Dietzia cinnamea: An increasingly recognized human pathogen.

The authors present the case of a bloodstream infection and sepsis due to Dietzia cinnamea in a severely malnourished patient with small bowel obstruction and pelvic abscess. The organism was identified with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The authors discuss the characteristics, diagnosis, treatment, and emerging scope of clinical infection caused by Dietzia species.

Multifocal multilobar focal cortical dysplasia type IIa in Febrile Infection Related Epilepsy Syndrome (FIRES).

A seven-year-old girl with history of type I diabetes and no history of seizures presented for altered mental status with convulsions nearly one week after a febrile illness. Serum and laboratory studies were normal with EEG showing biparietal fast activity and seizures originating from right occipital lobe consistent with FIRES. A collaborative decision was ultimately made to withdraw care. Post-mortem whole brain histopathological examination revealed diffuse abnormalities in multiple areas including both parietal lobes and the right parieto-occipital junction consistent with focal cortical dysplasia type IIa. We believe this to be the first report that describes focal cortical dysplasia type IIa co-localizing with epileptogenic areas on EEG in a case of FIRES, and recommend that focal cortical dysplasia be considered as an etiology early in the course of FIRES.

Brain abscess with pyogenic ventriculitis.

The authors present the case of a 57-year-old male with a large polymicrobial brain abscess complicated by eruption into the intraventricular space. He was treated with parenteral ampicillin, cefepime, and metronidazole and adjuvant intraventricular vancomycin/gentamicin as well as surgical debridement. The authors discuss the diagnosis, treatment, and prognosis of brain abscesses, with a focus on prior cases with pyogenic ventriculitis and those treated with intraventricular antimicrobials.

A Battery of Easily Accessible, Simple Tools for the Assessment of Concussion in Children.

OBJECTIVE: To determine whether a non-proprietary, novel testing battery can identify recently concussed children within 8 weeks of injury. STUDY DESIGN: In total, 568 clinic outpatients aged 10-18 years were sorted into 3 groups: 316 had never been concussed, 162 had ever been concussed before 8 weeks earlier, and 90 had been recently concussed within 8 weeks. At initial and any subsequent visits, a neurologic examination and 4 procedures were performed: Stick Drop, Wall Ball, Sharpened Modified Romberg (SMR), and Animal Naming. Analysis included inter-group and intra-person performance differences using a series of t tests on the Stick Drop, Wall Ball, SMR, and Animal Naming. RESULTS: The recently concussed group performed worse (P < .01 for all) on Stick Drop, total Wall Ball bounces and drops, and SMR compared with never-concussed and ever-concussed groups. This effect for Stick Drop, SMR, and Wall Ball but not Animal Naming persisted beyond the 4 weeks commonly stated to define recovery. Of 59 recently concussed subjects who returned for ≥1 visit, there were improvements in Stick Drop average (P = .004) and maxima (P = .02) as well as SMR (P = .01) but not Animal Naming between initial and subsequent visits. CONCLUSIONS: This novel, rapid testing battery distinguished groups of children ages 10-18 years who had and had not experienced a recent concussion. A view that physical concussion symptoms resolve within a month of injury may be incomplete. Deployment of this readily available, inexpensive and non-proprietary battery should be compared with other tools and studied further in serial assessments.

Population Structure, Movement Patterns, and Frequency of Multiple Matings in Tenodera sinensis (Mantodea: Mantidae).

Models of the evolution of sexual cannibalism show that the frequency of male mating opportunities has significant impact on male choice and male risk aversion. In this study, we examined ecological components that should affect opportunities for multiple mating in wild populations of the Chinese mantid (Tenodera sinensis Saussure). While conducting mark-recapture studies of two field populations over the course of two seasons, along with Global Positioning System data on locations of individuals, we collected data on population densities, movement patterns, and individual ranges to estimate the overlap of adult males and female mantids. Our results show that local populations of mantids range from 89 to 161 individuals and occur at densities ranging from 10 to 39 mantids per 1,000 m2. Males move greater distances daily compared with females, giving males larger home range sizes. The ranges of male mantids overlapped with multiple females, thus offering the potential for multiple mating by males. We directly observed 11 encounters between male and female T. sinensis, including one multiple mating by an individual male. The overall mate encounter rate for males was 12.5%. We also provide additional observations of interspecific sexual attraction between T. sinensis and Mantis religiosa Linne (Mantodea: Mantidae). Mantids were most commonly found within the top 20% of two flowering plants, goldenrod (Solidago Linnaeus spp. (Asterales: Asteraceae)) and mugwort (Artemisia vulgaris Linnaeus (Asterales: Asteraceae)), which should place them in prime locations for capturing flying pollinators.

