Posterior fossa endoscopic-assisted surgery: A systematization of its surgical corridors.

INTRODUCTION: The use of endoscopic-assisted techniques in neurosurgery has been implemented to improve better visualization and predict extent of resection. We aim to systematize the posterior fossa surgical regions and the endoscopic surgical corridors providing a quick reference of the anatomy and surgical nuances. METHODS: A retrospective review of patients undergoing endoscopic-assisted surgery of the posterior fossa at a single institution between 2019 and 2020 was conducted along with a description of the microsurgical anatomy from cadaveric specimens and surgical cases. RESULTS: The posterior fossa was segmented into three topographic regions, (upper, middle and lower), with three surgical corridors within each of these. Upper region is accessed through a supracerebellar infratentorial approach and comprises the pineal and pericuadrigeminal region constituted by the median corridor, the lateral corridor, and the extreme lateral corridor. Middle region is accessed through a retrosigmoid approach and comprises the cerebellopontine angle region constituted by the supralateral corridor containing the upper neurovascular complex (NVC), the median corridor containing the median NVC, and the infralateral corridor containing the lower NVC. The lower region is accessed through a far-lateral approach and contains the craniocervical junction region constituted by the upper corridor in between the VII-VIII and IX cranial nerves (CNs), the median corridor between the X and XI CNs, and the lower corridor between the cranial and spinal rootlets of the XI CN. CONCLUSION: We propose a simple and concise systematization, dividing the area into three regions with predefined corridors.

Oligomycins A and E, major bioactive secondary metabolites produced by Streptomyces sp. strain HG29 isolated from a Saharan soil.

An actinobacterial strain, HG29, with potent activity against pathogenic, toxigenic and phytopathogenic fungi was isolated from a Saharan soil sample of Algeria. On the basis of morphological and chemotaxonomic characteristics, the strain was classified in the genus Streptomyces. Analysis of the 16S rRNA gene sequence showed a similarity level of 99.3% with Streptomyces gancidicus NBRC 15412T. The comparison of its cultural and physiological characteristics with this species revealed significant differences. Moreover, the phylogenetic tree showed that strain HG29 forms a distinct phyletic line within the genus Streptomyces. Production of antifungal activity was investigated by following kinetics in shake broth. The highest antifungal activity was obtained after five days of fermentation, and in the dichloromethane extract. Two active compounds, NK1 and NK2, were purified by HPLC using a C18 column. Their chemical structures were identified through nuclear magnetic resonance experiments and mass spectrometry as oligomycins E and A, respectively, which have not been reported to be produced by S. gancidicus. The two bioactive compounds exhibited significant antifungal activity in vitro, showing minimal inhibitory concentrations (MICs) values between 2 and 75µg/mL.

BDNF-TrkB signaling through Erk1/2 MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids.

Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

A study of a population of Nyssomyia trapidoi (Diptera: Psychodidae) caught on the Pacific coast of Ecuador.

BACKGROUND: Cutaneous leishmaniasis is endemic to the Pacific coast of Ecuador, and Nyssomyia trapidoi is considered to be its main vector. Dujardin et al. [1] recorded some differences in body pigmentation and isoenzymatic profiles in sympatric populations of Ny. trapidoi from the Pacific coast of Ecuador and suggested the existence of two cryptic species. METHODS: Entomological collections were performed in November 2008 and March 2011 in the locality of Paraíso Escondido using CDC miniature light traps and human bait. Morphological, isoenzymatical and molecular (sequencing of cytochome b and cytochrome c oxidase 1 of the mitochondrial DNA) analyses, such as detection of Leishmania DNA and phlebovirus RNA in some females, were performed. RESULTS: Neighbor-joining trees from mitochondrial sequences grouped all of Ecuadorian Ny. trapidoi (including the two color variants) in one cluster, except for two specimens which clustered separately in both genes. Isoenzymatic characterization confirmed that the color variants belong to the same population. Additionally, 11.5% of females were found by PCR to contain Endotrypanum monterogeii kinetoplastid DNA. All pools of Ny. trapidoi were negative for phlebovirus RNA. CONCLUSION: Analysis of mitochondrial gene sequences and isoenzymes was unable to support the existence of two sibling species within Ny. trapidoi, which is a probable vector of Endotrypanum monterogeii.

