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The genus Pseudochrobactrum encompasses free-living bacteria phylogenetically close to Ochrobactrum opportunistic pathogens and to Brucella, facultative intracellular parasites causing brucellosis, a worldwide-extended and grave zoonosis. Recently, Pseudochrobactrum strains were isolated from Brucella natural hosts on Brucella selective media, potentially causing diagnostic confusions. Strikingly, P. algeriensis was isolated from cattle lymph nodes, organs that are inimical to bacteria. Here, we analyse P. algeriensis potential virulence factors in comparison with Ochrobactrum and Brucella. Consistent with genomic analyses, Western-Blot analyses confirmed that P. algeriensis lacks the ability to synthesize the N-formylperosamine O-polysaccharide characteristic of the lipopolysaccharide (LPS) of smooth Brucella core species. However, unlike other Pseudochrobactrum but similar to some early diverging brucellae, P. algeriensis carries genes potentially synthetizing a rhamnose-based O-polysaccharide LPS. Lipid A analysis by MALDI-TOF demonstrated that P. algeriensis LPS bears a lipid A with a reduced pathogen-associated molecular pattern, a trait shared with Ochrobactrum and Brucella that is essential to generate a highly stable outer membrane and to delay immune activation. Also, although not able to multiply intracellularly in macrophages, the analysis of P. algeriensis cell lipid envelope revealed the presence of large amounts of cationic aminolipids, which may account for the extremely high resistance of P. algeriensis to bactericidal peptides and could favor colonization of mucosae and transient survival in Brucella hosts. However, two traits critical in Brucella pathogenicity are either significantly different (T4SS [VirB]) or absent (erythritol catabolic pathway) in P. algeriensis. This work shows that, while diverging in other characteristics, lipidic envelope features relevant in Brucella pathogenicity are conserved in Brucellaceae. The constant presence of these features strongly suggests that reinforcement of the envelope integrity as an adaptive advantage in soil was maintained in Brucella because of the similarity of some environmental challenges, such as the action of cationic peptide antibiotics and host defense peptides. This information adds knowledge about the evolution of Brucellaceae, and also underlines the taxonomical differences of the three genera compared., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Etelcalcetide is an i.v. calcimimetic agent, effectively reducing parathyroid hormone levels in patients on maintenance hemodialysis (HD). The clinical impact of discontinuing etelcalcetide at the time of kidney transplantation is unknown., Methods: We retrospectively reviewed all patients on HD meeting predefined criteria who received a kidney transplant at our institution between January 1, 2015, and December 12, 2022. The incidence of parathyroidectomy and the evolution of calcium, phosphate, and intact parathyroid hormone (iPTH) levels after transplantation was analyzed according to the type of calcimimetic treatment before transplantation (cinacalcet vs. etelcalcetide vs. none)., Results: Overall, 372 patients (aged 53 years; interquartile range [IQR]: 42-62 years) were included. At the time of transplantation, 35, 75, and 262 patients were under etelcalcetide, cinacalcet, or no calcimimetic, respectively. After 1064 (IQR: 367-1658) days, the incidences of parathyroidectomy in the etelcalcetide, cinacalcet, no calcimimetic groups were 29%, 12%, and 1%, respectively ( P  < 0.001). Etelcalcetide was associated with an increased incidence of parathyroidectomy after adjustment for age, sex, and HD vintage (hazard ratio [HR]: 97.0, 95% confidence interval [CI]: 19.1-493.9, P  < 0.001). The incidence of parathyroidectomy was related to etelcalcetide dosage (6/11 [54.6%] in patients with ≥ 10 mg vs. 4/24 [16.7%] in patients with < 10 mg, P  = 0.02). Moreover, peak calcium levels were higher ( P  < 0.001) and parathyroidectomy was performed earlier (median 80 vs. 480 days, P  < 0.001) in the etelcalcetide compared with the cinacalcet group. Long-term graft function, graft loss, and mortality were similar., Conclusion: Etelcalcetide use during maintenance HD is associated with an increased incidence of early parathyroidectomy after transplantation compared to cinacalcet or no calcimimetic., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Endoscopic retrograde cholangiopancreatography (ERCP) has been established as the first line therapy for the resolution of biliary and pancreatic diseases. The main disadvantage of the procedure is the rate of adverse events, around 10%1. So, despite being a minimally invasive procedure, ERCP has a non-negligible rate of adverse effects (AEs) and secondary mortality.