Sexual cannibalism increases male material investment in offspring: quantifying terminal reproductive effort in a praying mantis.

Models of the evolution of sexual cannibalism argue that males may offset the cost of cannibalism if components of the male body are directly allocated to the eggs that they fertilize. We tested this idea in the praying mantid Tenodera sinensis Males and females were fed differently radiolabelled crickets and allowed to mate. Half of the pairs progressed to sexual cannibalism and we prevented cannibalism in the other half. We assess the relative allocation of both male-derived somatic materials and ejaculate materials into the eggs and soma of the female. Our results show that male somatic investment contributes to production of offspring. The eggs and reproductive tissues of cannibalistic females contained significantly more male-derived amino acids than those of non-cannibalistic females, and there was an increase in the number of eggs produced subsequent to sexual cannibalism. Sexual cannibalism thus increases male material investment in offspring. We also show that males provide substantial investment via the ejaculate, with males passing about 25% of their radiolabelled amino acids to females via the ejaculate even in the absence of cannibalism.

Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.

BACKGROUND: The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents. METHODS: Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D. RESULTS: All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP. CONCLUSIONS: We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases.

NS19504: a novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasic contractions.

Large-conductance Ca(2+)-activated K(+) channels (BK, KCa1.1, MaxiK) are important regulators of urinary bladder function and may be an attractive therapeutic target in bladder disorders. In this study, we established a high-throughput fluorometric imaging plate reader-based screening assay for BK channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.0 ± 1.4 µM. Hit validation was performed using high-throughput electrophysiology (QPatch), and further characterization was achieved in manual whole-cell and inside-out patch-clamp studies in human embryonic kidney 293 cells expressing hBK channels: NS19504 caused distinct activation from a concentration of 0.3 and 10 µM NS19504 left-shifted the voltage activation curve by 60 mV. Furthermore, whole-cell recording showed that NS19504 activated BK channels in native smooth muscle cells from guinea pig urinary bladder. In guinea pig urinary bladder strips, NS19504 (1 µM) reduced spontaneous phasic contractions, an effect that was significantly inhibited by the specific BK channel blocker iberiotoxin. In contrast, NS19504 (1 µM) only modestly inhibited nerve-evoked contractions and had no effect on contractions induced by a high K(+) concentration consistent with a K(+) channel-mediated action. Collectively, these results show that NS19504 is a positive modulator of BK channels and provide support for the role of BK channels in urinary bladder function. The pharmacologic profile of NS19504 indicates that this compound may have the potential to reduce nonvoiding contractions associated with spontaneous bladder overactivity while having a minimal effect on normal voiding.

Genotyping of Brucella species using clade specific SNPs.

BACKGROUND: Brucellosis is a worldwide disease of mammals caused by Alphaproteobacteria in the genus Brucella. The genus is genetically monomorphic, requiring extensive genotyping to differentiate isolates. We utilized two different genotyping strategies to characterize isolates. First, we developed a microarray-based assay based on 1000 single nucleotide polymorphisms (SNPs) that were identified from whole genome comparisons of two B. abortus isolates , one B. melitensis, and one B. suis. We then genotyped a diverse collection of 85 Brucella strains at these SNP loci and generated a phylogenetic tree of relationships. Second, we developed a selective primer-extension assay system using capillary electrophoresis that targeted 17 high value SNPs across 8 major branches of the phylogeny and determined their genotypes in a large collection ( n = 340) of diverse isolates. RESULTS: Our 1000 SNP microarray readily distinguished B. abortus, B. melitensis, and B. suis, differentiating B. melitensis and B. suis into two clades each. Brucella abortus was divided into four major clades. Our capillary-based SNP genotyping confirmed all major branches from the microarray assay and assigned all samples to defined lineages. Isolates from these lineages and closely related isolates, among the most commonly encountered lineages worldwide, can now be quickly and easily identified and genetically characterized. CONCLUSIONS: We have identified clade-specific SNPs in Brucella that can be used for rapid assignment into major groups below the species level in the three main Brucella species. Our assays represent SNP genotyping approaches that can reliably determine the evolutionary relationships of bacterial isolates without the need for whole genome sequencing of all isolates.

Low mate encounter rate increases male risk taking in a sexually cannibalistic praying mantis.

