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Dryness is one of the main environmental challenges to microbial survival. Understanding the threshold of microbial tolerance to extreme dryness is relevant to better constrain the environmental limits of life on Earth and critically evaluate long-term habitability models of Mars. Biomolecular proxies for microbial adaptation and growth were measured in Mars-like hyperarid surface soils in the Atacama Desert that experience only a few millimeters of precipitation per decade, and in biologically active soils a few hundred kilometers away that experience two- to fivefold more precipitation. Diversity and abundance of lipids and other biomolecules decreased with increasing dryness. Cyclopropane fatty acids (CFAs), which are indicative of adaptive response to environmental stress and growth in bacteria, were only detected in the wetter surface soils. The ratio of trans to cis isomers of an unsaturated fatty acid, another bacterial stress indicator, decreased with increasingly dry conditions. Aspartic acid racemization ratios increased from 0.01 in the wetter soils to 0.1 in the driest soils, which is indicative of racemization rates comparable to de novo biosynthesis over long timescales (∼10,000 years). The content and integrity of stress proteins profiled by immunoassays were additional indicators that biomass in the driest soils is not recycled at significant levels. Together, our results point to minimal or no in situ microbial growth in the driest surface soils of the Atacama, and any metabolic activity is likely to be basal for cellular repair and maintenance only. Our data add to a growing body of evidence that the driest Atacama surface soils represent a threshold for long-term habitability (i.e., growth and reproduction). These results place constraints on the potential for extant life on the surface of Mars, which is 100-1000 times drier than the driest regions in the Atacama. Key Words: Atacama Desert-Dryness-Growth-Habitability-Biomarker-Mars. Astrobiology 18, 955-966.

Geothermal springs support microbial communities at elevated temperatures in an ecosystem with high preservation potential that makes them interesting analogs for early evolution of the biogeosphere. The El Tatio geysers field in the Atacama Desert has astrobiological relevance due to the unique occurrence of geothermal features with steep hydrothermal gradients in an otherwise high altitude, hyper-arid environment. We present here results of our multidisciplinary field and molecular study of biogeochemical evidence for habitability and preservation in silica sinter at El Tatio. We sampled three morphologically similar geyser mounds characterized by differences in water activity (i.e., episodic liquid water, steam, and inactive geyser lacking hydrothermal activity). Multiple approaches were employed to determine (past and present) biological signatures and dominant metabolism. Lipid biomarkers indicated relative abundance of thermophiles (dicarboxylic acids) and sulfate reducing bacteria (branched carboxylic acids) in the sinter collected from the liquid water mound; photosynthetic microorganisms such as cyanobacteria (alkanes and isoprenoids) in the steam sinter mound; and archaea (squalane and crocetane) as well as purple sulfur bacteria (cyclopropyl acids) in the dry sinter from the inactive geyser. The three sinter structures preserved biosignatures representative of primary (thermophilic) and secondary (including endoliths and environmental contaminants) microbial communities. Sequencing of environmental 16S rRNA genes and immuno-assays generally corroborated the lipid-based microbial identification. The multiplex immunoassays and the compound-specific isotopic analysis of carboxylic acids, alkanols, and alkanes indicated that the principal microbial pathway for carbon fixation in the three sinter mounds was through the Calvin cycle, with a relative larger contribution of the reductive acetyl-CoA pathway in the dry system. Other inferred metabolic traits varied from the liquid mound (iron and sulfur chemistry), to the steam mound (nitrogen cycle), to the dry mound (perchlorate reduction). The combined results revealed different stages of colonization that reflect differences in the lifetime of the mounds, where primary communities dominated the biosignatures preserved in sinters from the still active geysers (liquid and steam mounds), in contrast to the surviving metabolisms and microbial communities at the end of lifetime of the inactive geothermal mound.

Intracranial pressure (ICP) measurement is an established monitoring modality in the ICU and can aid prognostication after acute brain injury. ICP monitoring is recommended in all patients with severe traumatic brain injury (TBI), and an abnormal cranial computed tomographic (CT) scan and the ability to control ICP is associated with improved outcome after TBI. The lessons from TBI studies can also be applied to other acute pathologies of the central nervous system where ICP can be increased. ICP measurement can warn of impending disaster and allow intervention. Furthermore, measurement of ICP allows the calculation of cerebral perfusion pressure (CPP) and maintenance of CPP may help to ensure adequate cerebral oxygen delivery. Various systems exist to monitor ICP. A recent trial in two South American countries suggested that ICP-guided management and management guided by clinical examination and repeated imaging produced equivalent outcomes. Although this trial currently provides the best evidence regarding the impact of monitoring ICP on outcome following TBI, but because of the inadequate power and questionable external validity, the generalizability of the results remain to be confirmed.

