[Patients and doctors in Greenland--70 years ago and today].
In April 1924 a 13 year old Greenlander died of tuberculosis in the hospital in Egedesminde. The boy had been transported on dog sled by the district doctor from the outpost Ikamiut two months earlier. Not because healing was considered possible, but because the conditions for nursing in his family's turf hut was too bad. The crowded living conditions in Greenland and the frequent hunger periods were the reason for the spread of TB, which in the nineteen twenties was the cause of 1/3 of all deaths. At the present moment it is psychiatric patients who take up most beds in the Greenlandic hospitals. The reason for so many patients with behaviour disorder is still--among other things--due to crowded living conditions but also to the sudden change in recent years of the way of living. The doctors living and working conditions in Greenland in 1924 were very different from conditions in Denmark which made it difficult to fill the vacancies. Nowadays doctors salaries are on the same level in Greenland and in Denmark, but a period in a Greenlandic hospital does not count very much for a doctor's special training, and when schools for children are not as good as in Denmark it is still difficult to get Danish doctors to stay in Greenland for a long time.


Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro.
Interleukin-1 (IL-1) alpha and beta and tumor necrosis factor (TNF) alpha and beta are potent stimulators of bone resorption in vitro and in vivo. However, the mechanisms underlying this increased bone resorption have not been clearly defined. Increased bone resorption can result from increased activity of individual osteoclasts, increased numbers of osteoclasts, or both. Therefore, we have used a long-term human marrow culture system that forms multinucleated cells (MNC) with the characteristics of osteoclasts to examine the effects of IL-1 and TNF on osteoclast formation. Human recombinant IL-1 alpha and IL-1 beta, and human recombinant TNF-alpha and TNF-beta stimulated MNC formation from 4- to 60-fold. IL-1 alpha, IL-1 beta, TNF-alpha, and TNF-beta significantly increased MNC formation at very low concentrations: 2.5 x 10(-13) M for IL-1 alpha and IL-1 beta, 10(-11) M for TNF-alpha, and 10(-10) M for TNF-beta In addition, these cytokines enhanced MNC formation in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a potent osteotropic factor that stimulates MNC formation by stimulating fusion of mononuclear precursor cells. Simultaneous addition of IL-1 and TNF to the cultures resulted in a synergistic stimulation of MNC formation. These results suggest that: (1) IL-1 and TNF stimulate bone resorption in part by increasing osteoclast formation and (2) an extremely low concentration of these factors can synergistically increase osteoclast formation in the absence of other factors, such as 1,25-(OH)2D3. These data suggest that synergistic interactions among cytokines play an important role in maintaining bone cell activity in normal and pathologic states.


Dynamic nature of the transition state for the SN1 reaction mechanism of diphenylmethyl acetates.
Picosecond absorption spectroscopy is employed in the study of the reaction dynamics for the contact ion pairs produced upon the photolysis of a series of substituted diphenylmethyl acetates in the solvents acetonitrile, dimethyl sulfoxide, and 2,2,2-trifluoroethanol. From the temperature dependence of the rate constants, the activation parameters associated with covalent bond formation and diffusional separation to the solvent-separated ion pair are obtained. The activation parameters for bond formation are examined within the context of the Hynes theory for solvent dynamical effects on the passage through the transition state; deviations from the transition-state theory are found to be large. Factors that control nucleophilicity are discussed. Finally the validity of applying the Marcus equation to the SN1 reaction mechanism is addressed.


Is clinical relevance sometimes lost in summative scores?
It is possible to have a reliable and valid measure of a clinical phenomenon but to score the measure in a way that inaccurately represents the clinical meaning of the measured phenomenon. The purpose of this article is to demonstrate the risk to research and clinical assessments caused by a discrepancy in the clinical meaning of scores obtained by total scale scoring and those obtained by individual item scoring. The clinical phenomenon that is used in this demonstration is symptom distress as measured by the Symptom Distress Scale (SDS). In this example, the discrepancy in meaning between total scale scores and the individual item scores of the SDS has potential clinical implications as more than 30% of participating adolescent patients at each of four time points spanning a 6-month time period would have been inaccurately assessed when the assessment was based on the total scale score.


Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.
Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation gene-mediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(11;14) and t(14;20) samples, respectively. The study indicates that in a significant number of cases the translocation-based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought.


Evalution of the effectiveness of multimodal approach to the management of cervical vertigo.
Vertigo is one of the most common complaints among patients consulting neurologists and general practitioners - family medicine. A special form of dizziness is cervical vertigo. However, the presence of chronic vertigo and imbalance in this group of patients makes it possible to include the treatment of vestibular rehabilitation in the program. Evalution of the effectiveness of multimodal approach to the management of cervical vertigo. 109 patients aged from 18 to 45 with vertigo together with myofascial pain syndrome of neck and shoulder area were examined. The survey included a sample of Dix-Hallpike, neurological and otoneurological examinations, Doppler ultrasound of the main arteries of the head and neck, brain MRI, functional spondylography of the cervical spine. For quantitive evaluation of the impact of vertigo on daily life the questionnaire DHI (Dizziness Handicap Inventory) was used. Testing was performed in two stages - before treatment and in 2 weeks' time. Patients were randomly divided into 3 groups which differ in their therapeutic tactics. In all three groups the normalization of the biomechanical pattern and elimination of musculo-tonic disorders accompanied by a decrease of a pain syndrome and a decrease in the severity or complete regression of dizziness and postural instability. At the same time, in groups 2 and 3, in which in addition to manual therapy, patients received acupuncture, there was a distinct positive dynamics of a pain syndrome according to VAS, Neck Disability Index and the Dizziness Handicap Inventory. A marked regression of vertigo and postural instability can be observed in patients in which the treatment along with manual therapy and acupuncture, a complex of vestibular rehabilitation was used. The multimodal approach using manual therapy in combination with acupuncture and vestibular rehabilitation showed the maximum therapeutic effect on elimination of musculo-tonic disorders, reduction of a pain syndrome with a complete regression of vertigo and postural instability.


Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation.
Anti-tumor necrosis factor alpha (anti-TNF-alpha) agents are being used increasingly in refractory inflammatory eye diseases. We reviewed our patients on etanercept and infliximab to determine whether these medications are equally efficacious in controlling ocular inflammation. Exploratory retrospective analysis. Patients with ocular inflammatory disease on an anti-TNF-alpha agent (etanercept, infliximab). Case records of 22 patients treated with anti-TNF-alpha therapy were reviewed for demographic information, ocular and systemic diagnosis, duration and dose of anti-TNF-alpha treatment, concomitant ocular and systemic immunosuppressive medications, and treatment response. Uveitis recurrence rate, initial treatment response, treatment response, and medication use at 6 months, 1 year, and last visit. Patients treated with infliximab had a significant decrease in uveitis recurrences after starting therapy compared with those treated with etanercept (59% vs. 0%, P = 0.004). One year after treatment initiation and at final visit, more infliximab-treated patients had an improvement in their ocular inflammation (100% vs. 33%, P = 0.002, and 94% vs. 0%, P<0.001, respectively) and a decreased requirement for topical prednisolone acetate 1% (94% vs. 33%, P = 0.009, and 89% vs. 29%, P = 0.007, respectively) compared with those treated with etanercept. No significant differences in the use of oral corticosteroids and immunosuppressive agents were noted between the 2 groups at 6 months, 1 year, and final visit. Infliximab was more effective than etanercept in the treatment of recalcitrant uveitis and decreased the use of topical steroids.


[Comments on the incidence of contact allergy].
Analysis of positive patch testing during the last years revealed increased occurrence of contact allergy against arnica. Our investigations were done at the Department of Dermatology of the General Hospital, Linz. We take the view that the frequency of this contact allergy represents the consequence of using household remedies containing arnica.


Relationship between sociability toward humans and physiological stress in dogs.
Sociability is an essential trait for dogs to successfully interact with humans. In this study, the relationship between sociability and physiological stress was examined. Additionally, whether differences exist between companion dogs (C group) and shelter dogs (S group) was examined. Overall, healthy 37 dogs (C group=21 and S group=16) were examined. After 5 min of walking, the dog and the owner (or the chief manager) rested freely in the experimental location for 5 min. The behavioral test with 6 categories was conducted to evaluate sociability over 4 min. The establishment of two groups (H group=dogs with high sociability; L group=dogs with low sociability) was supported by the statistical results of the behavioral tests. Saliva was collected before (P1) and after the test period (P2), and salivary cortisol levels were determined and statistically analyzed. The cortisol concentrations at P2 and the differences in concentrations between P1 and P2 (P2-P1) in the groups with high sociability were significantly lower than those in the groups with low sociability. These results may demonstrate that sociable dogs adapt more comfortably to strangers and unfamiliar situations. Meanwhile, there were significant differences in hormonal results between the C and S groups. For this reason, their sociability should be evaluated using behavioral and physiological assessments before re-adoption to ensure their successful adaptation.


Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody.
Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI.


