Influence of the typology and timing of childhood trauma in psychoticism.

PURPOSE: Child maltreatment (CM) is associated with psychosis; however little is known about the frequency, type, and timing of abuse in the personality pathology domain of psychoticism (PSY) in the DSM-5. The purpose of this study was to analyze childhood trauma typology and frequency according to gender and to identify sensitive periods of susceptibility to CM in women with high PSY. METHODS: The Maltreatment and Abuse Chronology Exposure (MACE) scale was used to evaluate the frequency, severity and timing of each type of maltreatment. The full sample consisted of 83 participants with different psychiatric diagnoses. Psychoticism was assessed with the DSM-5 Personality Inventory (PID-5). To identify the differences in CM exposure between the PSY+ (high psychoticism) and PSY- (low psychoticism) groups, the Mann-Whitney U test, the chi square test and random forest (RF) test were used. RESULTS: Comparing PSY + and PSY-, revealed gender differences in the impact of abuse, with highly frequent and severe types of abuse, in women. In women, PSY + and PSY-, were differentiated especially in non-verbal emotional abuse, peer physical bullying and parental verbal abuse. Several periods with a major peak at age seven followed by peaks at age 17 and 12 years old were identified. CONCLUSION: Increased exposure to CM occurs in women with PSY+. A sensitivity to CM exposure during early childhood and late adolescence could be a risk factor for psychoticism in women.

Number of repetitions for evaluating technological traits in cotton genotypes.

With the changes in spinning technology, technological cotton traits, such as fiber length, fiber uniformity, fiber strength, fineness, fiber maturity, percentage of fibers, and short fiber index, are of great importance for selecting cotton genotypes. However, for accurate discrimination of genotypes, it is important that these traits are evaluated with the best possible accuracy. The aim of this study was to determine the number of measurements (repetitions) needed to accurately assess technological traits of cotton genotypes. Seven experiments were conducted in four Brazilian States (Ceará, Rio Grande do Norte, Goiás, and Mato Grosso do Sul). We used nine brown and two white colored fiber lines in a randomized block design with four replications. After verifying the assumptions of residual normality and homogeneity of variances, analysis of variance was performed to estimate the repeatability coefficient and calculating the number of repetitions. Trials with four replications were found to be sufficient to identify superior cotton genotypes for all measured traits except short fiber index with a selective accuracy >90% and at least 81% accuracy in predicting their actual value. These results allow more accurate and reliable results in future researches with evaluating technological traits in cotton genotypes.

Mixed inheritance in the genetic control of ramulosis (Colletotrichum gossypii var. cephalosporioides) resistance in cotton.

Ramulosis is one of the most aggressive diseases in cotton, and understanding the genetic control of its resistance is imperative for selecting superior cotton genotypes in breeding programs. This study analyzed the inheritance pattern of this resistance using chi-square goodness-of-fit tests to determine the phenotypic proportions of the F2 generation, and a mixed inheritance approach to jointly model major gene and polygenes effects. F1, F2, Rc1, and Rc2 generations were obtained by crossing resistant (BRS Facual, CNPA 2984, or CNPA 2043) and susceptible (Delta Opal, CNPA 999, or CNPA 2161) genotypes, and were assessed under field conditions with artificial inoculation of the pathogen (Colletotrichum gossypii var. cephalosporioides). Genetic control of the trait varied among the crossings. For Delta Opal x BRS Facual and CNPA 2161 x BRS Facual, phenotypic segregations in the F2 generation did not differ from the expected proportions for the hypothesis of duplicate genes (15:1). For Delta Opal x CNPA 2043, the segregation did not differ from the expected proportions for dominant recessive epistasis (13:3). The hypothesis of genetic control by one major gene was supported only for the Delta Opal x CNPA 2043 crossing. Three other crossings showed evidence of polygenes in the inheritance of the trait. In conclusion, major genes and polygenes are likely involved in the genetic control of ramulosis resistance in cotton.

First Experimental Characterization of Microwave Emission from Cosmic Ray Air Showers.

