Community structure, trophic position and reproductive mode of soil and bark-living oribatid mites in an alpine grassland ecosystem.
The community structure, stable isotope ratios ((15)N/(14)N, (13)C/(12)C) and reproductive mode of oribatid mites (Acari, Oribatida) were investigated in four habitats (upper tree bark, lower tree bark, dry grassland soil, forest soil) at two sites in the Central Alps (Tyrol, Austria). We hypothesized that community structure and trophic position of oribatid mites of dry grassland soils and bark of trees are similar since these habitats have similar abiotic characteristics (open, dry) compared with forest soil. Further, we hypothesized that derived taxa of oribatid mites reproducing sexually dominate on the bark of trees since species in this habitat consume living resources such as lichens. In contrast to our hypothesis, the community structure of oribatid mites differed among grassland, forest and bark indicating the existence of niche differentiation in the respective oribatid mite species. In agreement with our hypothesis, sexually reproducing taxa of oribatid mites dominated on the bark of trees whereas parthenogenetic species were more frequent in soil. Several species of bark-living oribatid mites had stable isotope signatures that were similar to lichens indicating that they feed on lichens. However, nine species that frequently occurred on tree bark did not feed on lichens according to their stable isotope signatures. No oribatid mite species could be ascribed to moss feeding. We conclude that sexual reproduction served as preadaptation for oribatid mites allowing them to exploit new habitats and new resources on the bark of trees. Abiotic factors likely are of limited importance for bark-living oribatid mites since harsh abiotic conditions are assumed to favor parthenogenesis.


Comparative RNA-Seq Analysis Revealed Tissue-Specific Splicing Variations during the Generation of the PDX Model.
Tissue-specific gene expression generates fundamental differences in the function of each tissue and affects the characteristics of the tumors that are created as a result. However, it is unclear how much the tissue specificity is conserved during grafting of the primary tumor into an immune-compromised mouse model. Here, we performed a comparative RNA-seq analysis of four different primary-patient derived xenograft (PDX) tumors. The analysis revealed a conserved RNA biotype distribution of primary-PDX pairs, as revealed by previous works. Interestingly, we detected significant changes in the splicing pattern of PDX, which was mainly comprised of skipped exons. This was confirmed by splicing variant-specific RT-PCR analysis. On the other hand, the correlation analysis for the tissue-specific genes indicated overall strong positive correlations between the primary and PDX tumor pairs, with the exception of gastric cancer cases, which showed an inverse correlation. These data propose a tissue-specific change in splicing events during PDX formation as a variable factor that affects primary-PDX integrity.


Complications and Health Care Resource Utilization Associated with Systemic Corticosteroids in Children and Adolescents with Persistent Asthma.
Limited comparative data are available on the impact of systemic corticosteroid (SCS) use in children and adolescents. To determine if asthmatic children and adolescents treated with SCS have a higher likelihood of developing complications versus those not receiving SCS and to examine health care resource utilization (HCRU) in this population. A retrospective study of data from children and adolescents with persistent asthma retrieved from the MarketScan database, a large US health claims data set, for the period 2000 to 2017 was performed. Propensity score matching was used to pair patients in the SCS and control cohorts. For complications, SCS subgroups (≥4 or 1-3 annual prescriptions) were compared with asthmatic controls without SCS using logistic regression, and for HCRU, cohorts were compared using negative binomial regression. A total of 67,081 patients were included (SCS: 23,898; control: 43,183). The odds of having a complication were 2.9 (95% confidence interval [CI], 2.5-3.2; P < .001) and 1.6 (95% CI, 1.6-1.7; P < .001) times higher in the ≥4 and 1 to 3 SCS groups, respectively, in the first year of follow-up versus controls. For asthma-related hospitalizations, the incidence rate ratio (IRR) was 6.9 (95% CI, 5.6-8.6) and 3.1 (95% CI, 2.8-3.4) times greater in the ≥4 SCS and 1 to 3 SCS groups, respectively, versus controls; for asthma-related emergency department visits, IRR was 5.0 (95% CI, 4.4-5.6) and 2.9 (95% CI, 2.7-3.0) times greater, respectively, versus controls (all P < .01). Children and adolescents receiving SCS for persistent asthma have an increased risk of developing complications and have greater HCRU in the first year of follow-up versus those without SCS exposure.


The adoption of clinical pathways and the inclusion of likelihood ratios in the report: a controlled before and after study.
The aim of this study was to evaluate the consequence of the introduction of Clinical Pathways (CPs) and the inclusion of Likelihood Ratios (LRs) in test results instead of the reference intervals in the workload for the laboratory and in-patients. A controlled before (2003) and after (2004, 2005, and 2006) study compared the exams requested using CPs instead of single exams for three pathologies (pulmonary embolism, acute myocardial infarction, and bile-pancreatic pathologies) in order to evaluate if this procedure is followed in clinical care and if it provides useful and accurate investigation for clinical care. Data were collected from the laboratory computer archive system over 3 years (2004 - 2006). The total number of requests decreased between the "before" and "after" 2004 and 2005. We found an increase (30% to 40%) in the requests of CPs. The percentage for each of the considered CPs showed a significant increase for the pulmonary embolism (EP) and bile-pancreatic pathologies: during the semesters monitored, we found an 80% increase in the request of these CPs. The percentage of acute myocardial infarction (AMI) CPs did not show a difference between the semesters compared. We also found an improvement in the diagnostic effectiveness: the concordance between the emergency department (ED) and ward diagnosis for EP increased. We demonstrated that this procedure is followed in clinical care for the three pathologies studied and that the use of CPs and LRs provide useful tools in making a more appropriate diagnosis. We demonstrated also that clinical audit is very important for monitoring. Audit is integral to good clinical practice and, in fact, aims to influence activity on a local level and is useful in maintaining best practice.


Specificity of substrate analogue inhibitors of human urinary kallikrein.
A series of acetyl-peptidyl-amides containing the amino acid sequence around the Arg-Ser kallikrein cleavage site of bovine kininogen were synthesized and tested for their ability to inhibit both the kinin-releasing activity and the amidase activity of purified human urinary kallikrein. The substrate analogues were competitive inhibitors for human urinary kallikrein and the heptapeptides (P4-P3'), hexapeptides (P3-P3'), and pentapeptides (P2-P3') gave Ki values of 140, 64, and 18 microM respectively, while the tetrapeptides (P1-P3'), tripeptides (P1'-P3') and dipeptides (P2'-P3') had little or no inhibitory activity. The effective analogues had neither kinin-like nor kinin-blocking activity on the rat uterus either before or after exposure to human urinary kallikrein. The effective human urinary kallikrein inhibitors were further examined for their effect on other serine proteases, including human plasma kallikrein, plasmin, complement components (C1s, C1r), bovine coagulation factors (IIa, IXa, and Xa), elastase, and trypsin. These peptides showed little inhibition of the circulating serine proteases but yielded a Ki for the nonspecific protease trypsin in the microM range. These results should provide the basis for the development of highly specific tissue kallikrein inhibitors to aid in elucidating the in vivo role(s) of tissue kallikreins.


Metabolic, Affective and Neurocognitive Characterization of Metabolic Syndrome Patients with and without Food Addiction. Implications for Weight Progression.
According to the food addiction (FA) model, the consumption of certain types of food could be potentially addictive and can lead to changes in intake regulation. We aimed to describe metabolic parameters, dietary characteristics, and affective and neurocognitive vulnerabilities of individuals with and without FA, and to explore its influences on weight loss progression. The sample included 448 adults (55-75 years) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus cognition sub-study. Cognitive and psychopathological assessments, as well as dietary, biochemical, and metabolic measurements, were assessed at baseline. Weight progression was evaluated after a 3-year follow up. The presence of FA was associated with higher depressive symptomatology, neurocognitive decline, low quality of life, high body mass index (BMI), and high waist circumference, but not with metabolic comorbidities. No differences were observed in the dietary characteristics except for the saturated and monounsaturated fatty acids consumption. After three years, the presence of FA at baseline resulted in a significantly higher weight regain. FA is associated with worse psychological and neurocognitive state and higher weight regain in adults with metabolic syndrome. This condition could be an indicator of bad prognosis in the search for a successful weight loss process.


Prevalence of celiac disease in patients with severe food allergy.
The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.


