Hyperparasitism in bat flies (Diptera: Streblidae): new records and interaction networks in the Neotropics.

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.

Differential Impact of CD43 and CD28 on T-Cell Differentiation Depending on the Order of Engagement with the TCR.

The combination of signals from the T-cell receptor (TCR) and co-stimulatory molecules triggers transcriptional programs that lead to proliferation, cytokine secretion, and effector functions. We compared the impact of engaging the TCR with CD28 and/or CD43 at different time points relative to TCR engagement on T-cell function. TCR and CD43 simultaneous engagement resulted in higher CD69 and PD-1 expression levels than in TCR and CD28-stimulated cells, with a cytokine signature of mostly effector, inflammatory, and regulatory cytokines, while TCR and CD28-activated cells secreted all categories of cytokines, including stimulatory cytokines. Furthermore, the timing of CD43 engagement relative to TCR ligation, and to a lesser degree that of CD28, resulted in distinct patterns of expression of cytokines, chemokines, and growth factors. Complete cell activation was observed when CD28 or CD43 were engaged simultaneously with or before the TCR, but ligating the TCR before CD43 or CD28 failed to complete a cell activation program regarding cytokine secretion. As the order in which CD43 or CD28 and the TCR were engaged resulted in different combinations of cytokines that shape distinct T-cell immune programs, we analyzed their upstream sequences to assess whether the combinations of cytokines were associated with different sets of regulatory elements. We found that the order in which the TCR and CD28 or CD43 are engaged predicts the recruitment of specific sets of chromatin remodelers and TFSS, which ultimately regulate T-cell polarization and plasticity. Our data underscore that the combination of co-stimulatory molecules and the time when they are engaged relative to the TCR can change the cell differentiation program.

An incoherent feedforward loop formed by SirA/BarA, HilE and HilD is involved in controlling the growth cost of virulence factor expression by Salmonella Typhimurium.

An intricate regulatory network controls the expression of Salmonella virulence genes. The transcriptional regulator HilD plays a central role in this network by controlling the expression of tens of genes mainly required for intestinal colonization. Accordingly, the expression/activity of HilD is highly regulated by multiple factors, such as the SirA/BarA two-component system and the Hcp-like protein HilE. SirA/BarA positively regulates translation of hilD mRNA through a regulatory cascade involving the small RNAs CsrB and CsrC, and the RNA-binding protein CsrA, whereas HilE inhibits HilD activity by protein-protein interaction. In this study, we show that SirA/BarA also positively regulates translation of hilE mRNA through the same mentioned regulatory cascade. Thus, our results reveal a paradoxical regulation exerted by SirA/BarA-Csr on HilD, which involves simultaneous opposite effects, direct positive control and indirect negative control through HilE. This kind of regulation is called an incoherent type-1 feedforward loop (I1-FFL), which is a motif present in certain regulatory networks and represents a complex biological problem to decipher. Interestingly, our results, together with those from a previous study, indicate that HilE, the repressor component of the I1-FFL reported here (I1-FFLSirA/BarA-HilE-HilD), is required to reduce the growth cost imposed by the expression of the genes regulated by HilD. Moreover, we and others found that HilE is necessary for successful intestinal colonization by Salmonella. Thus, these findings support that I1-FFLSirA/BarA-HilE-HilD cooperates to control the precise amount and activity of HilD, for an appropriate balance between the growth cost and the virulence benefit generated by the expression of the genes induced by this regulator. I1-FFLSirA/BarA-HilE-HilD represents a complex regulatory I1-FFL that involves multiple regulators acting at distinct levels of gene expression, as well as showing different connections to the rest of the regulatory network governing Salmonella virulence.

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation.

AIMS: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. METHODS: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. RESULTS: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CLMAX  = 4.1 L/h) at 4.6 days post-transplantation (T50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h-1 ) and a 24% reduction in bioavailability (FNS ) at 14 days post-transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first-pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50 ). CONCLUSION: A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post-transplant time on clearance and the sedation status may be considered in routine dosing management.

Review: Understanding fish muscle biology in the indeterminate growth species pacu (Piaractus mesopotamicus).

The muscle phenotype of fish is regulated by numerous factors that, although widely explored, still need to be fully understood. In this context, several studies aimed to unravel how internal and external stimuli affect the muscle growth of these vertebrates. The pacu (Piaractus mesopotamicus) is a species of indeterminate muscular growth that quickly reaches high body weight. For this reason, it adds great importance to the productive sector, along with other round fish. In this context, we aimed to compile studies on fish biology and skeletal muscle growth, focusing on studies by our research group that used pacu as an experimental model along with other species. Based on these studies, new muscle phenotype regulators were identified and explored in vivo, in vitro, and in silico studies, which strongly contribute to advances in understanding muscle growth mechanisms with future applications in the productive sector.