We report the first direct measurement of the overall characteristics of microwave radio emission from extensive air showers. Using a trigger provided by the KASCADE-Grande air shower array, the signals of the microwave antennas of the Cosmic-Ray Observation via Microwave Emission experiment have been read out and searched for signatures of radio emission by high-energy air showers in the GHz frequency range. Microwave signals have been detected for more than 30 showers with energies above 3×10^{16} eV. The observations presented in this Letter are consistent with a mainly forward-directed and polarized emission process in the GHz frequency range. The measurements show that microwave radiation offers a new means of studying air showers at E≥10^{17} eV.

Kneelike structure in the spectrum of the heavy component of cosmic rays observed with KASCADE-Grande.

We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain.

BACKGROUND: Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic standard of amitriptyline hydrochloride. OBJECTIVE: To determine the efficacy of gabapentin compared with amitriptyline in treating diabetic peripheral neuropathy pain. DESIGN: Prospective, randomized, double-blind, double-dummy, crossover study. SETTING: Veterans Affairs San Diego Healthcare System, Ambulatory Care Clinic. PATIENTS: Twenty-eight veterans were referred by their primary care providers. Two patients withdrew before randomization because of no neuropathic pain after washout; a third withdrew for unexpected surgery that required analgesics. Three patients withdrew because of adverse effects and 1 for protocol violation. INTERVENTIONS: Patients with stable glycemic control and neuropathic pain randomized to 6 weeks of therapy with gabapentin, 900 to 1800 mg/d, or amitriptyline hydrochloride, 25 to 75 mg/d, with a 1-week washout before crossover. MAIN OUTCOME MEASURES: Pain relief measured by pain scale with verbal descriptors and global pain score assessment at treatment end. RESULTS: Participants and investigators were blinded throughout. Mean dosages were of gabapentin, 1565 mg/d, and of amitriptyline hydrochloride, 59 mg/d. Sixty-five percent of patients reached maximum dose with gabapentin and 54% with amitriptyline. Mean score diary analysis showed pain relief with gabapentin and amitriptyline was not significantly different (P = .26). Global data were obtained from 21 of 25 enrolled patients who completed the study. Moderate or greater pain relief was experienced in 11 (52%) of 21 patients with gabapentin and 14 (67%) of 21 patients with amitriptyline. There were no significant period or carry-over effects (P = .35). CONCLUSIONS: Although both drugs provide pain relief, mean pain score and global pain score data indicate no significant difference between gabapentin and amitriptyline. Gabapentin may be an alternative for treating diabetic peripheral neuropathy pain, yet does not appear to offer considerable advantage over amitriptyline and is more expensive. Larger trials are necessary to define gabapentin's place in treating diabetic peripheral neuropathy pain.

Effects of an anabolic steroid on reproduction in female rats.

Mature female rats given food and water ad libitum and maintained under a lighting schedule of 12h light/12h dark were treated with boldenone undecylenate. Neither dosage nor duration of treatment had a significant effect on weight gain when compared to controls. All treated females were characterized by the absence of cyclic ovarian activity that continued for several weeks following termination of treatment. Long term reproductive performance was altered by a significant reduction in both conception rate and neonatal survival. Behavioral patterns were modified for several months following steroid withdrawal.

Steroid and gonadotropin levels in women during the peri-menopausal years.

We obtained blood samples from 88 women 45-58 yr old who were having cyclic menses every 1-2 mth (37 women, 133 samples) or were amenorrheic for greater than 3 mth (51 women, 310 samples). Samples were obtained at intervals of 3-4 mth and analyzed for estrogens, androgens and gonadotropins using radioimmunoassay techniques. There was a gradual decline in the concentrations of estrone (E1), estradiol (E2), estrone sulfate (E1SO4) and progesterone (P) as the time from the last menses increased. A relatively stable concentration was reached in 12 mth for E1, E2, and E1SO4 and in 2 mth for P. The concentrations of testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate remained relatively constant as the time from the last menses increased. There was no apparent difference in the mean values of any of these hormones for any time interval from the last menses. The concentrations of both luteinizing hormone (LH) and follicle stimulating (FSH) were noted to increase initially but they appeared to become stable after 12 mth for FSH and after only 6 mth for LH. Using only the measurements made on the initial blood samples obtained in all patients, we found significant correlations between FSH concentrations and the concentrations of E1, E2 and E1SO4 for women who were less than 3 mth from a menses as well as those whose last menses had occurred 3 or more mth previously. The correlations were generally not significant for LH in either groups of women.(ABSTRACT TRUNCATED AT 250 WORDS)

Human growth hormone: a new substance of abuse among adolescents?