Tensions in the field: teaching standards of practice in optometry case presentations.
Professional identity formation and its relationship to case presentations were studied in an optometry school's onsite clinic. Eight optometry students and six faculty optometrists were audio-recorded during 31 oral case presentations and the teaching exchanges related to them. Using convenience sampling, interviews were audio-recorded of four of the students and four of the optometrists from the field observations. After transcribing these audio-recordings, the research team members applied a grounded theory method to identify, test, and revise emergent themes. The theme reported herein pertains to communicating standards of practice. Faculty optometrists demonstrated three ways of communicating standards of practice to optometry students during case presentations: Official Way, Our Way, and My Way. Although there were differences between these standards, the rationale for the disparities was rarely explicitly articulated by the instructors to the students. Without this information, the incongruity among the standards was left to the students to interpret on their own. The risk created by faculty not articulating the rationale underlying standards of practice was that students misinterpreted the optometrists' ways as idiosyncratic. Thus, opportunities were missed in the educational setting to assist students in making responsible decisions, locating their position in practice, and shaping their professional identity. Competing responsibilities of patient care and student education left instructors with little time to articulate rationale for standards of practice. Therefore, educators must reflect on innovative ways to bring into relief the logic behind their actions when working with novices.


A study to compare two models of community psychiatric nursing care delivery.
This study analyses data collected by the community psychiatric nursing team in the Bloomsbury Health Authority. After the 1982 National Health Service reorganization one large CPN team was created from two smaller ones each operating a separate mode of care delivery. Four CPNs were based at a day hospital and five CPNs worked from primary health care bases. Regular statistics collected by all the nurses were used to examine two hypotheses. First, there is a type of client seen by a CPN who varies according to the main base from which the nurse operates. Second, that there were differences in individual CPN 'caseload activity' that are determined by main work-setting. The results indicated that the characteristics of the two client-referral samples were indeed different using various measures of social deprivation and isolation. Substantial variations in 'caseload activity' between the two teams were also found, the largest difference being the number of hours spent in clinical activity, face to face with the client. Various implications of these findings for the overall planning and management of the CPN team are discussed. The overall conclusion reached is that, as Mangen & Griffith have suggested, the planning of CPN services requires the systematic collection of evaluative data on which to base future policies.


Tamoxifen-induced increase in the potential doubling time of MCF-7 xenografts as determined by bromodeoxyuridine labeling and flow cytometry.
The anti-estrogen tamoxifen (TAM) is widely used in the therapy of human breast cancer. Shown to induce a G1 transition delay in vitro, the kinetic effects of TAM on breast carcinoma cells growing as tumor xenografts in nude mice have been less well characterized. In this study, we demonstrate a significant increase in the tumor potential doubling time (Tpot) and decrease in the labeling index (%LI) of estradiol (E2)-stimulated MCF-7 xenografts following TAM treatment or E2 deprivation. MCF-7 tumor pieces were transplanted s.c. into nude mice supplemented with Silastic capsules containing E2. After 2-4 weeks, animals were randomized to continued E2 treatment, E2 and TAM treatment, or E2 deprivation. At times ranging from 0 to 23 days after treatment, animals were given injections of bromodeoxyuridine and tumors excised for kinetic analysis. Using flow-cytometric techniques, the Tpot and %LI were estimated for all tumors. Seven independent experiments were performed and data pooled for statistical analysis. At the time of hormonal manipulation, E2-stimulated tumors had a volume doubling time of 5 days, a Tpot of 2.3 days, and a %LI of 23%. Continued E2 treatment resulted in only minimal changes in Tpot and %LI over the remainder of the observation period. Treatment with TAM resulted in a slowing of tumor growth (tumor doubling time, 12 days), a significant (P < 0.001) increase in Tpot to 6.6 days, and a decrease in %LI to 8% by 23 days posttreatment. E2 deprivation resulted in a cessation of tumor growth and similar changes in Tpot and %LI to 5.3 days and 10%, respectively (P < 0.001). In contrast to previous reports, these data demonstrate that TAM treatment and E2 deprivation both significantly decrease tumor cell proliferation in MCF-7 xenografts.


Accessory hepatic lobe.
The aim of the present communication was to describe an accessory hepatic lobe in two patients and to outline the significance of the timely identification of this very rare anatomic variation for the clinical practice. In the course of right hemihepatectomy, accessory liver lobes were detected in two patients. Their diagnosis was confirmed by histopathology and cholangiography. Both accessory hepatic lobes arose from the left liver segments. The first lobe was detected in a 56-year-old male operated on for a retroperitoneal liposarcoma. It amounted to 15% of the standard liver volume and was attached to liver segments 2 and 3 by a stalk. The second accessory lobe was found out in 45-year-old female operated on for a colon cancer and synchronous liver metastases. It was less than 15 g in weight and attached to the main liver by a mesentery as its bile duct drained into an extrahepatic duct. The accessory hepatic lobes require timely diagnosis. They should be kept in mind in cases with acute surgical abdomen.


Clinical status and optimal use of rituximab for B-cell lymphomas.
Rituximab (IDEC-C2B8 [Rituxan]) is a chimeric anti-CD20 monoclonal antibody (MoAb) that was recently approved by the FDA for the treatment of patients with low-grade or follicular B-cell non-Hodgkin's lymphoma. Its potential efficacy in other B-cell malignancies is currently being explored. This article reviews the mechanisms of action of rituximab, as well as preclinical data and results of the clinical trials that led to its approval. Also discussed are the mechanics of administering rituximab on the recommended weekly x 4 outpatient schedule. Finally, the article describes ongoing and planned trials of rituximab in other dosage schedules, in other B-cell neoplasms, and in conjunction with chemotherapy. As the first MoAb to gain FDA approval for the treatment of a malignancy, rituximab signals the beginning of a promising new era in cancer therapy.


Hepatic necrosis induced by norepinephrine in rabbits.
Extensive hepatic necrosis was produced in rabbits 48 hr following infusion of a cardiopathogenic dose of norepinephrine (NE, 2 micrograms/kg/min for 90 min). Livers had necrotic areas of varying sizes and gross appearances. Histologically, the lesions were areas of varying sizes and gross appearances. Histologically, the lesions were areas of lytic-coagulative necrosis with massive mineralization by calcium. In addition, the serum glutamate-pyruvate transaminase (GPT) was significantly elevated (P less than 0.001). Pretreatment with the alpha 1-adrenoceptor blocker prazosin (200 micrograms/kg) 15 min prior to the standard NE infusion prevented both liver necrosis and serum GPT elevation. It is concluded that large doses of NE produce tissue injury in the liver. This may be the result of excessive activation of the alpha 1-adrenoceptor system, which leads to hepatic ischemia and necrosis.


Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease.
Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman's vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor-mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not "uropathogenic" in the classic sense. This "covert pathogenesis" paradigm may apply to other latent infections, (e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance.


[Structure and regulation of the assembly of bacteriophage T4 fibrillar proteins. II. Isolation and initial structural characteristics of whiskers].
A procedure for purification of bacteriophage T4 whiskers and it's monomeric subunits--gene product wac--has been developed. We have shown, that the whiskers are composed of two identical copies of gene product wac with molecular weight of 56 kDa each. The dimer of gene product wac is a highly ordered structure and it's length is about 70.0 +/- 10.0 nm, as revealed by electron microscopy. The amino acid composition of whiskers is very similar to that of watersoluble keratins. We have proposed a new term for the definition of the whiskers--the fibritin.


Opposing Roles of the Dorsolateral and Dorsomedial Striatum in the Acquisition of Skilled Action Sequencing in Rats.
The shift in control from dorsomedial to dorsolateral striatum during skill and habit formation has been well established, but whether striatal subregions orchestrate this shift cooperatively or competitively remains unclear. Cortical inputs have also been implicated in the shift toward automaticity, but it is unknown whether they mirror their downstream striatal targets across this transition. We addressed these questions using a five step heterogeneous action sequencing task in male rats that is optimally performed by automated chains of actions. By optimizing automatic habitual responding, we discovered that loss of function in the dorsomedial striatum accelerated sequence acquisition. In contrast, loss of function in the dorsolateral striatum impeded acquisition of sequencing, demonstrating functional opposition within the striatum. Unexpectedly, the mPFC was not involved; however, the lateral orbitofrontal cortex was critical. These results shift current theories about striatal control of behavior to a model of competitive opposition, where the dorsomedial striatum interferes with the development of dorsolateral-striatum dependent behavior.SIGNIFICANCE STATEMENT We provide the most direct evidence to date that the dorsomedial and dorsolateral striatum compete for control in the acquisition of habitual action sequences. The dorsolateral striatum was critical for sequencing behavior, but loss of dorsomedial striatum function enhanced acquisition. In addition, we found that the mPFC was not required for the formation of automated actions. Using a task that optimizes habitual responding, we demonstrate that the arbitration of dorsomedial and dorsolateral control is not modulated by medial prefrontal cortical activity. However, we find evidence for the role of the lateral orbitofrontal cortex in action sequencing. These results have implications for our understanding of how habits and skills form.