Improved Diagnosis of Viable Parenchymal Neurocysticercosis by Combining Antibody Banding Patterns on Enzyme-Linked Immunoelectrotransfer Blot (EITB) with Antigen Enzyme-Linked Immunosorbent Assay (ELISA).

The diagnosis of neurocysticercosis (NCC) depends on neuroimaging and serological confirmation. While antibody detection by enzyme-linked immunoelectrotransfer blot (EITB) fails to predict viable NCC, EITB banding patterns provide information about the host's infection course. Adding antigen enzyme-linked immunosorbent assay (Ag-ELISA) results to EITB banding patterns may improve their ability to predict or rule out of viable NCC. We assessed whether combining EITB banding patterns with Ag-ELISA improves discrimination of viable infection in imaging-confirmed parenchymal NCC. EITB banding patterns were grouped into classes using latent class analysis. True-positive and false-negative Ag-ELISA results in each class were compared using Fisher's exact test. Four classes were identified: 1, EITB negative or positive to GP50 alone (GP50 antigen family); 2, positive to GP42-39 and GP24 (T24/42 family), with or without GP50; and 3 and 4, positive to GP50, GP42-39, and GP24 and reacting to bands in the 8-kDa family. Most cases in classes 3 and 4 had viable NCC (82% and 88%, respectively) compared to classes 2 and 1 (53% and 5%, respectively). Adding positive Ag-ELISA results to class 2 predicted all viable NCC cases (22/22 [100%]), whereas 11/40 patients (27.5%) Ag-ELISA negative had viable NCC (P < 0.001). Only 1/4 patients (25%) Ag-ELISA positive in class 1 had viable NCC, whereas 1/36 patients (2.8%) Ag-ELISA negative had viable NCC (P = 0.192). In classes 3 and 4, adding Ag-ELISA was not contributory. Combining Ag-ELISA with EITB banding patterns improves discrimination of viable from nonviable NCC, particularly for class 2 responses. Together, these complement neuroimaging more appropriately for the diagnosis of viable NCC.

Amino Acids and IGF1 Regulation of Fish Muscle Growth Revealed by Transcriptome and microRNAome Integrative Analyses of Pacu (Piaractus mesopotamicus) Myotubes.

Amino acids (AA) and IGF1 have been demonstrated to play essential roles in protein synthesis and fish muscle growth. The myoblast cell culture is useful for studying muscle regulation, and omics data have contributed enormously to understanding its molecular biology. However, to our knowledge, no study has performed the large-scale sequencing of fish-cultured muscle cells stimulated with pro-growth signals. In this work, we obtained the transcriptome and microRNAome of pacu (Piaractus mesopotamicus)-cultured myotubes treated with AA or IGF1. We identified 1228 and 534 genes differentially expressed by AA and IGF1. An enrichment analysis showed that AA treatment induced chromosomal changes, mitosis, and muscle differentiation, while IGF1 modulated IGF/PI3K signaling, metabolic alteration, and matrix structure. In addition, potential molecular markers were similarly modulated by both treatments. Muscle-miRNAs (miR-1, -133, -206 and -499) were up-regulated, especially in AA samples, and we identified molecular networks with omics integration. Two pairs of genes and miRNAs demonstrated a high-level relationship, and involvement in myogenesis and muscle growth: marcksb and miR-29b in AA, and mmp14b and miR-338-5p in IGF1. Our work helps to elucidate fish muscle physiology and metabolism, highlights potential molecular markers, and creates a perspective for improvements in aquaculture and in in vitro meat production.

CD43 (sialophorin) is involved in the induction of extracellular matrix remodeling and angiogenesis by lung cancer cells.

Aberrant expression of CD43 in malignant tumors of nonhematopoietic origin such as those from lung, cervix, colon, and breast has been shown to correlate with poor prognosis, providing tumor cells with enhanced motility, anchorage-independent growth, and in vivo tumor size, while protecting the cells of NK lysis and apoptosis. To further characterize the role of CD43 in cell transformation, we tested whether interfering its expression modified the capacity of the A549 non-small cell lung cancer cells to secrete molecules contributing to malignancy. The proteomic analysis of the secretome of serum-starved A549 cells revealed that cells expressing normal levels of CD43 released significantly high levels of molecules involved in extracellular matrix organization, angiogenesis, platelet degranulation, collagen degradation, and inflammation, as compared to CD43 RNAi cells. This data reveals a novel and unexpected role for CD43 in lung cancer development, mainly in remodeling the tumor microenvironment.