Stressful situations and factors in students of nursing in clinical practice.
To assess the risk factors for stress in undergraduate students of nursing in clinical practice in a public university in the Northeast region of Brazil. Cross-sectional descriptive study with 116 students from the fifth to the ninth period. The bilingual KEZKAK questionnaire, validated for Portuguese, was used. Stress was considered to be present when the score was equal or superior to 2. The students with stress in clinical practice were 18 to 22 years old (2.82 ± 0.98), women (2.81 ± 0.96), married (2.80 ± 0.97), and who were permanent contracted employees (2.74 ± 0.94). The factors which were most associated with stress were: Lack of competence (2.99 ± 0.88); Impotence and uncertainty (2.98 ± 0.85); and Patients seeking a closer relationship (2.93 ± 1.01). The students of the sixth period were the most vulnerable to stress (2.85±0.96). The studies showed the main risk factors for stress among students of nursing in their clinical practice. These results could be used in the development of strategies seeking to reduce stress in this context as well as to contribute to promoting mental health.


Indoor air quality in preschools (3- to 5-year-old children) in the Northeast of Portugal during spring-summer season: pollutants and comfort parameters.
Indoor air quality at schools (elementary, primary) has been the subject of many studies; however, there are still relative few data regarding preschool (3- to 5-year-old children) environments. This investigation determined the concentrations of particulate matter (PM)2.5, total volatile organic compounds (TVOC), formaldehyde, carbon monoxide (CO), and ozone (O3) as well as the levels of carbon dioxide (CO2), temperature, and relative humidity (RH) in the indoor and outdoor air of two preschools situated in different geographical regions of Portugal. The indoor concentrations of TVOC, CO, O3, and CO2 were predominantly higher at the end of school day compared to early morning periods. The TVOC and CO2 concentrations were higher indoors than outdoors suggesting predominantly an indoor origin. Outdoor air infiltrations were the major contributing source of CO and O3 to indoor air in both preschools. The concentrations of all pollutants were within the limits defined by national regulations and international organizations, except for TVOC that exceeded 8-12-fold higher than the recommendation of 0.2 mg/m3 proposed by European Commission. The levels of CO2 were below the protective guideline of 2250 mg/m3 (Portuguese legislation); however, the observed ranges exceeded the Portuguese margin of tolerance (2925 mg/m3) at the end of school days, indicating the impact of occupancy rates particularly at one of the preschools. Regarding comfort parameters, temperature exerted a significant influence on O3 concentrations, while RH values were significantly correlated with TVOC levels in indoor air of preschools, particularly during the late afternoon periods.


State of hormonal balance in adolescent girls with menstrual function disorders associated with obesity.
Investigation of the mechanisms promoting the development of menstrual function disorders associated with obesity in adolescent girls is one of the most important issues of modern medicine. This study included 110 patients. 79 patients aged 12-18 with menstrual disorders associated with obesity were divided into two groups: group 1: 46 patients with apparent signs of hyperandrogenism, group 2: 33 patients without clinical manifestations of hyperandrogenism. The control group included 31 girls of the same age with a regular menstrual cycle. The complex of hormone examination of adolescent girls included determination of serum content: gonadotropic hormones (luteinizing hormone (LH) and follicle-stimulating hormone (FSH), prolactin (PRL), estradiol (E2), testosterone (T), progesterone (PR), dehydroepiandrosterone sulfate; insulin (In) - radioisotope method on a gamma counter "Narcotest" (reagents "IMMUNOTECH", Czech Republic). We identified hyperleptinemia and leptin resistance in patients with menstrual function impairment associated with obesity. In group I, the adiponectin level exceeded the values of the control group (p<0.05). The results revealed a decrease in A/L in group I - 5.4 times compared with patients in group II (p<0.05) and 4.3 times - compared with the control group (p<0.05). The results revealed a decrease in A/L among girls in the group I with MFI associated with obesity - 4.3 times - compared with girls in the control group (p<0,05).


Tetraphenylethylene-Based Multicomponent Emissive Metallacages as Solid-State Fluorescent Materials.
The construction of solid-state fluorescent materials with high quantum yield and good processability is of vital importance in the preparation of organic light-emitting devices. Herein, a series of tetraphenylethylene (TPE)-based multicomponent emissive metallacages are prepared by the coordination-driven self-assembly of tetra-(4-pyridylphenyl)ethylene, cis-Pt(PEt3 )2 (OTf)2 and tetracarboxylic ligands. These metallacages exhibit good emission both in solution and in the solid state because the coordination bonds and aggregation restrict the molecular motions of TPE synergistically, which suppresses the non-radiative decay of these metallacages. Impressively, one of the metallacages achieves very high fluorescence quantum yield (ΦF =88.46 %) in the solid state, which is further used as the coatings of a blue LED bulb to achieve white-light emission. The study not only provides a general method to the preparation of TPE-based metallacages but also explores their applications as solid-state fluorescent materials, which will promote the future design and applications of metallacages as useful emissive devices.


[Epidemiology of tuberculosis in Poland and in the world].
The paper describes the risk of tuberculosis infection and the incidence of the disease as measures of the epidemiological situation and presents data on the epidemiological situation of tuberculosis in Poland and the world. It also describes the effectiveness of the national tuberculosis control programme in Poland. The annual risk of tuberculosis infection in Poland is estimated at 0.2% which is about 10 times higher than the lowest one in Europe (the Netherland), but there are countries in the world with the risk of 2.0% and higher. The incidence of tuberculosis in Poland (all forms) declined from 182.6/100,000 in 1965 to less than 40,0/100,000 in 1996, of which less than half were bacteriologically positive cases. The incidence of smear positive cases, the most infectious group, declined from 18.7/100,000 in 1980 to 9.7/100,000 in 1995. All cases of tuberculosis in Poland are treated with 4-drugs regimen in the intensive phase of treatment and 3-drugs in the continuation phase. The duration of treatment is 6-8 months and the cure rate is above 90%.


Lymphocytic vasculitis: is it a specific clinicopathologic entity?
Seventy-one biopsy specimens taken at the Mayo Clinic from June 1977 through May 1981 demonstrated lymphocytic vasculitis. All specimens met the criteria for lymphocytic vasculitis, defined as (1) a predominantly lymphocytic infiltrate that involves and surrounds blood vessel walls, (2) fibrinoid necrosis of blood vessel walls, and (3) endothelial cell hyperplasia. Other histologic findings such as thrombosis, extravasation of erythrocytes, ulceration, epidermal infarction, and evidence of nuclear dust were seen only occasionally. Hypocomplementemia and other serologic abnormalities were very rare, even when lymphocytic vasculitis was extensive. The clinical diagnoses varied, with drug reaction (12 patients) and chronic urticaria (10 patients) being most frequent. In 32 cases, no specific diagnosis could be made at the time of dermatologic dismissal. In the remaining 39 cases, the diagnoses were varied and no definite clinical categories can be applied to them. We also observed typical lymphocytic vasculitis in some cases of other clinical entities, such as nodular scabies, erythema multiforme, and urticarial vasculitis, and so forth. We conclude that lymphocytic vasculitis is probably not a specific clinicopathologic entity but is more likely a reactive process, secondary to severe lymphocytic inflammation in the skin.


Type I collagen-functionalized supported lipid bilayer as a cell culture platform.
The supported phospholipid bilayer serves as an important biomimetic model for the cell membrane in both basic and applied scientific research. We have constructed a biomimetic platform based on a supported phospholipid bilayer that is functionalized with type I collagen to serve as a substrate for cell culture. To create the type I collagen-functionalized lipid bilayer assembly, a simple chemical approach was employed: lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(glutaryl) (DP-NGPE), a carboxylic acid-functionalized phospholipid, were prepared and then fused onto an SiO(2) substrate to form a supported lipid bilayer. Subsequently, type I collagen molecules were introduced to form stable collagen-lipid conjugates via amide linkages with activated DP-NGPE lipids. The binding kinetics of the conjugation process and the resultant changes in film thickness and viscoelasticity were followed using the quartz crystal microbalance with dissipation (QCM-D) monitoring. The morphology of the conjugated collagen adlayer was investigated with atomic force microscopy (AFM). We observed that the adsorbed collagen molecules tended to self-assemble into fibrillar structures. Fluorescence recovery after photobleaching (FRAP) was utilized to estimate lateral lipid mobility, which was reduced by up to 20% after the coupling of type I collagen to the underlying lipid bilayer. As a cell culture platform, the collagen-conjugated supported lipid bilayer showed promising results. Smooth muscle cells (A10) retained normal growth behavior on the collagen-functionalized platform, unlike the bare POPC lipid bilayer and the POPC/DG-NGPE bilayer without collagen. The biomimetic functionalized lipid system presented here is a simple, yet effective approach for constructing a cell culture platform to explore the interactions between extracellular matrix components and cells.


Bacterial interference by Streptococcus salivarius.
A strain of streptococcus salivarius, recognized in a throat culture because of its inhibition of the growth of a species of Corynebacterium, was studied in vitro to determine its antagonistic effects agains various other bacteria. It was found to be inhibitory to anaerobic Gram-positive cocci, streptococci belonging to Lancefields groups A, C, F, and G, and Corynebacterium diphtheriae, C. hofmanii, and C. xerosis.


[Research and development of enzymes used in feed].
Enzymes can degrade the anti-nutrient factors in feedstuff, increase nutrient digestibility, and reduce pollution to environment, and have been widely supplemented in animal feedstuff. However, the use of enzymes is limited because of their undesirable properties, such as thermoliability and susceptibility against protease digestions. And its commercialization is also limited by low production efficiency and high cost. Therefore, the focuses for future enzyme development will be: (1) to obtain novel enzymes with better properties by high-throughput screening of enzyme encoding genes, especially those from extreme and special environments; (2) to improve enzyme properties using directed mutagenesis and protein engineering methods; (3) to achieve high-level fermentation of enzymes by heterogonous expression and optimization of codons, vectors and fermentation conditions; (4) to determine the effect of enzymes to animals and utilize enzymes efficiently.