Determination of the optical properties of a two-layer tissue model by detecting photons migrating at progressively increasing depths.
We have investigated a method for solving the inverse problem of determining the optical properties of a two-layer turbid model. The method is based on deducing the optical properties (OPs) of the top layer from the absolute spatially resolved reflectance that results from photon migration within only the top layer by use of a multivariate calibration model. Then the OPs of the bottom layer are deduced from relative frequency-domain (FD) reflectance measurements by use of the two-layer FD diffusion model. The method was validated with Monte Carlo FD reflectance profiles and experimental measurements of two-layer phantoms. The results showed that the method is useful for two-layer models with interface depths of >5 mm; the OPs were estimated, within a relatively short time (<1 min), with a mean error of <10% for the Monte Carlo reflectance profiles and with errors of <25% for the phantom measurements.


Amblyopia in Children: Analysis Among Preschool and School Children in the City of Tuzla, Bosnia and Herzegovina.
This study measured the prevalence of amblyopia in preschool and school children between 4 and 15 years of age in Tuzla, Bosnia and Herzegovina and as well and to examine its relations with anisometropia and strabismus. Children from eight daycare centers and twenty four elementary schools were screened for amblyopia by volunteer personnel (medical students), any child who failed to pass the screening examination, was referred to the ophthalmologist for complete examination at University Clinic Center Tuzla. The examination included VA, stereopsis, cover testing, refractive retinoscopy, and examination of the red reflex and posterior pole. Total of 7415 children, which included 3790 males and 3625 females, in the age range of 3 to 15 years from 24 schools and 8 preschool were screened. Fifty night children (1.9%) were diagnosed with amblyopia, unilateral in 28 and bilateral in 31. Prevalence of significant refractive errors is high enough to justify a school eye screening program solely for this purpose. preschool and school screening program in children in critical period of development of amblyopia must be conducted to find out the ametropias and amblyopia in time; and treat them earlier.


Genipin Induces Autophagy and Suppresses Cell Growth of Oral Squamous Cell Carcinoma via PI3K/AKT/MTOR Pathway.
Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and it accounts for more than 90% of oral cancer. Due to high mortality, limitations of traditional treatment and many complications, new treatment methods are urgently needed. This study aimed to look into the effect of new potential anti-tumor drug, genipin, on OSCC treatment. In vitro, CCK-8, colony formation, and flow cytometry were used to detect the effect of genipin on SCC-9 and SCC-15 cell lines. Immunofluorescence, real-time PCR, and Western blotting were used to investigate its mechanism. Xenograft tumor model was used to explore the role of genipin in vivo. We found that genipin suppressed cell growth and induced apoptosis in vitro. In addition, the expression of p62 was down-regulated while Beclin1 and LC3II were up-regulated in SCC-25 and SCC-9 cells. 3-methyladenine (3-MA) significantly decreased LC3 (LC3II)+ puncta, but genipin rescuect 3d this reduction. Furthermore, genipin also reduced the expression of p-PI3K, p-AKT, and p-mTOR. In vivo experiment showed that genipin significantly curbed the tumor size and weight. The positive expression of Ki67 protein and number of apoptotic cells were increased. Conclusively, this study implicated that genipin suppresses cell proliferation and stimulated apoptosis, and is the first exploration showing that genipin induces OSCC cell autophagy via PI3K/AKT/mTOR pathway inhibition.


Application of spectral karyotyping to the analysis of the human chromosome complement of interspecies somatic cell hybrids.
Mouse-human somatic cell hybrids have been extensively used in the molecular genetic dissection of human disease-related chromosome rearrangements because of their ability to selectively and randomly eliminate human chromosomes. This technology allows the isolation of structural chromosome abnormalities, which then allows determination of the precise molecular address of chromosome breakpoints associated with deletions and translocations, down to the nucleotides involved. The main confounding problem with the analysis of somatic cell hybrids is determining the exact chromosome complement unequivocally and quickly. Spectral karyotyping can identify each of the individual human chromosomes in a normal metaphase spread, as well as structural chromosome rearrangements-although, because of potential cross-hybridization between the human probe and mouse DNA sequences during the hybridization reaction, it has not been determined whether the same analysis will selectively identify human chromosomes on a mouse background. We show (to our knowledge, for the first time) that, under modified conditions of chromosomal in situ suppression hybridization, the standard spectral karyotyping probe does not cross-react with mouse chromosomes and can be used to identify subtle structurally rearranged chromosomes in hybrid cells. This analysis allows for the rapid and unequivocal identification of the human chromosome complement in these hybrids, as well as structural chromosome rearrangements that occur between mouse and human chromosomes that might otherwise confound the analysis.


Threat alert: The effect of outliers on the alliance-outcome correlation.
Meta-analyses have established the alliance as the most robust predictor of outcome in psychotherapy. A growing number of studies have evaluated potential threats to the conclusion that alliance is a causal factor in psychotherapy. One potential threat that has not been systematically examined is the possibility that the alliance-outcome association is driven by low alliance outliers. We examined the influence of removing low alliance outliers on the alliance-outcome association using data drawn from two large-scale, naturalistic psychotherapy data sets (Ns = 1,052; 11,029). These data sets differed in setting (university counseling center, community mental health center), country (United States and Canada), alliance measure (four-item Working Alliance Inventory Short Form Revised, 10-item Session Rating Scale), and outcome measure (Counseling Center Assessment of Psychological Symptoms-34, Outcome Questionnaire-45). We examined the impact of treating outliers in five different ways: retaining them, removing values three or two standard deviations from the mean, and winsorizing values three or two standard deviations from the mean. We also examined the effect of outliers after disaggregating alliance ratings into within-therapist and between-therapist components. The alliance-outcome correlation and the proportion of variance in posttest outcomes explained by alliance when controlling for pretest outcomes were similar regardless of how low alliance outliers were treated (change in r ≤ .04, change in R² ≤ 1%). Results from the disaggregation were similar. Thus, it appears that the alliance-outcome association is not an artifact of the influence of low alliance outliers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Meta-analysis of HLA-DRB1 and HLA-DQB1 polymorphisms in Latin American patients with systemic lupus erythematosus.
To estimate the common effect size of HLA-DRB1 and -DQB1 alleles on systemic lupus erythematosus (SLE) susceptibility across Latin America populations through a meta-analysis. Case-control studies on HLA class II association with SLE in Latin America were searched up to August 2007. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model. Eleven studies were selected, which included 747 cases and 1180 controls. Associations with SLE susceptibility were found for HLA-DR2 (OR: 1.75; 95% CI: 1.40-2.19) and -DR3 (OR: 2.02; 95% CI: 1.44-2.83) groups. HLA-DRB1*0301 allele disclosed the strongest association (OR: 2.14; 95% CI: 1.28-3.56). HLA-DR3-DQ2 haplotype was a risk factor (OR: 2.92; 95% CI: 1.66-5.14). A protective effect was found for the HLA-DR5 group (OR: 0.43; 95% CI: 0.27-0.67), mainly due to a negative association between HLA-DRB1*1101 allele and disease (OR: 0.21; 95% CI: 0.06-0.72). Functional analysis of susceptibility and protective alleles revealed physicochemical differences of critical amino acids shaping the peptide-binding groove at DRbeta chain allowing us to infer an approach to understand the role of HLA in SLE. No significant association was established for HLA-DQB1 alleles. HLA-DRB1 gene is a mayor factor for development of SLE in Latin Americans.


Inundative practice for screening siRNA management candidates against a notorious predatory beetle using olfactory silencing.
Calosoma maximoviczi, a predatory pest beetle, poses a significant threat to wild silk farm production due to its predation on wild silkworms. Given the coexistence of this species with beneficial silkworms in the farm orchards, chemical pesticides are not an ideal solution for controlling its population. In this study, we employed a comprehensive multi-target RNA interference (RNAi) approach to disrupt the olfactory perception of C. maximoviczi through independently silencing 16 odorant receptors (ORs) in the respective genders. Specifically, gene-specific siRNAs were designed to target a panel of ORs, allowing us to investigate the specific interactions between odorant receptors and ligands within this species. Our investigation led to identifying four candidate siOR groups that effectively disrupted the beetle's olfactory tracking of various odorant ligands associated with different trophic levels. Furthermore, we observed sex-specific differences in innate RNAi responses reflected by subsequent gene expression, physiological and behavioral consequences, underscoring the complexity of olfactory signaling and emphasizing the significance of considering species/sex-specific traits when implementing pest control measures. These findings advance our understanding of olfactory coding patterns in C. maximoviczi beetles and establish a foundation for future research in the field of pest management strategies.


Three equine cases of mixed hepatoblastoma with teratoid features.
Hepatoblastoma was diagnosed in 3 Thoroughbreds at the University of Kentucky Livestock Disease Diagnostic Center (LDDC) since 1997. Case #1 involved a fetus with a well-demarcated, multilobulated, solitary mass that extended from the left liver lobe. Case #2 was observed in a neonate with a primary hepatic mass and multiple metastases in the skin, brain, meninges, and stylohyoid bone. Case #3 was a solitary hepatic mass incidentally discovered in a neonate at necropsy. Microscopically, the masses were similarly composed of sheets and cords of fetal and embryonal epithelial cells that frequently formed sinusoid-like structures. Intermixed with the neoplastic epithelial cells were variable amounts of hemorrhage, necrosis, osteoid, and bone. Immunohistochemically, the epithelial cells stained variably positive for alpha- fetoprotein, frequently positive for vimentin, and occasionally positive for cytokeratin. All 3 cases were diagnosed as mixed hepatoblastoma with teratoid features.