Male praying mantises are forced into the ultimate trade-off of mating versus complete loss of future reproduction if they fall prey to a female. The balance of this trade-off will depend both on (1) the level of predatory risk imposed by females and (2) the frequency of mating opportunities for males. We report the results of a set of experiments that examine the effects of these two variables on male risk-taking behavior and the frequency of sexual cannibalism in the praying mantis Tenodera sinensis. We experimentally altered the rate at which males encountered females and measured male approach and courtship behavior under conditions of high and low risk of being attacked by females. We show that male risk taking depends on prior access to females. Males with restricted access to females showed greater risk-taking behavior. When males were given daily female encounters, they responded to greater female-imposed risk by slowing their rate of approach and remained a greater distance from a potential mate. In contrast, males without recent access to mates were greater risk-takers; they approached females more rapidly and to closer proximity, regardless of risk. In a second experiment, we altered male encounter rate with females and measured rates of sexual cannibalism when paired with hungry or well-fed females. Greater risk-taking behavior by males with low mate encounter rates resulted in high rates of sexual cannibalism when these males were paired with hungry females.

Catalytic role of the conformational change in succinyl-CoA:3-oxoacid CoA transferase on binding CoA.

Catalysis by succinyl-CoA:3-oxoacid CoA transferase proceeds through a thioester intermediate in which CoA is covalently linked to the enzyme. To determine the conformation of the thioester intermediate, crystals of the pig enzyme were grown in the presence of the substrate acetoacetyl-CoA. X-ray diffraction data show the enzyme in both the free form and covalently bound to CoA via Glu305. In the complex, the protein adopts a conformation in which residues 267-275, 280-287, 357-373, and 398-477 have shifted toward Glu305, closing the enzyme around the thioester. Enzymes provide catalysis by stabilizing the transition state relative to complexes with substrates or products. In this case, the conformational change allows the enzyme to interact with parts of CoA distant from the reactive thiol while the thiol is covalently linked to the enzyme. The enzyme forms stabilizing interactions with both the nucleotide and pantoic acid portions of CoA, while the interactions with the amide groups of the pantetheine portion are poor. The results shed light on how the enzyme uses the binding energy for groups remote from the active center of CoA to destabilize atoms closer to the active center, leading to acceleration of the reaction by the enzyme.

Chronic active herpes simplex type 2 encephalitis in an asymptomatic immunocompetent child.

A unique form of chronic, active, granulomatous herpes simplex type 2 encephalitis is described in an asymptomatic, immunocompetent 8-year-old girl who acquired the virus as a neonate. The extensive, bilateral cerebral parenchymal involvement was discovered incidentally. Diagnosis was confirmed by a combination of serial neuroimaging, brain biopsy, and quantitative polymerase chain reaction targeted to DNA sequences in the glycoprotein G gene, allowing differentiation between herpes simplex virus types 1 and 2. The clinical course over a 5-year period, treatment with intermittent intravenous steroids, and daily valacyclovir, diagnostic imaging, and laboratory studies are reviewed in detail. This form of herpes simplex virus type 2 encephalitis hasn't been described previously and is significant because of its prolonged indolent course, absence of neurological findings or suggestive history, and benign behavior in this child, who is now 14 years old. The authors believe this entity can be unsuspected and underdiagnosed in the general pediatric population, especially in those with a prior maternal history of herpes simplex virus type 2 infection.

Real-time PCR assays of single-nucleotide polymorphisms defining the major Brucella clades.

Members of the genus Brucella are known worldwide as pathogens of wildlife and livestock and are the most common organisms of zoonotic infection in humans. In general, brucellae exhibit a range of host specificity in animals that has led to the identification of at least seven Brucella species. The genomes of the various Brucella species are highly conserved, which makes the differentiation of species highly challenging. However, we found single-nucleotide polymorphisms (SNPs) in housekeeping and other genes that differentiated the seven main Brucella species or clades and thus enabled us to develop real-time PCR assays based around these SNPs. Screening of a diverse panel of 338 diverse isolates with these assays correctly identified each isolate with its previously determined Brucella clade. Six of the seven clade-specific assays detected DNA concentrations of less than 10 fg, indicating a high level of sensitivity. This SNP-based approach places samples into a phylogenetic framework, allowing reliable comparisons to be made among the lineages of clonal bacteria and providing a solid basis for genotyping. These PCR assays provide a rapid and highly sensitive method of differentiating the major Brucella groups that will be valuable for clinical and forensic applications.

Comparison of accidental and nonaccidental traumatic head injury in children on noncontrast computed tomography.

