKO mixed BM chimeric mice, indicating a cell-autonomous defect. Our data demonstrate a novel pathophysiological role for HDAC1 in EAE and provide evidence that selective inhibition of HDAC1 might be a promising strategy for the treatment of MS.


Food allergy and intolerance.
This article focuses on intolerance to food proteins, discussing the definition and history of food intolerance, the basics of gastrointestinal mucosal immunity, specific food antigens, pathogenesis, clinical manifestations, as well as diagnosis, therapy, and prevention.


Does regular exercise during pregnancy influence lumbopelvic pain? A randomized controlled trial.
To study lumbopelvic pain in women randomized to a regular exercise program during pregnancy in comparison to women receiving standard antenatal care. A two-armed, two-center, randomized controlled trial. Setting. St Olavs Hospital, Trondheim University Hospital and Stavanger University Hospital. A total of 855 pregnant women were randomized to intervention or control groups. The intervention was a 12 week exercise program, including aerobic and strengthening exercises, conducted between 20 and 36 weeks of pregnancy. One weekly group session was led by physiotherapists, and home exercises were encouraged twice a week. The control group received standard antenatal care. Self-reports of lumbopelvic pain and sick leave due to lumbopelvic pain. The data were analysed according to the "intention-to-treat" principle. There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks (74 vs. 75%, p=0.76). The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group (22% vs 31%, p=0.01). Exercise during pregnancy does not influence the prevalence of lumbopelvic pain, but women offered a regular exercise course seem to handle the disorder better.


Characterization of the core gut microbiota of Nile tilapia (Oreochromis niloticus): indication of a putative novel Cetobacterium species and analysis of its potential function on nutrition.
The genus Cetobacterium has been considered a dominant group of gut bacteria in many freshwater fish, and members of this genus contribute to anaerobic metabolism. Because of its significant place in the gut of freshwater fish, many studies on Cetobacterium were performed. Those studies mostly focused on the temporal and spatial changes of its abundance in fish intestine, which were affected by food or other environmental conditions. However, only a few studies isolated strains from genus Cetobacterium and reported their characteristics. In the present study, we performed 16S rRNA sequencing of the intestinal mucosa of Nile tilapia (Oreochromis niloticus) and found that Cetobacterium sp. existed widely in the foregut, midgut and hindgut mucosa, and a strain of Cetobacterium was successfully isolated from the gut of tilapia. We sequenced its whole genome and predicted it to be a novel candidate species of Cetobacterium sp. and named it NK01. The size of its genome was 3,095,946 bp, with a guanine + cytosine content of 28.8%. Among the identified genes, 2855 were predicted to be coding DNA sequences, 84 were tRNA and 34 were rRNA. We found that NK01 produced amino acids, including leucine, isoleucine, valine, glycine, alanine, phenylalanine and proline. Strain NK01 could use starch, sucrose, maltose, glucose, and mannose and synthesize and utilize glycogen. INV, GPI, malQ, malZ, sacA, scrK, glgC, glgA and glk, which were related to carbohydrate metabolism, were detected. yiaY and adhE, which oxidize ethanol to acetaldehyde and participate in a variety of metabolic pathways, were also present in the genome. No coding genes directly involved in acetate or butyrate production were detected. NK01 could also catabolize a variety of vitamins, and all genes involved in folate synthesis were detected, including folP, folC, folA and eutT, which converted vitamin B12s into vitamin B12 coenzyme. Here, we investigated the draft genome and in vitro function of Cetobacterium isolated from the intestinal tract of Nile tilapia. The results provided a preliminary understanding of the core microbiota of fish gut.


Several subpopulations of neuropeptide Y-containing neurons exist in the infundibular nucleus of sheep: an immunohistochemical study of animals on different diets.
Conversely to rodents, the involvement of hypothalamic neuropeptide Y (NPY) neurons in the control of nutrition is poorly understood in ruminants such as sheep. Therefore, the aim of this work was to describe the NPY neurons of the diencephalon in ewes submitted to different diets. In colchicine-treated animals, large populations of NPY-immunoreactive (-ir) neurons were observed in a ventral and a lateral subpopulation of the infundibular nucleus (IN), in the median eminence, the pituitary stalk, and the dorsomedian and dorsocaudal nuclei. No labeled perikaryon was observed in the magnocellular neurons of the hypothalamus, although numerous labeled fibers were noted in the neural part of the pituitary. The pattern of distribution of NPY-ir neurons in the sheep hypothalamus is similar in many ways to those of rodents, but it presents also many specific characteristics that have not been previously described. In ewes that were fasted for 24 hours, or fed ad libitum, the number of NPY-ir neurons was the same whatever the hypothalamic structures. In underfed ewes (40% of maintenance for 24 weeks), the lateral subpopulation of the IN presented a higher number of NPY-ir neurons than observed in the 100% fed ewes. Conversely, in the ventral subpopulation, the animals refed ad libitum (at least 150% of maintenance for 4 days) presented a lower number of NPY-ir neurons than the other groups. The other NPY neuronal populations of the hypothalamus were not significantly modified by the dietary treatments. For the first time, we demonstrated the presence of two functionally distinct subpopulations of NPY neurons in the sheep IN. The variations of labeled neurons were correlated with plasma nonesterified fatty acid levels but not with leptinemia.


Reflections of low calcium epileptiform activity from area CA1 into dentate gyrus in the rat hippocampal slice.
Lowering of [Ca2+]o induces epileptiform activity in hippocampal area CA1, characterized by slow negative field potentials with superimposed trains of population spikes and by rises in [K+]o. In dentate gyrus slow positive field potentials occur simultaneously with the activity in area CA1. The accompanying small rises in [K+]o may stem from spatial K+ redistribution through glial cells from area CA1.


Monoclonal antibodies generated against activated B-cells: unexpected specific reactivity to T-cells.
Monoclonal antibodies (Mabs) were produced against C57B1/6 "nude" lymphoblast cells. They are IgG2a and do not react with mouse serum proteins. Five Mabs were characterized functionally by immunohistochemistry and immunofluorescence in spleen, lymph nodes and Peyer's patches from nude and normal mice, and normal mouse thymus. Two Mabs reacted with regions containing B-cells as indicated by immunoperoxidase staining, another recognized T- and B-cell sites and two specifically stained T lymphocyte-containing areas. Immunofluorescence studies confirmed the sites identified above by immunohistochemistry.


Acquisition of plasmin activity and induction of arachidonic acid release by Streptococcus suis in contact with human brain microvascular endothelial cells.
Infections caused by Streptococcus suis, a major swine pathogen, include meningitis, arthritis, pneumonia and septicaemia. In this study, we investigated interactions that may occur between human brain microvascular endothelial cells (HBMEC), the main constituent of the blood-brain barrier, and S. suis. We show that S. suis acquires plasmin activity in a time-dependent manner when in contact with cultured HBMEC. Cell-associated plasmin activity reached a plateau following a 48h co-incubation period. Zymography analysis revealed that HBMEC produce urokinase, which is probably involved in activation of plasminogen bound to S. suis. We also show that a S. suis culture supernatant which possesses both phospholipase C and haemolysin (suilysin) activities was able to induce the release of arachidonic acid from the membrane of HBMEC. Evidence suggests that the action of suilysin on HBMEC may be a prerequisite for the action of additional molecules such as phospholipase C. These new biological effects associated with S. suis may play an important role in the migration of S. suis through the blood-brain barrier and in the modulation of local inflammation.


Peak flow and voice pathology.
Lung function influences voice quality. The aim of this study was to determine if there was a link between subjective voice pathology and peak flow in patients newly presenting with voice problems. A prospective, multigroup study design was designed, with three groups: New voice pathology patients presenting to voice clinics or speech therapists; General patients from ear, nose, and throat clinics with no voice or hearing abnormality; and Asthmatics presenting to general practitioner surgeries or asthma groups for review of asthma treatment. Fifty general ENT patients, 50 voice pathology patients, and 26 asthmatics were included. Peak flow and Voice Handicap Index (VHI) were measured in all subjects. Analysis of the correlation between VHI and percentage of expected peak flow showed a small correlation between the two for voice pathology patients (r=-0.304, P=0.016). No significant correlation was found for the other two groups. These results do not justify the routine measurement of peak flow in all voice clinic patients, but suggest that peak flow measurement and optimization may have a place in those with the most severely impaired VHI.