Experiments were conducted during November 2003 in the dry core of the Atacama Desert, Yungay, Chile to test the hypothesis that UV radiation, in environments where liquid water is not available, and thus enzymatic repair of UV-induced damage is inhibited, can prevent epilithic colonization. Novel dosimeters made from the cryptoendolithic, desiccation and radiation-resistant cyanobacterium Chroococcidiopsis sp. isolated from the dry Negev desert, Israel, showed that monolayers of this organism were killed within one day. The diurnal profile of microbial loss of viability was investigated with dosimeters of Bacillus subtilis, which similarly showed cell death within one day. Soil grains obtained from south of Yungay where liquid water is more abundant and transported to the hyperarid core showed killing of indigenous vegetative organisms within one day. Gypsum and mineral grain coverings of 1 mm were sufficient to prevent measurable UV-induced damage of Chroococcidiopsis and B. subtilis after 8 d exposure. These results show that under extreme desiccation and an ambient UV flux the surface of rocks can potentially be rendered sterile, but that millimetre thick mineral coverings can protect organisms from UV-induced killing, consistent with the observed patterns of lithophytic colonization in the Atacama Desert. These data further show that UV radiation can be an important limiting factor in surface biological rock weathering in arid regions.

Highfin grouper Epinephelus maculatus sampled in Chuuk, Micronesia, exhibited a moderate growth rate and a relatively short life span compared to other epinephelids of a similar size. Combined gonad and otolith analysis provide preliminary evidence that the species conforms to a protogynous sexual pattern. Mean total length at maturity for females was 308 mm with first age at maturity 2·8 years for females and 4 years for males, which differs from other regional studies. Based on the gonado-somatic index and microscopic analysis of gonads, E. maculatus in Chuuk have a 4 month spawning season (January to April) that corresponds with seasonal lows in sea surface water temperature and overlaps with that of other aggregating epinephelids. The estimated von Bertalanffy growth factor (K) was 0·51 year(-1) , while total mortality was 0·34 year(-1) . Current management for E. maculatus in Chuuk includes a January to May catch, sale and export ban, which overlaps with its reproductive season. The effectiveness of these arrangements will require on-going monitoring to determine whether alternative management strategies are required to ensure population persistence.

The aim of this study is to establish the nature (urgent vs. non-urgent), demographics, presentation and management of Achenbach’s syndrome and to formulate an algorithmic approach for their diagnosis and management. A systematic review and met-aggregation of literature from 1944 to 2015 in English language in MedLine, Embase and Cochrane database were conducted. Achenbach’s syndrome is a female-dominant disease with median age of 49.5 years (range 22–76) (age ≤60, n = 11/12, 91 %). It presents with unilateral volar discoloration of a finger (100 %). It is associated with pain (n = 7/12, 58. %), edema (n = 7/12, 58 %), and paresthesia (n = 3/12, 25 %). The median time to resolution of symptoms without any intervention was 4 days (range 2–14). AS is self-limiting and a non-urgent surgical condition. It can be differentiated from other pathologies by clinical spectrum, patient demographics and in doubtful circumstances (acute limb ischemia) by Doppler sonography. An algorithmic approach can avoid hospital admissions, partially unnecessary investigation and assist in patient assurance.

The aim of this study is to establish the biomechanics, presentation and diagnosis of mesenteric avulsions following blunt abdominal trauma and reach a consensus on their overall management. A systematic review of literature in MedLine, Embase, Scopus and CINHAL in English language from 1951 to November 2014 was performed. A total of 20 reported cases were identified. Variables including patient’s demographics, signs and symptoms, mechanism of injury, investigative modality, management, length of stay, follow-up and outcomes were reviewed and analyzed. The median age of the cohort was 28.5 years (range 10–58 years), with a male-to-female ratio of 3:1. The commonest mechanism of injury was road traffic accident due to seat belt restraint (n = 12, 60 %). The commonest presentation was diffuse abdominal tenderness (n = 10, 45 %) followed by ecchymosis/bruising (n = 9, 40 %). Computed tomography (CT) remained the investigative modality of choice (n = 9, 45 %). All cases had an emergency exploratory laparotomy (n = 18, 90 %) within the initial 24 h and the median length of stay was 19 days (range 4–90 days). The overall mortality was 15 % (n = 3). Mesenteric avulsion is rare and has a complex and vague presentation. Due to its potential mortality and morbidity, emergency physicians should keep a high index of suspicion in individuals with blunt abdominal trauma from any mechanism of injury.

The objective of the present study was to in- vestigate the population genetic structure of the com- mercially important camouflage grouper, Epinephelus polyphekadion (Bleeker, 1849), in the western and central Pacific Ocean to improve existing management. Cam- ouflage grouper are widely distributed in the Indo-Pa- cific and form brief, seasonal, spawning aggregations that are often heavily fished. The present study exam- ined populations sampled in 1997-1998 at five sites in the western central Pacific spanning a geographic dis- tance of 5,000 km: New Caledonia, Great Barrier Reef, Palau, Marshall Islands, and Pohnpei (Microne- sia). Primer pairs were developed to examine genetic variation at three polymorphic microsatellite loci. Cluster analysis, using genetic distance, revealed three regional groupings: (1) Palau, (2) Pohnpei and the Marshall Islands, and (3) the Great Barrier Reef and New Caledonia. Highly significant allele frequency dif- ferences were observed among sites. At Pohnpei, sig- nificant allele frequency differences in successive years were also apparent, possibly related to genetic variation among cohorts or between local spawning groups. The inter-annual differences at Pohnpei suggest that there may be further genetic structuring over relatively modest distances, a finding relative to determining management units for this commercially valuable species and suggests that future studies need to incorporate possible small- scale temporal or spatial components into study design.

