Endogenous indole-3-acetamide levels contribute to the crosstalk between auxin and abscisic acid, and trigger plant stress responses in Arabidopsis.

The evolutionary success of plants relies to a large extent on their extraordinary ability to adapt to changes in their environment. These adaptations require that plants balance their growth with their stress responses. Plant hormones are crucial mediators orchestrating the underlying adaptive processes. However, whether and how the growth-related hormone auxin and the stress-related hormones jasmonic acid, salicylic acid, and abscisic acid (ABA) are coordinated remains largely elusive. Here, we analyse the physiological role of AMIDASE 1 (AMI1) in Arabidopsis plant growth and its possible connection to plant adaptations to abiotic stresses. AMI1 contributes to cellular auxin homeostasis by catalysing the conversion of indole-acetamide into the major plant auxin indole-3-acetic acid. Functional impairment of AMI1 increases the plant's stress status rendering mutant plants more susceptible to abiotic stresses. Transcriptomic analysis of ami1 mutants disclosed the reprogramming of a considerable number of stress-related genes, including jasmonic acid and ABA biosynthesis genes. The ami1 mutants exhibit only moderately repressed growth but an enhanced ABA accumulation, which suggests a role for AMI1 in the crosstalk between auxin and ABA. Altogether, our results suggest that AMI1 is involved in coordinating the trade-off between plant growth and stress responses, balancing auxin and ABA homeostasis.

Dogs are resistant to prion infection, due to the presence of aspartic or glutamic acid at position 163 of their prion protein.

Unlike other species, prion disease has never been described in dogs even though they were similarly exposed to the bovine spongiform encephalopathy (BSE) agent. This resistance prompted a thorough analysis of the canine PRNP gene and the presence of a negatively charged amino acid residue in position 163 was readily identified as potentially fundamental as it differed from all known susceptible species. In the present study, the first transgenic mouse model expressing dog prion protein (PrP) was generated and challenged intracerebrally with a panel of prion isolates, none of which could infect them. The brains of these mice were subjected to in vitro prion amplification and failed to find even minimal amounts of misfolded prions providing definitive experimental evidence that dogs are resistant to prion disease. Subsequently, a second transgenic model was generated in which aspartic acid in position 163 was substituted for asparagine (the most common in prion susceptible species) resulting in susceptibility to BSE-derived isolates. These findings strongly support the hypothesis that the amino acid residue at position 163 of canine cellular prion protein (PrPC ) is a major determinant of the exceptional resistance of the canidae family to prion infection and establish this as a promising therapeutic target for prion diseases.

A case-control study of factors associated with SARS-CoV-2 infection among healthcare workers in Colombia.

BACKGROUND: Healthcare Workers (HCW) are repeatedly exposed to SARS-CoV-2 infection. The aim of this study was to identify factors associated with SARS-CoV-2 infection among HCW in one of the largest cities in Colombia. METHODS: We conducted a case-control study, where cases had a positive reverse transcription-polymerase chain reaction and controls had a negative result. Participants were randomly selected and interviewed by phone. Analyses were performed using logistic regression models. RESULTS: A total of 110 cases and 113 controls were included. Men (AdjOR 4.13 95% CI 1.70-10.05), Nurses (AdjOR 11.24 95% CI 1.05-119.63), not using a high-performance filtering mask (AdjOR 2.27 95% CI 1.02-5.05) and inadequate use of personal protective equipment (AdjOR 4.82 95% CI 1.18-19.65) were identified as risk factors. Conversely, graduate (AdjOR 0.06 95% CI 0.01-0.53) and postgraduate (AdjOR 0.05 95% CI 0.005-0.7) education, feeling scared or nervous (AdjOR 0.45 95% CI 0.22-0.91), not always wearing any gloves, caps and goggles/face shields (AdjOR 0.10 95% CI 0.02-0.41), and the use of high-performance filtering or a combination of fabric plus surgical mask (AdjOR 0.27 95% CI 0.09-0.80) outside the workplace were protective factors. CONCLUSION: This study highlights the protection provided by high-performance filtering masks or double masking among HCW. Modifiable and non-modifiable factors and the difficulty of wearing other protective equipment needs to be considered in designing, implementing and monitoring COVID-19 biosafety protocols for HCW.