[General practitioners' knowledge on means of prescribing speech therapy].
General practitioners are the first prescribers of speech therapy in France, a country in which speech therapists can practice only on medical prescription. The objective of this study was to measure general practioner's knowledge on means of prescribing speech therapy. Cross-sectional study by self-questionnaires for general practitioners and residents in general practice in France. The test assessed five types of knowledge conducive to correct prescription of speech therapy: requirements for prescription, indications, prescription wording, ages of treatment eligibility, and reimbursement. The questionnaires were tested on an expert population, whose median score was used as a cut-off to separate doctors who knew the modalities of speech therapy prescription from those whose knowledge was insufficient. The characteristics differentiating the two groups were compared by multiple logistic regression. Five hundred and three general practitioners and five hundred and two residents in general medicine were included; 82.3% of the physicians having written a thesis and 86.2% of the residents had insufficient knowledge of the modalities of speech therapy prescription. Age, number of years since acquisition of a medical diploma and urban practice all had a negative impact on general practitioners' knowledge of speech therapy. French general practitioners' knowledge of speech therapy prescription seems insufficient. It is consequently necessary to improve the initial and continuing training of doctors. Collaborative work between general practitioners and speech therapists should be carried on, developed and strengthened.


Transwindow Suture Technique for Pseudocyst of Pinna.
Pseudocyst or seroma of the pinna is the accumulation of serous fluid between the perichondrium and cartilage of pinna. Though there are several surgical techniques in the treatment of seroma, recurrence is common. The aim and objective of this preliminary study is to present and discuss a novel technique of treating pseudocyst of pinna which is practiced at Karwar Institute of Medical sciences. A prospective study was done with a novel procedure "Transwindow suture technique" for the treatment of pseudocyst of pinna in four patients. Three of the four patients had a very good results without any recurrence. One patient had a small quantity of recollection due to premature closure of the skin window which was successfully corrected. In this preliminary study we had encouraging results in the treatment of pseudocyst of pinna. A large scale prospective study would demonstrate the effectiveness of this procedure.


Time dependence of the magnetic grain concentration and secondary grain aggregation in ferronematic lyotropic liquid crystals subjected to magnetic field gradients.
The dynamical behavior of lyotropic nematic liquid crystals doped with ionic and surfacted magnetic fluids (ferronematics) is studied using a linear optical technique. The response of these mesophases to a combination of a static and a pulsed magnetic field is investigated by measuring the relaxation times as a function of the pulse width. A reversible modification of the magnetic grain concentration in the bulk of the samples and a secondary aggregation process due to the presence of a field gradient introduced by the pulsed field is discussed.


[A clinical application and study of analysis system of sound spectrography].
The phonetic features were studied for non-velopharyngeal dysfunction in postoperative patients with cleft plate. The feature of velopharyngeal competency of 32 postoperative patients with cleft palate were analyzed with KAY-7800 sound spectrograph, compared with characteristic of 30 subjects with normal phonogram. There were three types of abnormal phonogram for the postoperative patients of cleft palate with velopharyngeal competence. The heavy noise was a common sight. An analytic system of sound spectrography has certain value for evaluation of phonic function in cleft palate patients.


Antagonism of fentanyl with naloxone during N2O+O2+ halothane anaesthesia.
To investigate the antagonistic effect of naloxone on fentanyl-induced respiratory depression, 55 patients (randomly divided into various study and control groups were studied during nitrous-oxide-oxygen-halothane anaesthesia. Respiratory depression after 0.1 mg of fentanyl was totally reversed by 10 microgram/kg of naloxone, measured as 100% restoration of spontaneous respiration, normal minute volume and end-tidal CO2, while 15 microgram/kg of naloxone was needed to antagonize 0.2 mg of fentanyl. The respective control groups remained apnoeic. If no fentanyl had previously been administered, there was no difference in the respiratory behaviour of naloxone-treated and control patients, which indicates that no unspecific analeptic effect of naloxone could be demonstrated. The circulatory changes after fentanyl were nearly reversed by naloxone, as has been found earlier with other narcotics. Recovery from anaesthesia was scored from 0 to 10 (using a modification of Apgar scores for newborns), and somewhat higher mean scores were obtained with the naloxone-treated patients than with their controls. However, higher postoperative pain scores were recorded in these patients as well as a higher incidence of nausea and vomiting. The study demonstrates the dose-relationships of fetanyl and naloxone for estimation of total antagonism; however, the use of naloxone for partial antagonism at the termination of anaesthesia cannot be based on these findings.


Adeno-associated viral vector serotype 9-based gene replacement therapy for SURF1-related Leigh syndrome.
SURF1 (surfeit locus protein 1)-related Leigh syndrome is an early-onset neurodegenerative disorder, characterized by reduction in complex IV activity, resulting in disrupted mitochondrial function. Currently, there are no treatment options available. To test our hypothesis that adeno-associated viral vector serotype 9 (AAV9)/human SURF1 (hSURF1) gene replacement therapy can provide a potentially meaningful and long-term therapeutic benefit, we conducted preclinical efficacy studies using SURF1 knockout mice and safety evaluations with wild-type (WT) mice. Our data indicate that with a single intrathecal (i.t.) administration, our treatment partially and significantly rescued complex IV activity in all tissues tested, including liver, brain, and muscle. Accordingly, complex IV content (examined via MT-CO1 protein expression level) also increased with our treatment. In a separate group of mice, AAV9/hSURF1 mitigated the blood lactic acidosis induced by exhaustive exercise at 9 months post-dosing. A toxicity study in WT mice showed no adverse effects in either the in-life portion or after microscopic examination of major tissues up to a year following the same treatment regimen. Taken together, our data suggest a single dose, i.t. administration of AAV9/hSURF1 is safe and effective in improving biochemical abnormalities induced by SURF1 deficiency with potential applicability for SURF1-related Leigh syndrome patients.


Polyamines as biological markers in malignant lymphomas.
The urinary polyamines putrescine (PU) and spermidine (SPD) were measured for 67 patients with lymphomas: 48 non-Hodgkin (NHL) and 18 Hodgkin's disease (HD). Monthly repeat measurements were obtained over an average follow-up period of 12.5 months. For NHL, a good association was observed between polyamine levels and the severity of the the stage; the distribution of values between nodular and diffuse forms was also significantly different. No such correlations were seen for HD. The evolution of PU values in time has been shown to reflect disease activity for NHL. Non-specific fluctuating Pu values were found in the case of HD. In the case of 20 patients with NHL undergoing chemotherapy, comparison of polyamine levels before and after chemotherapy allowed differentiation between the population of complete responders to treatment and those with only partial or no response.


A data analysis microcomputer package (DAMP) for biomedical signals.
The advent of cheap, powerful microcomputer systems makes the analysis of data via sophisticated techniques available to the personnel who are non-specialists in computing systems. The DAMP package described here is intended for use on personal computers and has therefore been written in BASIC for portability. The analysis techniques are powerful, comprising algorithms to perform sample-data generation, plotting displays, digital data filtering, auto-correlation functions, fast Fourier transforms and autoregressive modelling. The last technique contains a number of options including the display of z-plane plots, frequency response of the model, residual plotting and auto-correlation of the residuals. Illustrative results are shown from psychological mood data and rat locomotor activity. The package is designed both to instruct a user in the techniques of spectral analysis, and also to provide a range of methods for investigating time and frequency behaviour of biomedical data.


Accuracy of a high prostate-specific antigen level for prostate cancer diagnosis upon initial biopsy in Korean men.
This study aimed to evaluate the cancer detection rate in a Korean population with prostate-specific antigen (PSA) levels greater than or equal to 20.0 ng/mL. A total of 174 men 50 to 79 years old (median 69) included in the study. The median prostate volume of the patients was 44.8 mL (range 14.1 to 210.0) and their serum PSA ranged from 20.0 to 9725.0 ng/mL (median 44.8). Of 174 men 141 (81.0%) were diagnosed with prostate cancer on initial biopsy. In the total number of patients, the positive predictive value (PPV) was 62.9% for PSA 20 to 29.9, 72.7% for PSA 30 to 39.9 and 100% for PSA 40 to 49.9 ng/mL. In patients with an abnormal digital rectal examination (DRE), the values for these PSA ranges increased to 89.5%, 91.7% and 100%, respectively. The PPV was 81.0% for PSA cutoff of 20, 89.2% for a cutoff of 30, 95.4% for a cutoff of 40, and 94.7% for a cutoff of 50 ng/mL. In conjunction with an abnormal DRE, the values for these PSA cutoffs increased to 95.9%, 98.1%, 100%, and 100%, respectively. Our data suggest the ability to predict the presence of prostate cancer reliably on initial biopsy when PSA threshold is greater than or equal to 50 ng/mL. This PSA threshold may be lowered to 40 ng/mL in the presence of an abnormal DRE. In Korean men with high PSA, the detection rate of prostate cancer on biopsy appears to be comparable to that for American men.