Temperature can have a profound effect on the phenotype of reptilian offspring, yet the bulk of current research considers the effects of constant incubation temperatures on offspring morphology, with few studies examining the natural thermal variance that occurs in the wild. Over two consecutive nesting seasons, we placed temperature data loggers in 57 naturally incubating clutches of loggerhead sea turtles Caretta caretta and found that greater diel thermal variance during incubation significantly reduced offspring mass, potentially reducing survival of hatchlings during their journey from the nest to offshore waters and beyond. With predicted scenarios of climate change, behavioral plasticity in nest site selection may be key for the survival of ectothermic species, particularly those with temperature-dependent sex determination.

Bluespine unicornfish Naso unicornis and orangespine unicornfish Naso lituratus were sampled in Pohnpei and Guam, Micronesia, over 13 months to identify reproductive and age-based demographic features necessary for informed management. Age and reproductive information were derived from analysis of sagittal otoliths and gonads. Both species had moderate life spans [maximum ages of 23 (N. unicornis) and 14 years (N. lituratus)] compared with published estimates of conspecifics from other locations (30 years) and of other Naso species. Length at maturation for N. unicornis was similar between Pohnpei and Guam while females consistently matured at a larger size [c. 30 cm fork length (LF )] than males (c. 27 cm LF ). This sex-specific pattern was reversed in N. lituratus for which estimates of maturation length (females: 15 cm LF ; males: 18 cm LF ) were only obtained from Guam. Developmental patterns in female gonads of both species suggested that initiation of maturation occurs very early. Growth patterns of N. lituratus displayed rapid asymptotic growth compared with N. unicornis and other congeners as well as slight sex-specific patterns of length-at-age. Results highlight the considerable spatial variation that may occur in the population biology of these species across various scales. Additionally, proper management remains complicated without improved knowledge of fishery trends and reproductive behaviour in unicornfishes, species that are prime fishery targets in Micronesia and elsewhere.

In this article, we discuss antimicrobial regimens for both outpatient and inpatient use in infants and children. A substantial number of pediatric patient visits annually result in the prescribing of antimicrobial drugs. The emergence of bacteria resistant to commonly used antimicrobial agents is a growing concern. Information on newer drugs such as meropenem, which is active against penicillin-resistant Streptococcus pneumoniae and gram-negative bacilli, and cefepime, which has activity against gram-negative bacilli including Pseudomonas aeruginosa and against gram-positive cocci is also presented. Management of patients with congenital or acquired immunodeficiencies continues to be challenging in regard to the use of antimicrobial drugs to treat various fungal and viral infections. New formulations of older drugs such as aerosolized tobramycin and amphotericin B lipid complex are available. New antiviral agents have been approved, most of which are antiretroviral agents. Childhood tuberculosis is an ongoing concern, and regimens to treat Mycobacterium tuberculosis in children are discussed.

The squaretail coralgrouper Plectropomus areolatus was identified as a fast-growing, early maturing and relatively short-lived aggregation-spawning epinephelid. Examinations of sectioned otoliths found females and males first maturing at 2 and 3 years, respectively, suggesting protogynous hermaphroditism; however, no transitionals were observed in samples. Age distribution for the two sexes was similar and both were represented in the oldest age class; however, significant sex-specific differences in size-at-age were identified. Both sexes fully recruit into the fishery at age 4 years and reach 90% of asymptotic length by age 3 years. Underwater visual assessments, combined with the gonado-somatic indices, revealed a 5 month reproductive season, with interannual variability observed in the month of highest density within the spawning aggregation. Catch restrictions on adults during spawning times and at reproductive sites, combined with gear-based management and enhanced enforcement, are recommended to maintain spawning stocks. Based on the available evidence, the sexual pattern for this species is unresolved.

We describe an emulsion-coated coverslip autoradiographic technique for large (50 x 50 mm) sections of monkey or human brain. The technique uses adhesive-backed, teflon-reinforced aluminum foil as a flexible hinge that allows the coverslip to swing away from the slide so that the emulsion and tissue can be processed independently. We also describe a plexiglas incubation chamber that allows two slides with coverslips folded away to be processed back-to-back in 5 ml of reagent solution. In general use, the chamber minimizes the volume of solution needed to cover large slide-mounted sections and is ideal for radioligand or immunohistochemical reactions that use expensive reagents. For autoradiography, the chamber greatly facilitates independent processing of the emulsion and tissue section. Together, the foil-hinge method and incubation chamber virtually eliminate the major technical pitfalls of previous emulsion-coated coverslip methods. Moreover, they facilitate combination of histochemical or immunocytochemical staining with autoradiographic localization of neurotransmitter receptors in the same tissue section. This is demonstrated by thioflavin S staining of neuritic plaques and tangles and autoradiographic localization of serotonin 1A receptors in sections of Alzheimer disease brain.