Volumetric and shape analysis of the thalamus in first-episode schizophrenia.
Thalamic abnormalities have been implicated in the pathogenesis of schizophrenia, although the majority of studies used chronic samples treated extensively with antipsychotics. Moreover, the clinical and neuropsychological correlates of these abnormalities remain largely unknown. Using high-resolution MR imaging and novel methods for shape analysis, we investigated thalamic subregions in 35 (25 M/10 F) first-episode schizophrenia patients compared with 33 (23 M/10 F) healthy volunteers. The right and left thalami were traced bilaterally on coronal brain slices and volumes were compared between groups. In addition, regional abnormalities were identified by comparing distances, measured from homologous thalamic surface points to the central core of each individual's surface model, between groups in 3D space. Patients had significantly less total thalamic volume compared with healthy volunteers. Statistical mapping demonstrated most pronounced shape abnormalities in the pulvinar; however, estimated false discovery rates in these regions were sizable. Smaller thalamus volume was significantly correlated with worse overall neuropsychological functioning and specific deficits were observed in the language, motor, and executive domains. There were no significant associations between thalamus volume and positive or negative symptoms. Our findings suggest that thalamic abnormalities are evident at the onset of a first episode of schizophrenia prior to extensive pharmacologic intervention and that these abnormalities have neuropsychological correlates.


Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin.
Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found that LTM, isomigrastatin and analogs have a potent antiproliferative effect on tumor cell lines and selectively inhibit translation. A systematic comparative study of the effects of CHX and LTM on protein synthesis revealed both similarities and differences between the two inhibitors. Both LTM and CHX were found to block the translocation step in elongation. Footprinting experiments revealed protection of a single cytidine nucleotide (C3993) in the E-site of the 60S ribosomal subunit, thus defining a common binding pocket for the two inhibitors in the ribosome. These results shed new light on the molecular mechanism of inhibition of translation elongation by both CHX and LTM.


Correlation between urothelial differentiation and sensory proteins P2X3, P2X5, TRPV1, and TRPV4 in normal urothelium and papillary carcinoma of human bladder.
Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.


Concept of Lethal Triad in Critical Care of Severe Burn Injury.
The trinity of hypothermia, acidosis and coagulopathy, the lethal triad in trauma setting is a well-known risk factor associated with high risk of death. Burn is also a pathological situation where inflammatory response, endothelial injury, hypovolemia, reduced end-organ perfusion, cellular hypoxia, and myocardial depression are frequently encountered. This study aimed to study the occurrence and outcome of patients presenting with the 'triad of death' in burn population. The study population included patients between 18 years and 60 years presenting to the department with thermal and scald burns with total body surface area involving 50-70%. The study was conducted for a period of 180 days and patients were followed up for 30 days. A p value <0.05 was considered statistically significant. One hundred and ninety-six patients were admitted during study period. Fifty patients out of them were eligible and were included in the study. The average abbreviated burns score index was 11 in lethal triad subgroup when compared to eight in the subgroup without the lethal triad. The mortality in the subgroup with lethal triad was higher (68.8% vs 17.6%, p = 0.0009). The "on admission" acidosis, hypothermia, and coagulopathy were independently associated with significantly increased mortality. The overall relative risk of mortality in the presence of lethal triad was 3.896. This study reiterates the fact that the lethal triad is seen in burn patient. Burn associated with on admission lethal triad has significantly higher mortality rates. There are only countable studies addressing this issue in burn setting. Muthukumar V, Karki D, Jatin B. Concept of Lethal Triad in Critical Care of Severe Burn Injury. Indian J Crit Care Med 2019;23(5):206-209.


Lipid recognition propensities of amino acids in membrane proteins from atomic resolution data.
Protein-lipid interactions play essential roles in the conformational stability and biological functions of membrane proteins. However, few of the previous computational studies have taken into account the atomic details of protein-lipid interactions explicitly. To gain an insight into the molecular mechanisms of the recognition of lipid molecules by membrane proteins, we investigated amino acid propensities in membrane proteins for interacting with the head and tail groups of lipid molecules. We observed a common pattern of lipid tail-amino acid interactions in two different data sources, crystal structures and molecular dynamics simulations. These interactions are largely explained by general lipophilicity, whereas the preferences for lipid head groups vary among individual proteins. We also found that membrane and water-soluble proteins utilize essentially an identical set of amino acids for interacting with lipid head and tail groups. We showed that the lipophilicity of amino acid residues determines the amino acid preferences for lipid tail groups in both membrane and water-soluble proteins, suggesting that tightly-bound lipid molecules and lipids in the annular shell interact with membrane proteins in a similar manner. In contrast, interactions between lipid head groups and amino acids showed a more variable pattern, apparently constrained by each protein's specific molecular function.


Effects of Age and Sex on Subcortical Volumes.
In an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala. We analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set. The sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased. The results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.


Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity.
Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5'-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5'-phosphatase-defective SHIP2 (Delta IP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor beta subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or Delta IP-SHIP2. Because WT-SHIP2 possesses the 5'-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of Delta IP-SHIP2, indicating that Delta IP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase C lambda in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase C lambda, whereas these activations were increased by expression of Delta IP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of Delta IP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3beta and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of Delta IP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5'-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.


Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice.
This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50 µl/paw) or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks), and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20 mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and anti-inflammatory agents bupropion and celecoxib might represent an attractive therapeutic strategy for depression.


Hippocampal volume is related to body mass index in Alzheimer's disease.
Obesity is associated with lower brain volumes in early Alzheimer's disease, but its effects on hippocampal volumes are unclear, as weight loss is also associated with Alzheimer's disease. To address this question, we applied an automated hippocampal mapping method to brain MRI scans for 162 patients with Alzheimer's disease. We hypothesized that obesity, measured by body mass index, would be associated with lower hippocampal volumes in mildly affected patients. Statistical maps showed a selective pattern of hippocampal volume differences that were significantly associated with body mass index. Associations were detected in the anterior hippocampus, and confirmed by permutation testing. Cardiovascular risk factors, such as high body mass index, may promote additional neurodegenerative changes, and should therefore be considered in epidemiological studies and clinical trials.


Nitrogen yield advantage from grass-legume mixtures is robust over a wide range of legume proportions and environmental conditions.
Current challenges to global food security require sustainable intensification of agriculture through initiatives that include more efficient use of nitrogen (N), increased protein self-sufficiency through homegrown crops, and reduced N losses to the environment. Such challenges were addressed in a continental-scale field experiment conducted over 3 years, in which the amount of total nitrogen yield (Ntot ) and the gain of N yield in mixtures as compared to grass monocultures (Ngainmix ) was quantified from four-species grass-legume stands with greatly varying legume proportions. Stands consisted of monocultures and mixtures of two N2 -fixing legumes and two nonfixing grasses. The amount of Ntot of mixtures was significantly greater (P ≤ 0.05) than that of grass monocultures at the majority of evaluated sites in all 3 years. Ntot and thus Ngainmix increased with increasing legume proportion up to one-third of legumes. With higher legume percentages, Ntot and Ngainmix did not continue to increase. Thus, across sites and years, mixtures with one-third proportion of legumes attained ~95% of the maximum Ntot acquired by any stand and had 57% higher Ntot than grass monocultures. Realized legume proportion in stands and the relative N gain in mixture (Ngainmix /Ntot in mixture) were most severely impaired by minimum site temperature (R = 0.70, P = 0.003 for legume proportion; R = 0.64, P = 0.010 for Ngainmix /Ntot in mixture). Nevertheless, the relative N gain in mixture was not correlated to site productivity (P = 0.500), suggesting that, within climatic restrictions, balanced grass-legume mixtures can benefit from comparable relative gains in N yield across largely differing productivity levels. We conclude that the use of grass-legume mixtures can substantially contribute to resource-efficient agricultural grassland systems over a wide range of productivity levels, implying important savings in N fertilizers and thus greenhouse gas emissions and a considerable potential for climate change mitigation.