Hyperamylasemia with papillary serous cystadenocarcinoma of the ovary.
A case of a 49-year-old housewife with persistent hyperamylasemia, intractable amylase-rich ascites, and papillary serous cystadenocarcinoma of the ovaries is presented. The hyperamylasemia was attributable to neoplastic production of salivary-type isoamylase by analysis of isoamylase in the serum, urine, ascites, primary tumor of the ovaries and metastatic tumor of the lymph nodes. Cellular localization of amylase in the tumor tissues was demonstrated immunohistochemically in the primary and metastatic tumors using an indirect immunoperoxidase method.


Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome.
Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.


The relationship among psychopathology, religiosity, and nicotine dependence in Croatian war veterans with posttraumatic stress disorder.
To examine relationships among combat exposure, posttraumatic stress disorder (PTSD) symptoms, depression, suicidality, nicotine dependence, and religiosity in Croatian veterans. This cross-sectional study used Combat Exposure Scale (CES) to quantify the stressor severity, PTSD Checklist 5 (PCL) to quantify PTSD severity, Duke University Religion Index to quantify religiosity, Montgomery Asberg (MADRS) and Hamilton Depression (HAM-D) rating scales to measure depression/suicidality, and Fagerstrom Test for Nicotine Dependence to assess nicotine dependence. Zero-order correlations, cluster analysis, multivariate regression, and mediation models were used for data analysis. Of 69 patients included, 71% met "high religiosity" criteria and 29% had moderate/high nicotine dependence. PTSD was severe (median PCL 71), depression was mild/moderate (median MADRS 19, HAM-D 14), while suicidality was mild. A subset of patients was identified with more severe PTSD/depression/suicidality and nicotine dependence (all P<0.001). Two "chains" of direct and indirect independent associations were detected. Higher CES was associated with higher level of re-experiencing and, through re-experiencing, with higher negativity and hyperarousal. It also showed "downstream" division into two arms, one including a direct and indirect association with higher depression and lower probability of high religiosity, and the other including associations with higher suicidality and lower probability of high nicotine dependence. Psychopathology, religiosity, and nicotine dependence are intertwined in a complex way not detectable by simple direct associations. Heavy smoking might be a marker of severe PTSD psychopathology, while spirituality might be targeted in attempts of its alleviation. Oxford Centre for Evidence-based Medicine level of evidence: 3.


[Quantiative determination of radiopaque contrast media by means of HPLC. I. Determination of diatrizoic acid, iothalamic acid and iodamide].
A rapid method for the quantitative analysis of radiopaque contrast media HPLC is described. Method can greatly help in solving problems of clinical and forensic interest.


The effect of temperature on the turnover of taste bud cells in catfish.
Renewal of taste bud cells on the barbels of channel catfish was studied. Groups of catfish, held in and acclimitized to 14 degrees C, 18 degrees C, 22 degrees C and 30 degrees C dechlorinated tap water were injected with [3H]thymidine (3.0 muCi/g body weight intraperitoneally). Barbels were sampled at various times after injection and prepared for light microscope autoradiography. Results show that epithelial cells surrounding the taste buds divide and some of their daughter cells migrate into the taste buds. The time at which 50% of the labelled cells have degenerated is taken as the average turnover time or average life span of the taste bud cells. The average life span as well as the time spent inside the taste buds is highly temperature-dependent. At 14 degrees C, 18 degrees C, 22 degrees C and 30 degrees C the average life span is on the order of 40, 30, 15 and 12 days respectively. Further studies indicate that both light and dark staining cells of the taste bud were labelled.


Psychiatric treatment of children and adolescents in rural communities. Myths and realities.
Rural child and adolescent psychiatry offers many challenges, a varied and interesting practice, and the satisfaction of performing needed and important work in an environment in which one's presence is valued. The successful psychiatrist can expect to be an integrated and appreciated member of the community. The fit is not a good one for every practitioner, however. Not only are incomes lower, although the cost of living is low as well, but practitioners may find they have only exchanged urban stresses for rural pressures. The characteristics important for the child and adolescent psychiatrist are the same for rural and urban settings: flexibility, creativity and innovation, competence, self confidence, a good sense of boundaries, a good balance between personal and private life, supportive personal relationships, and a sense of humor. One must be a child advocate, have a willingness to give of one's self and one's time, and be down to earth, comfortable with oneself, and capable of self entertainment. Training programs with access to rural populations can introduce residents to rural child and adolescent psychiatry while supporting those who are already in practice. The authors hope that this article will promote a dialogue with psychiatrists considering relocation to a rural area and encourage training programs to prepare residents for rural practice.


Implementation of a viable air-sampling program using a volumetric collection device.
Implementation of the United States Pharmacopeia Chapter 7797 viable air sampling process can be done via various methods. This multi-site infusion pharmacy organization considered several factors in developing an air-sampling program. This article reviews the factors that should be considered, challenges of implementation, and results of deciding to conduct in-house testing.


Salivary gland choristoma of the middle ear in an infant: a case report.
Salivary gland choristoma of the middle ear cavity is an extremely rare entity. Many patients with this entity usually present with conductive hearing loss. Many reports concentrate on the importance of conservative treatment of choristoma for fear of the possible injury of the facial nerve. We report another case of salivary choristoma of the middle ear in an 11-month-old girl. We performed a reconstruction surgery of the hearing mechanism, as well as tumor removal, and achieved satisfactory hearing results. If no remarkable facial nerve anomaly is detected in the preoperative evaluation, the reconstruction of the hearing mechanism with complete tumor removal might be considered.


High-performance liquid chromatographic assay for the experimental anticancer agent oxantrazole.
Oxantrazole is an anthrapyrazole analogue developed as an anthracycline-like agent with potentially reduced cardiotoxicity. A reversed-phase high-performance liquid chromatographic assay was developed using a C2 column and mobile solvent system of dimethylformamide-acetonitrile-0.2 M ammonium acetate, pH 4.5 (20:5:75, v/v/v) at a flow-rate of 1 ml/min. Drug and internal standard were detected by ultraviolet absorbance at 514 nm. Isolation of drug and internal standard was afforded by elution from C18 disposable isolation columns with a mixture of methanol-glacial acetic acid-0.02 M sodium acetate, pH 4.0 (12:1:3, v/v/v). The assay was linear (r2 greater than 0.99) over concentrations of 0.025-2.5 micrograms/ml and the limit of detection was 10 ng/ml plasma. Oxantrazole was unstable in neutral and particularly alkaline aqueous solutions. Utilizing this assay, plasma pharmacokinetics were determined following intravenous infusion of oxantrazole to beagle dogs. Plasma elimination was rapid with elimination phase half-life values less than 45 min.


The longitudinal association of symptom-related and psychological factors with health-related quality of life in patients with chronic pelvic pain syndrome.
To analyze the course of symptom-related measures, psychological variables and health-related quality of life (HRQoL) over a 12-month period, and to longitudinally examine symptom-related and psychological factors as predictors for HRQoL in male and female patients with chronic pelvic pain syndrome (CPPS). Data from 125 patients aged 19-83 years at baseline attending an interdisciplinary outpatient clinic for CPPS were analyzed. Participants completed a self-administered questionnaire on subjective health issues, and a postal follow-up survey was conducted 12 months later. We assessed physical and mental HRQoL, CPPS symptom severity, pain intensity, severity of somatic, depressive and anxiety symptoms, pain catastrophizing, and data on treatments during the follow-up period. Data were analyzed using multilevel linear modelling. CPPS symptom severity, pain intensity, and pain catastrophizing significantly decreased over time. HRQoL and levels of somatic symptoms, depressive symptoms and anxiety remained stable. Lower baseline levels of somatic symptoms were associated with an increase in physical HRQoL, and lower baseline levels of depressive symptoms, anxiety and pain catastrophizing were associated with an increase in mental HRQoL after 12 months. Treatment utilization was neither related to decrease in CPPS symptom severity, pain intensity and pain catastrophizing, nor to HRQoL after 12 months. Our data suggest that CPPS is related to persistently diminished HRQoL. Somatic symptoms and psychological factors are important determinants of HRQoL and potential therapeutic targets. To evaluate the efficacy and impact of treatment on CPPS-related outcomes, future large-scaled studies should systematically assess detailed data about therapies patients receive in routine care.