Brucellosis is a worldwide extended zoonosis caused by pathogens of the genus Brucella . While most B. abortus , B. melitensis , and B. suis biovars grow slowly in complex media, they multiply intensely in livestock genitals and placenta indicating high metabolic capacities. Mutant analyses in vitro and in infection models emphasize that erythritol (abundant in placenta and genitals) is a preferred substrate of brucellae, and suggest hexoses, pentoses, and gluconeogenic substrates use in host cells. While Brucella sugar and erythritol catabolic pathways are known, growth on 3-4 carbon substrates persists in Fbp- and GlpX-deleted mutants, the canonical gluconeogenic fructose 1,6-bisphosphate (F1,6bP) bisphosphatases. Exploiting the prototrophic and fast-growing properties of B. suis biovar 5, we show that gluconeogenesis requires fructose-bisphosphate aldolase (Fba); the existence of a novel broad substrate bisphosphatase (Bbp) active on sedoheptulose 1,7-bisphosphate (S1,7bP), F1,6bP, and other phosphorylated substrates; that Brucella Fbp unexpectedly acts on S1,7bP and F1,6bP; and that, while active in B. abortus and B. melitensis , GlpX is disabled in B. suis biovar 5. Thus, two Fba-dependent reactions (dihydroxyacetone-phosphate + glyceraldehyde 3-phosphate ⇌ F1,6bP; and dihydroxyacetone-phosphate + erythrose 4-phosphate ⇌ S1,7bP) can, respectively, yield fructose 6-phosphate and sedoheptulose 7-phosphate for classical gluconeogenesis and the Pentose Phosphate Shunt (PPS), the latter reaction opening a new gluconeogenic route. Since erythritol generates the PPS-intermediate erythrose 4-phosphate, and the Fba/Fbp-Bbp route predicts sedoheptulose 7-phosphate generation from erythrose 4-phosphate, we re-examined the erythritol connections with PPS. Growth on erythritol required transaldolase or the Fba/Fbp-Bbp pathway, strongly suggesting that Fba/Fbp-Bbp works as a PPS entry for both erythritol and gluconeogenic substrates in Brucella . We propose that, by increasing erythritol channeling into PPS through these peculiar routes, brucellae proliferate in livestock genitals and placenta in the high numbers that cause abortion and infertility, and make brucellosis highly contagious. These findings could be the basis for developing attenuated brucellosis vaccines safer in pregnant animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lázaro-Antón, Veiga-da-Cunha, Elizalde-Bielsa, Chevalier, Conde-Álvarez, Iriarte, Letesson, Moriyón, Van Schaftingen and Zúñiga-Ripa.)