Electromagnetic-Guided Bedside Placement of Nasoenteral Feeding Tubes by Nurses Is Non-Inferior to Endoscopic Placement by Gastroenterologists: A Multicenter Randomized Controlled Trial.
Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement. We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals. Patients were randomly assigned (1:1) to undergo EM-guided or endoscopic nasoenteral feeding tube placement. The primary end point was the need for reinsertion of the feeding tube (e.g., after failed initial placement or owing to tube-related complications) with a prespecified non-inferiority margin of 10%. Reinsertion was required in 29 (36%) of the 80 patients in the EM-guided group and 31 (42%) of the 74 patients in the endoscopy group (absolute risk difference -6%, upper limit of one-sided 95% confidence interval 7%; P for non-inferiority=0.022). No differences were noted in success and complication rates. In the EM-guided group, there was a reduced time to start of feeding (424 vs. 535 min, P=0.001). Although the level of discomfort was higher in the EM-guided group (Visual Analog Scale (VAS) 3.9 vs. 2.0, P=0.009), EM-guided placement received higher recommendation scores (VAS 8.2 vs. 5.5, P=0.008). EM-guided bedside placement of nasoenteral feeding tubes by nurses was non-inferior to endoscopic placement by gastroenterologists in surgical patients and may be considered the preferred technique for nasoenteral feeding tube placement.


NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses.
DNA vaccines have been shown to elicit tumor-protective cytotoxic T lymphocyte (CTL) immunity in preclinical models, but have shown limited efficacy in cancer patients. Plasmids used for DNA vaccines can stimulate several innate immune receptors, triggering the activation of master transcription factors, including interferon regulatory factor 3 (IRF3) and nuclear factor κ B (NF-κB). These transcription factors drive the production of type I interferons (IFNs) and pro-inflammatory cytokines, which promote the induction of CTL responses. Understanding the innate immune signaling pathways triggered by DNA vaccines that control the generation of CTL responses will increase our ability to design more effective vaccines. To gain insight into the contribution of these pathways, we vaccinated mice lacking different signaling components with plasmids encoding tyrosinase-related protein 2 (TRP2) or ovalbumin (OVA) using intradermal electroporation. Antigen-specific CTL responses were detected by intracellular IFN-γ staining and in vivo cytotoxicity. Mice lacking IRF3, IFN-α receptor, IL-1β/IL-18, TLR9 or MyD88 showed similar CTL responses to wild-type mice, arguing that none of these molecules were required for the immunogenicity of DNA vaccines. To elucidate the role of NF-κB activation we co-vaccinated mice with pIκBα-SR, a plasmid encoding a mutant IκBα that blocks NF-κB activity. Mice vaccinated with pIκBα-SR and the TRP2-encoding plasmid (pTRP2) drastically reduced the frequencies of TRP2-specific CTLs and were unable to suppress lung melanoma metastasis in vivo, as compared with mice vaccinated only with pTRP2. Taken together these results indicate that the activation of NF-κB is essential for the immunogenicity of intradermal DNA vaccines.


Safety and Efficacy of Endoscopic Submucosal Dissection in the Management of Gastric Tube Cancers After Esophagectomy: A Systematic Review.
Esophagectomy is the proposed standard of care for resectable primary esophageal cancers and recurrent lesions in the reconstructed gastric tube (GT); however, it carries significant morbidity and mortality. Endoscopic submucosal dissection (ESD) has established its role in the management of primary esophageal cancers with growing evidence of its safety in resecting recurrent primary lesions in GT. Our study aims to evaluate the safety and efficacy of ESD in the management of recurrent, localized primary esophageal cancers in GT. We searched PubMed, CENTRAL, EMBASE, Scopus, and clinical trial registries from inception to March 2023 for articles evaluating the safety and efficacy of ESD in the management of recurrent cancerous lesions in GT. Our primary outcome was the en bloc resection rate. Secondary outcomes were curative resection rate, complete resection rate, intra-procedural complication rate, post-procedure complication rate, and five-year survival rate. Seven studies with a total of 165 patients undergoing 192 ESDs were included in the review. The pooled en bloc resection rate was 92.5% (95% CI: 87.7-95.6), which was reported in all seven studies. Pooled complete resection rate was 78.9% (95% CI: 64.5-88.5) per three studies, pooled curative resection rate was 73.9% (95% CI: 63.5-82.2) per four studies, and pooled intra-procedural complication rate was 10.2% (95% CI: 1.5-46.3), which was reported in four studies. Only three studies reported a five-year survival rate that was 65.5% (95% CI: 56.0-73.9). ESD is safe and efficacious in the management of GT cancer after esophagectomy.


[Mental health of youths: effect of education on changes in attitude and behavior].
Two final classes of Bjelovar Secondary Medical School were questioned twice about alcohol, nicotine and drugs abuse, early sexual intercourse and confidence in parents and teachers, in order to estimate their knowledge, attitudes and behaviour: at the beginning and at the end of the winter term of the year 2000/2001. The answers show that significant improvement in the knowledge of mental hygiene does not necessarily change the behavior of the examines. Three quarters of the examinees smoke tobacco, over 90% of them consume alcohol and one quarter have been experimenting with the so called "light" drugs. The majority of the examinees consider early sexual intercourse (before the age of sixteen) undesirable. Less than half of the examinees are satisfied with their relationship with parents. Small number of examinees is willing to ask for the teachers' help in solving noneducational problems. The results of this study have showed the need for the constant performing of preventive school programs for the improvement of communication skills between parents, pupils and teachers.


Large particles increase viscosity and yield stress of pig cecal contents without changing basic viscoelastic properties.
The viscosity of gut contents should influence digestion and absorption. Earlier investigators measured the viscosity of intestinal contents after the removal of solid particles. However, we previously found that removal of solid particles from pig cecal contents dramatically lowered the viscosity of the contents. Accordingly, we examined the contribution of large solid particles to viscoelastic parameters of gut contents in the present study. We removed large particles from pig cecal contents by filtration through surgical gauze. Then, we reconstructed the cecal contents by returning all, one half or none of the original amount of the large particles to the filtrate. We measured the viscosity, shear stress and shear rate of these reconstructed cecal contents using a tube-flow viscometer. The coefficient of viscosity was larger when the large-particle content was higher (P < 0.01). Cecal contents behaved as a non-Newtonian fluid and showed an apparent Bingham plastic nature irrespective of large-particle content. We calculated the yield stress of these fluids assuming that the fluids behave as Bingham plastic. The yield stress of the cecal contents was greater (P < 0.05) when the large-particle content was higher. The above results indicated that large particles elevated the viscosity and yield stress of gut contents without changing their basic viscoelastic character. Integrating the present and our previous results, we conclude that it is likely that finer particles such as bacteria should provide non-Newtonian and apparent Bingham plastic characteristics to pig cecal contents.


Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome.
Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) (overlap syndrome) are more likely to develop pulmonary hypertension than patients with either condition alone. To assess the relation of overlap syndrome to mortality and first-time hospitalization because of COPD exacerbation and the effect of continuous positive airway pressure (CPAP) on these major outcomes. We included 228 patients with overlap syndrome treated with CPAP, 213 patients with overlap syndrome not treated with CPAP, and 210 patients with COPD without OSA. All were free of heart failure, myocardial infarction, or stroke. Median follow-up was 9.4 years (range, 3.3-12.7). End points were all-cause mortality and first-time COPD exacerbation leading to hospitalization. After adjustment for age, sex, body mass index, smoking status, alcohol consumption, comorbidities, severity of COPD, apnea-hypopnea index, and daytime sleepiness, patients with overlap syndrome not treated with CPAP had a higher mortality (relative risk, 1.79; 95% confidence interval, 1.16-2.77) and were more likely to suffer a severe COPD exacerbation leading to hospitalization (relative risk, 1.70; 95% confidence interval, 1.21-2.38) versus the COPD-only group. Patients with overlap syndrome treated with CPAP had no increased risk for either outcome compared with patients with COPD-only. The overlap syndrome is associated with an increased risk of death and hospitalization because of COPD exacerbation. CPAP treatment was associated with improved survival and decreased hospitalizations in patients with overlap syndrome.


Hemoglobin A2 in hyperthyroidism.
Erythrocyte hemoglobin A2 (Hb A2) was quantitated in 28 hyperthyroid patients prior to antithyroid therapy and at intervals during therapy. Fetal hemoglobin (Hb F) levels and red cell mean corpuscular volume (MCV) were also monitored. Before therapy, Hb A2 was significantly elevated (mean +/- SD, 3.3 +/- 0.5%: normals, 2.5 +/- 0.3%: p less than 0.001). Hb F levels exceeded 1.0% in 10 cases. A tendency to red cell microcytosis was also observed (mean MCV 81.1 fl). To-date 10 of these subjects have had adequate studies following appropriate and sustained responses to antithyroid therapy. All showed a fall in Hb A2, usually accompanied by a rise in red cell MCV. A hematologic profile for hyperthyroidism is proposed.