LincRNA-p21 promotes p21-mediated cell cycle arrest in benzene-induced hematotoxicity by sponging miRNA-17-5p.
Benzene is widely employed in manufacturing and causes hematotoxic effects and leukemia in humans. A long intergenic noncoding RNA (lincRNA)-microRNA (miRNA)-mRNA coexpression and competing endogenous RNA (ceRNA) regulatory network was constructed by bioinformatics analysis based on a benzene-induced aplastic anemia (BIAA) mouse model. In this population-based study, we observed a trend consistent with that in the BIAA mice: lincRNA-p21 and p21 were upregulated, while miRNA-17-5p expression was downregulated in benzene-exposed workers. Moreover, multiple linear regressions indicated that lincRNA-p21 was negatively associated with white blood cell (WBC) counts. Predictive thresholds of hematotoxicity were identified by ROC curve analysis with S-phenylmercapturic acid (SPMA) and lincRNA-p21 showing a better predictive ability than the other parameters and the combination of SPMA and lincRNA-p21 exhibiting the highest predictive value for hematotoxicity. LincRNA-p21 was predominantly present in the cytoplasm of bone marrow cells (BMCs) and K562 cells as assessed by fluorescence in situ hybridization (FISH). Upon exploring the underlying mechanism by which lincRNA-p21 mediates benzene-induced hematotoxicity, we observed that the negative regulation of 1,4-benzoquinone (1,4-BQ) on cell cycle arrest and inhibition of K562 cell proliferation was partially relieved by lincRNA-p21 knockdown, which can inhibit the expression of P21 and thereby suppress the toxic effects of 1,4-BQ. Finally, dual-luciferase reporter gene and RIP assay showed that, by acting as a sponge, lincRNA-p21 reduced the activity of miRNA-17-5p and consequently increased the expression of p21. In conclusion, our research suggested that benzene induces hematotoxicity via the lincRNA-p21/miRNA-17-5p/p21 signaling which might contribute to the underlying mechanism of lincRNA-p21 in benzene-induced hematotoxicity. Therefore, lincRNA-p21 can serve as a potential biomarker for the early detection of hematopoiesis inhibition in individuals with long-term exposure to low-dose benzene.


Freezing survival, body ice content and blood composition of the freeze-tolerant European common lizard, Lacerta vivipara.
To investigate the freeze tolerance of the European common lizard, Lacerta vivipara, we froze 17 individuals to body temperatures as low as -4 degrees C under controlled laboratory conditions. The data show that this species tolerates the freezing of 50% of total body water and can survive freezing exposures of at least 24-h duration. Currently, this represents the best known development of freeze tolerance among squamate reptiles. Freezing stimulated a significant increase in blood glucose levels (16.15+/- 1.73 micromol x ml(-1) for controls versus 25.06 +/- 2.92 micromol x ml(-1) after thawing) but this increase had no significant effect on serum osmolality which was unchanged between control and freeze-exposed lizards (506.0 +/- 23.8 mosmol x l(-1) versus 501.0 +/- 25.3 mosmol x l(-1), respectively). Tests that assessed the possible presence of antifreeze proteins in lizard blood were negative. Recovery at 5 degrees C after freezing was assessed by measurements of the mean time for the return of breathing (5.9 +/- 0.5 h) and of the righting reflex (44.8 +/- 4.5 h). Because this species hibernates in wet substrates inoculative freezing may frequently occur in nature and the substantial freeze tolerance of this lizard should play a key role in its winter survival.


The cost of plant defense: an experimental analysis with inducible proteinase inhibitors in tomato.
The cost of producing inducible proteinase inhibitors was investigated by manipulating their production with chitin injections in genetically homogeneous tomato plants grown at different nitrogen levels. Proteinase inhibitor production had no detectable effect on fitness-related characters, probably because it represented only a small portion of the nitrogen budget. Nitrogen availability did not influence inhibitor production or its impact on plant fitness.


Comparison of receptors for cholera and Escherichia coli enterotoxins in human intestine.
Extraction of lipids from human small intestinal epithelial cells or brush borders removed specific binding sites for cholera toxin completely, but only about 50% of the receptor sites for Escherichia coli heat-labile enterotoxin. Both cholera toxin and E. coli heat-labile enterotoxin bound strongly to ganglioside GM1 in the lipid extract and, to a lesser extent, to another monosialoganglioside and to GD1b. The results suggest that E. coli heat-labile enterotoxin binds to both ganglioside and glycoprotein receptor sites of the human small intestinal epithelium, whereas cholera toxin binding was restricted to the ganglioside receptors.


Visualization of chronic myocardial infarction using the intravascular contrast agent MS-325 (gadofosveset) in patients.
The aim of this study was to evaluate the potential of visualizing chronic myocardial infarction in patients using the intravascular CA MS-325 (gadofosveset, EPIX Pharmaceuticals, Mass, USA). Nine patients were enrolled in a clinical phase II multicenter trial for MRCA and perfusion imaging using MS-325. They had objective evidence of chronic myocardial infarction as visualized by previously performed late gadolinium (Gd) enhancement imaging (LGE) with a conventional extracellular Gd-DTPA CA (Magnevist, Bayer Healthcare, Germany, 0.2 mmol/kg/body weight) serving as reference standard. A prepulse-optimized LGE study was performed immediately and at several time points after injection of MS-325 (0.05 mmol/kg/body weight). The number and localization of segments demonstrating LGE with MS-325 as well as signal intensities were compared with the reference standard (Gd-DTPA). Using MS-325, LGE could be detected at every time point in all 9 patients. The accuracy of LGE with MS-325 as compared to LGE with Gd-DTPA was highest 54 ± 4 minutes after contrast injection, resulting in a sensitivity of 84% with a specificity of 98%. The intravascular CA MS-325 has the potential to visualize chronic myocardial infarction. However, in comparison with Gd-DTPA, the transmural extent and the number of segments are smaller.


Studies on prolactin-secreting cells in aging rats of different strains. I. Alterations in pituitary histology and serum prolactin levels as related to aging.
Serum PRL levels and histologically tumor-free pituitary glands of 91 aging rats of the BN/BiRij strain, the WAG/Rij strain and their F1 hybrid were studied. In rats with pituitary glands without signs of hyperplasia, serum PRL levels were, in comparison to rats of 15-24 months, increased 25-29-month-old female BN/BiRij rats and showed a decline with further aging. This rise and decline during aging correlated with changes in the PRL cell volume density and in ultrastructural signs of their synthetic activity. Rats with hyperplastic pituitaries showed similar age-related changes in serum PRL levels, but these levels were higher. Concerning the hyperplasia, some strain differences were found. In BN/BiRij rats anti-r-PRL positive hyperplasia, and in WAG/Rij and F1 rats, anti-r-PRL negative and anti-r-PRL positive hyperplasia were present. All foci of hyperplasia were negative for anti-ACTH and anti-h-GH. In male rats no age-related changes of serum PRL levels could be established, although a decline of PRL cell volume density in the oldest rats is indicated. We conclude that the absence of a continuous age-related rise of serum PRL levels in our animals is caused by exclusion of animals with pituitary tumors.


Safety of mometasone furoate nasal spray in the treatment of nasal polyps in children.
Mometasone furoate nasal spray (MFNS) improves nasal symptoms and reduces polyp size in adults with nasal polyposis. This 4-month, multinational, randomized, double-blind study was conducted to assess the safety of MFNS in pediatric subjects aged 6-17 yr. Subjects aged 6-11 yr with bilateral nasal polyps received MFNS 100 μg once or twice daily or placebo; those aged 12-17 yr received MFNS 200 μg once or twice daily or placebo. End-points included change in 24-h urinary free cortisol (primary), change in 24-h urinary free cortisol corrected for creatinine (key secondary), and adverse events. Efficacy parameters included polyp size, nasal symptoms, and investigator-evaluated therapeutic response, although the study was not powered for statistical analysis of efficacy. Least squares baseline mean urinary free cortisol level (nmol/24 h) for both age groups combined (N = 127) was 49.5 in the MFNS once-daily group, 39.6 in the MFNS twice-daily group, and 49.8 in the placebo group. Change in 24-h urinary free cortisol did not significantly differ among MFNS- and placebo-treated subjects. Least squares mean 24-h urinary free cortisol levels corrected for creatinine also showed no significant differences among MFNS- and placebo-treated subjects. No safety issues emerged. Results of this study confirm the safety profile of MFNS in pediatric patients with bilateral nasal polyps over 4 months, even at double the recommended pediatric dosage for allergic rhinitis.