OBJECTIVE: Mixed-density convexity subdural hematoma and interhemispheric subdural hematoma suggest nonaccidental head injury. The purpose of this retrospective observational study is to investigate subdural hematoma on noncontrast computed tomography in infants with nonaccidental head injury and to compare these findings in infants with accidental head trauma for whom the date of injury was known. PATIENTS AND METHODS: Two blinded, independent observers retrospectively reviewed computed tomography scans with subdural hematoma performed on the day of presentation on 9 infant victims of nonaccidental head injury (mean age: 6.8 months; range: 1-25 months) and on 38 infants (mean age: 4.8 months; range: newborn to 34 months) with accidental head trauma (birth-related: 19; short fall: 17; motor vehicle accident: 2). RESULTS: Homogeneous hyperdense subdural hematoma was significantly more common in children with accidental head trauma (28 of 38 [74%]; nonaccidental head trauma: 3 of 9 [33%]), whereas mixed-density subdural hematoma was significantly more common in cases of nonaccidental head injury (6 of 9 [67%]; accidental head trauma: 7 of 38 [18%]). Twenty-two (79%) subdural hematomas were homogeneously hyperdense on noncontrast computed tomography performed within two days of accidental head trauma, one (4%) was homogeneous and isodense compared to brain tissue, one (4%) was homogeneous and hypodense, and four (14%) were mixed-density. There was no statistically significant difference in the proportion of interhemispheric subdural hematoma, epidural hematoma, calvarial fracture, brain contusion, or subarachnoid hemorrhage. CONCLUSIONS: Homogeneous hyperdense subdural hematoma is more frequent in cases of accidental head trauma; mixed-density subdural hematoma is more frequent in cases of nonaccidental head injury but may be observed within 48 hours of accidental head trauma. Interhemispheric subdural hematoma is not specific for inflicted head injury.

Complicity or conflict over sexual cannibalism? Male risk taking in the praying mantis Tenodera aridifolia sinensis.

Male complicity versus conflict over sexual cannibalism in mantids remains extremely controversial, yet few studies have attempted to establish a causal relationship between risk of cannibalism and male reproductive behavior. We studied male risk-taking behavior in the praying mantid Tenodera aridifolia sinensis by altering the risk imposed by females and measuring changes in male behavior. We show that males were less likely to approach hungrier, more rapacious females, and when they did approach, they moved more slowly, courted with greater intensity, and mounted from a greater distance. Similarly, when forced to approach females head-on, within better view and better reach of females, males also approached more slowly and courted with greater intensity. Thus, males behaved in a manner clearly indicative of risk avoidance, and we support the hypothesis of sexual conflict over sexual cannibalism.

No evidence that polyandry benefits females in Drosophila melanogaster.

Understanding the evolution of polyandry (mating with multiple males) is a major issue in the study of animal breeding systems. We examined the adaptive significance of polyandry in Drosophila melanogaster, a species with well-documented costs of mating in which males generally cannot force copulations. We found no direct fitness advantages of polyandry. Females that mated with multiple males had no greater mean fitness and no different variance in fitness than females that mated repeatedly with the same male. Subcomponents of reproductive success, including fecundity, egg hatch rate, larval viability, and larval development time, also did not differ between polyandrous and monogamous females. Polyandry had no affect on progeny sex ratios, suggesting that polyandry does not function against costly sex-ratio distorters. We also found no evidence that polyandry functions to favor the paternity of males successful in precopulatory sexual selection. Experimentally controlled opportunities for precopulatory sexual selection had no effect on postcopulatory sperm precedence. Although these results were generally negative, they are supported with substantial statistical power and they help narrow the list of evolutionary explanations for polyandry in an important model species.

Attention deficit hyperactivity disorder in elementary school children in Rhode Island: associated psychosocial factors and medications used.

This study was undertaken to explore psychosocial factors associated with referral for attention deficit hyperactivity disorder (ADHD) evaluation or ADHD diagnosis among elementary school children in Rhode Island, as well as to examine the extent of drug therapy among this population. A survey was distributed to parents/guardians of 2,800 3rd- to 5th-grade public school students in 4 Rhode Island school districts. The average age of the children was 9.0 +/- 1.0 years with 52% girls. Approximately 12% of the students had been referred for ADHD evaluation (RFE). Of these, 52% (6% of all children in the survey) were receiving psychoactive prescription medications daily. While the male:female ratio in the non-RFE group was almost 1:1, there were more boys than girls in the RFE group (male/female ratio of 3:1, p < 0.0001) and in the medicated group (male/female ratio 4:1, p < 0.0001). RFE children and medicated children were older than classroom peers (p < 0.0001), and had a greater degree of school misconduct (p < 0.0001). RFE children and medicated children were significantly less likely to have parents who completed college (p < 0.05), were significantly more likely to have stepparents (p < 0.05), and to be only children (p < 0.05) when compared with their peers. Amphetamine was the most commonly prescribed drug (used by 54% of the medicated children) followed by methylphenidate (43%). Nearly 18% of the medicated children were receiving 1 to 3 additional psychoactive prescription medications on a daily basis. In conclusion, RFE children and children medicated for ADHD were more likely to have a stepparent, have no siblings, and have parents that had not completed college. Amphetamine rather than methylphenidate accounted for the majority of medications used in this study, and simultaneous use of multiple psychoactive medications was reported in 18% of the medicated children.