[1] We examined soil organic C (OC) turnover and transport across the rainfall transition from a biotic, arid site to a largely abiotic, hyperarid site. With this transition, OC concentrations decrease, and C cycling slows precipitously, both in surface horizons and below ground. The concentration and isotopic character of soil OC across this transition reflect decreasing rates of inputs, decomposition, and downward transport. OC concentrations in the arid soil increase slightly with depth in the upper meter, but are generally low and variable (∼0.05%; total inventory of 1.82 kg m−2); OC-Δ14C values decrease from modern (+7‰) to very 14C-depleted (−966‰) with depth; and OC-δ13C values are variable (−23.7‰ to –14.1‰). Using a transport model, we show that these trends reflect relatively rapid cycling in the upper few centimeters, and spatially variable preservation of belowground OC from root inputs, possibly during a previous, wetter climate supporting higher soil OC concentrations. In the driest soil, the OC inventory is the lowest among the sites (0.19 kg m−2), and radiocarbon values are 14C-depleted (−365‰ to –696‰) but show no trend with depth, indicating belowground OC inputs and long OC residence times throughout the upper meter (104 y). A distinct depth trend in δ13C values and OC/ON values within the upper 40 cm at the driest site may reflect photochemical alteration of organic matter at the soil surface, combined with limited subsurface decomposition and downward transport. We argue that while root inputs are preserved at the wetter sites, C cycling in the most hyperarid soil occurs through infrequent, rapid dissolved transport of highly photodegraded organic matter during rare rain events, each followed by a pulse of decomposition and subsequent prolonged drought. These belowground inputs are likely a primary control on the character, activity, and depth distribution of small microbial populations. While the lack of water is the dominant control on C cycling, very low C/N ratios of organic matter suggest that when rainfall occurs, hyperarid soils are effectively C limited. The preservation of fossil root fragments in the sediment beneath the driest soil indicates that wetter climate conditions preceded formation of this soil, and that vadose zone microbial activity has been extremely limited for the past 2 My.

A daylight fluorescence imager was deployed on an autonomous rover, Zoe, to detect life on the surface and shallow subsurface in regions of the Atacama Desert in Chile during field tests between 2003 and 2005. In situ fluorescent measurements were acquired from naturally fluorescing biomolecules such as chlorophyll and from specific fluorescent probes sprayed on the samples, targeting each of the four biological macromolecule classes: DNA, protein, lipid, and carbohydrate. RGB context images were also acquired. Preparatory reagents were applied to enhance the dye probe penetration and fluorescence intensity of chlorophyll. Fluorescence imager data sets from 257 samples were returned to the Life in the Atacama science team. A variety of visible life forms, such as lichens, were detected, and several of the dye probes produced signals from nonphotosynthetic microorganisms.

One hundred four normal subjects ranging in age from 17 to 77 years and in height from 115 to 203 cm underwent nerve conduction studies of sural, peroneal, tibial, and median nerves. Foot temperature was measured in each patient. A strong inverse correlation was found between height and sural (r = -0.7104), peroneal (r = -0.6842), and tibial (r = -0.5044) conduction velocities. These correlations were significant at the P less than 0.001 level. Median conduction velocity was not correlated with height. Height was correlated with the distal latencies of all nerves studied (sural r = 0.6518, peroneal r = 0.4583, tibial r = 0.7217, median r = 0.5440). These correlations were significant at the P less than 0.001 level. Age was inversely correlated with both tibial (r = -0.4071) and median (r = -0.3464) nerve conduction velocities but not with sural and peroneal conductions. There were no correlations between distal latencies and age. If the variation in conduction velocity accounted for by the linear relationship with height was removed, then age would be inversely correlated to all conduction velocity measurements with the exception of the sural. Temperature is inversely correlated with the sural (r = -0.2233), peroneal (r = -0.2102), and tibial (r = -0.2710) distal latencies. In all instances, the effects of age and temperature were minor determinants when compared with the effects of height. Diagnostic conclusions made from nerve conduction data without correcting for height may be invalid in patients taller and shorter than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

[1] The science goals of the Life in the Atacama (LITA) robotic field experiment are to understand habitat and seek out life in the Atacama Desert, Chile, as an analog to future missions to Mars. To those ends, we present a new data analysis tool, the LITA Data Scoring System (DSS), which (1) integrates rover and orbital data relevant to environmental habitability and life detection, and (2) provides a standard metric, or “score” to evaluate (a) the potential habitability, and (b) the strength of evidence for life at all locales along the rover's traverse. Designed and tested during the 2005 field campaign, first results from the DSS indicate that the three selected sites in the Atacama Desert are generally inhospitable. The strength of evidence for life is positively correlated with potential habitability at two of the three sites. Using factor analysis, we find three factors explain 79.9% of the variance in biological observations and five factors explain 96.2% of the variance in potential habitability across all sites. These factors are used to focus a discussion of scoring variable definitions for future robotic missions in the Atacama and of instrument selection and strategy development for future robotic missions on Earth and Mars.