Adverse events related to topical drug treatments for acne vulgaris.
Introduction: Acne vulgaris is a widespread skin disease. Topical therapy is a standard treatment for mild to moderate acne. Given the complex pathophysiology of acne, various agents with complementary action are nowadays frequently combined to increase the efficacy of therapy.Area covered: This review focus on safety profile of topical agents used for the treatment of acne vulgaris, including topical retinoids, benzyl peroxide, azelaic acid, topical antibiotic, and combined agents. Data from clinical trials but also metanalyses, systematic reviews, and other secondary analyses are presented.Expert opinion: In general, topical agents used for acne vulgaris have a favorable safety profile. The most commonly reported AEs were associated with local skin irritation, usually mild to moderate in intensity, intermittent, and rarely led to the cessation of therapy. Irritative potential seems to be highest for BPO and topical retinoids. Due to the possibility of development of Cutibacterium acnes resistance, topical antibiotics should not be used in monotherapy but as a part of combination therapy. In female adolescent and adults of childbearing potential, topical retinoids should be used with caution, because they are contraindicated in pregnant females (FDA Pregnancy category) C (adapalene, tretinoin) and X (tazarotene).


Endocrine composition of follicular fluid comparing human chorionic gonadotrophin to a gonadotrophin-releasing hormone agonist for ovulation induction.
Concentrations of inhibin, oestradiol and progesterone were determined in pre-ovulatory follicular fluid from 16 women undergoing in-vitro fertilization and embryo transfer treatment. A prospective randomized design was used such that ovulation was induced in eight women with human chorionic gonadotrophin (HCG) (9000 IU), and in eight women with an endogenous surge of luteinizing hormone (LH) and follicle stimulating hormone (FSH) caused by a single injection of gonadotrophin-releasing hormone agonist (GnRHa). Inhibin was measured by an enzyme-linked immunosorbent assay, and oestradiol and progesterone were measured by radio-immunoassay. Concentrations of inhibin and progesterone are significantly higher in follicular fluids collected after ovulation induction with HCG compared with ovulation induction with GnRHa (P < 0.001, P < 0.02, respectively). Concentrations of oestradiol were similar in the two groups. This study shows that the method by which ovulation is triggered significantly affects the micro-environment of the oocyte just prior to ovulation. The results indicate that HCG causes a prolonged luteotrophic effect well before ovulation, compared to an endogenous surge of gonadotrophins caused by GnRHa, and suggest that follicular maturation with an endogenous surge of gonadotrophins may be closer to the natural cycle than those cycles in which HCG is administered for ovulation induction. In addition, this study shows that the concentrations of inhibin and progesterone in follicular fluid may be valuable parameters in assessing the midcycle LH surge requirements for induction of ovulation.


[Rhythmic transcranial magnetic stimulation in the treatment of resistant depression in schizophrenia].
Rhythmic transcranial magnetic stimulation (rTMS) has long been actively used in the treatment of depressive disorders in various mental illnesses. At the same time, the question of the predictability of the results of this method for an individual patient remains open. Based on the existing ideas about the relationship of rTMS mechanisms with changes in the state of neural networks, one of the most perspective line is the search for prognostically significant neurophysiological markers. The study analyzed a wide range of EEG characteristics and evoked potentials recorded before treatment in the groups of responders and nonresponders in patients with depressive symptoms in schizophrenia, who have completed a course of rhythmic transcranial magnetic stimulation. The study revealed associations between an unfavorable treatment outcome and greater coherence in the alpha range (mainly in the caudal regions bilaterally) and less coherence in the beta1 range (involving temporal leads and left-hemisphere asymmetry). At the same time, such indicators as the amplitude of the N100 wave and the negativity of the mismatch were uninformative in terms of predicting the effectiveness of therapy.


Alterations of the Subchondral Bone in Osteoarthritis: Complying with Wolff's Law.
Osteoarthritis (OA) is a whole joint disease that is significantly related to abnormal mechanical loads. Subchondral bone alterations, during the evolution course of OA, are considered a reflection of the adaptation of the bone tissue to mechanical loads. However, some of these alterations are taken as a detriment and paradoxical. What are these structure, composition, and mechanical property alterations or mechanical functions for are not quite clear. In this review, we discuss the possibility that these alterations are used for maintaining the joint function. With taking excessive load as a risk factor and under conditions of articular cartilage gradually lose its thickness and its function of evenly distributing the load on the subchondral bone plate, and applying Poroelasticity to bone mechanics; moreover, Boussinesq's pressure bulb theory and bone optimal design principles are utilized. We found that each subchondral bone alteration has its unique mechanical function in resisting loads and maintaining the joint function, and these alterations comply with both bone optimal design principles and Wolff's law within a proper range.


Ouabain-induced hypertension in the rat: relationships among plasma and tissue ouabain and blood pressure.
To determine the steady-state dose-dependence of blood pressure, plasma and tissue ouabain during continuous infusion of ouabain in the rat, and to evaluate the adrenal dependence and effect of a high salt intake on this form of hypertension. Ouabain was administered, via subcutaneous osmotic pumps, to normal and adrenalectomized male Sprague-Dawley rats for 5 weeks. Blood pressure, plasma renin and aldosterone, and circulating and tissue levels of ouabain were determined. Following a latent period, blood pressures and circulating ouabain were significantly elevated dose-dependently in glycoside-infused rats at 5 weeks. Upon withdrawal of the ouabain infusion, blood pressure and plasma ouabain levels normalized within 1 week. In rats that received 30 micrograms ouabain/kg per day, the circulating, kidney, hypothalamic and anterior pituitary levels of ouabain were increased significantly (by 7-, 15-, 2.8- and 2.1-fold, respectively), whereas the content of other tissues tested was unchanged. Blood pressure and plasma levels of ouabain correlated with hypothalamic and kidney glycoside content in the infused rats. High-performance liquid chromatography of the adrenal, renal, hypothalamic and pituitary extracts showed one major peak of ouabain immunoreactivity, with a retention time equivalent to that of commercial ouabain. Plasma renin activity was normal, whereas aldosterone levels were increased significantly to 2.9- and sevenfold in rats that received 10 and 30 micrograms ouabain/kg per day, respectively. Dietary salt loading suppressed aldosterone and did not exacerbate hypertension. In bilaterally adrenalectomized rats the ambient circulating and kidney levels of ouabain were low and ouabain infusion raised glycoside levels and blood pressure significantly. Prolonged infusion of ouabain in the normal rat raises the circulating, kidney, hypothalamic and anterior pituitary levels and induces a reversible hypertension with normal plasma renin activity. Although characterized by raised aldosterone levels, the hypertension does not require the adrenal glands and is not salt-sensitive. This model may be useful for exploring novel mechanisms of long-term regulation of blood pressure.


Cortical ependymoma with unusual histologic features.
Cortical ependymomas are rare gliomas with classic ependymal features but are unusual in primarily involving the cerebral cortex. Here, we present a 19-year old woman with new-onset seizures who was found to have a large, cortically based non-enhancing lesion with scalloping of the overlying calvarium. Abundant ependymal features were present including classic ependymal cytology, diffuse GFAP and dot-like EMA positivity, and well developed cilia, microvilli, and intercellular junctions on ultrastructural analysis. Additionally, the tumor showed areas of infiltrative growth similar to angiocentric glioma as well as striking mucin-filled microcystic spaces somewhat reminiscent of myxopapillary ependymoma. Thus far, the patient shows no evidence of recurrence following gross total resection. This case demonstrates detailed morphologic, immunohistochemical, and ultrastructural evidence supporting a relationship between cortical ependymoma and angiocentric glioma and suggesting that cortical ependymomas can have myxopapillary as well as classic features.


Enhancing the intrinsic bioremediation of PAH-contaminated anoxic estuarine sediments with biostimulating agents.
Estuarine sediments are frequently polluted with hydrocarbons from fuel spills and industrial wastes. Polycyclic aromatic hydrocarbons (PAHs) are components of these contaminants that tend to accumulate in the sediment due to their low aqueous solubility, low volatility, and high affinity for particulate matter. The toxic, recalcitrant, mutagenic, and carcinogenic nature of these compounds may require aggressive treatment to remediate polluted sites effectively. In petroleum-contaminated sediments near a petrochemical industry in Gwangyang Bay, Korea, in situ PAH concentrations ranged from 10 to 2,900 microg/kg dry sediment. To enhance the biodegradation rate of PAHs under anaerobic conditions, sediment samples were amended with biostimulating agents alone or in combination: nitrogen and phosphorus in the form of slow-release fertilizer (SRF), lactate, yeast extract (YE), and Tween 80. When added to the sediment individually, all tested agents enhanced the degradation of PAHs, including naphthalene, acenaphthene, anthracene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, and benzo[a]pyrene. Moreover, the combination of SRF, Tween 80, and lactate increased the PAH degradation rate 1.2-8.2 times above that of untreated sediment (0.01-10 microg PAH/kg dry sediment/day). Our results indicated that in situ contaminant PAHs in anoxic sediment, including high molecular weight PAHs, were degraded biologically and that the addition of stimulators increased the biodegradation potential of the intrinsic microbial populations. Our results will contribute to the development of new strategies for in situ treatment of PAH-contaminated anoxic sediments.


From net topology to synchronization in hr neuron grids.
In this paper, we investigate the role of topology on synchronization, a fundamental feature of many technological and biological fields. We study it in Hindmarsh-Rose neural networks, with electrical and chemical synapses, where neurons are placed on a bi-dimensional lattice, folded on a torus, and the synapses are set according to several topologies. In addition to the standard topologies used in other studies, we introduce a new model that generalizes the Barabasi-Albert scale-free model, taking into account the physical distance between nodes. Such a model, because of its plausibility both in the static characteristics and in the dynamical evolution, is a good representation for those real networks (such as a network of neurons) whose edges are not costless. We investigate synchronization in several topologies; the results strongly depend on the adopted synapse model.