Glucose and lactate biosensors based on redox polymer/oxidoreductase nanocomposite thin films.
Glucose and lactate enzyme electrodes have been fabricated through the deposition of an anionic self-assembled monolayer and subsequent redox polymer/enzyme electrostatic complexation on gold substrates. These surfaces were functionalized with a negative charge using 11-mercaptoundecanoic acid (MUA), followed by alternating immersions in cationic redox polymer solutions and anionic glucose oxidase (GOX) or lactate oxidase (LAX) solutions to build the nanocomposite structure. The presence of the multilayer structure was verified by ellipsometry and sensor function characterized electrochemically. Reproducible analyte response curves from 2 to 20 mM (GOX) and 2-10 mM (LAX) were generated with the standard deviation between multiple sensors between 12 and 17%, a direct result of the reproducibility of the fabrication technique. In the case of glucose enzyme electrodes, the multilayer structure was further stabilized through the introduction of covalent bonds within and between the layers. Chemical cross-linking was accomplished by exposing the thin film to glutaraldehyde vapors, inducing linkage formation between lysine and arginine residues present on the enzyme periphery with amine groups present on a novel redox polymer, poly[vinylpyridine Os(bisbipyridine)2Cl]-co-allylamine. Finally, an initial demonstration of thin-film patterning was performed as a precursor to the development of redundant sensor arrays. Microcontact printing was used to functionalize portions of a gold surface with a blocking agent, typically 1-hexadecanethiol. This was followed by immersion in MUA to functionalize the remaining portions of gold with negative charges. The multilayer deposition process was then followed, resulting in growth only on the regions containing MUA, resulting in a "positive"-type pattern. This technique may be used for fabrication of thin-film redundant sensor arrays, with thickness under 100 angstrom and lateral dimensions on a micrometer scale.


New Insights of Transcriptional Regulator AflR in Aspergillus flavus Physiology.
Aspergillus flavus aflR, a gene encoding a Zn(II)2Cys6 DNA-binding domain, is an important transcriptional regulator of the aflatoxin biosynthesis gene cluster. Our previous results of Gene ontology (GO) analysis for the binding sites of AflR in A. flavus suggest that AflR may play an integrative regulatory role. In this study the ΔaflR and overexpression (OE) strains based on the well-established double-crossover recombinational technique were constructed to investigate the integrative function of the aflR gene in A. flavus. The disruption of aflR severely affected the aflatoxin biosynthetic pathway, resulting in a significant decrease in aflatoxin production. The aflatoxin B1 (AFB1) of the ΔaflR strain was 180 ng/mL and aflatoxin B2 (AFB2) was 2.95 ng/mL on YES medium for 5 days, which was 1/1,000 of that produced by the wild-type strain (WT). In addition, the ΔaflR strain produced relatively sparse conidia and a very small number of sclerotia. On the seventh day, the sclerotia yield on each plate of the WT and OE strains exceeded 1,000, while the sclerotial formation of the ΔaflR strain was not detected until 14 days. However, the biosynthesis of cyclopiazonic acid (CPA) was not affected by aflR gene disruption. Transcriptomic analysis of the ΔaflR strain grown on potato dextrose agar (PDA) plates at 0 h, 24 h, and 72 h showed that expression of clustering genes involved in the biosynthesis of aflatoxin was significantly downregulated. Meanwhile, the ΔaflR strain compared with the WT strain showed significant expression differences in genes involved in spore germination, sclerotial development, and carbohydrate metabolism compared to the WT. The results demonstrated that the A. flavus aflR gene also played a positive role in the fungal growth and development in addition to aflatoxin biosynthesis. IMPORTANCE Past studies of the A. flavus aflR gene and its orthologues in related Aspergillus species were solely focused on their roles in secondary metabolism. In this study, we used the ΔaflR and OE strains to demonstrate the role of aflR in growth and development of A. flavus. For the first time, we confirmed that the ΔaflR strain also was defective in production of conidia and sclerotia, asexual propagules of A. flavus. Our transcriptomic analysis further showed that genes involved in spore germination, sclerotial development, aflatoxin biosynssssthesis, and carbohydrate metabolism exhibited significant differences in the ΔaflR strain compared with the WT strain. Our study indicates that AflR not only plays an important role in regulating aflatoxin synthesis but also in playing a positive role in the conidial formation and sclerotial development in A. flavus. This study reveals the critical and positive role of the aflR gene in fungal growth and development, and provides a theoretical basis for the genetic studies of other aspergilli.


Abolition of lifelong specific phobia: a novel therapeutic consequence of left mesial temporal lobectomy.
Numerous imaging studies have confirmed the amygdala as prominent within a neural network mediating specific phobia, including arachnophobia. We report the case of a patient in whom arachnophobia was abolished after left temporal mesial lobectomy, with unchanged fear responses to other stimuli. The phenomenon of abolition of specific phobia after amygdala removal has not, to our knowledge, been previously reported.


Assessment of the nutritional status of preschool-age children during the second Intifada in Palestine.
The Palestinian economy has dramatically deteriorated at all levels since the Al-Aqsa Intifada (uprising) began in 2000, resulting in an unprecedented catastrophe to the livelihoods of the Palestinians residing in the West Bank and Gaza. It was also marked by lack of household physical and financial access to food and health care, which placed children at increased risk of malnutrition and poor health. This prompted a significant increase in food aid from 2002 until the summer of 2003. To assess the nutritional status of children 6 to 59 months of age after 1 year of food assistance. In the West Bank and Gaza, a nationally representative sample of children 6 to 59 months of age was randomly selected with a validated multistage clustered design, with the Health Survey 1999 sample used as the sampling frame. The sample was stratified according to governorate, place of residence (urban, nonurban, or refugee camp), locality, and size of locality (number of households). A cross-sectional survey of nutritional status was carried out. Data were collected by interviews with the primary caregivers of the children. Measurements were made of children's weight and height or length. Food-intake data were collected by the 24-hour food-recall method with the use of a booklet of photographs of foods commonly eaten in Palestine. A total of 3,089 children were assessed, of whom 3.1% in the West Bank and 3.9% in the Gaza Strip were suffering from acute malnutrition; the prevalence of chronic malnutrition was 9.2% in the West Bank and 12.7% in the Gaza Strip (p = .02). Sex, refugee status, locality, and maternal education were not significantly associated with acute malnutrition by logistic regression analysis, whereas infants 6 to 23 months of age were significantly at risk. Calorie and protein intakes were generally lower than recommended dietary allowances. The prevalence rates of both acute and chronic malnutrition among children in the West Bank and Gaza are significantly higher than the national Palestinian averages. There is a need to establish nutritional surveillance systems to monitor the nutritional status of children in conflict areas.


Cumulative childhood adversity, adolescent psychiatric disorder and violent offending in young adulthood.
Childhood adversity (CA) is a risk indicator for psychiatric morbidity. Although CA has been linked to violent offending, limited research has considered adolescent psychiatric disorder as a mediating factor. The current study examined whether adolescent psychiatric disorder mediates the association between CA and violent offending. We used a cohort of 476 103 individuals born in 1984-1988 in Sweden. Register-based CAs included parental death, substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance, child welfare intervention and residential instability. Adolescent psychiatric disorder was defined as being treated with a psychiatric diagnosis prior to age 20. Estimates of risk of violent offending after age 20 were calculated as incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Mediation was tested with the bootstrap method. Exposure to CA was positively associated with violent offending, especially when accumulated. Individuals exposed to 4+ CAs who were also treated for psychiatric disorder had a 12-fold elevated risk for violent offending (adjusted IRR 12.2, 95% CI 10.6-14.0). Corresponding IRR among 4+ CA youth with no psychiatric disorder was 5.1 (95% CI 4.5-5.6). Psychiatric disorder mediated the association between CA and violent offending. CA is associated with elevated risk for violent offending in early adulthood, and the association is partly mediated by adolescent psychiatric disorder. Individuals exposed to cumulative CA who also develop adolescent psychopathology should be regarded as a high-risk group for violent offending, by professionals in social and health services that come into contact with this group.


The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2.
Although it is known that nano-TiO2or other nanoparticles can induce liver toxicities, the mechanisms and the molecular pathogenesis are still unclear. In this study, nano-anatase TiO2(5 nm) was injected into the abdominal cavity of ICR mice for consecutive 14 days, and the inflammatory responses of liver of mice was investigated. The results showed the obvious titanium accumulation in liver DNA, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by higher doses nano-anatase TiO2. The real-time quantitative RT-PCR and ELISA analyses showed that nano-anatase TiO2can significantly alter the mRNA and protein expressions of several inflammatory cytokines, including nucleic factor-κB, macrophage migration inhibitory factor, tumor necrosis factor-α, interleukin-6, interleukin-1β, cross-reaction protein, interleukin-4, and interleukin-10. Our results also implied that the inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity.


Alteration of rabbit alveolar and peritoneal macrophage function by herpes simplex virus.
Exposure of rabbit alveolar and peritoneal macrophages to infectious herpes simplex virus resulted in inhibition of antibody-dependent cellular cytotoxicity and either enhancement or inhibition of phagocytosis. At all times after exposure, virus was inhibitory to peritoneal macrophage phagocytosis. Alveolar macrophages showed enhanced phagocytic activity in the early stages of virus exposure and inhibition at later time points.