Overexpression of microRNA-202-3p protects against myocardial ischemia-reperfusion injury through activation of TGF-β1/Smads signaling pathway by targeting TRPM6.
MicroRNAs (miRNAs) have been found to act as key regulators in the pathogenesis of myocardial ischemic-reperfusion (I/R) injury. In this study, we explore the role and mechanism of microRNA-202-3p (miR-202-3p) in regulating cardiomyocyte apoptosis, in respective of the TGF-β1/Smads signaling pathway by targeting the transient receptor potential cation channel, subfamily M, member 6 (TRPM6). The targeting relationship between miR-202-3p and TRPM6 was verified by a dual-luciferase reporter gene assay. Sprague-Dawley rat models of myocardial I/R injury were initially established and treated with different mimics, inhibitors and siRNAs to test the effects of miR-202-3p and TRPM6 on myocardial I/R injury. The levels of inflammatory factors; IL-1β, IL-6, TNF-α as well as the degree of myocardial fibrosis and cardiomyocyte apoptosis were determined in rats transfected with different plasmids. TRPM6 was found to be the target of miR-202-3p. Up-regulated miR-202-3p or knockdown of TRPM-6 alleviated oxidative stress and inflammatory response, reduced ventricular mass, altered cardiac hemodynamics, suppressed myocardial infarction, attenuated cell apoptosis, and inhibited myocardial fibrosis. MiR-202-3p overexpression activates the TGF-β1/Smads signaling pathway by negatively regulating TRPM6 expression. Taken together, these findings suggest that miR-202-3p offers protection against ventricular remodeling after myocardial I/R injury via activation of the TGF-β1/Smads signaling pathway.


Self-Injurious Behavior in People with Intellectual Disabilities and Co-Occurring Psychopathology using the Self-Harm Scale: A Pilot Study.
Self-injurious behavior (SIB) is one of the most detrimental behaviors for the person showing it, as well as for their environment. Nevertheless, structured clinical assessments of SIB are scarce. Staff completed a Self-Harm Scale (SHS) every time they witnessed SIB in clients with an intellectual disability (ID) and co-occurring psychopathology (N = 33). Descriptive statistics were conducted to explore the nature of the incidents of SIB and the characteristics of the people involved in the incidents. In 41 weeks, 104 SIB incidents were reported for 8 out of 33 clients (24%). Incidents were most prevalent on Mondays (23%). As far as the methods of SIB concerned, cutting was the most used method (63%). Clients who showed SIB differed significantly from clients who did not on gender, having a personality disorder and communicative abilities. This study was one of the few that used an incident-based record form to report SIB by direct observation. It is hoped that the SHS helps to gain more information about SIB, to improve individualized interventions. Further research is necessary to determine the psychometric properties and clinical utility of the scale.


Asymmetric effects in waveguide systems using PT symmetry and zero index metamaterials.
Here we demonstrate directional excitation and asymmetric reflection by using parity-time (PT) symmetric and zero index metamaterials (ZIMs) in a three-port waveguide system. The principle lies on that the field distribution at gain/ loss interface is significantly affected by the incident direction of electromagnetic wave. By taking advantage of the empty volume feature of ZIMs, these asymmetric effects are extended to a more general three-port waveguide system. In addition, by exciting a weak modulated signal in branch port in our proposed design, unidirectional transmission with an unbroken propagation state is achieved, opening up a new way distinguished from the present technologies.


Neuroinflammation in Alzheimer's disease: microglial signature and their relevance to disease.
Alzheimer's disease (AD) is the most common form of dementia, pathologically characterized by senile plaques and neurofibrillary tangles (NFTs), resulting in neurodegeneration. Neuroinflammation, defined as the activation of glial cells such as microglia and astrocytes, is observed surrounding senile plaques and affected neurons in AD. Recently conducted genome-wide association studies (GWAS) indicate that a large section of identified AD risk genes are involved in immune responses and are enriched in microglia. Microglia are innate immune cells in the central nervous system (CNS), which are involved in immune surveillance and maintenance of homeostasis in the CNS. Recently, a novel subpopulation of activated microglia named as disease-associated microglia (DAM), also known as activated response microglia (ARM) or microglial neurodegenerative phenotype (MGnD), was identified in AD model mice. These microglia closely associate with β-amyloid (Aβ) plaques and exhibit characteristic gene expression profiles accompanied with reduced expressions of homeostatic microglial genes. However, it remains unclear whether decreased homeostatic microglia functions or increased DAM/ARM/MGnD functions correlate with the degree of neuronal loss in AD. To translate the results of rodent studies to human AD, precuneus, the brain region vulnerable to β-amyloid accumulation in preclinical AD, is of high interest, as it can provide novel insights into the mechanisms of microglia response to Aβ in early AD. In this study, we performed comparative analyses of gene expression profiles of microglia among three representative neurodegenerative mouse models and the human precunei with early AD pathology. We proceeded to evaluate the identified genes as potential therapeutic targets for AD. We believe that our findings will provide important resources to better understand the role of glial dysfunction in AD.


The optimal cut-off value of immunohistochemical parameter P53 for predicting recurrence of endometrial cancer.
To explore the optimal cut-off value of immunohistochemical parameter P53 for predicting the recurrence of Stage I-III endometrial cancer. A total of 473 patients who were treated between October 2013 and May 2018 were retrospectively studied. Receiver operating characteristic (ROC) curves and the Youden index were used to calculate the optimal cut-off value of P53. Cox regression analysis was used to detect the association between the threshold of P53 and recurrence of endometrial cancer. Recurrence-free survival (RFS) and overall survival (OS) were exhibited by Kaplan-Meier curve. The study showed that 67% was the optimal cut-off value of P53 to predict the recurrence of endometrial cancer. P53 above 67% was an independent predictor for relapse of endometrial cancer (p < 0.001). The 3-year RFS was 89.7% in the low-value group and 66.6% in the high-value group (p < 0.001), while the 3-year OS was 93.9% and 76.4%, respectively (p < 0.001). Furthermore, the 3-year RFS of patients who did not receive adjuvant chemotherapy or radiotherapy was 95.7% and 78.2% between the two groups (p < 0.001). The optimal cut-off value of immunohistochemical parameter P53 for predicting recurrence was confirmed as 67% and a P53 index above 67% was an independent prognostic factor.


Clinical implications of mismatch repair deficiency screening in patients with mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN).
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are rare tumors, mainly encountered in the gastroenteropancreatic tract. Based on the limited available data, MiNEN is usually a highly aggressive neoplasm combining a high-grade neuroendocrine and a non-neuroendocrine component, associated with a poor prognostic outlook. Deficient DNA mismatch repair (MMR) results in microsatellite instability, which is a useful screening marker for identifying patients with Lynch syndrome and a prognostic factor for chemotherapeutic interventions. Little information on MMR status in MiNEN is available in published studies. Therefore, the purpose of this study was to explore the status and putative role of MMR on MiNEN. We investigated the MMR status in 44 cases and characterized their clinicopathological features and prognoses. Immunohistochemistry was performed for four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Mean age at diagnosis was 61 years, and 75% of the patients were male. Lymph node metastases were observed in 14 (35.9%) patients. The most common tumor localizations were gastric (28 patients, 63.6%). Lack of immunohistochemical expression of MMR proteins was shown in 38.6% of cases. The common deletion rates of one or more proteins were 29.4% (5/17) for MLH1/PMS2 and 23.5% (4/17) for MLH1. Correlation between clinicopathological parameters showed that MMR deficiency was significantly associated with early TNM stage and better prognoses in patients with MiNEN. MiNENs showed frequent losses of MMR protein expression, which contributes to the knowledge of the pathological and clinical aspects of MiNEN tumors.