Interactions of chrysotile asbestos fibres with the complement system.
Type A chrysotile fibres (white asbestos) were tested in vitro for activation of the complement system. Fibres were incubated in normal human serum (NHS), factor B-depleted human serum, and normal and C4-deficient guinea-pig sera; the supernates were assayed for the remaining complement activity. Activation of the alternative pathway (AP) was shown in three ways. First, quantitative measurement of factor B; second, kinetic analysis of rabbit red blood cell lysis in whole alternative pathway (AP) and factor B lytic assays; third, qualitative measurement of C3 and factor B conversion by crossed immunoelectrophoresis. No C3 convertase activity could be demonstrated on the fibres but other possible mechanisms of AP activation are discussed. Magnesium itself is not responsible for this activation because acid-treated fibres retain this property. The early classical pathway is not involved as shown by normal whole complement activity of a factor B-depleted human serum and the absence of decrease of C4 functional activity. Knowing that complement proteins are present in pulmonary alveoli, mainly provided by cell synthesis, we suggest that complement activation in vivo may be relevant to the genesis of the chronic inflammation and fibrosis in the lung.


VDACs: An Outlook on Biochemical Regulation and Function in Animal and Plant Systems.
The voltage-dependent anion channels (VDACs) are the most abundant proteins present on the outer mitochondrial membrane. They serve a myriad of functions ranging from energy and metabolite exchange to highly debatable roles in apoptosis. Their role in molecular transport puts them on the center stage as communicators between cytoplasmic and mitochondrial signaling events. Beyond their general role as interchangeable pores, members of this family may exhibit specific functions. Even after nearly five decades of their discovery, their role in plant systems is still a new and rapidly emerging field. The information on biochemical regulation of VDACs is limited. Various interacting proteins and post-translational modifications (PTMs) modulate VDAC functions, amongst these, phosphorylation is quite noticeable. In this review, we have tried to give a glimpse of the recent advancements in the biochemical/interactional regulation of plant VDACs. We also cover a critical analysis on the importance of PTMs in the functional regulation of VDACs. Besides, the review also encompasses numerous studies which can identify VDACs as a connecting link between Ca2+ and reactive oxygen species signaling in special reference to the plant systems.


Flow-independent heterogeneity of brain capillary plasma perfusion after blood exchange with a Newtonian fluid.
Previous studies from our group have indicated a heterogeneity of plasma transit times in brain capillaries. The heterogeneity was decreased with increasing cerebral blood flow during hypercapnia. In the present study, the hypothesis was tested that these apparent changes in microvascular plasma perfusion heterogeneity depend on the existence of red blood cells (RBC). To this end, the blood of anesthetized and paralyzed rats was replaced by a shear rate-independent oxygen-carrying substitute, ultrapurified polymerized bovine hemoglobin (UPBHB). Cerebral blood flow ([14C]iodoantipyrine technique) or microvascular perfusion pattern (intravenous bolus injection of Evans blue and decapitation 3-4 s later) was measured. After exchange transfusion with UPBHB, cerebral blood flow still varied with arterial PCO2, whereas in contrast to the unexchanged condition, the heterogeneity of the intracapillary Evans blue concentration remained unchanged. Compared with the unexchanged normocapnic condition, the heterogeneity of intracapillary dye concentration was decreased by one-quarter. It is concluded that RBC contribute to the microvascular perfusion heterogeneity in the brain.


Capillary condensation of short-chain molecules.
A density-functional study of capillary condensation of fluids of short-chain molecules confined to slitlike pores is presented. The molecules are modeled as freely jointed tangent spherical segments with a hard core and with short-range attractive interaction between all the segments. We investigate how the critical parameters of capillary condensation of the fluid change when the pore width decreases and eventually becomes smaller than the nominal linear dimension of the single-chain molecule. We find that the dependence of critical parameters for a fluid of dimers and of tetramers on pore width is similar to that of the monomer fluid. On the other hand, for a fluid of chains consisting of a larger number of segments we observe an inversion effect. Namely, the critical temperature of capillary condensation decreases with increasing pore width for a certain interval of values of the pore width. This anomalous behavior is also influenced by the interaction between molecules and pore walls. We attribute this behavior to the effect of conformational changes of molecules upon confinement.


[Study of a new technique on the prevention of Oncomelania hupensis snail dispersal in the irrigation schemes in middle reaches of Yangtze River].
To explore a new technique to prevent the dispersal of Oncomelania hupensis snail through leading flood for irrigation by floodgate in irrigation schemes. Hydromechanical and biological were applied and to combine laboratory experiment with the field observation to form a new multidisciplinary regarding snail biological hydraulics and technical line. Findings including characteristics of hydraulics and biomechanics and move regulation etc. Physics parameter of snails were used to design and construct as well as to exam the effect of facilities and rebuilt floodgate which could prevent the snail dispersal. Through five years efforts, the major achievements were found as: 1) the method in testing the special gravity of snail and snail eggs was determined. 2) the special gravity of snail was (1.8 +/- 0.01) g/cm(3) and special gravity snail eggs was (2.29 +/- 0.01) g/cm(3); the classification method and classified criterion of snail size were made based on geometrical characteristics of snail shell. Six special values indicating dropping and start speed of snail in running water were obtained; Five practical formula of snail dropping and start in water were established; threshold value and movement characteristics in water were observed and tested and move mechanism of snail dispersal in water was also clarified. Based on the findings from fundamental research, the facilities of "precipitation pool for snail" and "leading water from middle level of water body" that could prevent snail dispersal were designed and rebuilt in the endemic area. Through examination to these facilities, the rate of precipitating and blocking of snails reached 100%. The achievement of the study provided reliable theoretical basis for the rebuilt of floodgate and to development of models that could prevent the dispersal of snail effectively.


Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy.
Although ghrelin has been demonstrated to improve cardiac function in heart failure, its therapeutic efficacy on the life expectancy remains unknown. We aim to examine whether ghrelin can improve the life survival in heart failure using a mouse model of inherited dilated cardiomyopathy (DCM) caused by a deletion mutation ΔK210 in cardiac troponin T (cTnT). From 30 days of age, ghrelin (150 μg/kg) was administered subcutaneously to DCM mice once daily, control mice received saline only. The survival rates were compared between the two groups for 30 days. After 30-day treatment, functional and morphological measurements were conducted. Ghrelin-treated DCM mice had significantly prolonged life spans compared with saline-treated control DCM mice. Echocardiography showed that ghrelin reduced left ventricular (LV) end-diastolic dimensions and increased LV ejection fraction. Moreover, histoanatomical data revealed that ghrelin decreased the heart-to-body weight ratio, prevented cardiac remodeling and fibrosis, and markedly decreased the expression of brain natriuretic peptide. Telemetry recording and heart rate variability analysis showed that ghrelin suppressed the excessive cardiac sympathetic nerve activity (CSNA) and recovered the cardiac parasympathetic nerve activity. These results suggest that ghrelin has therapeutic benefits for survival as well as for the cardiac function and remodeling in heart failure probably through suppression of CSNA and recovery of cardiac parasympathetic nerve activity.


iOI: An Iterative Orbital Interaction Approach for Solving the Self-Consistent Field Problem.
An iterative orbital interaction (iOI) approach is proposed to solve, in a bottom-up fashion, the self-consistent field problem in quantum chemistry. While it belongs grossly to the family of fragment-based quantum chemical methods, iOI is distinctive in that (1) it divides and conquers not only the energy but also the wave function and that (2) the subsystem sizes are automatically determined by successively merging neighboring small subsystems until they are just enough for converging the wave function to a given accuracy. Orthonormal occupied and virtual localized molecular orbitals are obtained in a natural manner, which can be used for all post-SCF purposes.


Building intuition for binding free energy calculations: Bound state definition, restraints, and symmetry.
The theory behind computation of absolute binding free energies using explicit-solvent molecular simulations is well-established, yet somewhat complex, with counter-intuitive aspects. This leads to frequent frustration, common misconceptions, and sometimes erroneous numerical treatment. To improve this, we present the main practically relevant segments of the theory with constant reference to physical intuition. We pinpoint the role of the implicit or explicit definition of the bound state (or the binding site) to make a robust link between an experimental measurement and a computational result. We clarify the role of symmetry and discuss cases where symmetry number corrections have been misinterpreted. In particular, we argue that symmetry corrections as classically presented are a source of confusion and could be advantageously replaced by restraint free energy contributions. We establish that contrary to a common intuition, partial or missing sampling of some modes of symmetric bound states does not affect the calculated decoupling free energies. Finally, we review these questions and pitfalls in the context of a few common practical situations: binding to a symmetric receptor (equivalent binding sites), binding of a symmetric ligand (equivalent poses), and formation of a symmetric complex, in the case of homodimerization.


Thermal Hall Effect of Magnons in Collinear Antiferromagnetic Insulators: Signatures of Magnetic and Topological Phase Transitions.
We demonstrate theoretically that the thermal Hall effect of magnons in collinear antiferromagnetic insulators is an indicator of magnetic and topological phase transitions in the magnon spectrum. The transversal heat current of magnons caused by a thermal gradient is calculated for an antiferromagnet on a honeycomb lattice. An applied magnetic field drives the system from the antiferromagnetic phase via a spin-flop phase into the field-polarized phase. In addition to these magnetic phase transitions, we find topological phase transitions within the spin-flop phase. Both types of transitions manifest themselves in prominent and distinguishing features in the thermal conductivity, which changes by several orders of magnitude. The variation of temperature provides a tool to discern experimentally the two types of phase transitions. We include numerical results for the van der Waals magnet MnPS_{3}.