RNApuzzler: efficient outerplanar drawing of RNA-secondary structures.
RNA secondary structure is a useful representation for studying the function of RNA, which captures most of the free energy of RNA folding. Using empirically determined energy parameters, secondary structures of nucleic acids can be efficiently computed by recursive algorithms. Several software packages supporting this task are readily available. As RNA secondary structures are outerplanar graphs, they can be drawn without intersection in the plane. Interpretation by the practitioner is eased when these drawings conform to a series of additional constraints beyond outerplanarity. These constraints are the reason why RNA drawing is difficult. Many RNA drawing algorithms therefore do not always produce intersection-free (outerplanar) drawings. To remedy this shortcoming we propose here the RNApuzzler algorithm which is guaranteed to produce intersection-free drawings. It is based on a drawing algorithm respecting constraints based on nucleotide distances (RNAturtle). We investigate relaxations of these constraints allowing for intersection-free drawings. Based on these relaxations, we implemented a fully automated, simple, and robust algorithm that produces aesthetic drawings adhering to previously established guidelines. We tested our algorithm using the RFAM database and found that we can compute intersection-free drawings of all RNAs therein efficiently. The software can be accessed freely at: https://github.com/dwiegreffe/RNApuzzler. Supplementary data are available at Bioinformatics online.


Breast US: assessment of technical quality and image interpretation.
To determine whether ultrasonography (US) of the breast performed at a wide range of clinical practices conforms to the American College of Radiology (ACR) standards for quality and to assess the interpretations of breast sonograms. Static images from 152 breast US examinations performed at 86 institutions were evaluated for compliance with ACR guidelines for breast US hardware, technical factors, imaging protocol, and image annotation. Official interpretations submitted by the referring facilities were compared with static images submitted by the facility. Discrepancies were confirmed by two dedicated breast radiologists after repeat imaging, short-interval follow-up imaging, or biopsy. A total of 60.5% of cases did not comply with at least one ACR guideline on breast US and included 9.2% of cases with inadequate equipment, 14.7% of cases with inappropriate focal zone placement, at least 14% of cases with static images in only one imaging plane, and 25% of cases with incomplete patient identifiers. Clinically relevant interpretation errors and interpretation discrepancies were confirmed in 23 (15.1%) of 152 cases. The majority of breast US examinations did not comply with at least some of the standards for quality set forth by the ACR. Attention to these basic standards could substantially improve image quality.


De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.
Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal-dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five individuals who had been putatively diagnosed with "DA2A with severe neurological abnormalities" and for whom congenital contractures of the limbs and face, hypotonia, and global developmental delay had resulted in early death in three cases; this is a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in the sodium leak channel, non-selective (NALCN) in four families affected by CLIFAHDD syndrome. We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN mutations in ten additional families with "atypical" forms of DA. All 14 mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that NALCN alterations nearly abolished the expression of wild-type NALCN, suggesting that alterations that cause CLIFAHDD syndrome have a dominant-negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families affected by an autosomal-recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition characterized by varied though overlapping phenotypic features, perhaps based on the type of mutation and affected protein domain(s).


In vitro viral expression as a criterion for development of control procedures for enzootic bovine leukosis.
In a university beef herd of 304 cattle in which six died of lymphosarcoma between 1980 and 1984, 77% of the Angus and 26% of the Charolais cattle were determined to be infected with bovine leukemia virus (BLV). Changes in iatrogenic procedures were initiated as early control measures. In vitro viral expression (VE) was used as a criterion to identify cattle for subsequent segregation or culling. This involved determinations of percentages of BLV-associated lymphocyte profiles among thin-sectioned Ficoll-Paque-isolated blood lymphocytes that were processed into plastic after culture for 48 h. Cattle retained until completion of nutritional studies or as breeding stock were separated into two groups. The BLV-seronegative cattle, BLV-seropositive cattle with 0% VE, and BLV-seropositive cattle with 1% to 4% VE were placed in group 1. Seropositive cattle with greater than or equal to 5% VE were placed in group 2. In 1985, evaluation of in vitro VE in 108 mature BLV-seropositive cattle retained for breeding revealed 36 (33%) had no observable VE. In 1986, 58 of 108 cattle were available to be reexamined, and 21 (36%) had 0% VE in both years. The VE expression values for individual cattle were generally comparable over the 2-year period. Of 48 initial seronegative breeding stock housed in group 1 with BLV-seropositive cattle with low or no VE, 21 (44%) seroconverted during 1985 to 1986. A positive correlation of 0.585 was found between VE and age-related absolute lymphocyte number.


Gelatin-coated magnetic iron oxide nanoparticles as carrier system: drug loading and in vitro drug release study.
Magnetic iron oxide nanoparticles (IOPs) were coated with gelatin A and B and drug-loading efficiency was investigated using doxorubicin (DXR) as a model drug to evaluate their potential as a carrier system for magnetic drug targeting. Drug loading to coated IOPs was done using adsorption as well as desolvation/cross-linking techniques to understand their role. Drug loading by adsorption technique was done by incubating mixture of coated IOPs and drug in various conditions of pH, DXR-to-coated IOPs ratio, gelatin types and IOPs amounts. Drug loading by desolvation/cross-linking technique was done by adding acetone and glutaraldehyde (GTA) to the mixture of coated IOPs and DXR. The results indicated involvement of electrostatic interaction during loading of DXR-to-coated IOPs. Compared to adsorption technique, desolvation/cross-linking technique improved the efficiency of drug loading regardless of type of gelatin used for the coating. The DXR-loaded particles showed pH responsive drug release leading to accelerate release of drug at pH 4 compared to pH 7.4.


The Clinical Course of Severe Alpha-1-Antitrypsin Deficiency in Patients Identified by Screening.
Severe alpha-1-antitrypsin deficiency (AATD) is a genetic condition predisposing to chronic obstructive pulmonary disease (COPD) and liver disease. Its natural course is not well known. Our aim was to study the natural course of AATD by analyzing the clinical course in individuals with severe AATD identified by screening. Of the 1585 individuals included in the Swedish AATD register, 377 (24%) were identified by screening and included in this retrospective study. The follow-up time was from the date of inclusion in the register to the first lung transplantation, death or the termination of the study on June 1st, 2016. The risk factors for having a diagnosis of COPD were investigated through a proportional hazards model, adjusted for sex, diagnosis before the age of 14 years, smoking habits, occupational exposure to airway irritants and respiratory symptoms or diseases. At inclusion, 71% of the individuals were asymptomatic, ie, without any respiratory symptoms. Compared to the 156 (41%) ever-smokers, the 221 (59%) never-smokers had better lung function (mean FEV1 98 (SD 18) vs 85 (SD 28) % predicted; p < 0.001), and fewer of them were symptomatic, ie, with respiratory symptoms, at inclusion (20% vs 42%; p < 0.001). They also had a lower annual decline in FEV1 (mean 42 (95% CI 36-47) vs 53 (95% CI 47-60) mL·yr-1; p = 0.011) and better survival than the ever-smokers. The risk factors for having a diagnosis of COPD were the identification of severe AATD at an age of ≥14 years and the presence of respiratory symptoms or diseases. Never-smoking individuals with severe AATD identified by screening have better lung function, fewer symptoms, and better survival compared with the ever-smokers. Screening for AATD at an early age may improve the prognosis of AATD.


Generation, characterization and immunogenicity of a novel chimeric recombinant protein based on Plasmodium vivax AMA-1 and MSP119.
Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119). The recombinant PvAMA166-MSP119 was successfully expressed in Pichia pastoris and used to immunize two different mouse strains (BALB/c and C57BL/6) in the presence of the Poly (I:C) as an adjuvant. Immunization with the chimeric protein induced high antibody titers against both proteins in both strains of mice as detected by ELISA. Antisera also recognized the native proteins expressed on the merozoites of mature P. vivax schizonts. Moreover, this antigen was able to induce IFN-gamma-secreting cells in C57BL/6 mice. These findings indicate that this novel yeast recombinant protein containing PvAMA166 and PvMSP119 is advantageous, because of improved antibody titers and cellular immune response. Therefore, this formulation should be further developed for pre-clinical trials in non-human primates as a potential candidate for a P. vivax vaccine.


Reliability of a visual analog version of the QuickDASH.
The QuickDASH, an abbreviated form of the Disabilities of the Arm, Shoulder and Hand Questionnaire, uses a graded-adjectives ordinal measurement response scale. In order to improve the sensitivity of the measure and to make it compatible with widely used measures of pain and disability, a visual analog scale version was developed. The present study investigated the reliability of the new version over time when used for the evaluation of patients undergoing treatment. A test-retest model with a two-day interval was used to evaluate a sample of thirty-eight consecutive patients in an interdisciplinary tertiary rehabilitation setting who were identified as having an upper extremity disorder. The intraclass correlation coefficient indicating test-retest reliability was 0.90 for the eleven-item QuickDASH visual analog scale questionnaire (without the work component) and 0.94 for the fifteen-item questionnaire (with the work component), neither of which was significantly different from the results reported for the original questionnaire. The QuickDASH visual analog scale questionnaire has acceptable reliability over time, and it can be used as an alternative to the original QuickDASH.