It has been estimated that as many as 250,000 adolescents are using anabolic steroids (AS). Recently, anecdotal reports suggest that athletes may also be using human growth hormone (HGH). The purpose of the present study was to determine the following: 1) if adolescents in two suburban midwestern high schools (83% white, 14% Asian, and 3% black) were using HGH; 2) knowledge of its effects; 3) reasons for use; and 4) concurrent AS use. After we obtained informed written consent, 224 male and 208 female 10th-grade students were surveyed using a 15-item questionnaire. Of male students surveyed, 5% (n = 11) reported past or present use of HGH, and one female student reported use. Our data suggest that among male adolescents surveyed, a majority had heard of this substance, and 31% of males reported knowing someone who was using HGH. Chi-square analysis found a significant association between AS and HGH use where seven AS users reported past or present use of HGH. Most HGH users were unaware of its side effects and reported first use between 14 and 15 years of age. No differences in sports activity, ethnicity, or age were found between users and nonusers of HGH.

Retrospective cohort study evaluating exenatide twice daily and long-acting insulin analogs in a Veterans Health Administration population with type 2 diabetes.

AIM: This was a retrospective cohort study that evaluated the differences in glycated haemoglobin (HbA1c) and body mass index (BMI) in veterans with type 2 diabetes mellitus (T2DM), prescribed exenatide twice daily (BID) versus long-acting insulin analog (LAIA) two years after initiation in the United States (US) veteran population. MATERIALS AND METHODS: Patients were included if they were ≥ 18 years old with T2DM, and initiated exenatide BID or LAIA at the Veterans Health Administration between January 1, 2006 and December 31, 2010. Multivariate models were used to evaluate the changes in HbA1c and BMI between groups, controlling for potential confounders. Logistic regression was used to evaluate the odds of achieving ≥ 0.5% HbA1c reduction based on baseline HbA1c stratifications: low,<7%; moderate, 7% to<9%; and high,≥ 9%. RESULTS: A total of 446 exenatide BID and 51,531 LAIA patients met inclusion/exclusion criteria. On average, exenatide BID patients were significantly older (64 versus 60 years) with a higher BMI (37.8 versus 32.9 kg/m(2)). Baseline HbA1c was 8.2% and 8.8% for exenatide BID and LAIA patients, respectively (P<0.001); otherwise, patients were similar for all other characteristics. Exenatide BID treatment was significantly associated with a 0.32% (95%CI: 0.18-0.47%) greater reduction in HbA1c at two years compared with LAIA. Similar findings were observed for BMI reduction (0.68 kg/m(2); 95%CI: 0.42-0.95 kg/m(2)). Exenatide BID patients with moderate baseline HbA1c had significantly higher odds of achieving ≥ 0.5% HbA1c reduction compared with LAIA patients (OR=1.5; 95%CI: 1.2-2.0). CONCLUSIONS: Veterans treated with exenatide BID had significantly greater reduction in HbA1c and BMI compared with patients treated with LAIA patients two years after initiation.

Pharmacokinetics of ibafloxacin in healthy cats.

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.

Suppression of murine cytomegalovirus (MCMV) replication with a DNA vaccine encoding MCMV M84 (a homolog of human cytomegalovirus pp65).