Thyrotoxic myopathy associated with subacute thyroiditis.
We report a case of subacute thyroiditis complicated by thyrotoxic myopathy. Previously thyrotoxic myopathy has been described as being associated with Graves' disease. The patient in this study was a 35-year-old man who developed proximal dominant muscular weakness and atrophy during the course of subacute thyroiditis. His myopathic symptoms regressed as his serum thyroxine and triiodothyronine levels returned to normal, however it took a relatively long period of time for them to do so. This suggests that marked myopathy may develop even in cases of subacute thyroiditis if the thyrotoxic state persists for a long period of time.


A company of women and men: men's recollections of childbirth in medieval England.
The events that took place in medieval English birthing chambers were witnessed and assisted by a company of women. Although these events may have been isolated, they did not exist in isolation. Rather, they interacted in complex ways with the lives and activities of the men in the manor hall. This article examines those interactions as they are evidenced in proof-of-age inquests, legal documents that record the recollections of husbands, fathers, and male relatives and neighbors regarding the events surrounding the birth of an heir to crown land. It concludes that even though men rarely entered the birthing chamber, their dynastic interests and social politics routinely penetrated its walls, blurring the boundary between private and public spheres, female and male space.


Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model.
To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and butyrate. Dexamethasone cholesteryl butyrate-solid lipid nanoparticles (DxCb-SLN) were obtained with the warm microemulsion method. The anti-inflammatory activity of this novel nanoformulation has been investigated in vitro (cell adhesion to human vascular endothelial cells and pro-inflammatory cytokine release by lipopolysaccharide-induced polymorphonuclear cells) and in vivo (disease activity index and cytokine plasma concentrations in a dextran sulfate sodium-induced mouse colitis) models. Each drug was also administered separately to compare its effects with those induced by their co-administration in SLN at the same concentrations. DxCb-SLN at the lowest concentration tested (Dx 2.5 nmol/L and Cb 0.1 μmol/L) were able to exert a more than additive effect compared to the sum of the individual effects of each drug, inducing a significant in vitro inhibition of cell adhesion and a significant decrease of pro-inflammatory cytokine (IL-1β and TNF-α) in both in vitro and in vivo models. Notably, only the DxCb nanoformulation administration was able to achieve a significant cytokine decrease compared to the cytokine plasma concentration of the untreated mice with dextran sulfate sodium-induced colitis. Specifically, DxCb-SLN induced a IL-1β plasma concentration of 61.77% ± 3.19%, whereas Dx or Cb used separately induced a concentration of 90.0% ± 2.8% and 91.40% ± 7.5%, respectively; DxCb-SLN induced a TNF-α plasma concentration of 30.8% ± 8.9%, whereas Dx or Cb used separately induced ones of 99.5% ± 4.9% and 71.1% ± 10.9%, respectively. Our results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.


Early results of posterior leaflet folding plasty for mitral valve reconstruction.
Standard reconstruction for posterior mitral leaflet (PML) disease is quadrangular resection and annular plication; when the PML is excessively high, a sliding plasty is used. We have developed an alternative technique, a posterior leaflet folding plasty. It is performed by folding down the cut vertical edges of the PML. The central height of the PML is reduced, leaflet coaptation is moved posteriorly, and annular plication is unnecessary. From March 1995 to August 1996, 26 (17.9%) of 145 patients undergoing mitral reconstruction had a posterior leaflet folding plasty. Concomitant procedures included anterior leaflet resection or resuspension and myotomy and myectomy. In 3 patients, the PML resection extended to a commissure. There was one death and no reoperations. The mean New York Heart Association class was improved from 2.4 preoperatively to 1.4. There was no major postoperative mitral insufficiency in the 26 patients. Systolic anterior motion was transiently seen in 1 patient in whom left ventricular outflow tract obstruction was present preoperatively. The data demonstrate the safety and short-term efficacy of posterior leaflet folding plasty. This technique may help avoid systolic anterior motion after reconstruction of the PML.


Microbiological effects of periodontal therapy plus azithromycin in patients with diabetes: results from a randomized clinical trial.
Current evidence suggests that periodontal infection may aggravate diabetes control. The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a randomized clinical trial. One hundred and five (105) patients with diabetes and chronic periodontitis were randomly assigned to three treatment groups: subgingival mechanical therapy with azithromycin, subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin. Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline, 3, 6 and 9 months after periodontal therapy. The frequency with which Porphyromonas gingivalis, Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups. Tannerella forsythia increased after3 months in all groups. All organisms had similar frequencies at 9 months in all groups. Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes.


[Gastrointestinal bleeding in the elderly].
Peptic ulcer disease is a common cause of gastrointestinal bleeding, independent of the patient's age. With advancing age, an increase of lower gastrointestinal bleeding (diverticula, angiodysplasia) has been observed. The administration of non-steroidal anti-inflammatory drugs and aspirin is an important risk factor for upper and lower gastrointestinal bleeding, thus in patients aged 65 years and more a concomitant therapy with proton pump inhibitors is recommended in order to prevent ulcer bleeding. Even in very old individuals endoscopy should be used for the diagnosis of gastrointestinal bleeding, providing the opportunity for definite endoscopic bleeding therapy. In elderly patients with comorbidities and recurrent bleeding after endoscopic therapy or continuous blood loss, surgery or transarterial embolisation should be considered in good time.


Effect of PAR irradiance intensity on Phaeocystis antarctica (Prymnesiophyceae) growth and DMSP, DMSO, and acrylate concentrations.
Phaeocystis antarctica forms extensive spring blooms in the Southern Ocean that coincide with high concentrations of dimethylsulfoniopropionate (DMSP), dimethylsulfoxide (DMSO), dimethylsulfide (DMS), and acrylate. We determined how concentrations of these compounds changed during the growth of axenic P. antarctica cultures exposed to light-limiting, sub-saturating, and saturating PAR irradiances. Cellular DMSP concentrations per liter cell volume (CV) ranged between 199 and 403 mmol · LCV -1 , with the highest concentrations observed under light-limiting PAR. Cellular acrylate concentrations did not change appreciably with a change in irradiance level or growth, ranging between 18 and 45 mmol · LCV -1 , constituting an estimated 0.2%-2.8% of cellular carbon. Both dissolved acrylate and DMSO increased substantially with irradiance during exponential growth on a per-cell basis, ranging from 0.91 to 3.15 and 0.24 to 1.39 fmol · cell-1 , respectively, indicating substantial export of these compounds into the dissolved phase. Average cellular DMSO:DMSP ratios increased 7.6-fold between exponential and stationary phases of batch growth, with a 3- to 13-fold increase in cellular DMSO likely formed from abiotic reactions of DMSP and DMS with reactive oxygen species (ROS). At mM levels, cellular DMSP and acrylate are proposed to serve as de facto antioxidants in P. antarctica not regulated by oxidative stress or changes in ROS. Instead, cellular DMSP concentrations are likely controlled by other physiological processes including an overflow mechanism to remove excess carbon via acrylate, DMS, and DMSO during times of unbalanced growth brought on by physical stress or nutrient limitation. Together, these compounds should aid P. antarctica in adapting to a range of PAR irradiances by maintaining cellular functions and reducing oxidative stress.


Order from disorder: Self-organization in mammalian hair patterning.
Hairs, feathers, and scales normally exhibit precise orientations with respect to the body axes. In Frizzled6 (Fz6)(-/-) mice, the global orientation of hair follicles is disrupted, leading to waves, whorls, and tufts, each comprising many hundreds of hairs. By analyzing the orientation of developing hair follicles, we observed that the nearly parallel arrangement of wild-type (WT) hairs arises from fields of imperfectly aligned follicles, and that the Fz6(-/-) hair patterns arise from fields of grossly misoriented or randomly oriented follicles. Despite their large size, both mutant and WT hair follicles display a remarkable and unexpected plasticity, reorienting on a time scale of days in what seems to be a self-organized refinement process. The essential features of this process can be studied with a simple cellular automata model in which a local consensus "rule" acts iteratively to bias each hair's orientation in favor of the average orientation of its neighbors. These experiments define two systems for hair orientation: a global orienting system that acts early in development and is Fz6-dependent, and a local self-organizing system that acts later and is Fz6 independent.