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib.

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GR(NesCre)), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress.

A transiting giant planet with a temperature between 250 K and 430 K.

Of the over 400 known exoplanets, there are about 70 planets that transit their central star, a situation that permits the derivation of their basic parameters and facilitates investigations of their atmospheres. Some short-period planets, including the first terrestrial exoplanet (CoRoT-7b), have been discovered using a space mission designed to find smaller and more distant planets than can be seen from the ground. Here we report transit observations of CoRoT-9b, which orbits with a period of 95.274 days on a low eccentricity of 0.11 +/- 0.04 around a solar-like star. Its periastron distance of 0.36 astronomical units is by far the largest of all transiting planets, yielding a 'temperate' photospheric temperature estimated to be between 250 and 430 K. Unlike previously known transiting planets, the present size of CoRoT-9b should not have been affected by tidal heat dissipation processes. Indeed, the planet is found to be well described by standard evolution models with an inferred interior composition consistent with that of Jupiter and Saturn.

Is Lutzomyia serrana (Diptera, Psychodidae, Phlebotominae) present in Ecuador?

We describe a multivariate metric comparison of three sandfly species showing strong differences in size, which questions the geographical distribution of one of them. Two species are represented by a single population (L. robusta and L. guilvardae) and one by two populations (L. serrana). All of them belong to the series serrana (Diptera, Psychodidae, Phlebotominae). The morphometric data confirm that L. guilvardae is a distinct species. However, they suggest that L. robusta and L. serrana in Ecuador are the same taxon, and that it is distinguishable from the population of L. serrana in Bolivia. A multilocus enzyme electrophoresis analysis comparing L. serrana in Bolivia and L. robusta in Ecuador adds further evidence that these two populations are distinct species. Thus, our data seem to indicate that, in Ecuador, the population previously identified as L. serrana is actually the same species as the allopatric population previously identified as L. robusta. Accepting L. serrana in Ecuador as small-sized L. robusta, the resulting geographic distribution of this latter becomes in closer agreement with ecology and epidemiology.

Human mixed infections of Leishmania spp. and Leishmania-Trypanosoma cruzi in a sub Andean Bolivian area: identification by polymerase chain reaction/hybridization and isoenzyme.

Parasites belonging to Leishmania braziliensis, Leishmania donovani, Leishmania mexicana complexes and Trypanosoma cruzi (clones 20 and 39) were searched in blood, lesions and strains collected from 28 patients with active cutaneous leishmaniasis and one patient with visceral leishmaniasis. PCR-hybridization with specific probes of Leishmania complexes (L. braziliensis, L. donovani and L. mexicana) and T. cruzi clones was applied to the different DNA samples. Over 29 patients, 8 (27.6%) presented a mixed infection Leishmania complex species, 17 (58.6%) a mixed infection Leishmania-T. cruzi, and 4 (13.8%) a multi Leishmania-T. cruzi infection. Several patients were infected by the two Bolivian major clones 20 and 39 of T. cruzi (44.8%). The L. braziliensis complex was more frequently detected in lesions than in blood and a reverse result was observed for L. mexicana complex. The polymerase chain reaction-hybridization design offers new arguments supporting the idea of an underestimated rate of visceral leishmanisis in Bolivia. Parasites were isolated by culture from the blood of two patients and lesions of 10 patients. The UPGMA (unweighted pair-group method with arithmetic averages) dendrogram computed from Jaccard's distances obtained from 11 isoenzyme loci data confirmed the presence of the three Leishmania complexes and undoubtedly identified human infections by L. (V.) braziliensis, L. (L.) chagasi and L. (L.) mexicana species. Additional evidence of parasite mixtures was visualized through mixed isoenzyme profiles, L. (V.) braziliensis-L. (L.) mexicana and Leishmania spp.-T. cruzi. The epidemiological profile in the studied area appeared more complex than currently known. This is the first report of parasitological evidence of Bolivian patients with trypanosomatidae multi infections and consequences on the diseases' control and patient treatments are discussed.