[1] The Life in the Atacama project examined six different sites in the Atacama Desert (Chile) over 3 years in an attempt to remotely detect the presence of life with a rover. The remote science team, using only orbital and rover data sets, identified areas with a high potential for life as targets for further inspection by the rover. Orbital data in the visible/near infrared (VNIR) and in the thermal infrared (TIR) were used to examine the mineralogy, geomorphology, and chlorophyll potential of the field sites. Field instruments included two spectrometers (VNIR reflectance and TIR emission) and a neutron detector: this project represents the first time a neutron detector has been used as part of a “science-blind” rover field test. Rover-based spectroscopy was used to identify the composition of small scale features not visible in the orbital images and to improve interpretations of those data sets. The orbital and ground-based data sets produced consistent results, suggesting that much of the field sites consist of altered volcanic terrains with later deposits of sulfates, quartz, and iron oxides. At one location (Site A), the ground-based spectral data revealed considerably greater compositional diversity than was seen from the orbital view. One neutron detector transect provided insight into subsurface hydrogen concentrations, which correlated with life and surface features. The results presented here have implications for targeting strategies, especially for future Mars rover missions looking for potential habitats/paleohabitats.

[1] As part of the three-year ‘Life in the Atacama’ (LITA) project, plant and microbial abundance were mapped within three sites in the Atacama Desert, Chile, using an automated robotic rover. On-board fluorescence imaging of six biological signatures (e.g., chlorophyll, DNA, proteins) was used to assess abundance, based on a percent positive sample rating system and standardized robotic ecological transects. The percent positive rating system scored each sample based on the measured signal strength (0 for no signal to 2 for strong signal) for each biological signature relative to the total rating possible. The 2005 field experiment results show that percent positive ratings varied significantly across Site D (coastal site with fog), with patchy zones of high abundance correlated with orbital and microscale habitat types (heaved surface crust and gravel bars); alluvial fan habitats generally had lower abundance. Non-random multi-scale biological patchiness also characterized interior desert Sites E and F, with relatively high abundance associated with (paleo)aqueous habitats such as playas. Localized variables, including topography, played an important, albeit complex, role in microbial spatial distribution. Site D biosignature trends correlated with culturable soil bacteria, with MPN ranging from 10-1000 CFU/g-soil, and chlorophyll ratings accurately mapped lichen/moss abundance (Site D) and higher plant (Site F) distributions. Climate also affected biological patchiness, with significant correlation shown between abundance and (rover) air relative humidity, while lichen patterns were linked to the presence of fog. Rover biological mapping results across sites parallel longitudinal W-E wet/dry/wet Atacama climate trends. Overall, the study highlights the success of targeting of aqueousassociated habitats identifiable from orbital geology and mineralogy. The LITA experience also suggests the terrestrial study of life and its distribution, particularly the fields of landscape ecology and ecohydrology, hold critical lessons for the search for life on other planets. Their applications to robotic sampling strategies on Mars should be further exploited.

[1] The scientific success of a remote exploration rover mission depends on the right combination of technology, teamwork and scientific insight. In order to quantitatively evaluate the success of a rover field trial, it is necessary to assess the accuracy of scientific interpretations made during the field test. This work compares three structured approaches to assessing the ground truth of scientific findings from a science team conducting a remote investigation of a locale using an autonomous rover. For the first approach, independent assessment, the daily science summaries were analyzed and reduced to a series of 1082 factual statements, which were treated as hypotheses. An independent scientist traveled to the field area to assess these hypotheses. For the second approach, guided self-study, the mission scientists themselves traveled to the field area and evaluated their own scientific interpretations. The third approach, discrepancy investigation, searched for the root causes of differences between the scientific interpretations made in the control room and those made in the field. The independent investigation provided sensitive, quantitative data, but suffered from the lack of context and continuity developed in the mission control room. The guided evaluation benefited from the context of the mission, but lacked clarity and consistency. The discrepancy investigation provided insight into the root causes behind the discrepancies, but was expensive and time consuming. The independent investigation method yielded particularly compelling results, but each method offers advantages and a comprehensive rover field trial assessment should include a combination of all three.

[1] The Life in the Atacama project investigated the regional distribution of life and habitats in the Atacama Desert of Chile. We sought to create biogeologic maps through survey traverses across the desert using a rover carrying biologic and geologic instruments. Elements of our science approach were to: Perform ecological transects from the relatively wet coastal range to the arid core of the desert; use converging evidence from science instruments to reach conclusions about microbial abundance; and develop and test exploration strategies adapted to the search of scattered surface and shallow subsurface microbial oases. Understanding the ability of science teams to detect and characterize microbial life signatures remotely using a rover became central to the project. Traverses were accomplished using an autonomous rover in a method that is technologically relevant to Mars exploration. We present an overview of the results of the 2003, 2004, and 2005 field investigations. They include: The confirmed identification of microbial habitats in daylight by detecting fluorescence signals from chlorophyll and dye probes; the characterization of geology by imaging and spectral measurement; the mapping of life along transects; the characterization of environmental conditions; the development of mapping techniques including homogeneous biological scoring and predictive models of habitat location; the development of exploration strategies adapted to the search for life with an autonomous rover capable of up to 10 km of daily traverse; and the autonomous detection of life by the rover as it interprets observations on-the-fly and decides which targets to pursue with further analysis.