Distinct B cell profiles characterise healthy weight and obesity pre- and post-bariatric surgery.
Obesity-associated metabolic dysfunction and inflammation can be ameliorated by bariatric surgery. While obesity is also linked to impaired B cell activation, differentiation, and persistence in response to infection and vaccination little is known about post-operative immune B cell compartment and to what extent dysregulation in B cell pathways can be reversed. To bridge this gap in knowledge, we carried out in-depth evaluation of B cell composition in individuals with obesity prior to and following bariatric surgery compared to lean controls. We recruited individuals with obesity (BMI at least 35 kg/m2) before bariatric surgery (n = 21) and followed them up 6 months post-operatively (n = 17). As controls we recruited age- and sex-matched lean (BMI < 25) individuals (n = 18). We carried out comprehensive immunophenotyping of peripheral blood B cells as well as interrogated their association with inflammatory and metabolic parameters. In obesity the balance of antigen-inexperienced and memory B cells in the peripheral blood is altered, with an expansion of naïve and a reduction in total memory B cells. 6 months following bariatric surgery this balance is restored. However, post-operative patients are uniquely characterised by an increase in B cell subsets associated with chronic inflammation - CD11c+CXCR5-IgD-CD27- double negative 2 (DN2) B cells and CD27+CD38++ plasmablasts. Correlations between B cells subsets, inflammatory and metabolic parameters were distinct in lean people and individuals with obesity pre- and post-bariatric surgery. Bariatric surgery patients display a unique B cell profile 6 months post-operatively; this bears minimal resemblance to that of pre-operative patients and only partially overlaps with that of lean controls. Post-operative differences in the B cell compartment compared to lean controls are detected despite global amelioration of inflammation and restoration of metabolic health. Collectively, this indicates that bariatric surgery creates a specific immunometabolic state with potential implications for health outcomes.


Characterizing treatment pathways at scale using the OHDSI network.
Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.


Allograft tolerance induced by intact active bone co-transplantation and anti-CD40L monoclonal antibody therapy.
One of the most promising approaches to achieving allograft tolerance involves the transient inhibition of co-stimulatory signals in T cells. There is, however, increasing evidence that this approach alone cannot universally elicit allograft tolerance and that adjunct therapies capable of synergizing with co-stimulation blockade may be necessary. We developed a novel tolerance strategy involving co-transplantation of intact allogeneic bone fragments containing active bone marrow (intact active bone [IAB]) with heart allograft and transient anti-CD40L monoclonal antibody therapy. Mice treated with IAB and anti-CD40L were tolerant to major histocompatibility complex and minor antigen-mismatched cardiac and skin allografts. Heart allografts had normal histology up to 270 days posttransplantation, and the production of graft-reactive antibodies was inhibited. Microchimerism, but no macrochimerism, of donor cells was detected in the peripheral blood or lymphoid organs of tolerant mice receiving IAB and anti-CD40L. Lymphocytes from tolerant mice retained normal proliferative responsiveness to donor cells in vitro but demonstrated a donor-specific loss in the priming of interferon-gamma responses. The ability to produce interleukin-2 or -4 when stimulated with donor cells was normal. Contrary to previous reports of the ability of bone marrow cells to induce central deletional tolerance, our data suggest that the regimen involving co-transplantation of IAB on the day of heart allograft transplantation and transient anti-CD40L therapy induces a robust donor-specific peripheral tolerance.


Renal Cell Carcinoma with monosomy 8: A Case Series and Review of the Literature.
Renal cell carcinoma (RCC) is a malignancy commonly encountered by both clinicians and pathologists. Different RCC subtypes are classified based on histologic features, immunohistochemistry profiles, and cytogenetic abnormalities. Accurate diagnosis of subtypes is important as it has prognostic and therapeutic implications. The most common RCC subtype is clear cell renal cell carcinoma (CCRCC); the most frequent genetic abnormalities associated with CCRCC are a deletion of the short arm of chromosome 3 involving 3p21 and mutations involving the Von Hippel-Lindau (VHL) gene. Advances in molecular pathology have identified additional molecular pathways leading to CCRCC. Researchers identified mutations of TCEB-1, monosomy 8, intact chromosome 3 and lack of VHL gene mutations in 4.7% of CCRCC. Additional evidence has been found recognizing RCC with monosomy 8 as a unique RCC subtype by describing cases with similar genetic profiles, non-specific immunohistochemistry, and histomorphology that overlapped with other known RCC types. At the University of Vermont Medical Center (UVMMC), conventional cytogenetics are obtained on all renal neoplasms. Three recent cases of RCC with monosomy 8, normal chromosome 3 morphology, clear cell cytology and non-specific immunohistochemistry profiles were identified. We present these cases to further document this unique subtype and highlight the importance of conventional cytogenetics in the diagnosis of renal cell carcinoma.


Use of immunohistochemical methods for diagnosis of equine pythiosis.
Excisional biopsy specimens were received from 8 horses with lesions suspected of being caused by Pythium sp. Pythium sp was isolated from all specimens. An indirect peroxidase technique was applied to formalin-fixed tissues from the biopsy material and there was distinct staining of hyphal cell walls in all specimens. Sections containing hyphae, other than those of Pythium sp, failed to stain. The indirect peroxidase technique could be used for confirmation of suspected cases of pythiosis.


Effects of Word Frequency and Transitional Probability on Word Reading Durations of Younger and Older Speakers.
High-frequency units are usually processed faster than low-frequency units in language comprehension and language production. Frequency effects have been shown for words as well as word combinations. Word co-occurrence effects can be operationalized in terms of transitional probability (TP). TPs reflect how probable a word is, conditioned by its right or left neighbouring word. This corpus study investigates whether three different age groups-younger children (8-12 years), adolescents (12-18 years) and older (62-95 years) Dutch speakers-show frequency and TP context effects on spoken word durations in reading aloud, and whether age groups differ in the size of these effects. Results show consistent effects of TP on word durations for all age groups. Thus, TP seems to influence the processing of words in context, beyond the well-established effect of word frequency, across the entire age range. However, the study also indicates that age groups differ in the size of TP effects, with older adults having smaller TP effects than adolescent readers. Our results show that probabilistic reduction effects in reading aloud may at least partly stem from contextual facilitation that leads to faster reading times in skilled readers, as well as in young language learners.


Effectiveness of pulse-shape criteria for the selection of dicentric chromosomes by slit-scan flow cytometry and sorting.
A method was developed to detect dicentric chromosomes by slit-scan flow cytometry. The two centromeres of dicentric chromosomes are represented by the two dips in the trimodal fluorescence profile. A trimodal profile can, however, also be generated by aggregates of chromosomes. We tested the effectiveness of slit-scan profile criteria that were applied to discriminate between trimodal profiles generated by dicentrics and trimodal profiles generated by artefacts. A Profile-Dip Counter (PDC) module was designed that can assess, in real time, the number of dips in slit-scan profiles. The PDC module was used in combination with a Cytofluorograph System 50 cell sorter for slit-scan sorting of chromosomes prepared from irradiated V79 cells. Chromosomes corresponding to trimodal profiles were sorted individually onto slides for subsequent visual inspection by fluorescence microscopy. The isolated chromosomes were stretched by treatment with trypsin to increase the efficiency for centromere detection. When fixed with glutaraldehyde, chromosomes could be sorted intact on slides. We found that trimodal profiles are generated by dicentric chromosomes as well as by monocentric and aggregated chromosomes. When stringent pulse-shape criteria were applied for the selection of profiles, the yield of dicentric chromosomes was 70% of the sorted chromosomes.


Antibacterial use and Streptococcus pneumoniae penicillin resistance: A temporal relationship model.
The nature of the temporal relationship between antibacterial consumption and Streptococcus pneumoniae penicillin resistance is investigated using population level data across time. IMS Health Global Services provided national outpatient antibiotic prescription data for the years 1996-2003 from France, Spain, Italy, Germany, the United Kingdom, and the United States. Surveillance data consist of S. pneumoniae isolates obtained from a surveillance database in the same geographic regions from 1996 to 2003. A linear mixed model for repeated measures was used to analyze the association between resistance and several antibacterial classes through time. Changes in penicillin resistance through time in any country are better explained by the weighted cumulative antibacterial consumption with a 2-year lag. Narrow-spectrum penicillins are associated with lower resistance rates. Large reductions in consumption at the population level are needed to affect resistance. There is a peak level of penicillin resistance associated with cumulative exposure to a combination of antibiotic classes that is unique for every country.


[Treatment of perineal wounds during the post partum period: evaluation of whether or not antibiotic should be systematically prescribed].
Genital tract integrity is not always mantained during childbirth. No treatment protocol for post-partum perineal wounds (tears and episiotomies) existed in our Department, thus their management depends upon clinician. This study aimed to establish the role of antibiotic in the treatment of post-partum perineal wounds as well as the impact of antibioprophylaxis on wound healing and on prevention of infectious complications after repair. We conducted a prospective cohort study in the Department of Gynecology and Obstetrics at the Central Hospital of Yaoundé over a period of 6 months, from 1 January to 31 May 2016. Post-partum women with perineal tear and/or episiotomy were divided into two groups (A and B) and followed up. The group A was composed by 85 post-partum women under treatment protocol based on compresses soaked in Betadine® (placebo). The Group B (or test group) was composed of post-partum women who had received placebo plus antibiotic (oral amoxicillin/clavulanic acid 875 mg/125 mg twice a day for 05 days). Both groups were followed up on day 0, day 2 and day 9. Our criteria for the evaluation of treatment were: pain, infection, swelling, cleanliness of the wounds and average healing time. Data were collected and analyzed using the software Epidata analysis version 3.2 and STATA version 12.0 (Texas USA 2001). The correlations between the variables were identified by chi-square, odds ratio and p value (using any p-value ≤ 0.05 as statistical significance cut-off) according to the case. The average age was 26.32 ± 6.5 years, ranging between 15 and 43 years. Primiparous women accouted for 55.9% of the study population. At day 0 post-partum the main symptom was pain, without significant predominance of a group (OR = 0.9; CI = 0.14-7.19; p = 1). Swollen wounds were the second complaint, without significant variation between the two groups (OR = 1.69; CI = 0.88-3.24; p = 0.13). At day 0, day 2 and day 9 no significant variation was observed between the two treatment protocols with regard to the indicators analyzed: pain evolution, infection, swelling and average healing time. At day 9 the healing was complete in both groups and the two treatment protocols were shown to be equivalent in their effectiveness and prevention of infections. At the end of this study the two treatment protocols were shown to be equivalent. Antibiotics should not be prescribed for perineal wounds in order to contain the healthcare costs.