FAT10: Function and Relationship with Cancer.
Posttranslational protein modifications are known to be extensively involved in cancer, and a growing number of studies have revealed that the ubiquitin-like modifier FAT10 is directly involved in cancer development. FAT10 was found to be highly upregulated in various cancer types, such as glioma, hepatocellular carcinoma, breast cancer and gastrointestinal cancer. Protein FAT10ylation and interactions with FAT10 lead to the functional change of proteins, including proteasomal degradation, subcellular delocalization and stabilization, eventually having significant effects on cancer cell proliferation, invasion, metastasis and even tumorigenesis. In this review, we summarized the current knowledge on FAT10 and discussed its biological functions in cancer, as well as potential therapeutic strategies based on the FAT10 pathway.


Predictive factors for functional recovery after free tissue transfer oromandibular reconstruction.
Recovery of upper aerodigestive tract function after reconstruction of segmental oromandiblectomy defects is frequently incomplete. The purpose of this study was to quantitate postreconstruction function and define variables that predict functional outcome in this population. A prospective study of 21 patients who underwent microvascular free tissue transfer reconstruction of segmental oromandibular defects was performed. Measures of swallowing, speech, bite, and oral intake were performed preoperatively and at 1, 3, 6, and 12 months postoperatively or until plateau. Preoperative versus maximal postoperative measures were compared and correlated with nine potentially predictive variables. Univariate and multivariate analyses were performed to determine the most significant predictive factors. Baseline function in the study population was abnormal. Postoperative bite force improved, but swallowing, speech, and oral intake were worse than preoperative. Significant (univariate) predictors of outcome included diagnosis of cancer, tongue resection, pharynx resection, and flap skin paddle area. Only tongue resection remained significant in multivariate analysis. Increasing need for oropharyngeal lining replacement, especially after tongue resection, is the most important predictor of functional outcome in reconstruction of segmental mandible defects.


Primary structure of a 7Fe ferredoxin from Streptomyces griseus.
The complete primary structure of a Streptomyces griseus (ATCC 13273) 7Fe ferredoxin, which can couple electron transfer between spinach ferredoxin reductase and S. griseus cytochrome P-450soy for NADPH-dependent substrate oxidation, has been determined by Edman degradation of the whole protein and peptides derived by Staphylococcus aureus V8 proteinase and trypsin digestion. The protein consists of 105 amino acids and has a calculated molecular weight, including seven irons and eight sulfurs, of 12,291. The ferredoxin sequence is highly homologous (73%) to that of the 7Fe ferredoxin from Mycobacterium smegmatis. The N-terminal half of the sequence, which is the Fe-S clusters binding domain, has more than 50% homology with other 7Fe ferredoxins. In particular, the seven cysteines known from the crystal structure of Azotobacter vinelandii ferredoxin I to be involved in binding the two Fe-S clusters are conserved.


Higher SLPI expression, lower immune activation, and increased frequency of immune cells in a cohort of Colombian HIV-1 controllers.
There are 2 new phenotypes of HIV-1-positive individuals who exhibit a spontaneous and sustained control of viral replication at least for 1 year without antiretroviral therapy (elite controllers <50 copies/mL and viremic controllers <2000 copies/mL). Mechanisms related to this spontaneous control of viral replication are poorly understood. The study included HIV-1 controllers (patients with at least 1 year of HIV-1 diagnosis, highly active antiretroviral therapy naive, and with viral loads less than 2000 copies/mL) and HIV-1 progressors without antiretroviral therapy (viral load >2500 copies/mL, and CD4 T-cell count >250 cells/μL at the time of sampling). The expression of soluble factors, leukocyte protease inhibitor (SLPI) and human α-defensins-1 (HAD-1), was measured by real-time polymerase chain reaction from neutrophil cultures with or without HIV stimulation; the frequency and phenotype of innate and adaptive immune cells were determined by flow cytometry, and frequency of human leukocyte antigen alleles was determined by polymerase chain reaction sequence-specific oligonucleotide typing. As expected, HIV-1 controllers had higher CD4 T-cell counts and lower viral load when compared with HIV-1 progressor individuals; in addition, they exhibited lower expression of activation markers, higher frequency of myeloid dendritic cell, lower percentage of regulatory T cells and natural killer cells, and higher expression of SLPI. All together, these findings suggest that the control of the immune activation status and the production of antiviral proteins by innate immune cells could be associated to the mechanisms involved in the control of HIV-1 replication and better preservation of the CD4 T-cell count.


Efficacy and safety of the XEN45 implant in glaucoma surgery: Retrospective study of our first 73 cases.
To analyze the results of the Xen45 implant in our hospital center, both in terms of efficacy and safety. Observational, retrospective, single-center study of patients undergoing Xen45 surgery at the University Hospital of Jaén between January 1, 2018 and June 31, 2021. A total of 73 patients were implanted with the Xen45 device (48 with in combined surgery with phacoemulsification of the crystalline lens and 25 standalone Xen45 surgery). IOP decreased from 19.9 ± 4.9 mmHg at the first visit to a mean of 17.1 ± 5.3 (P = .001) at the sixth month. Drug use required between the first visit and Xen implantation was reduced from 2.1 ± 0.9 to 0.6 (P < .000). A second surgery was necessary in 18 patients (26.6%) in the first 6 months. Glaucoma surgery by Xen45 implant, alone or combined with cataract surgery, is an effective and safe procedure for IOP lowering.


[Clinico-statistical survey of neoplasms of the oral cavity in a Sardinian population].
The AA. examine 14,987 bioptic investigations comings from Anatomy and Pathologic Histology Institute of Cagliari University relieved during the period 1936-1968 (twenty-eight years). They stop on main data giving prominence to: incidence of stomatologic cases, of benignant and malignant tumours, of inflammatory and precancerous states in the mouth. They moreover describe neoplasia frequency in reference to histologic type, to sex, to age and to localization.


Medicinal and therapeutic potential of Sea buckthorn (Hippophae rhamnoides L.).
ETHNOPHARMACOLOGICAL CONTEXT: This review explores the medicinal and therapeutic applications of Sea buckthorn (Hippophae rhamnoides L.) in curtailing different types of acute as well as chronic maladies. The plant is being used in different parts of the world for its nutritional and medicinal properties. Sea buckthorn based preparations have been extensively exploited in folklore treatment of slow digestion, stomach malfunctioning, cardiovascular problems, liver injury, tendon and ligament injuries, skin diseases and ulcers. In the recent years, medicinal and pharmacological activities of Sea buckthorn have been well investigated using various in vitro and in vivo models as well as limited clinical trials. Sea buckthorn has been scientifically analyzed and many of its traditional uses have been established using several biochemical and pharmacological studies. Various pharmacological activities such as cytoprotective, anti-stress, immunomodulatory, hepatoprotective, radioprotective, anti-atherogenic, anti-tumor, anti-microbial and tissue regeneration have been reported. It is clear that Sea buckthorn is an important plant because of its immense medicinal and therapeutic potential. However, several knowledge gaps identified in this paper would give impetus to new academic and R&D activities especially for the development of Sea buckthorn based herbal medicine and nutraceuticals.


Bio-inspired nitric-oxide-driven nanomotor.
Current chemical-fuel-driven nanomotors are driven by gas (e.g. H2, O2, NH3) which only provides motion ability, and can produce waste (e.g. Mg(OH)2, Pt). Here, inspired by endogenous biochemical reactions in the human body involving conversion of amino acid L-arginine to nitric oxide (NO) by NO synthase (NOS) or reactive oxygen species (ROS), we report on a nanomotor made of hyperbranched polyamide/L-arginine (HLA). The nanomotor utilizes L-arginine as fuel for the production of NO both as driving force and to provide beneficial effects, including promoting endothelialisation and anticancer effects, along with other beneficial by-products. In addition, the HLA nanomotors are fluorescent and can be used to monitor the movement of nanomotors in vivo in the future. This work presents a zero-waste, self-destroyed and self-imaging nanomotor with potential biological application for the treatment of various diseases in different tissues including blood vessels and tumours.


TOFE human-B-cell-line-based adsorption-inhibition assay to detect HCV neutralizing antibodies.
We previously demonstrated that the human lymphoblastoid B-cell line (LCL) TOFE, derived from normal human bone marrow, is permissive to HCV infection. In this report we developed an in vitro HCV adsorption-inhibition assay based on TOFE cells, to reveal the presence of neutralizing antibodies in sera from acutely infected patients.


Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers.
Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence. We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers. A group of current heavy smokers (n = 24), ex-smokers who were abstinent for at least 5 years (n = 20), and never-smokers (n = 20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges. Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers. These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.