Human mixed infections of Leishmania spp. and Leishmania-Trypanosoma cruzi in a sub Andean Bolivian area: identification by polymerase chain reaction/hybridization and isoenzyme

Parasites belonging to Leishmania braziliensis, Leishmania donovani, Leishmania mexicana complexes and Trypanosoma cruzi (clones 20 and 39) were searched in blood, lesions and strains collected from 28 patients with active cutaneous leishmaniasis and one patient with visceral leishmaniasis. PCR-hybridization with specific probes of Leishmania complexes (L. braziliensis, L. donovani and L. mexicana) and T. cruzi clones was applied to the different DNA samples. Over 29 patients, 8 (27.6 percent) presented a mixed infection Leishmania complex species, 17 (58.6 percent) a mixed infection Leishmania-T. cruzi, and 4 (13.8 percent) a multi Leishmania-T. cruzi infection. Several patients were infected by the two Bolivian major clones 20 and 39 of T. cruzi (44.8 percent). The L. braziliensis complex was more frequently detected in lesions than in blood and a reverse result was observed for L. mexicana complex. The polymerase chain reaction-hybridization design offers new arguments supporting the idea of an underestimated rate of visceral leishmanisis in Bolivia. Parasites were isolated by culture from the blood of two patients and lesions of 10 patients. The UPGMA (unweighted pair-group method with arithmetic averages) dendrogram computed from Jaccard's distances obtained from 11 isoenzyme loci data confirmed the presence of the three Leishmania complexes and undoubtedly identified human infections by L. (V.) braziliensis, L. (L.) chagasi and L. (L.) mexicana species. Additional evidence of parasite mixtures was visualized through mixed isoenzyme profiles, L. (V.) braziliensis-L. (L.) mexicana and Leishmania spp.-T. cruzi.The epidemiological profile in the studied area appeared more complex than currently known. This is the first report of parasitological evidence of Bolivian patients with trypanosomatidae multi infections and consequences on the diseases' control and patient treatments are discussed

Co-infection by Leishmania amazonensis and L. infantum/L. chagasi in a case of diffuse cutaneous leishmaniasis in Bolivia.

We present the first report of a co-infection by Leishmania amazonensis and L. infantum/L. chagasi isolated in 1993 from a patient with diffuse cutaneous leishmaniasis (DCL), living in the sub-Andean region of Bolivia. This is the third reported case of DCL in Bolivia, but the first one with isoenzymatic identification of the aetiological agents involved and the first one giving evidence for a mixed infection by 2 Leishmania parasites in the same lesion.

First evidence of transmission of Leishmania (Viannia) lainsoni in a Sub Andean region of Bolivia.

Using ubiquitous primers which amplify the variable parts of kDNA minicircle of all Leishmania spp, we obtained for Leishmania (viannia) lainsoni a major band of 605 bp (band 1) shared with L. V. braziliensis and a minor 524 bp band (band 2) specific of L. V. lainsoni. The specificity of the two bands was examined through Southern blot hybridization of kDNA PCR obtained from reference strains belonging to L. braziliensis, L. mexicana, L. donovani complexes with L. V. lainsoni species. Band 1 was not specific of L. V. lainsoni since it hybridized with some isolates belonging to L. braziliensis complex. In contrast, band 2 was L. V. lainsoni specific. PCR-based detection followed by hybridization with the new L. V. lainsoni probe (Band 2) and L. V. braziliensis probe (564 bp), was assayed using sample from a pool of 25 females of Lutzomiya nuneztovari anglesi, blood, skin and liver samples of 18 mammals, spinal cords of four mammals and blood and cutaneous ulcers aspirates from 95 patents from Sub Andean region of La Paz, Bolivia. We observed a ositive hybridization of four patients lesions and the pool of L. nuneztovari anglesi with the L. V. lainsoni probe. It is the first time that L. V. lainsoni is observed in a cycle of transmission in Bolivia. PCR products of three patients lesions and the pool of L. nuneztovari anglesi were also hybridized with the specific probe of L. V. braziliensis suggesting mixed infection in this focus.