Control of Fc and C3 receptors on myeloid leukemic cells.
An experimental system has been developed to study in cloned lines of cells the control of Fc and C3 receptors by different compounds. The cells used were clones of mouse myeloid leukemic cells and the compounds used were the protein MGI2 (macrophage and granulocyte inducer) in serum from mice injected with bacterial endotoxin and the steroid inducer (SI) dexamethasone. Eight clones were isolated which could be divided into three groups. One group (MGI+SI+) was induced to form EA and EAC rosettes by MGI and only EAC rosettes by SI, the second group (MGI-SI+) was not inducible by MGI but was induced by SI to form EA or EA and EAC rosettes, and the third group (MGI-SI-) was not inducible for EA or EAC by MGI or SI. There were two types of MGI+SI+ clones, one type (D+) could be induced by MGI to differentiate to mature macrophages and granulocytes, and the other type (D-) could not be induced to differentiate to mature cells. The MGI-SI+ and MGI-SI- clones were all D-. The results indicate that there are different cellular sites for MGI and SI and that induction of EA and EAC rosettes did not seem to be mediated by cyclic AMP. Experiments with specifically bound 3H-BSA-anti-BSA complexes have indicated that there was an increase in the amount of 3H-BSA-anti-BSA bound per rosette-forming cell following induction by MGI or SI, and there were differences in the amount of 3H-BSA-anti-BSA bound per rosette-forming cell in different clones. These clones also showed differences in the shape of the curve for the number of EA rosette-forming cells obtained with erythrocytes coated with decreasing concentrations of antibody. The results suggest that such curves and those obtained with EAC rosettes can be used to determine the relative abundance of EA and EAC receptors on rosette-forming cells. EA rosettes on the myeloid leukemic cells, like those on normal macrophages and granulocytes, were specifically inhibited by IgG2a and by the Fc but not the Fab fragment of IgG. The EAC rosettes were inhibited by destroying the C3 component of complement. The different clones maintained their specific properties for at least 6 months in culture. The present system should, therefore, also be useful for studies on the genetic control of the regulation of Fc and C3 receptors.


Severe herpetic keratitis. I: Prevalence of visual impairment in a clinic population.
We report a prevalence study of the best visual acuity in the affected eye of 100 selected patients with herpetic keratitis seen during a two-year period. Sixty-two patients retained an acuity of 6/9 or better without requiring penetrating keratoplasty (PK). The prevalence of reduced visual acuity severe enough to warrant PK was 33%. Patients requiring PK for whom full clinical records were available suffered a mean of 6.8 episodes of keratitis. In this group of patients the vision of 18 fell from 6/6 to 6/60 over a mean period of 8.5 years. Once visual acuity was permanently reduced to 6/12, 78% of patients proceeded to lose vision to 6/60. Unilateral visual impairment occurs in at least a third of patients with severe herpetic keratitis. Once vision falls permanently to 6/12, the long-term prognosis for vision appears to be poor.


Effects of angiotensin II type 1 receptor antagonist on pressor responses to pulsatile compression of the rostral ventrolateral medulla in rats.
The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.


Peritonitis and catheter exit-site infection in patients on peritoneal dialysis at home.
to analyze the complications related to peritonitis and catheter exit-site infections, in patients on peritoneal dialysis at home. quantitative and cross-sectional study, carried out with 90 patients on peritoneal dialysis at home, in a municipality in the Northeast region of Brazil. For data collection, it was used two structured scripts and consultation on medical records. Descriptive analysis and comparison tests among independent groups were used, considering p<0.05 as level of statistical significance. by comparing the frequency of peritonitis and the length of treatment, it was found that patients over two years of peritoneal dialysis were more likely to develop peritonitis (X²=6.39; p=0.01). The number of episodes of peritoneal catheter exit-site infection showed association with the length of treatment (U=224,000; p=0.015). peritonitis and catheter exit-site infection are associated with the length of treatment.


Genomics of foam cells and nonfoamy macrophages from rabbits identifies arginase-I as a differential regulator of nitric oxide production.
Conversion of macrophages to foam cells is a critical step in the initiation and progression of atherosclerosis. We sought to identify genes differentially regulated in foam cells, since these are likely to include new targets for intervention. We used suppression subtraction hybridization to compare foam cells and nonfoamy macrophages isolated from subcutaneous granulomas of rabbits fed a cholesterol-rich or normal chow diet and confirmed upregulation of 3 genes, including matrix metalloproteinase-12 (mRNA 2.0-fold, P<0.005; protein 3.9-fold, P<0.03). Arginase-I mRNA showed the biggest decrease among 11 downregulated genes in foam cells (2.7-fold, P<0.001) and was accompanied by significantly reduced arginase enzymatic activity (60-fold, P<0.01). Arginase-I competes for substrate L-arginine with nitric oxide synthase and consequently nitric oxide production was significantly increased (3-fold, P<0.02) in foam cells compared with nonfoamy macrophages despite no difference in nitric oxide synthase isoenzyme expression. We validated upregulation of matrix metalloproteinase-12 and downregulation of arginase-1 in foam cells of rabbit and human atherosclerotic plaques. Our study identified several differentially expressed genes in foam cells and nonfoamy macrophages derived from live rabbits. The altered pattern of gene expression in foam cells is likely to influence atherosclerosis formation and stability.


A modified end-to-side method for peripheral nerve repair: large epineurial window helicoid technique versus small epineurial window standard end-to-side technique.
This study evaluated 2 end-to-side nerve repair techniques for ability to induce nerve sprouting and muscular recovery. Twenty-four rats underwent identical surgeries. The helicoid method of neurorrhaphy was used on the left (large epineurial window) side and the standard end-to-side (small epineurial window) repair on the right side of each rat to repair the peroneal nerve. The helicoid configuration markedly increases the area from which axons can sprout into the recipient nerve. At 11 months after surgery, axons were counted in donor and recipient nerves, and muscle moist weight of the extensor digitorum longus (EDL) and tetanic force were measured. Muscle volume, tetanic force, and moist weight of EDL muscles were significantly higher on the left side (helicoid) than on the right (end-to-side). Histologic analysis and nerve axon counting of the recipient peroneal nerve showed significantly more regenerative nerves on the left than on the right. There were no significant differences between sites above and below the repair site in the donor tibial nerve in regard to mean number of nerve fibers. Helicoid nerve repair can entice more nerve fiber sprouts from the intact donor nerve, improve muscular recovery, and maintain donor nerve health.


Stochastic model for electric field-induced membrane pores. Electroporation.
Electric impulses (1-20 kV cm-1, 1-5 microseconds) cause transient structural changes in biological membranes and lipid bilayers, leading to apparently reversible pore formation ( electroporation ) with cross-membrane material flow and, if two membranes are in contact, to irreversible membrane fusion ( electrofusion ). The fundamental process operative in electroporation and electrofusion is treated in terms of a periodic lipid block model, a block being a nearest-neighbour pair of lipid molecules in either of two states: (i) the polar head group in the bilayer plane or (ii) facing the centre of a pore (or defect site). The number of blocks in the pore wall is the stochastic variable of the model describing pore size and stability. The Helmholtz free energy function characterizing the transition probabilities of the various pore states contains the surface energies of the pore wall and the planar bilayer and, if an electric field is present, also a dielectric polarization term (dominated by the polarization of the water layer adjacent to the pore wall). Assuming a Poisson process the average number of blocks in a pore wall is given by the solution of a non-linear differential equation. At subcritical electric fields the average pore size is stationary and very small. At supercritical field strengths the pore radius increases and, reaching a critical pore size, the membrane ruptures (dielectric breakdown). If, however, the electric field is switched off, before the critical pore radius is reached, the pore apparently completely reseals to the closed bilayer configuration (reversible electroporation ).


Transformation of hydrogel-based inverse opal photonic sensors from FCC to L1(1) during swelling.
The structural evolution of Bragg diffracting inverse opal hydrogel sensors during swelling is directly observed by two-photon laser scanning fluorescence microscopy and compared to predictions from finite element analysis. A fluorescently labeled pH-sensitive hydrogel is UV-polymerized in a dried polystyrene colloidal crystal template, which is etched to yield an inverse opal. Fluorescence imaging of the hydrogel at different pH values reveals an inhomogeneous deformation of the FCC array of aqueous pores. The pores elongate along the sample normal direction and collapse along the sample parallel directions, consistent with the Bragg response, which indicates a 1-D increase in the interlayer distance. Interconnects between the pores serve as anchor points during hydrogel expansion into the pores. Pinning of the hydrogel to the substrate causes a change of the hydrogel lattice symmetry during deformation, from FCC (ABC stacking) to L1(1) (ABCA'B'C' stacking). Reconstructed cross-sections confirm that a 1-D increase in the interlayer distance along the substrate normal direction is responsible for the diffraction response of an inverse opal hydrogel sensor. Comparison with predictions from finite element analysis shows qualitative agreement, although the experimental mesostructure is significantly more deformed than the calculated data, due to buckling in the experimental system that is not captured by the model.