The effect of age on psoas and paraspinal muscle morphology in patients undergoing posterior lumbar fusion surgery.
The aim of this study was to determine the effect of age on the psoas and posterior paraspinal muscles (PPM; multifidus muscle and erector spinae) and to evaluate potential sex-related differences. MRI-based quantitative assessments of the cross-sectional area (CSA), the functional cross-sectional area (fCSA), the fat area (FAT) and the proportion of intramuscular fat (FI) were conducted on patients undergoing lumbar fusion surgery between 2014 and 2021. The regions of interest were the psoas muscle and the PPM at the superior endplate of L4. The left and right sides of the muscle groups were summarized and normalized by the patient's height (cm2/m2). The relationships between age and muscular parameters were analyzed stratified by sex. A total of 195 patients (57.9%female) with a median age of 64.2 years and a body mass index of 28.3 kg/m2 were analyzed. The CSAPsoas was 7.7 cm2/m2 and differed significantly between females and males (p < 0.001); likewise, the fCSAPsoas differed significantly between the sexes. The CSAPPM was 18.8 cm2/m2 with no sex-specific differences. Significant differences were found in the FIPPM (males: 41.1% vs. females: 47.9%; p < 0.001), but not in the FIPsoas (males: 3.7% vs. females: 4.5%; p = 0.276). Considering the effect of age on FI, a significant positive correlation was observed for the PPMs for both sexes. Only in women, there was a negative correlation between age and CSAPsoas (ρ = - 0.248; p = 0.008), FATPsoas (ρ = - 0.421; p < 0.001) and FIPsoas (ρ = - 0.371; p < 0.001). This study demonstrated sex-specific differences in spinal muscle morphology in relation to patient age. With increasing age there was a decrease in FIPsoas in women only, unlike in the PPMs in which there was increased FI that was significantly higher in women compared to men.


Expression of H-2 antigen on oligodendrocytes is induced by soluble factors from concanavalin A activated T cells.
It has been shown that soluble factors from activated T cells, or interferon alone, enhance the expression of major histocompatibility complex (MHC) antigens in several cell types. In this study we have demonstrated, by means of indirect immunofluorescence and radioimmunoassay, that the expression of mouse MHC class I antigen (H-2) on isolated mouse oligodendrocytes is induced by soluble factors from concanavalin A activated T cells. Autoradiographic studies indicate that this induction of H-2 expression is not accompanied by proliferation of oligodendrocytes.


Static and dynamic stabilometric force platform study of spinopelvic anterior sagittal imbalance.
Anterior sagittal imbalance (ASI) is a severity factor in spinal pathology. Stabilometric study of the dynamic position of the center of pressure (CoP) assesses orthostatic control. These analyses provide the energy expenditure used for this control. Stabilometric signs are associated with ASI indicate increased energy expenditure. Healthy male volunteers were subjected to reversible ASI induced by wearing a kyphotic thermoformed thoracolumbar corset. The deformation was assessed by C7 tilt on EOS whole-spine views. Static and dynamic posturographic force platform study was performed under conditions of anteroposterior and mediolateral instability. Mean CoP position (Xmean, Ymean) was studied on statokinesigram, with scatter assessed as confidence ellipse (CE). Path length according to CE surface (LAS) indicated energy expenditure. The stabilogram quantified displacement over time as lengths (Lx, Ly) and amplitudes (Ax, Ay). The corset significantly increased C7 tilt (p<0.0001). This did not significantly change mean CoP positions (Xmean and Ymean), but LAS was significantly increased (p=0.003). Static tests showed changes in Ly (p=0.0008) and Ax (p=0.003), and dynamic tests showed changes in Ly (p<0.0001), Lx (p<0.0001), Ax (p<0.0001), Ay (p<0.05) and CE (p<0.004). Posturographic parameters were impacted by inducing ASI in healthy subjects. Significant differences were seen in stabilography, CE and LAS, were greater on dynamic testing, and correlated with radiologic sagittal balance. Force platforms can reveal increased energy expenditure in maintaining posture. II; Single-center prospective study involving healthy volunteers.


Free Energy Landscape for the Entire Transport Cycle of Triose-Phosphate/Phosphate Translocator.
Secondary active transporters translocate their substrates using the electrochemical potentials of other chemicals and undergo large-scale conformational changes. Despite extensive structural studies, the atomic details of the transport mechanism still remain elusive. We performed a series of all-atom molecular dynamics simulations of the triose-phosphate/phosphate translocator (TPT), which exports organic phosphates in the chloroplast stroma in strict counter exchange with inorganic phosphate (Pi). Biased sampling methods, including the string method and umbrella sampling, successfully reproduced the conformational changes between the inward- and outward-facing states, along with the substrate binding. The free energy landscape of this entire TPT transition pathway demonstrated the alternating access and substrate translocation mechanisms, which revealed that Pi is relayed by positively charged residues along the transition pathway. Furthermore, the conserved Glu207 functions as a "molecular switch", linking the local substrate binding and the global conformational transition. Our results provide atomic-detailed insights into the substrate transport mechanism of the antiporter.


Influence of the base and diluent monomer on network characteristics and mechanical properties of neat resin and composite materials.
This study evaluated the effect of the combination of two dimethacrylate-based monomers [bisphenol A diglycidyl dimethacrylate (BisGMA) or bisphenol A ethoxylated dimethacrylate (BisEMA)] with diluents either derived from ethylene glycol dimethacrylate (ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate) or 1,10-decanediol dimethacrylate (D3MA) on network characteristics and mechanical properties of neat resin and composite materials. The degree of conversion, maximum rate of polymerization and water sorption/solubility of unfilled resins and the flexural strength and microhardness of composites (after 24 h storage in water and 3 months storage in a 75 vol% ethanol aqueous solution) were evaluated. Data were analyzed with two-way ANOVA and Tukey's test (α = 0.05). The higher conversion and lower water sorption presented by BisEMA co-polymers resulted in greater resistance to degradation in ethanol compared with BisGMA-based materials. In general, conversion and mechanical properties were optimized with the use of long-chain dimethacrylate derivatives of ethylene glycol. D3MA rendered more hydrophobic materials, but with relatively low conversion and mechanical properties.


Evaluation of Ideal Extent of Corpus Callosotomy Based on the Location of Intracallosal Motor Fibers.
The corpus callosotomy (CCT) has been reported as an effective procedure to alleviate drop attacks. However, the extent of CCT remains debatable. Classical studies suggest that motor fibers traverse mainly through the anterior half of the corpus callosum (CC), although recent diffusion tensor imaging studies described that motor fibers crossed the CC in a more posterior location, emphasizing the posterior midbody and the isthmus. Cortical and subcortical structures were examined in 30 hemispheres prepared for white matter fiber dissection. Dissections were carried out under surgical magnification to trace fibers originating from the primary motor cortex and their course through the CC. The distance of the most anterior and posterior motor fibers to the tip of the genu were measured, and the extent of CCT enabling disconnection of all motor fibers was calculated. Motor fibers coursed through the posterior half of the CC in the majority of hemispheres, mainly locating in posterior midbody and the isthmus. Callosal fibers should be interrupted to an average of 61% ± 0.07% point of the CC to reach the anterior limit of motor fibers and to an average of 69% ± 0.07% point to include posterior limit of motor fibers. Motor fibers were extending until the posterior one third of the CC in 22 specimens. Anterior-half CCT did not include all motor fibers in any specimen. Anterior two thirds CCT disrupted all motor fibers in one fourth of the cases. Our findings suggest that an ideal CCT should extend to the posterior midbody and isthmus of the CC.


Engineered Zinc Finger DNA-Binding Domains: Synthesis, Assessment of DNA-Binding Affinity, and Direct Protein Delivery to Mammalian Cells.
Zinc finger proteins are the most common among families of DNA-binding transcription factors. Designer transcription factors generated by the fusion of engineered zinc finger DNA-binding domains (ZF-DBDs) to effector domains have been valuable tools for the modulation of gene expression and for targeted genome editing. However, ZF-DBDs without effector domains have also been shown to effectively modulate gene expression by competing with sequence-specific DNA-binding transcription factors. Here, we describe the methodology and provide a detailed workflow for the cloning, expression, purification, and direct cell delivery of engineered ZF-DBDs. Using this protocol, ZF-DBDs can be generated with high efficiency in less than 2 weeks. We also describe a nonradioactive method for measuring DNA binding affinity of the purified ZF-DBD proteins as well as a method for direct delivery of the purified ZF-DBDs to mammalian cells.