New-onset epilepsy risk factors in older veterans.
To identify risk factors for new-onset geriatric epilepsy that may trigger clinicians to consider a differential diagnosis of epilepsy at symptom onset. Retrospective cohort study. National Veterans Affairs (VA) databases. Veterans aged 66 and older in fiscal year 2000 (FY00) who received VA care in FY99 and FY00. Individuals with new-onset epilepsy based on a validated algorithm constituted the epilepsy cohort (n=1,843), and individuals without epilepsy constituted the geriatric cohort (n=1,023,376). Age, sex, and race were derived from VA databases. Clinical conditions associated with new-onset geriatric epilepsy (e.g., cerebrovascular disease, dementia, brain tumor) and stroke risk-factors (e.g., hypertension, diabetes mellitus, cardiovascular disease) were identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification, codes before epilepsy onset (epilepsy cohort) and in FY00 (geriatric cohort). Multivariable logistic regression analysis indicated that patients with cerebrovascular disease (odds ratio (OR)=3.50, 95% confidence interval (CI)=3.13-3.91), cerebrovascular disease and dementia (OR=4.14, 95% CI=3.46-4.96), brain tumor (OR=2.14, 95% CI=1.46-3.13), head injury (OR=2.11, 95% CI=1.41-3.14), and other central nervous system (CNS) conditions (OR=1.57, 95% CI=1.32-1.88) were more likely to experience new-onset epilepsy. Statin prescription (OR=0.64, 95% CI=0.56-0.73), older age (> or =85 vs 66-74, OR=0.66, 95% CI=0.50-0.87), obesity (OR=0.74, 95% CI=0.62-0.87), and hypercholesterolemia (OR=0.87, 95% CI=0.76-0.98) were associated with a lower likelihood of epilepsy. These data suggest greater epilepsy risk for older individuals with CNS insult and an additive effect of cerebrovascular disease and dementia. The statin finding requires further exploration but points to a possible target for prevention of geriatric epilepsy.


[Primary tuberculosis of the lingual tonsil. A case report].
A case of primary tuberculosis of the lingual amygdala is reported. This is a highly unusual location in the head and neck area. This entity can be easily misdiagnosed as a result of confusion with other pathologies.


A comparison of sap flow measurements and potometry in two tropical lowland tree species with contrasting wood properties.
We evaluated the performance of the Heat Dissipation Technique (HDT) to measure sap flow in whole trees by comparison with potometric water uptake. Two tropical lowland species, Ochroma lagopus (balsa), a pioneer species with light wood and Hyeronima alchorneoides (pilón), a late-successional species with hard wood were examined. Diurnal courses of sap flow measured with the HDT showed good agreement with potometry. At the low sap flow rates (below 1 Kg h(-1)) occurring during nocturnal recharge HDT consistently underestimated sap flow rates. This resulted in the failure of the current version of the HDT to measure nocturnal water uptake, an important component of the water budget of at least one of the two species examined.


[Diagnosis, treatment and prophylaxis of acute ulcero-erosive gastroduodenal bleedings at cardiosurgical patients].
Results of treatment of 495 patients who has undergone various cardiac operations with artificial circulation are analyzed. The complex program "Blood-free surgery" was used at 388 (78.4%) of them. Among the patients treated traditionally the acute gastroduodenal erosions and ulcers were diagnosed at 25.7% patients, the rate of gastroduodenal bleedings was 3.0%. Complex of prophylactic measures permits to reduce the rate of acute erosions and ulcers in 1.5 times (18.4%) and the rate of postoperative gastroduodenal bleedings--to 0.7%. Control of risk factors, timely diagnosis, complex prophylaxis and treatment of acute gastroduodenal erosions and ulcers are effective way to improvement of operations results at cardiosurgical patients. "Blood-free" program doesn't lead to increase of acute postoperative gastroduodenal erosions and ulcers rate. Endoscopic (including repeated) hemostasis at acute ulcero-erosive gastroduodenal bleedings is available method and permits to achieve the stable hemostasis.


A hydrogen borrowing annulation strategy for the stereocontrolled synthesis of saturated aza-heterocycles.
An iridium catalyzed method for the synthesis of saturated aza-heterocycles from amines and diols is reported. A wide range of substituted heterocycles can be obtained using this approach including products bearing substituents at the C2, C3 and C4 positions. Employing water as the solvent, enantiopure diols could undergo annulation with minimal racemization, enabling the synthesis of valuable enantioenriched C3 and C4-substituted saturated aza-heterocycles.


Correlative anatomic and CT study of the lumbar lateral recess.
The lumbosacral nerve roots and their relation to the lateral recess in the lumbar region were studied by computed tomography both in anatomic specimens from six cadavers and in vivo in 100 patients with or without disk herniation. The anatomic and tomodensitometric correlations are discussed. The normal morphology and contents of the lumbar spinal canal can be used as a guide to radiologic diagnostic exploration, which in turn can indicate the etiology and extent of lumbar sciatica and the course of treatment.


Epigenetic programming alterations in alligators from environmentally contaminated lakes.
Previous studies examining the reproductive health of alligators in Florida lakes indicate that a variety of developmental and health impacts can be attributed to a combination of environmental quality and exposures to environmental contaminants. The majority of these environmental contaminants have been shown to disrupt normal endocrine signaling. The potential that these environmental conditions and contaminants may influence epigenetic status and correlate to the health abnormalities was investigated in the current study. The red blood cell (RBC) (erythrocyte) in the alligator is nucleated so was used as an easily purified marker cell to investigate epigenetic programming. RBCs were collected from adult male alligators captured at three sites in Florida, each characterized by varying degrees of contamination. While Lake Woodruff (WO) has remained relatively pristine, Lake Apopka (AP) and Merritt Island (MI) convey exposures to different suites of contaminants. DNA was isolated and methylated DNA immunoprecipitation (MeDIP) was used to isolate methylated DNA that was then analyzed in a competitive hybridization using a genome-wide alligator tiling array for a MeDIP-Chip analysis. Pairwise comparisons of alligators from AP and MI to WO revealed alterations in the DNA methylome. The AP vs. WO comparison identified 85 differential DNA methylation regions (DMRs) with ⩾3 adjacent oligonucleotide tiling array probes and 15,451 DMRs with a single oligo probe analysis. The MI vs. WO comparison identified 75 DMRs with the ⩾3 oligo probe and 17,411 DMRs with the single oligo probe analysis. There was negligible overlap between the DMRs identified in AP vs. WO and MI vs. WO comparisons. In both comparisons DMRs were primarily associated with CpG deserts which are regions of low CpG density (1-2CpG/100bp). Although the alligator genome is not fully annotated, gene associations were identified and correlated to major gene class functional categories and pathways of endocrine relevance. Observations demonstrate that environmental quality may be associated with epigenetic programming and health status in the alligator. The epigenetic alterations may provide biomarkers to assess the environmental exposures and health impacts on these populations of alligators.


Biochemical characterization of a factor produced by trypomastigotes of Trypanosoma cruzi that accelerates the decay of complement C3 convertases.
Infective- and vertebrate-stage trypomastigotes of Trypanosoma cruzi resist serum killing by the alternative complement pathway, whereas noninfective vector-stage epimastigotes, from which trypomastigotes derive, are serum-sensitive. This form of developmental preadaption is commonly observed in protozoan parasites, but its mechanisms are poorly understood. We have demonstrated previously that trypomastigotes spontaneously shed molecules which interfere with formation and accelerate the intrinsic decay of complement C3 convertases, a finding which may explain the evasion of complement lysis by trypomastigotes. We now describe the partial purification and characterization of the T. cruzi C3 convertase inhibitor from the supernatant of culture metacyclic and tissue culture trypomastigotes. Decay-accelerating activity for both classical and alternative pathway C3 convertases copurifies on anion-exchange fast protein liquid chromatography and chromatofocusing with 35S-labeled molecules of 87-93 kDa, pI 5.6-5.8. The labeled components are destroyed by papain and retained on concanavalin A-Sepharose, procedures which remove functional decay-accelerating activity from the supernatant. The 87-93-kDa components are immunoprecipitated by sera from patients chronically infected with T. cruzi, but not by antisera to any known regulatory proteins of the human complement cascade. Lytic activity for tissue culture trypomastigotes in chagasic sera is associated with antibody reactivity against the 87-93-kDa 35S-labeled components and with inhibition of decay-accelerating activity. The T. cruzi factor is the first developmentally regulated microbial complement inhibitor to be biochemically characterized.


[Rapid method for crown removal].
A makeshift technique to loosen a crown fastened on its stump just before cementing is released as well as some possible causes for such a problem.