High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study.

AIMS/HYPOTHESIS: Mechanisms responsible for the decreased high-density lipoprotein (HDL) cholesterol level associated with insulin resistance in obese patients are not clearly understood. To determine the influence of insulin resistance at an early stage on HDL metabolism, we performed a stable isotope kinetic study of apolipoprotein (apo) A-I, in five obese insulin resistant women with normal fasting triglycerides and without impaired glucose tolerance, and in five age-matched control women. METHODS: Each subject received a 16 h constant infusion of L-[1-(13)C]leucine at 0.7 mg/kg/h following a primed bolus of 0.7 mg/kg. RESULTS: ApoA-I fractional catabolic rate (FCR) was significantly increased in insulin-resistant women compared to controls (0.316+/-0.056 vs 0.210+/-0.040 per day, P<0.01), indicating a significant 50% increase of apoA-I catabolism, leading to an important reduction of plasma apoA-I residence time (3.25+/-0.59 vs 4.92+/-1.11, P<0.01). ApoA-I production rate tended to be higher in insulin resistant women than in controls (364+/-77 vs 258+/-60 mg/l/day, P=0.13), but the difference was not statistically significant. ApoA-I FCR was correlated with triglycerides during the fed state (r=0.69; P=0.026) and HDL triglycerides-esterified cholesterol ratio (r=0.73; P=0.016), suggesting that alteration of apoA-I metabolism in insulin resistance may be partly related to HDL enrichment in triglycerides. CONCLUSIONS: Our kinetic study shows that patients, at an early stage of insulin resistance (without impaired glucose tolerance nor fasting hypertriglyceridaemia), already have a significant alteration of apoA-I metabolism (increased apoA-I catabolism), which is consistent with the increased risk of atherosclerosis in this population.

[Obesity persistent scleredema: study of 49 cases]. / Scléroedème persistant de l'obèse.

BACKGROUND: Buschke sclerodema is a very rare disease. Our objective was to show that persistent scleredema is frequent in certain group of patients at risk. PATIENTS AND METHODS: We studied 49 patients, diagnosed between 1995 and 1999 in dermatology, pneumology and endocrinology departments in Martinique. Diagnosis was performed on classical clinical and histopathological aspects of sclerodema. Data studied were age, sex, mode of occurrence, clinical and histopathological aspects and associated diseases. RESULTS: The 49 patients presented with cutaneous infiltration of the upper part of the trunk, with thick dermis and large collagen bundles on histopathological examination. Forty-two had mucoid substance deposition, stained with Alcian Blue (this criteria was considered as inconstant by most authors in the literature). Sex ratio H/F was 0.06 (93 p. 100 females). Mediam age at onset was 50 years ranging from 20 to 79 years. The occurrence was insidious in 97 p. 100 of cases. All patients had neck and nuchae involvement. The disease involved the back in 93 p. 100, upper limbs in 50 p. 100 and lower limbs and face in 43 p. 100 of patients. Fifty-six percent of patients had limitation of shoulder movements, 16 p. 100 limitation of mouth opening, 20 p. 100 limitation of eyelid opening, 36 p. 100 had myalgia, 73 p. 100 had pruritus and 66 p. 100 had dyspnea. Obesity was present in 95 p. 100, diabetes in 79.5 p. 100, elevated blood pressure in 81.5 p. 100 and monoclonal dysglobulinemia in 46 p. 100 of patients. Twenty-five patients had a polysomnography showing severe obstructive sleep apnea syndrome. DISCUSSION: The large number of patients in our study can be explained by the search for sclerodema in patients with obesity, diabetes and high blood pressure. The disease is usually unknown by patients and physicians unless a systematic examination is performed. Association with obstructive sleep apnea syndrome was not previously reported and a larger study is ongoing.