Integrative microRNAome analysis of skeletal muscle of Colossoma macropomum (tambaqui), Piaractus mesopotamicus (pacu), and the hybrid tambacu, based on next-generation sequencing data.

BACKGROUND: Colossoma macropomum (tambaqui) and Piaractus mesopotamicus (pacu) are good fish species for aquaculture. The tambacu, individuals originating from the induced hybridization of the female tambaqui with the male pacu, present rapid growth and robustness, characteristics which have made the tambacu a good choice for Brazilian fish farms. Here, we used small RNA sequencing to examine global miRNA expression in the genotypes pacu (PC), tambaqui (TQ), and hybrid tambacu (TC), (Juveniles, n = 5 per genotype), to better understand the relationship between tambacu and its parental species, and also to clarify the mechanisms involved in tambacu muscle growth and maintenance based on miRNAs expression. RESULTS: Regarding differentially expressed (DE) miRNAs between the three genotypes, we observed 8 upregulated and 7 downregulated miRNAs considering TC vs. PC; 14 miRNAs were upregulated and 10 were downregulated considering TC vs. TQ, and 15 miRNAs upregulated and 9 were downregulated considering PC vs. TQ. The majority of the miRNAs showed specific regulation for each genotype pair, and no miRNA were shared between the 3 genotype pairs, in both up- and down-regulated miRNAs. Considering only the miRNAs with validated target genes, we observed the miRNAs miR-144-3p, miR-138-5p, miR-206-3p, and miR-499-5p. GO enrichment analysis showed that the main target genes for these miRNAs were grouped in pathways related to oxygen homeostasis, blood vessel modulation, and oxidative metabolism. CONCLUSIONS: Our global miRNA analysis provided interesting DE miRNAs in the skeletal muscle of pacu, tambaqui, and the hybrid tambacu. In addition, in the hybrid tambacu, we identified some miRNAs controlling important molecular muscle markers that could be relevant for the farming maximization.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Slow electroencephalographic oscillations and behavioral measures as predictors of high executive processing in early postmenopausal females: A discriminant analysis approach.

Decline in cognitive function is frequent in early postmenopause. There are postmenopausal females who show high performance while others display low performance in executive function, modulated by the prefrontal cortex. These differences have led to confusing and inconclusive results, which have not been explained entirely by the decline in estrogens, which affect the prefrontal cortex functions. An analysis of brain function and the application of a discriminant analysis can help to clarify the deficits in executive function shown by some postmenopausal females. The objective was to examine electroencephalographic recording during the performance of an executive function test in early postmenopausal females, ten with a high level of performance and ten with a low level of performance. Absolute power of delta, theta, alpha1, alpha2, beta1 and beta2 and the numbers of completed categories, trials, perseverative errors and overall errors were submitted to stepwise discriminant analysis to identify predictor variables. Four predictors emerged as significant of group membership based on cognitive performance, with the high-performance group characterized by more completed categories, more delta power, less theta power and more alpha1 power. These findings suggest that postmenopausal females classified in the high-performance group displayed appropriate temporary activation in slow oscillations during executive processing.

Germ cells: a useful tool for the taxonomy of Rhipicephalus sanguineus s.l. and species of the Amblyomma cajennense complex (Acari: Ixodidae).

The systematics of several ticks species (Acari: Ixodidae) remains controversial. Many species, including those of the Amblyomma cajennense complex and Rhipicephalus sanguineus s.l., are given special attention since they are cryptic species complexes and are also important in human and veterinary medicine. The A. cajennense complex was recently reorganized into six valid species, among which Amblyomma patinoi and Amblyomma mixtum have been confirmed in Colombia. On the other hand, the taxonomic status of R. sanguineus s.l. is controversial since it is a cosmopolitan cryptic species complex with a high reproductive capacity and a broad range of hosts (including man). To address this challenge, the germ cells of male ticks display a diverse morphology that offers novel opportunities for taxonomy. This study describes the events of spermatogenesis in A. mixtum and R. sanguineus s.l. individuals collected during active feeding on domestic hosts in the department of Caldas, Colombia. The individuals were identified using dichotomous keys and through PCR amplification of a fragment of the mitochondrial 16S ribosomal DNA gene. The male reproductive systems of A. mixtum and R. sanguineus s.l. were fixed in 2.5% glutaraldehyde for 48 h and dehydrated in increasing dilutions of ethanol. The samples were then embedded and mounted in historesin to obtain sections of 3 µm that were stained with hematoxylin-eosin (HE), photographed, and visualized through optical microscopy. The results show that the morphology of mature germ cells displays excellent diagnostic traits that can be used for tick taxonomy.

Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation.

BACKGROUND: In T cells, the Kv1.3 and the KCa3.1 potassium channels regulate the membrane potential and calcium homeostasis. Notably, during TEM cell activation, the number of Kv1.3 channels on the cell membrane dramatically increases. Kv1.3 blockade results in inhibition of Ca2+ signaling in TEM cells, thus eliciting an immunomodulatory effect. Among the naturally occurring peptides, the Vm24 toxin from the Mexican scorpion Vaejovis mexicanus is the most potent and selective Kv1.3 channel blocker known, which makes it a promissory candidate for its use in the clinic. We have shown that addition of Vm24 to TCR-activated human T cells inhibits CD25 expression, cell proliferation and reduces delayed-type hypersensitivity reactions in a chronic inflammation model. Here, we used the Vm24 toxin as a tool to investigate the molecular events that follow Kv1.3 blockade specifically on human CD4+ TEM cells as they are actively involved in inflammation and are key mediators of autoimmune diseases. METHODS: We combined cell viability, activation, and multiplex cytokine assays with a proteomic analysis to identify the biological processes affected by Kv1.3 blockade on healthy donors CD4+ TEM cells, following TCR activation in the presence or absence of the Vm24 toxin. RESULTS: The peptide completely blocked Kv1.3 channels currents without impairing TEM cell viability, and in response to TCR stimulation, it inhibited the expression of the activation markers CD25 and CD40L (but not that of CD69), as well as the secretion of the pro-inflammatory cytokines IFN-γ and TNF and the anti-inflammatory cytokines IL-4, IL-5, IL-9, IL-10, and IL-13. These results, in combination with data from the proteomic analysis, indicate that the biological processes most affected by the blockade of Kv1.3 channels in a T cell activation context were cytokine-cytokine receptor interaction, mRNA processing via spliceosome, response to unfolded proteins and intracellular vesicle transport, targeting the cell protein synthesis machinery. CONCLUSIONS: The Vm24 toxin, a highly specific inhibitor of Kv1.3 channels allowed us to define downstream functions of the Kv1.3 channels in human CD4+ TEM lymphocytes. Blocking Kv1.3 channels profoundly affects the mRNA synthesis machinery, the unfolded protein response and the intracellular vesicle transport, impairing the synthesis and secretion of cytokines in response to TCR engagement, underscoring the role of Kv1.3 channels in regulating TEM lymphocyte function.

Sonographic characterization of Hoffa's fat pad. A pilot study.

This study addresses a topic that was previously unaddressed in the literature: the normal sonographic appearance of the Hoffa's fat pad (HFP) in young, asymptomatic subjects. The aim of the study is to describe the sonoanatomical features of HFP, including its echostructure, echogenicity, elasticity, and vascularization, in subjects without knee pathology. Knees of healthy subjects were examined with grayscale ultrasound (US) to determine the sonographic characteristics of the HFP. Echogenicity was assessed by pixel intensity quantification. Vascularity was evaluated by color Doppler (CD) US. Elasticity of the adipose tissue was examined by sonoelastography. The absence of HFP pathology was confirmed clinically in all participants and by magnetic resonance imaging in randomly selected participants. Seventy-two knees from 36 subjects were assessed. The HFP presented a characteristic well-defined two-layered echostructure: the superficial adipose tissue was hypoechoic with respect to the nearby patellar tendon and contained septae, whereas the deeper layer was homogeneously hypoechoic and lacked connective tissue septae. Echogenicity differed between the superficial and deeper layers (the deeper layer was brighter), suggesting that the degree of acoustic impedance differed between layers. CD detected blood flow in 55.5% of HFPs. The superficial HFP layer presented greater elasticity than the deeper HFP layer (88.8 vs. 75.3 Kpa; p < .001). Our study provides a comprehensive description of the normal sonographic features of the HFP, which is useful to increase the potential of US for the discrimination of pathological findings involving this anatomical area.

Preliminary Report of Microcephaly Potentially Associated with Zika Virus Infection During Pregnancy - Colombia, January-November 2016.