An experimental study on the impact of clinical interruptions on simulated trainee performances of central venous catheterization.
Interruptions are common in the healthcare setting. This experimental study compares the effects of interruptions on simulated performances of central venous catheterization during a highly versus minimally complex portion of the task. Twenty-six residents were assigned to interruptions during tasks that are (1) highly complex: establishing ultrasound-guided venous access (experimental group, n = 15) or (2) minimally complex: skin cleansing (control group, n = 11). Primary outcomes were (a) performance scores at three time points measured with a validated checklist, (b) time spent on the respective tasks, and (c) number of attempts to establish venous access. Repeated measure analyses of variances of performance scores over time indicated no main effect of time or group. The interaction between time and group was significant: F (2, 44) = 4.28, p = 0.02, and partial eta2 = 0.16, indicating a large effect size. The experimental group scores decreased steadily over time, while the control group scores increased with time. The experimental group required longer to access the vein (148 s; interquartile range (IQR) 60 to 361 vs. 44 s; IQR 27 to 133 s; p = 0.034). Median number of attempts to establish venous access was higher in the experimental group (2, IQR 1-7 vs. 1, IQR 1-2; p = 0.03). Interruptions during a highly complex task resulted in a consistent decrement in performance scores, longer time required to perform the task, and a higher number of venous access attempts than interruptions during a minimally complex tasks. We recommend avoiding interrupting trainees performing bedside procedures.


Spontaneous fracture and pulmonary embolization of a central venous catheter.
The use of peripherally inserted central catheter is occasionally complicated by fracture and embolization of the catheter fragment. Here we report a 28 year old male with acute myeloid leukemia, who had spontaneous fracture of the central venous catheter and subsequent migration of the catheter fragment through the heart and into the lower lobe of the right lung. The catheter fragment was retrieved by retrograde femoral vein catheterization.


Long-term efficacy and safety of internal neurolysis for trigeminal neuralgia without neurovascular compression.
OBJECT Trigeminal neuralgia (TN) occurs and recurs in the absence of neurovascular compression (NVC). While microvascular decompression (MVD) is the most effective treatment for TN, it is not possible when NVC is not present. Therefore, the authors sought to evaluate the safety, efficacy, and durability of internal neurolysis (IN), or "nerve combing," as a treatment for TN without NVC. METHODS This was a retrospective review of all cases of Type 1 TN involving all patients 18 years of age or older who underwent evaluation (and surgery when appropriate) at Oregon Health & Science University between July 2006 and February 2013. Chart reviews and telephone interviews were conducted to assess patient outcomes. Pain intensity was evaluated with the Barrow Neurological Institute (BNI) Pain Intensity scale, and the Brief Pain Inventory-Facial (BPI-Facial) was used to assess general and face-specific activity. Pain-free survival and durability of successful pain relief (BNI pain scores of 1 or 2) were statistically evaluated with Kaplan-Meier analysis. Prognostic factors were identified and analyzed using Cox proportional hazards regression. RESULTS A total of 177 patients with Type 1 TN were identified. A subgroup of 27 was found to have no NVC on high-resolution MRI/MR angiography or at surgery. These patients were significantly younger than patients with classic Type 1 TN. Long-term follow-up was available for 26 of 27 patients, and 23 responded to the telephone survey. The median follow-up duration was 43.4 months. Immediate postoperative results were comparable to MVD, with 85% of patients pain free and 96% of patients with successful pain relief. At 1 year and 5 years, the rate of pain-free survival was 58% and 47%, respectively. Successful pain relief at those intervals was maintained in 77% and 72% of patients. Almost all patients experienced some degree of numbness or hypesthesia (96%), but in patients with successful pain relief, this numbness did not significantly impact their quality of life. There was 1 patient with a CSF leak and 1 patient with anesthesia dolorosa. Previous treatment for TN was identified as a poor prognostic factor for successful outcome. CONCLUSIONS This is the first report of IN with meaningful outcomes data. This study demonstrated that IN is a safe, effective, and durable treatment for TN in the absence of NVC. Pain-free outcomes with IN appeared to be more durable than radiofrequency gangliolysis, and IN appears to be more effective than stereotactic radiosurgery, 2 alternatives to posterior fossa exploration in cases of TN without NVC. Given the younger age distribution of patients in this group, consideration should be given to performing IN as an initial treatment. Accrual of further outcomes data is warranted.


Regioselective photolabeling of glycoprotein A in membranes.
We have developed a chemical method for directly identifying the amino acid residues of the transmembrane domain of a protein that are located right in the center of the membrane. Glycophorin A (GPA), the major sialoglycoprotein of human erythrocytes, was the first membrane protein whose primary sequence was elucidated, but its three-dimensional structure is still not known. GPA has been reconstituted into liposomes formed from dimyristoylphosphatidylcholine, dimyristoylphosphatidylserine, cholesterol, and a bola-amphiphilic phospholipidic photoactivatable probe (radioactive probe 1) by a detergent-mediated method. Electron microscopy confirmed the formation of spherical vesicular structures, and sucrose-density gradients revealed that the proteoliposomes comprised only one membrane fraction. Proteinase-K digestion of GPA in the proteoliposomes suggested that the orientation of GPA in reconstituted proteoliposomes was virtually identical to that observed in natural erythrocyte membranes. After photo-irradiation of the reconstituted proteoliposomes and in situ tryptic digestion, the photolabeled amino acid residues were analyzed by Edman degradation and their radioactivity was measured. Val80 and Met81, which had been assumed to be located near the center of the transmembrane domain of GPA, were indeed highly selectively photolabeled by probe 1. The new method might be applied to analyze the three-dimensional arrangement of the transmembrane domain of protein complexes that are made up from several subunits.


Immunoreactivity of ATF-2 and Fra-2 in human dental follicle.
It is asserted that epithelial rests in dental follicle (DF) existing around the impacted teeth in adults are effective in cyst formation. In this study, it is intended for determining and comparing the immunoreactivity (IR) ratio of ATF-2 and Fra-2 proteins, the members of Activator Protein-1 (AP-1) family which regulates important cellular activities such as growth, proliferation and differentiation, in DF epithelial cells (EC) and connective tissue cells (CC). In this study, ATF-2 and Fra-2 immunoreactivity (ATF-2-IR and Fra-2-IR) in EC and CC in DF tissues obtained from 30 patients were analyzed by using immunohistochemical method. Ratios of ATF-2-IR positive cells were found 17.36+/-9.55% in EC, 27.27+/-14.86% in CC and ratios of Fra-2-IR positive cells were found 20.04+/-11.47% in EC, 16.71+/-9.05% in CC. In the statistically comparison performed; significant differences were found between EC and CC in terms of both ATF-2-IR (p<0.001) and Fra-2-IR (p<0.05). In EC, no significant difference was found between ATF-2-IR and Fra-2-IR (p>0.05), whereas significant difference was found between ATF-2-IR and Fra-2-IR in CC (p<0.001). According to these data, it can be suggested that Fra-2 protein may be more effective than ATF-2 protein in cyst formation originated from EC of DF. Besides, finding that ATF-2-IR and Fra-2-IR are different in CC although similar in EC shows that AP-1 members can be expressed at different ratios in same tissues.


Markets and the needy: organ sales or aid?
As organ shortages have become more accute, support for a market in organs has steadily increased. Whilst many have argued for such a market, it is Gerald Dworkin who most persuasively defends its ethics. As Dworkin points out, there are two possibilities here--a futures market and a current market. I follow Dworkin in focusing on a current market in the sale of organs from living donors, as this is generally considered to be the most difficult to justify. One of the most pressing concerns here is that such a market will exploit the poor. I outline this concern and scrutinize Dworkin's and others' rejection of it. Briefly, I argue that the arguments Dworkin employs for allowing the poor to sell their organs fail, and in fact better support an argument for increasing aid to the needy.


Ultrastructural study of the posterior cornea of the dogfish "Scyliorhinus canicula L".
The cornea of Elasmobranchs remains transparent and exhibits a remarkable resistance against swelling when deprived of its endothelium. Sutural fibers, which traverse the corneal stroma anteroposteriorly, may be responsible for this property. We studied the structure of the cornea of Scyliorhinus canicula L., a galeiform Elasmobranch, with special emphasis on the presence of a corneal endothelium and on its appearance during development. Observations were made with the aid of several microscopic techniques: light and specular microscopy, transmission and scanning electron microscopy. We found that the posterior corneal surface was always covered by a fibrillar material. A structural counterpart of endothelial-like cells on the posterior cornea or in the anterior chamber was never observed in adult fishes and in embryos of different stages. In contrast, in Torpedo ocellata, a torpediniform Elasmobranch, endothelial cells were seen. The significance of these findings is discussed in context with the possibility of technical artefacts and compared with other studies.


A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior.
Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (1H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: 1H-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups. Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.