Temporal and spatial variations of gyne production in the ant Formica exsecta.

Social insects have become a general model for tests of sex allocation theory. However, despite tremendous interest in the topic, we still know remarkably little about the factors that cause dramatic differences in sex allocation among local populations. A number of studies have suggested that environmental factors may influence sex allocation in ant populations. In polygynous (multiple queens per nest) populations of the ant Formica exsecta, sex allocation is extremely male biased at the population level, with only a small proportion of nests producing any gynes (female reproductive brood). We analysed the proportion of gyne-producing nests in 12 F. exsecta populations during three successive breeding seasons and found considerable temporal and spatial variability in the proportion of gyne-producing nests. The populations differed in a number of characteristics, including elevation, nest density, size of the nest mound, and number of nests per population. However, the proportion of gyne-producing nests was not associated with any of these geographic and demographic variables. Moreover, differences between populations in the production of gynes were not consistent between years. Thus, the proportion of gyne-producing nests appears to vary stochastically, perhaps because of stochastic variations in environmental factors. For example, year-to-year variations in the proportion of gyne-producing nests were associated with differences in spring weather conditions between years. The finding that gyne production varies greatly between years suggests that it may not always be adaptive at a local scale.

Sex-ratio dependent execution of queens in polygynous colonies of the ant Formica exsecta.

Formica exsecta has become an important model system for studying intraspecific variation in sex ratios. Patterns of sex allocation in polygynous (multiple queen per nest) populations of F. exsecta are generally consistent with the queen-replenishment hypothesis. This hypothesis states that colonies produce gynes (reproductive females) in order to increase queen number and enhance colony survival and/or productivity when the number of resident queens is low. However, the small proportion of colonies that raise gynes produce more than necessary for simple queen replenishment. It has been hypothesized that excess production of gynes may occur to reduce the frequency of accepting foreign unrelated gynes into the colony when workers cannot distinguish nestmate from non-nestmate queens. This explanation for excess gynes requires weak or no aggression between non-nestmates and is expected to lead to the selective execution of new queens by colonies that do not invest in the production of gynes. Experimental studies where gynes were introduced into natal and foreign colonies indeed suggested that polygynous populations of F. exsecta have a poor nestmate recognition system. Although gynes were significantly more likely to be accepted in their parental colony compared to another foreign female-producing colony, the difference was small. Moreover, encounters between workers from different colonies within the population showed very little aggression and were no more aggressive than encounters between nestmates, again suggesting a weak capacity for nestmate recognition. Our experiment also showed that colonies that produced only males executed most of the gynes that were experimentally introduced into the colony, whereas female-producing colonies accepted most gynes. This is consistent with ants using a simple rule of thumb to decrease parasitism by unrelated queens, whereby colonies selectively destroy gynes whenever gynes are not produced in the colonies.

FEMALE CHOICE FOR AN INDICATOR OF MALE SIZE IN THE SONG OF THE BLACK-HORNED TREE CRICKET, OECANTHUS NIGRICORNIS (ORTHOPTERA: GRYLLIDAE: OECANTHINAE).

The calling song of male crickets, including Oecanthus nigricornis (Walker), attracts females for mating and provides a model system of sexual communication. We give the first conclusive identification of a feature of cricket song that is both attractive to females and indicates a phenotypic feature (body size) that determines male mating success and female reproductive benefits. We do this by first testing for correlations between song characteristics and aspects of male phenotype that are hypothesized to indicate male quality. We show that song is a reliable indicator of male size and male age, and that large male size is associated with increased female fecundity. We then use playbacks of synthetic songs that mimic natural variation in song parameters to study song preferences and we compare preferences under different presentation regimes to determine whether choices are based on relative song quality or some fixed criterion. Females show a preference for the lower frequency songs produced by large males, but only during simultaneous playbacks. Thus female choice is based on the relative quality of calls that can be sampled simultaneously. These results provide strong support for the hypothesis that females use variation in calling song to assess male mate quality.