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Jasmonic Acid-Dependent MYC Transcription Factors Bind to a Tandem G-Box Motif in the YUCCA8 and YUCCA9 Promoters to Regulate Biotic Stress Responses.

The indole-3-pyruvic acid pathway is the main route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of l-tryptophan via indole-3-pyruvic acid to indole-3-acetic acid (IAA). It has been described that jasmonic acid (JA) locally produced in response to mechanical wounding triggers the de novo formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of the expression of the YUC8 and YUC9 genes depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. Furthermore, transactivation assays provided experimental evidence for the binding of MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in the promoters of the other YUCCA isogenes. Moreover, we demonstrate that plants that constitutively overexpress YUC8 and YUC9 show less damage after spider mite infestation, thereby underlining the role of auxin in plant responses to biotic stress signals.

Accumulation of the Auxin Precursor Indole-3-Acetamide Curtails Growth through the Repression of Ribosome-Biogenesis and Development-Related Transcriptional Networks.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize the ami1rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a simultaneous genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsisthaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

Looping Star fMRI in Cognitive Tasks and Resting State.

BACKGROUND: Conventional T2 *-weighted functional magnetic resonance imaging (fMRI) is performed with echo-planar imaging (EPI) sequences that create substantial acoustic noise. The loud acoustic noise not only affects the activation of the auditory cortex, but may also interfere with resting state and task fMRI experiments. PURPOSE: To demonstrate the feasibility of a novel, quiet, T2 *, whole-brain blood oxygenation level-dependent (BOLD)-fMRI method, termed Looping Star, compared to conventional multislice gradient-echo EPI. STUDY TYPE: Prospective. PHANTOM/SUBJECTS: Glover stability QA phantom; 10 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T: gradient echo (GE)-EPI and T2 * Looping Star fMRI. ASSESSMENT: Looping Star fMRI was presented and compared to GE-EPI with a working memory (WM) task and resting state (RS) experiments. Temporal stability and acoustic measurements were obtained for both methods. Functional maps and activation accuracy were compared to evaluate the performance of the novel sequence. STATISTICAL TESTS: Mean and standard deviation values were analyzed for temporal stability and acoustic noise tests. Activation maps were assessed with one-sample t-tests and contrast estimates (CE). Paired t-tests and receiver operator characteristic (ROC) were used to compare fMRI sensitivity and performance. RESULTS: Looping Star presented a 98% reduction in sound pressure compared with GE-EPI, with stable temporal stability (0.09% percent fluctuation), but reduced temporal signal-to-noise ratio (tSNR) (mean difference = 15.9%). The novel method yielded consistent activations for RS and WM (83.4% and 69.5% relative BOLD sensitivity), which increased with task difficulty (mean CE 2-back = 0.56 vs. 0-back = 0.08, P < 0.05). A few differences in spatial activations were found between sequences, leading to a 4-8% lower activation accuracy with Looping Star. DATA CONCLUSION: Looping Star provides a suitable approach for whole-brain coverage with sufficient spatiotemporal resolution and BOLD sensitivity, with only 0.5 dB above ambient noise. From the comparison with GE-EPI, further developments of Looping Star fMRI should target increased sensitivity and spatial specificity for both RS and task experiments. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:739-751.

Guillain-Barré Syndrome Associated with Zika Virus Infection in Colombia.

BACKGROUND: Zika virus (ZIKV) infection has been linked to the Guillain-Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain-Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain-Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection. METHODS: A total of 68 patients with the Guillain-Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays. RESULTS: A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain-Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain-Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain-Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain-Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain-Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain-Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR. CONCLUSIONS: The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).

Unraveling the key to the resistance of canids to prion diseases.