The cytotoxic T-lymphocyte (CTL) response against the murine cytomegalovirus (MCMV) immediate-early gene 1 (IE1) 89-kDa phosphoprotein pp89 plays a major role in protecting BALB/c mice against the lethal effects of the viral infection. CTL populations specific to MCMV early-phase and structural antigens are also generated during infection, but the identities of these antigens and their relative contributions to overall immunity against MCMV are not known. We previously demonstrated that DNA vaccination with a pp89-expressing plasmid effectively generated a CTL response and conferred protection against infection (J. C. Gonzalez Armas, C. S. Morello, L. D. Cranmer, and D. H. Spector, J. Virol. 70:7921-7928, 1996). In this report, we have sought (i) to identify other viral antigens that contribute to immunity against MCMV and (ii) to determine whether the protective response is haplotype specific. DNA immunization was used to test the protective efficacies of plasmids encoding MCMV homologs of human cytomegalovirus (HCMV) tegument (M32, M48, M56, M82, M83, M69, and M99), capsid (M85 and M86), and nonstructural antigens (IE1-pp89 and M84). BALB/c (H-2(d)) and C3H/HeN (H-2(k)) mice were immunized by intradermal injection of either single plasmids or cocktails of up to four expression plasmids and then challenged with sublethal doses of virulent MCMV administered intraperitoneally. In this way, we identified a new viral gene product, M84, that conferred protection against viral replication in the spleens of BALB/c mice. M84 is expressed early in the infection and encodes a nonstructural protein that shares significant amino acid homology with the HCMV UL83-pp65 tegument protein, a major target of protective CTLs in humans. Specificity of the immune response to the M84 protein was confirmed by showing that immunization with pp89 DNA, but not M84 DNA, protected mice against subsequent infection with an MCMV deletion mutant lacking the M84 gene. The other MCMV genes tested did not generate a protective response even when mice were immunized with vaccinia viruses expressing the viral proteins. However, the M84 plasmid was protective when injected in combination with nonprotective plasmids, and coimmunization of BALB/c mice with pp89 and M84 provided a synergistic level of protection in the spleen. Viral titers in the salivary glands were also reduced, but not to the same extent as observed in the spleen, and the decrease was seen only when the BALB/c mice were immunized with pp89 plus M84 or with pp89 alone. The experiments with the C3H/HeN mice showed that the immunity conferred by DNA vaccination was haplotype dependent. In this strain of mice, only pp89 elicited a protective response as measured by a reduction in spleen titer. These results suggest that DNA immunization with the appropriate combination of CMV genes may provide a strategy for improving vaccine efficacy.

In vivo replication, latency, and immunogenicity of murine cytomegalovirus mutants with deletions in the M83 and M84 genes, the putative homologs of human cytomegalovirus pp65 (UL83).

We previously identified two open reading frames (ORFs) of murine cytomegalovirus (MCMV), M83 and M84, which are putative homologs of the human cytomegalovirus (HCMV) UL83 tegument phosphoprotein pp65 (L. D. Cranmer, C. L. Clark, C. S. Morello, H. E. Farrell, W. D. Rawlinson, and D. H. Spector, J. Virol. 70:7929-7939, 1996). In this report, we show that unlike the M83 gene product, the M84 protein is expressed at early times in the infection and cannot be detected in the virion. To elucidate the functional differences between the two pp65 homologs in acute and latent MCMV infections, we constructed two MCMV K181 mutants in which either the M83 or M84 ORF was deleted. The resultant viruses, designated DeltaM83 and DeltaM84, respectively, were found to replicate in NIH 3T3 cells with kinetics identical to those of the parent strain. Western blot analysis demonstrated that except for the absence of M83 or M84 protein expression in the respective mutants, no global perturbations of protein expression were detected. When DeltaM83 and DeltaM84 were inoculated intraperitoneally (i.p.) into BALB/c mice, both viruses showed similar attenuated growth in the spleen, liver, and kidney. However, only DeltaM83 was severely growth restricted in the salivary glands, a phenotype that was abolished upon restoration of the M83 ORF. DeltaM83's growth was similarly restricted in the salivary glands of the resistant C3H/HeN or highly sensitive 129/J strain, as well as in the lungs of all three strains following intranasal inoculation. Using a nested-PCR assay, we found that both DeltaM83 and DeltaM84 established latency in BALB/c mice, with slightly decreased levels of DeltaM83 and DeltaM84 genomic DNAs, relative to K181, observed in the salivary glands and lungs. Immunization of BALB/c mice with 10(5) PFU of K181, DeltaM83, or DeltaM84 i.p. provided similar levels of protection against lethal challenge. Although immunization with 200 PFU of DeltaM83 also provided complete protection, this dose allowed both the immunizing and challenge viruses to establish latency in the spleen. Our results show that the two MCMV pp65 homologs differ in their expression kinetics, virion association, and influence on viral tropism and/or dissemination.