Cutaneous tuberculosis remains a rare entity in the United States. We describe a case of cutaneous tuberculosis in a child. (J Am Acad Dermatol 1999;41:860-2.)

Here we investigate differences in the temporal and spatial patterning, and subunit interactions of two of the major Na(+) channel alpha-subunit isoforms in mammalian brain, the type I and type II Na(+) channels. By using subtype-specific antibodies, we find that both isoforms are abundant in adult rat brain, where both interact with the covalently bound beta2 auxiliary subunit. Immunoblot analysis reveals complementary levels of type I and type II in different brain regions, with the highest levels of type I in brainstem, cortex, substantia nigra, and caudate, where it is found predominantly on the soma of neurons, and the highest levels of type II in globus pallidus, hippocampus and thalamus, where it is preferentially localized to axons. Developmentally, type I Na(+) channel polypeptide expression in brain increases dramatically during the third postnatal week, peaks at the end of the first postnatal month, and then decreases such that adult levels are approximately 50% of those at peak. Type II Na(+) channel polypeptide expression in brain also undergoes large increases in the third postnatal week, but levels continue to increase such that peak expression levels are maintained in adult animals. Type I Na(+) channels are found associated with the auxiliary beta2 subunit at all ages, whereas free type II Na(+) channels exist during the first two postnatal weeks. Thus, although expression of these two Na(+) channel alpha subunits in heterologous systems yields currents with very similar electrophysiological and pharmacological properties, their distinct spatial and temporal patterning, and association with auxiliary subunits in brain, suggest that they perform distinct, nonoverlapping functions in situ.

Recent studies suggest that metabotropic glutamate receptors (mGluRs) may play a significant role in regulating basal ganglia functions. In this study, we investigated the localization of mGluR4a protein in the mouse and rat basal ganglia. Polyclonal antibodies that specifically react with the metabotropic glutamate receptor subtype mGluR4a were produced and characterized by Western blot analysis. These antibodies recognized a native protein in wild-type mouse brain with a molecular weight similar to the molecular weight of the band from a mGluR4a-transfected cell line. The immunoreactivity was absent in brains of knockout mice deficient in mGluR4. mGluR4a immunoreactivity was most intense in the molecular layer of the cerebellum. We also found a striking mGluR4a immunoreactivity in globus pallidus, and moderate staining in substantia nigra pars reticulata and entopeduncular nucleus. Moderate to low mGluR4a immunoreactivity was present in striatum and other brain regions, including hippocampus, neocortex, and thalamus. Double labeling with mGluR4a antibodies and antibodies to either a dendritic marker or a marker of presynaptic terminals suggest a localization of mGluR4a on presynaptic terminals. Immunocytochemistry at electron microscopy level confirmed these results, revealing that in the globus pallidus, mGluR4a is mainly localized in presynaptic sites in axonal elements. Finally, quinolinic acid lesion of striatal projection neurons decreased mGluR4a immunoreactivity in globus pallidus, suggesting a localization of mGluR4a on striatopallidal terminals. These data support the hypothesis that mGluR4a serves as a presynaptic heteroreceptor in the globus pallidus, where it may play an important role in regulating g-amino-n-butyric acid (GABA) release from striatopallidal terminals.

1. The purpose of this study was to investigate the mechanism of nicotine-evoked relaxation of the guinea-pig isolated basilar artery and to study the effects of drugs associated with the aetiology or treatment of migraine on the nicotine response. 2. The guinea-pig isolated basilar artery, pre-contracted with prostaglandin F2alpha (PGF2alpha), in the presence of atropine (3 microM) and guanethidine (3 microM), relaxed on addition of nicotine (0.1 mM) in approximately 50% of preparations. The responses to nicotine were of short duration and blocked in preparations pre-treated for 10 min with capsaicin (1 microM) and are therefore probably a consequence of the stimulation of trigeminal C fibre terminals. 3. Responses to nicotine were reduced in the presence of 5-carboxamidotryptamine, 5-hydroxytryptamine and sumatriptan in that order of potency. This is consistent with a 5-HT1 receptor mechanism. These agonists evoked small additional contractions in vessels pre-contracted with PGF2alpha. 4. Indomethacin (0.3-10 microM), aspirin (10-30 microM), and nitro-L-arginine methyl ester (L-NAME, 0.1 mM) reduced nicotine-evoked relaxation of the basilar artery, suggesting the involvement of both nitric oxide and cyclo-oxygenase products in this response. 5. Progesterone (1 microM) markedly reduced the response to nicotine, a possible reflection of the ion channel blocking activity of high concentrations of this compound. 6. The guinea-pig basilar artery is a preparation in which the effects of drugs on responses to stimulation of trigeminal nerve terminals can be studied in vitro and may thus be of interest in assessing the actions of drugs used in treatment of headache.