Lead fixation in dogs achieved with RF energy.
The purpose of this study was to test whether radiofrequency (RF) energy could be used to fixate leads to the endocardium. In six dogs we measured the dislodgment force and pacing threshold before and after RF fixation in the coronary sinus (CS) and right ventricle (RV). RF fixation was achieved with a CardioRhythm Atakr ablation unit. The dislodgment force of CS leads fixed with RF energy was 1.63+/-0.65 oz, compared with < 0.1 oz for similar leads placed in the CS of six separate dogs. In the RV, leads fixed with RF energy had a dislodgment force of 1.29+/-0.27 oz, compared with 0.48+/-0.28 oz. for urethane (P < 0.01) and 1.01+/-0.21 oz for silicone (P = 0.41) tined leads. In the CS, the pacing threshold for RF fixed leads increased significantly from 2.2+/-1.1 V (0.5 msec) before fixation to 4.2+/-1.3 V after fixation (P < 0.01), while in the RV, the pacing threshold increased from 0.41+/-0.05 V (0.5 msec) before fixation to a mean of 2.03+/-0.44 V after fixation (P < 0.01). In another group of six dogs studied for 12 weeks, 5 of 6 RF fixed CS leads remained attached, as did 8 of 10 RF fixed RV leads. For the RV leads, the mean pacing threshold was 0.90+/-0.35 V, compared with 0.53+/-0.18 V (0.5 msec) for similar tined leads (P = 0.02) and 1.2+/-0.30 V (0.5 msec) for screw leads (P = 0.18) in the RV. We conclude that RF energy can be used to attach leads to the RV and CS endocardium. While the RV pacing thresholds increased acutely, the mean chronic thresholds were not significantly different for RF fixed leads and standard tined or screw leads.


Effect of feeding CLA on plasma and granules fatty acid composition of eggs and prepared mayonnaise quality.
Eggs rich in trans, trans conjugated linoleic acid (CLA) are significantly more viscous, have more phospholipids containing linoleic acid (LA), and more saturated triacylglycerol species than control eggs. However, the fatty acid (FA) composition of yolk plasma and granule fractions are unreported. Furthermore, there are no reports of mayonnaise rheological properties or emulsion stability by using CLA-rich eggs. Therefore, the objectives were (1) compare the FA composition of CLA-rich yolk granules and plasma, relative to standard control and LA-rich control yolks, (2) compare the rheological properties of mayonnaise prepared with CLA-rich eggs to control eggs and (3) compare the emulsion stability of CLA-yolk mayonnaise. CLA-rich eggs and soy control eggs were produced by adding 10% CLA-rich soy oil or 10% of control unmodified soy oil to the hen's diet. The eggs were used in subsequent mayonnaise preparation. CLA-yolk mayonnaise was more viscous, had greater storage modulus, resisted thinning, and was a more stable emulsion, relative to mayonnaise prepared with control yolks or soy control yolks.


[Laser in dentistry. Characteristics and utilization].
Authors present this review article in the beginning of an experimental study about lasers applications in dentistry. They also show the main characteristics of lasers involved in this kind of research.


On the role of correctional officers in prison mental health.
This article discusses the role of correctional line staff in treatment of prison inmates with serious mental illness. The authors assert that many roles and duties traditionally attributed to clinicians can and often should be performed not only by mental health professionals, but by line staff such as correctional officers and nurses. Moreover, the optimal climate for effective treatment is one in which mental health professionals and line staff work collaboratively, especially since line staff alone are in contact with inmates 24 hours per day. The specific activities which comprise mental health treatment in prison are described as: 1) counseling and psychotherapy-talking with inmates, 2) consultation-talking about inmates, 3) special housing, activities, and behavioral programs, and 4) medication. Case examples demonstrate how correctional officers, nurses, and other line staff perform each of these activities. Recognition and nurturance of these activities will improve the quality of services and reduce stress on staff and inmates alike. Consultation with line staff, joint training, and use of multi-disciplinary treatment teams are advocated as methods of reaching these goals.


The cellular neurobiology of neuronal development: the cerebellar granule cell.
Cerebellar granule cells in vivo and in vitro have been widely used in the study of the cellular neurobiology of neuronal development. We have described the basic neuroanatomical data on the granule cell in the developing and mature cerebellum. The importance of the cytoskeleton in determining the morphology of the granule cell and in process outgrowth and cell migration has been described. Extensive information is now available on the composition of the granule cell cytoskeleton. Cell surface glycoproteins are thought to be involved in the control of cell adhesion and cellular interactions during development. A number of surface molecules belonging to either the N-CAM or the Ng-CAM groups of glycoproteins have been studied in detail in the cerebellum. The role of these proteins in cell adhesion and in granule cell-astroglial interactions during granule cell migration has been reviewed. The survival and differentiation of neurones is controlled by soluble trophic factors. Several factors have been described which act as trophic factors for granule cells in vitro and may do the same in vivo. The numerous studies that have been carried out on the cerebellar granule cell have allowed us to describe certain aspects of the cellular neurobiology of this class of neurones as an example with general significance for the understanding of neuronal differentiation and function.


What is the role played by pregnancy in the construction of a woman's identity and her association with her child-to-be?
Objective: The present work aimed to evaluate: (a) the psychometric properties of the Centrality of Event Scale in Italian primiparous and multiparous women; (b) individual differences in those demographic variables that influence change in women's identity and the maternal role acquisition during pregnancy; (c) the association between the extent to which pregnancy has an impact on woman's life story and identity and prenatal attachment; (c) how the centrality of the pregnancy event is related to the experience of PTSD during pregnancy.Background: Pregnancy is a crucial phase in women's life that involves many changes for a woman's role and identity.Methods 319 pregnant women were assessd during the third trimester of pregnancy.Results: Exploratory Factor Analyses confirmed a one-factor solution of the CES. Moreover, the perception of pregnancy as central in women's lives is significantly related to prenatal attachment. Finally, the perception of pregnancy as central in women's lives is positively correlated to PTSD symptoms.Conclusion: Our findings provide evidence on the validity of the scale with pregnant women samples, which may contribute for a better understanding of the impact of pregnancy on women's identity and life story, as well as the underlying psychological challenges related to pregnancy.


Emergence of a Bilaterally Symmetric Pattern from Chiral Components in the Planarian Epidermis.
Most animals exhibit mirror-symmetric body plans, yet the molecular constituents from which they are formed are often chiral. In planarian flatworms, centrioles are arranged in a bilaterally symmetric pattern across the ventral epidermis. Here, we found that this pattern is generated by a network of centrioles with prominent chiral asymmetric properties. We identify centriole components required for establishing asymmetric connections between centrioles and balancing their effects to align centrioles along polarity fields. SMED-ODF2, SMED-VFL1, and SMED-VFL3 affect the assembly of centriole appendages that tether cytoskeletal connectors to position the centrioles. We further show that the medio-lateral polarization of centrioles relies on mechanisms that are partly distinct on the left and right sides of the planarian body. Our findings shed light on how bilaterally symmetrical patterns can emerge from chiral cellular organizations.


A pilot randomized controlled trial of pioglitazone for the treatment of poorly controlled asthma in obesity.
Obese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications. The purpose of this study was to determine the efficacy of pioglitazone, an anti-diabetic medication which can alter circulating adipokines and have direct effects on asthmatic inflammation, in the treatment of asthma in obesity. A two-center, 12-week, randomized, placebo-controlled, double-blinded trial. Treatments were randomly assigned with concealment of allocation. The primary outcome was difference in change in airway reactivity between participants assigned to pioglitazone versus placebo at 12 weeks. Twenty-three participants were randomized to treatment, 19 completed the study. Median airway reactivity, measured by PC20 to methacholine was 1.99 (IQR 3.08) and 1.60 (5.91) mg/ml in placebo and pioglitazone group at baseline, and 2.37 (15.22) and 5.08 (7.42) mg/ml after 12 weeks, p = 0.38. There was no difference in exhaled nitric oxide, asthma control or lung function between treatment groups over the 12 week trial. Participants assigned to pioglitazone gained a significant amount more weight than those assigned to placebo (pioglitazone group mean weight 113.6, CI 94.5-132.7 kg at randomization and 115.9, CI 96.9-135.1 at 12 weeks; placebo mean weight 127.5, CI 108.4 - 146.6 kg at randomization and 124.5, CI 105.4 - 143.6 kg at 12 weeks; p = 0.04). This pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma. Clinicaltrials.gov (NCT00634036).