DNA immunization confers protection against murine cytomegalovirus infection.

The murine cytomegalovirus (MCMV) immediate-early gene 1 (IE1) encodes an 89-kDa phosphoprotein (pp89) which plays a key role in protecting BALB/c mice against the lethal effects of the MCMV infection. In this report, we have addressed the question of whether "naked DNA" vaccination with a eukaryotic expression vector (pcDNA-89) that contains the MCMV IE1 gene driven by a strong enhancer/promoter can confer protection. BALB/c mice were immunized intradermally with pcDNA-89 or with the plasmid backbone pcDNAI/Amp (pcDNA) and then challenged 2 weeks later with either a lethal or a sublethal intraperitoneal dose of the K181 strain of MCMV. Variable results were obtained for the individual experiments in which mice received a lethal challenge. In four separate trials, an average of 63% of the mice immunized with pcDNA-89 survived, compared with 18% of the mice immunized with pcDNA. However, in two other trials there was no specific protection. The results of experiments in which mice were injected with a sublethal dose of MCMV were more consistent, and significant decreases in viral titer in the spleen and salivary glands of pcDNA-89-immunized mice were observed, relative to controls. At the time of peak viral replication, titers in the spleens of immunized mice were reduced 18- to >63-fold, while those in the salivary gland were reduced approximately 24- to 48-fold. Although DNA immunization elicited only a low level of seroconversion in these mice, by 7 weeks postimmunization the mice had generated a cytotoxic T-lymphocyte response against pp89. These results suggest that DNA vaccination with selected CMV genes may provide a safe and efficient means of immunizing against CMV disease.

Identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus UL82 (pp71) and UL83 (pp65) matrix phosphoproteins.

We have identified three open reading frames (ORFs) in murine cytomegalovirus (MCMV), designated M82, M83, and M84, which likely encode homologs of the human cytomegalovirus (HCMV) UL82 and UL83 matrix phosphoproteins. These ORFs, in the HindIII C fragment of MCMV, are colinear with the UL82, UL83, and UL84 ORFs of HCMV. M82 encodes a 598-amino-acid (aa) protein with homology to UL82, M83 encodes an 809-aa protein with homology to UL82 and UL83, and M84 encodes a 587-aa protein with homology to UL83 and UL84. Analysis of transcription by Northern (RNA) blotting indicated that the M82 and M83 ORFs are transcribed as 2.2- and 5-kb mRNAs, respectively, at 24 to 48 h postinfection (p.i.), while M84 is transcribed as a 6.9-kb mRNA only at 8 h p.i. All transcripts appear to terminate at the same position 3' of the M82 ORF. Of the products of the three ORFs, only M83 is strongly recognized by hyperimmune mouse serum. The M83 protein is a virion-associated phosphoprotein with an apparent molecular mass of 125 kDa. In MCMV-infected cells, it is detectable by Western blotting (immunoblotting) only at 48 h p.i. in the absence of phosphonoacetic acid, consistent with late gene expression. The M83 ORF is also expressed at high levels in cells infected by a recombinant vaccinia virus and yields a protein which is serologically cross-reactive and comigrates with the authentic MCMV protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Delta infection and liver disease in hemophilic carriers of hepatitis B surface antigen.

The prevalence of infection with hepatitis B virus (HBV)-associated delta (delta) agent was assessed in 277 treated hemophiliacs (primarily adolescents and adults) and 24 treated hemophilic children. Hemophiliacs who carry hepatitis B surface antigen (HBsAg) are at high risk of delta infection. Antibody to delta (anti-delta) was found in 14 (49%) of 29 HBsAg-positive adult or adolescent hemophiliacs and four (25%) of 16 HBsAg-positive hemophilic children; it was identified in none of the patients without serologic evidence of exposure to HBV and only occasionally and in low titers in hemophiliacs convalescent from HBV infection. Either histologic or biochemical evidence of chronic hepatitis was found in 10 (56%) of 18 HBsAg-positive hemophiliacs with anti-delta. In two patients with anti-delta a potentially pathogenic role for delta was suggested by the intrahepatic expression of delta antigen, detected by immunofluorescence. It appears that delta infection is a major cause of chronic liver disease in hemophiliacs.