Background The ability to discriminate cuteness may aid caregivers in prioritising care to the neediest child. This biologically important ability has been indirectly linked to higher levels of female reproductive hormones via studies of hormonal contraception and menopausal status. Pregnancy provides an opportunity to further investigate the role of reproductive hormones in cuteness discrimination since it is a time of substantial natural hormonal fluctuation. Methods Pregnant (n=23) and matched non-pregnant women (n=11) were assessed four times over 8 months (at 20 weeks of gestation, 32 weeks of gestation, 2 weeks postpartum, 12 weeks postpartum). At each visit, cuteness sensitivity, cuteness intensity ratings, and basic visuospatial perception were assessed. Cuteness sensitivity was assessed by presenting two versions of the same face side by side, with one subtly altered by graphics software to be more or less cute than the other; women were asked to select the cuter face. Cuteness intensity was rated on a seven-point Likert scale. Results were analysed with repeated measures ANOVA. Findings There was no difference between pregnant/postpartum mothers and control women in cuteness sensitivity, cuteness intensity ratings, or basic visuospatial perception. There was no change in these abilities across time. Interpretation This result is not what we hypothesised. It seems that the link between female reproductive hormones and cuteness sensitivity is more indirect and complex than initially thought. Possibly female reproductive hormones other than those elevated in pregnancy are important in determining cuteness sensitivity. Funding Wellcome Trust.

Recent cloning of K+ channel beta subunits revealed that these cytoplasmic polypeptides can dramatically alter the kinetics of current inactivation and promote efficient glycosylation and surface expression of the channel-forming alpha subunits. Here, we examined the expression, distribution, and association of two of these beta subunits, Kv beta 1 and Kv beta 2, in adult rat brain. In situ hybridization using cRNA probes revealed that these beta-subunit genes are heterogeneously expressed, with high densities of Kv beta 1 mRNA in the striatum, CA1 subfield of the hippocampus, and cerebellar Purkinje cells, and high densities of Kv beta 2 mRNA in the cerebral cortex, cerebellum, and brainstem. Immunohistochemical staining using subunit-specific monoclonal and affinity-purified polyclonal antibodies revealed that the Kv beta 1 and Kv beta 2 polypeptides frequently co-localize and are concentrated in neuronal perikarya, dendrites, and terminal fields, and in the juxtaparanodal region of myelinated axons. Immunoblot and reciprocal co-immunoprecipitation analyses indicated that Kv beta 2 is the major beta subunit present in rat brain membranes, and that most K+ channel complexes containing Kv beta 1 also contain Kv beta 2. Taken together, these data suggest that Kv beta 2 is a component of almost all K+ channel complexes containing Kv 1 alpha subunits, and that individual channels may contain two or more biochemically and functionally distinct beta-subunit polypeptides.

A putative 5-HT4 receptor-mediated depolarization of the rat isolated vagus nerve has been studied using a grease-gap extracellular recording technique. Ondansetron (1 microM) was used to block the predominant 5-HT3 receptor mediated depolarization in this preparation and the effects of the 5-HT4 receptor antagonists DAU 6285 (endo-8-methyl-8-azabicyclo [3.2.1] oct-3-yl-2,3-dihydro-6-methoxy-2-oxo-1H-benzimidazole-1- carboxylate HCl); 0.3, 1.0 or 3.0 microM and SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)-ethyl ester HCl); 0.1, 0.3 or 1.0 microM were studied on the residual, ondansetron-resistant, component of the response. The effects of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) and of forskolin on the ondansetron-resistant response were also studied. Both DAU 6285 and SDZ 205-557 acted as competitive antagonists of the ondansetron-resistant response to 5-HT with pA2 values of 6.8 (6.7-7.1, n = 12) and 7.1 (6.9-7.5, n = 12) respectively. The vagus nerve was depolarized by IBMX (100 microM) or forskolin (10 microM), the effects being similar to the maximum response to 5-HT. In the presence of IBMX (100 microM) or forskolin (10 microM) the ondansetron-resistant component of the response to 5-HT was enhanced and the 5-HT3 receptor-mediated component reduced. These results with DAU 6285 and SDZ 205-557 are consistent with a 5-HT4 receptor-mediated mechanism of the ondansetron-resistant depolarizing response to 5-HT.

Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival.We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data.Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services.The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables.

During a 4-year period from November 1985 to November 1989, Aeromonas was isolated from wounds and soft tissues with clinical evidence of infection in 28 patients at our institution. Of the 28 patients, 23 (82%) had sustained an acute open or penetrating injury, more than half of which (13 of the 23) were water-related trauma. One patient had Aeromonas osteomyelitis. Five patients had no history of trauma, and three of these five had an underlying chronic disease. Treatment included débridement and antimicrobial agents. Susceptibility testing on 25 isolates from 23 patients showed uniform resistance to ampicillin and considerable resistance to cefazolin sodium (68%), but all isolates were sensitive to gentamicin sulfate, cefuroxime sodium, and the third-generation cephalosporins.