One of the characteristics of prions is their ability to infect some species but not others and prion resistant species have been of special interest because of their potential in deciphering the determinants for susceptibility. Previously, we developed different in vitro and in vivo models to assess the susceptibility of species that were erroneously considered resistant to prion infection, such as members of the Leporidae and Equidae families. Here we undertake in vitro and in vivo approaches to understand the unresolved low prion susceptibility of canids. Studies based on the amino acid sequence of the canine prion protein (PrP), together with a structural analysis in silico, identified unique key amino acids whose characteristics could orchestrate its high resistance to prion disease. Cell- and brain-based PMCA studies were performed highlighting the relevance of the D163 amino acid in proneness to protein misfolding. This was also investigated by the generation of a novel transgenic mouse model carrying this substitution and these mice showed complete resistance to disease despite intracerebral challenge with three different mouse prion strains (RML, 22L and 301C) known to cause disease in wild-type mice. These findings suggest that dog D163 amino acid is primarily, if not totally, responsible for the prion resistance of canids.

Preventing legionellosis outbreaks by a quick detection of airborne Legionella pneumophila.

Legionellosis is a severe pneumonic infection caused by inhaling bacteria of the genus Legionella. Most cases reported in the USA and Europe are associated with the species Legionella pneumophila. This Gram-negative bacterium can survive within a wide spectrum of temperatures, and be transmitted via aerosols from multiple aquatic sources: fountains, thermal spas and other water systems. Although the PCR is one of the most popular methods to verify its presence in environmental or clinical samples, the direct application of this technique to ambient air samples is unusual because of the scarce material in the specimens. Here, we have developed a two-PCR assay, carried out over the V3 and V5 hypervariable regions of the 16S rRNA gene, to detect specifically the pathogenic bacteria Legionella pneumophila in outdoor air samples with low concentration of DNA. The application of this protocol does not require culture and retrieves quick results to activate the corresponding public alerts to prevent legionellosis outbreaks.

Phenotypic, molecular and genomic characterization of Actinobaculum suis isolated from swine in Brazil.

Urinary tract infections (UTI) are considered one of the most important diseases of sows due to its close relationship with reproductive problems such as reduced litter size, increase in the rate of return to estrous, vulvar discharge, abortion, mastitis and anestrus. Actinobaculum suis is one of the main agents involved in porcine urinary tract infection and is responsible for the most severe and fatal cases in sows. In the present report, 23 A. suis strains isolated from a sow and boars in Brazil were identified by PCR and further characterized by broth microdilution, molecular typing by pulsed-field gel electrophoresis (PFGE), single-enzyme amplified fragment length polymorphism (SE-AFLP), and whole-genome sequencing. All strains were sensitive to ceftiofur, linezolid, nitrofurantoin, quinupristin-dalfopristin and vancomycin. Ciprofloxacin, daptomycin, lincomycin, erythromycin and tylosin resistance was observed in 100% of tested strains. Tetracycline and tigecycline also presented high resistance rates (87% and 30.4%, respectively). PFGE with eight different restriction enzymes and three programs did not enable strain characterization; however, all strains were typed by SE-AFLP that clustered strains according to their origin, thus proving an effective tool for A. suis genotyping. Whole-genome sequencing and comparative analysis enabled species differentiation from closely related genus. This is the first report of genomic characterization of A. suis.

Comprehensive analysis of different adhesives in aerobiological sampling using optical microscopy and high-throughput DNA sequencing.

The standardization and unification of the procedures to analyze and quantify the airborne pollen concentrations are very important topics. In this work, the effectiveness of the two most used adhesives in aerobiological sampling, silicone prepared with cyclohexane solvent (Silicone) and petroleum jelly (Vaseline), was compared under outdoor conditions. This comparison was carried out using the traditional method based on the identification and quantification by optical microscopy (OM) of the airborne pollen and the novel methodology by high-throughput sequencing analysis (HTS). Globally, the results from both methods of analysis (OM and HTS) showed a good agreement between the two adhesives tested regarding the abundance of the main pollen types present in the samples: Cupressaceae, Olea, Poaceae, Platanus, Quercus. We concluded that the results from both adhesives are comparable data. Furthermore, the comparisons between methodologies, OM vs. HTS, showed that both techniques can accurately identify the most abundant pollen types in the atmosphere for the studied periods, with a good agreement of their relative abundances especially when the airborne pollen diversity is low but showing some divergences as the number of pollen types increases.

Cofactors influence the biological properties of infectious recombinant prions.