Wing geometry as a tool for studying the Lutzomyia longipalpis (Diptera: Psychodidae) complex

Toro Toro (T) and Yungas (Y) have been described as genetically well differentiated populations of the Lutzomyia longipalpis (Lutz & Neiva, 1912) complex in Bolivia. Here we use geometric morphometrics to compare samples from these populations and new populations (Bolivia and Nicaragua), representing distant geographical origins, qualitative morphological variation ("one-spot" or "two-spots" phenotypes), ecologically distinct traits (peridomestic and silvatic populations), and possibly different epidemiological roles (transmitting or nor transmitting Leishmania chagasi). The Nicaragua (N) (Somotillo) sample was "one-spot" phenotype and a possible peridomestic vector. The Bolivian sample of the Y was also "one-spot" phenotype and a demonstrated peridomestic vector of visceral leishmaniasis (VL). The three remaining samples were silvatic, "two-spots" phenotypes. Two of them (Uyuni and T) were collected in the highlands of Bolivian where VL never has been reported. The last one (Robore, R) came from the lowlands of Bolivia, where human cases of VL are sporadically reported. The decomposition of metric variation into size and shape by geometric morphometric techniques suggests the existence of two groups (N/Y/R, and U/T). Several arguments indicate that such subdivision of Lu. longipalpis could correspond to different evolutionary units

A first case of cutaneous leishmaniasis due to Leishmania (Viannia) lainsoni in Bolivia.

We present the first known case of cutaneous leishmaniasis due to Leishmania (Viannia) lainsoni detected in Bolivia. The parasite was isolated from a young girl living in the subtropical region of Carrasco (900-1000 m above sea level, Caranavi Province, Department of La Paz, Bolivia). The parasite identification was confirmed by multilocus enzyme electrophoresis.

Characterization of phosphoantigens by high-performance anion-exchange chromatography-electrospray ionization ion trap mass spectrometry and nanoelectrospray ionization ion trap mass spectrometry.

New phosphorylated microbial metabolites referred to as phosphoantigens activate immune responses in humans. Although these molecules have leading applications in medical research, no direct method allows their rapid and unambiguous structural identification. Here, we interfaced online HPAEC (high performance anion-exchange chromatography) with ESI-ITMS (electrospray ionization ion trap mass spectrometry) to identify such pyrophosphorylated molecules. A self-regenerating anion suppressor located upstream of electrospray ionization enabled the simultaneous detection of pyrophosphoester by conductimetry, UV and MS. By HPAEC-ITMS and HPAEC-ITMS2, a single run permitted characterization of reference phosphoantigens and of related structures. Although all compounds were resolved by HPAEC, MS enabled their detection and identification by [M-H]- and fragment ions. Isobaric phosphoantigen analogues were also separated by HPAEC and distinguished by MS2. The relevance of this device was demonstrated for phosphoantigens analysis in human urine and plasma. Furthermore, identification of natural phosphoantigens by automatically generated 2D mass spectra from nano-ESI-ITMS is presented. This last technique permits the simultaneous performance of molecular screening of natural phosphoantigen extracts and their identification.

Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human gamma delta T cells.

Small phosphorylated metabolites from mycobacteria stimulate human gammadelta T lymphocytes. Although such phosphoantigens could prove useful in the composition of vaccines involving gammadelta T cell-mediated immunity, their very low abundance in natural sources limits such applications. Here, we describe the chemical production, purification, and bioactivity of a phosphorylated bromohydrin (BrHPP) analogue that mimics the biological properties of natural phosphoantigens. This compound can be obtained in gram amounts, is easy to detect, and is of high stability in aqueous solutions. Whereas unspecific binding of BrHPP to a wide panel of cell surface receptors is not detected even at micromolar concentrations, nanomolar concentrations specifically trigger effector responses of human gammadelta T lymphocytes. Thus, BrHPP is a novel molecule enabling potent immunostimulation of human gammadelta T lymphocytes.