A cross-sectional survey of the prescription and monitoring of diuretic drugs for long-term use was performed in a Nottinghamshire training practice, which has 7619 patients. It was found that 330 patients were long-term users of diuretic drugs, with 79% of these patients aged 60 years or over. Twenty three different diuretic drugs were prescribed with a total cost of 13,643 pounds per year. A few drugs accounted for a disproportionate amount of the total cost, with combination diuretic drugs being particularly expensive. The most common indications for the prescription of diuretic drugs were hypertension and congestive cardiac failure. General practitioners initiated the prescribing of diuretic drugs in 87% of cases, with only a small proportion being prescribed by hospital doctors. One third of the patients had no record of urea and electrolyte levels in their notes after commencing treatment with a diuretic drug. On the basis of these findings recommendations are made for the initiation and monitoring of the long-term use of diuretic drugs.

In infants and children, the absorption, distribution, metabolism, and excretion of drugs may differ considerably in comparison with these factors in adults; consequently, differences exist in therapeutic efficacy and toxicity of various antibiotic agents. Because of known toxicity, certain drugs--such as chloramphenicol in high doses, the sulfonamides, and tetracycline--should not be used in neonates. Antibiotic therapy should be modified in neonates because of biologic immaturity of organs important for the termination of drug action. Because of poor conjugation, inactivation, or excretion, the serum concentrations of many antibiotics may be higher and more prolonged in neonates than in older infants; thus, lower doses and longer intervals between administration may be necessary. In this article, we suggest dosages of antimicrobial agents for severe infections in children, older infants, and neonates. Included in the discussion are the cephalosporins, especially the third-generation cephalosporins that have assumed an important role in empiric treatment of bacterial meningitis in pediatric patients because of their ability to penetrate the central nervous system and their effectiveness against beta-lactamase-positive and negative strains of Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis, and many gram-negative bacteria in the Enterobacteriaceae group. In patients with congenital or acquired immunodeficiencies, antifungal, antiviral, or anti-Pneumocystis agents are often added to the antimicrobial regimen for severe infections. We review the agents available for such treatment in children, the drugs used for childhood tuberculosis, and certain new antibiotics (aztreonam, ticarcillin-clavulanate, ciprofloxacin, and imipenem-cilastatin) that have proved useful in select cases but whose precise role in pediatric practice will necessitate additional clinical experience.

Endocrinopathies in domestic animals exhibit a variety of metabolic abnormalities. Cutaneous manifestations of these disorders are more limited and are primarily characterized as a bilaterally symmetric nonpruritic alopecia. Subtle changes in skin texture, thickness, fragility, etc. may, in some cases, aid in establishing a diagnostic plan.

Agriculture is the only industry in the nation in which children are allowed to work and play around dangerous machinery. In most nonagricultural industrial situations, great advances have been made in eliminating or decreasing occupational hazards largely through agencies, employees, or unions. Such regulatory mechanisms are not in operation for the farmer, however, and farms with fewer than 11 nonfamily employees are still not within the jurisdiction of the Occupational Safety and Health Administration. 1 Furthermore, the prohibition of activities around farm machinery declared hazardous by the Secretary of Labor for minors younger than 16 years does not apply to youths on farms operated "by their parents or by persons standing in the place of their parents on farms owned or operated by such parents or persons." 2 In a recent comprehensive review of all injury death certificates for children aged 0 to 9 years in two states with large

• Infection played an important role in prolonging hospitalization and increasing morbidity in 68 children injured in farm settings. Predominantly gram-negative enteric organisms, group D streptococci, and anaerobic organisms were isolated in cultures of specimens obtained from wounds. Infection was more often associated with severe injuries of the large bones of the extremities than in amputation injuries of the digits and crush or rollover injuries when the skin barrier was intact. The occurrence of infection in farm injuries was associated with prolonged hospitalization for parenteral antibiotic therapy, multiple surgical debridements with a need for general anesthesia, and permanent disability (decreased range of motion and loss of limbs and digits). Early aggressive surgical debridement and antimicrobial therapy guided by isolation and sensitivity testing of the major organisms are required because of polymicrobial invasion of vascularly compromised tissue. ( AJDC. 1990;144:710-713)

The alpha 2-adrenoceptor antagonist potencies of the benzoquinolizines (Wy 26 703, Wy 25 309, Wy 26 392), the benzodioxans (RX 781 094, RS 21 361), yohimbine and rauwolscine have been compared at presynaptic alpha 2-adrenoceptors in the isolated vasa deferentia of the rat and rabbit. Yohimbine and rauwolscine are of equal potency as antagonists in both the rat and rabbit against the agonists clonidine or UK 14304. The benzoquinolizines and benzodioxans are very weak antagonists of clonidine or UK 14304 at the presynaptic alpha 2-adrenoceptors of the rabbit vas deferens when compared to their potency at the presynaptic alpha 2-adrenoceptors of the rat vas deferens. This suggests that the presynaptic alpha 2-adrenoceptors present in the rat vasa deferentia may be different from those present in the rabbit vasa deferentia.