In Colombia, approximately 105,000 suspected cases of Zika virus disease (diagnosed based on clinical symptoms, regardless of laboratory confirmation) were reported during August 9, 2015-November 12, 2016, including nearly 20,000 in pregnant women (1,2). Zika virus infection during pregnancy is a known cause of microcephaly and serious congenital brain abnormalities and has been associated with other birth defects related to central nervous system damage (3). Colombia's Instituto Nacional de Salud (INS) maintains national surveillance for birth defects, including microcephaly and other central nervous system defects. This report provides preliminary information on cases of congenital microcephaly identified in Colombia during epidemiologic weeks 5-45 (January 31-November 12) in 2016. During this period, 476 cases of microcephaly were reported, compared with 110 cases reported during the same period in 2015. The temporal association between reported Zika virus infections and the occurrence of microcephaly, with the peak number of reported microcephaly cases occurring approximately 24 weeks after the peak of the Zika virus disease outbreak, provides evidence suggesting that the period of highest risk is during the first trimester of pregnancy and early in the second trimester of pregnancy. Microcephaly prevalence increased more than fourfold overall during the study period, from 2.1 per 10,000 live births in 2015 to 9.6 in 2016. Ongoing population-based birth defects surveillance is essential for monitoring the impact of Zika virus infection during pregnancy on birth defects prevalence and measuring the success in preventing Zika virus infection and its consequences, including microcephaly.

Nicotine enhances excitability of medial habenular neurons via facilitation of neurokinin signaling.

The medial habenula (MHb) densely expresses nicotinic acetylcholine receptors (nAChRs) and participates in nicotine-related behaviors such as nicotine withdrawal and regulating nicotine intake. Although specific nAChR subunits are identified as being involved in withdrawal behavior, the cellular mechanisms through which nicotine acts to cause this aversive experience is unclear. Here, we demonstrate an interaction between the nicotinic and neurokinin signaling systems that may form the basis for some symptoms experienced during nicotine withdrawal. Using patch-clamp electrophysiology in mouse brain slices, we show that nicotine (1 µm) increases intrinsic excitability in MHb neurons. This nicotine-induced phenomenon requires α5-containing nAChRs and depends on intact neurokinin signaling. The effect is blocked by preincubation with neurokinin 1 (NK1; L-732138, 10 µm) and NK3 (SB222200, 2 µm) antagonists and mimicked by NK1 (substance P, 100 nm) and NK3 (neurokinin B [NKB], 100 nm) agonists. Microinjections (1 µl) of L-732138 (50 nm) and SB222200 (100 nm) into the MHb induces withdrawal behavior in chronic nicotine-treated (8.4 mg/kg/d, 2 weeks) mice. Conversely, withdrawal behavior is absent with analogous microinjections into the lateral habenula of nicotine-treated mice or in mice chronically treated with a vehicle solution. Further, chronic nicotine reduces nicotine's acute modulation of intrinsic excitability while sparing modulation by NKB. Our work elucidates the interplay between two neuromodulatory signaling systems in the brain through which nicotine acts to influence intrinsic excitability. More importantly, we document a neuroadaptation of this mechanism to chronic nicotine exposure and implicate these mechanisms collectively in the emergence of nicotine withdrawal behavior.

Increased Prevalence of Antibodies to Hepatitis E Virus in Patients with Neurocysticercosis.

We explored the association between serological status for hepatitis E and neurocysticercosis (NCC) in neurologic patients attending a national neurological referral center in Lima, Perú, between the years 2008 and 2012. Anti-hepatitis E antibodies were evaluated in patients with and without NCC, and a control group of rural general population. Anti-hepatitis E IgG was found in 23.8% of patients with NCC, compared with 14.3% in subjects without NCC from a general rural population (P = 0.023) and 14.4% in subjects with neurological complaints without NCC (P = 0.027). Seropositive patients had a median age of 44 years compared with 30 years in seronegative patients (P <0.001). No significant differences in sex, region of residence, or liver enzyme values were found. Seropositivity to hepatitis E was frequent in this Peruvian population and higher in patients with NCC, suggesting shared common routes of infection.

Characterization of a New Immunosuppressive and Antimicrobial Peptide, DRS-DA2, Isolated from the Mexican Frog, Pachymedusa dacnicolor.

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections.

Atraumatic Splenic Rupture: A Notable Complication of Rivaroxaban Use.

Direct oral anticoagulants (DOACs) are well known to be associated with bleeding complications. However, little is known about their association with atraumatic splenic rupture, a potentially fatal condition. We present the case of a 73-year-old female with paroxysmal atrial fibrillation managed with rivaroxaban who developed a spontaneous atraumatic splenic rupture. This highlights the importance of recognizing this complication in patients without previous risk factors, such as abdominal trauma or infiltrative splenic disease, who are under anticoagulation with DOACs. There is a strong need for further research on this complication's underlying mechanism and management.