Prion diseases are caused by a misfolding of the cellular prion protein (PrP) to a pathogenic isoform named PrPSc. Prions exist as strains, which are characterized by specific pathological and biochemical properties likely encoded in the three-dimensional structure of PrPSc. However, whether cofactors determine these different PrPSc conformations and how this relates to their specific biological properties is largely unknown. To understand how different cofactors modulate prion strain generation and selection, Protein Misfolding Cyclic Amplification was used to create a diversity of infectious recombinant prion strains by propagation in the presence of brain homogenate. Brain homogenate is known to contain these mentioned cofactors, whose identity is only partially known, and which facilitate conversion of PrPC to PrPSc. We thus obtained a mix of distinguishable infectious prion strains. Subsequently, we replaced brain homogenate, by different polyanionic cofactors that were able to drive the evolution of mixed prion populations toward specific strains. Thus, our results show that a variety of infectious recombinant prions can be generated in vitro and that their specific type of conformation, i.e., the strain, is dependent on the cofactors available during the propagation process. These observations have significant implications for understanding the pathogenesis of prion diseases and their ability to replicate in different tissues and hosts. Importantly, these considerations might apply to other neurodegenerative diseases for which different conformations of misfolded proteins have been described.

Emerging Viral Infections and Their Impact on the Global Burden of Neurological Disease.

Emerging viral infections of the nervous system represent a major global public health concern in the 21st century. They are caused primarily by RNA viruses and are mostly associated with acute or subacute encephalitis. The spectrum of associated central or peripheral nervous system disorders is broad, and results either from a direct viral effect or due to the host immune responses against the infection. Emerging viral infections impose substantial neurological morbidity and mortality, particularly in low- and middle-income regions. In the past five decades, vector-borne viruses primarily transmitted by arthropods, or arboviruses, have been responsible for epidemics with a high burden of neurological disease, like the 2015-2016 Zika virus epidemic in the Americas. Viruses that have become neurovirulent for humans after geographical expansion include West Nile, Dengue, and Zika viruses. Factors such as animal migration, disruption of ecological niches, and cross-species contact have caused old viruses to reappear and cause neurological disease, as is the case of Ebola virus. In addition to these biological challenges, current preventive strategies, vaccination, and diagnostic and therapeutic approaches remain limited. We review the clinical-virological features and global impact of the most relevant emerging viral infections of the nervous system as they are projected over the 21st century.

Neurological Implications of Zika Virus Infection in Adults.

The 2015-2016 epidemic of Zika virus (ZIKV) in the Americas and the Caribbean was associated with an unprecedented burden of neurological disease among adults. Clinically, Guillain-Barre syndrome (GBS) predominated among regions affected by the ZIKV epidemic, but the spectrum of neurological disease in the adults appears broader as cases of encephalopathy, encephalitis, meningitis, myelitis, and seizures have also been reported. A para-infectious temporal profile of ZIKV-associated GBS (ZIKV-GBS) has been described in clinical studies, which may suggest a direct viral neuropathic effect. However, ZIKV neuropathogenesis has not yet been fully understood. Mechanisms for ZIKV-GBS and other neurological syndromes have been hypothesized, such as adaptive viral genetic changes, immunological interactions with other circulating flaviviruses, and host and factors. This review summarizes the current evidence on ZIKV-associated neurological complications in the adults.

The use of rapid dengue diagnostic tests in a routine clinical setting in a dengue-endemic area of Colombia.

There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.

The Entrapment and Concentration of SARS-CoV-2 Particles with Graphene Oxide: An In Vitro Assay.

Previous studies have suggested that graphene oxide (GO) has some antiviral capacity against some enveloped viruses, including SARS-CoV-2. Given this background, we wanted to test the in vitro antiviral ability to GO using the viral plaque assay technique. Two-dimensional graphene oxide (GO) nanoparticles were synthesized using the modified Hummers method, varying the oxidation conditions to achieve nanoparticles between 390 and 718 nm. The antiviral activity of GO was evaluated by experimental infection and plaque formation units assay of the SARS-CoV-2 virus in VERO cells using a titrated viral clinical isolate. It was found that GO at concentrations of 400 µg/mL, 100 µg/mL, 40 µg/mL, and 4 µg/mL was not toxic to cell culture and also did not inhibit the infection of VERO cells by SARS-CoV-2. However, it was evident that GO generated a novel virus entrapment phenomenon directly proportional to its concentration in the suspension. Similarly, this effect of GO was maintained in assays performed with the Zika virus. A new application for GO nanoparticles is proposed as part of a system to trap viruses in surgical mask filters, air conditioning equipment filters, and air purifier filters, complemented with the use of viricidal agents that can destroy the trapped viruses, an application of broad interest for human beings.

Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.

BACKGROUND AND OBJECTIVES: Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear. We used rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in the sera of patients with ZIKV with and without GBS. METHODS: In this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. RESULTS: Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal root ganglia neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared with other controls, whereas IgM reactivity to cocultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from 1 patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV-infected patient without GBS displayed strong myelin-binding and putative antilipid antigen reaction characteristics. There was, however, no significant association of ZIKV-GBS with any known antiglycolipid antibodies. DISCUSSION: Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

Antibody deficiencies with normal IgG in adults with Non-cystic fibrosis bronchiectasis or recurrent pneumonia: Cross-sectional study.

Background: Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective: To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods: Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Results: Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions: Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.

Antecedentes: Los Errores Innatos de la Inmunidad principalmente las Deficiencias Predominantemente de anticuerpos con niveles normales de IgG no se conocen en adultos con enfermedades pulmonares como las bronquiectasias o la neumonía recurrente. Objetivo: Determinar las deficiencias de IgM, IgA y de subclase de IgG2 y la Deficiencia Específica de Anticuerpos (anticuerpos antineumocócicos de polisacáridos) en adultos con Bronquiectasias no Fibrosis Quística (BQnoFQ) o neumonía recurrente. Métodos: Estudio observacional prospectivo. Se reclutaron 110 pacientes consecutivos con BQnoFQ o neumonía recurrente en Cali, Colombia. Se midieron los niveles séricos de IgG, IgA, IgM e IgE, subclase IgG2 y anticuerpos anti-neumococo. Resultados: Se encontraron deficiencias de anticuerpos con niveles normales de IgG en el 10% de los sujetos; Cuatro casos con IgG2 baja, incluido 1 caso de deficiencia de IgG2 + IgA, 1 caso de ataxia-telangiectasia, 3 deficiencias de IgA (IgAD), 2 deficiencias selectiva de IgM (IgMD), 1 síndrome de Hiper-IgE (HIES-AR) y 1 deficiencia específica de anticuerpos. Ocho pacientes fueron diagnosticados con enfermedades relacionadas con la hipogammaglobulinemia IgG. Conclusiones: Las deficiencias predominantemente de anticuerpos con niveles normales de IgG son una etiología importante de BQnoFQ y neumonía recurrente en adultos. Los sujetos con bronquiectasias o neumonía recurrente requieren una evaluación exhaustiva de la respuesta inmune humoral y clínica.

A Rapid RT-LAMP Assay for SARS-CoV-2 with Colorimetric Detection Assisted by a Mobile Application.

Loop-mediated amplification has been promoted for SARS-CoV-2 screening, however, antigen tests are preferred in low-income countries and remote zones. Poor training in molecular biology, plus the need for RNA purification or reading instruments to overcome issues of sensitivity in colorimetric detection, are some of the reasons limiting the use of this technique. In this study, nasopharyngeal swabs, aspirates and saliva were amplified in an in-house LAMP assay and subject to colorimetric detection, achieved by the naked eye and by image analysis with a mobile application. Accuracy of detection by the naked eye ranged from 61-74% but improved to 75-86% when using the application. Sensitivity of the digital approach was 81% and specificity 83%, with poor positive predictive value, and acceptable negative predictive value. Additionally to the reported effect of some transport media's pH, the presence of mucus and warming up of reagents while setting up the reaction critically affected performance. Accuracy per type of sample was 55, 70 and 80%, for swabs, aspirates and saliva, respectively, suggesting potential to improve the test in saliva. This assay, carried out in a closed tube, reduces contamination, has few pipetting steps and requires minimal equipment. Strategies to improve performance and implications of the use this sort of colorimetric LAMP for massive testing are discussed.