Introduction: This study aimed to evaluate the association between the use of remote patient monitoring (RPM) in patients on automated peritoneal dialysis (APD) and the Standardized Outcomes in Nephrology in peritoneal dialysis (SONG-PD) clinical outcomes., Methods: A prospective and multicenter cohort study was conducted on patients with advanced chronic kidney disease on APD, recruited at 16 Spanish Hospitals, between June 1 and December 31, 2021. Patients were divided into 2 cohorts, namely patients on APD with RPM (APD-RPM) and patients on APD without RPM. The primary endpoints were the standardized outcomes of the SONG-PD clinical outcomes: PD-associated infection, cardiovascular disease (CVD), mortality rate, technique survival, and life participation (assessed as health-related quality of life [QoL]). Propensity score matching (PSM) was used to evaluate the association of RPM exposure with the clinical outcomes., Results: A total of 232 patients were included, 176 (75.9%) in the APD-RPM group and 56 (24.1%) in the APD-without-RPM group. The mean patient follow-up time was significantly longer in the APD-RPM group than in the APD-without-RPM group (10.4 ± 2.8 vs. 9.4 ± 3.1 months, respectively; P  = 0.02). In the overall study sample, the APD-RPM group was associated with a lower mortality rate (hazard ratio [HR]: 0.08; 95% confidence interval [CI]: 0.01 to 0.69; P  = 0.020) and greater technique survival rate (HR: 0.25; 95% CI: 0.11 to 0.59; P  = 0.001). After PSM, APD-RPM continued to be associated with better technique survival (HR: 0.23; 95% CI: 0.06 to 0.83; P  = 0.024)., Conclusion: The use of RPM programs in patients on APD was associated with better survival of the technique and lower mortality rates. However, after PSM, only technique survival was significant., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Con el fin de conocer un índice de selección para el peso al nacer y al destete en la finca Costa Rica, Montería (Colombia), se analizaron 895 registros, de los cuales se obtuvieron las covarianzas y varianzas genéticas y fenotípicas, para la construcción de un determinante, y a través de cálculos algebraicos se obtuvo la ecuación I = x 1 + 0.4215 x2, con la cual se seleccionaron los animales que presentaron un mayor índice.

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related Ochrobactrum spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic Ochrobactrum spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or Ochrobactrum ; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and Ochrobactrum genera separate to avoid further bewilderment and harm., Competing Interests: The authors declare no conflict of interest.

The main purpose of this study was to evaluate the effects of a package of activities, known as "Portfolio", on cognitive functioning, self-regulation, and academic achievement. The study was carried out with a group of 40 students from Compulsory Secondary Education (mean age 13 years old) during 120 hours distributed over two school years. A quasi-experimental pretest-posttest-1 and posttest-2 design was employed. Treatment consisted of the administration of specifically selected tasks, assessed in previous studies, from the psycho-pedagogical Instrumental Enrichment Program, the Philosophy for Children Program, and Project Intelligence. The students were evaluated in the criteria variables at the beginning and at the end of treatment, and once again two years later. The results indicate that the procedure was effective in all the variables studied and that the gains observed at posttest-1 were maintained for at least two years after the intervention. Some relevant conclusions and suggestions at the educational and scientific level are commented upon. (Contains 3 tables.)

Examined the effects of teaching self-regulation strategies and social skills to 40 middle school students who presented difficulties in self-reflection, self-inquiry, assertiveness, and empathy. Significant gains were observed in the experimental group in self-regulation of learning, self-control of behavior, assertiveness, empathy, and consideration of others. (SLD)

Epicardially derived cells (EPDCs) delaminate from the primitive epicardium through an epithelial-to-mesenchymal transformation (EMT). After this transformation, a subpopulation of cells progressively invades myocardial and valvuloseptal tissues. The first aim of the study was to determine the tissue-specific distribution of two molecules that are thought to play a crucial function in the interaction between EPDCs and other cardiac tissues, namely the Wilms' Tumor transcription factor (WT1) and retinaldehyde-dehydrogenase2 (RALDH2). This study was performed in normal avian and in quail-to-chick chimeric embryos. It was found that EPDCs that maintain the expression of WT1 and RALDH2 initially populate the subepicardial space and subsequently invade the ventricular myocardium. As EPDCs differentiate into the smooth muscle and endothelial cell lineage of the coronary vessels, the expression of WT1 and RALDH2 becomes downregulated. This process is accompanied by the upregulation of lineage-specific markers. We also observed EPDCs that continued to express WT1 (but very little RALDH2) which did not contribute to the formation of the coronary system. A subset of these cells eventually migrates into the atrioventricular (AV) cushions, at which point they no longer express WT1. The WT1/ RALDH2-negative EPDCs in the AV cushions do, however, express the smooth muscle cell marker caldesmon. The second aim of this study was to determine the impact of abnormal epicardial growth on cardiac development. Experimental delay of epicardial growth distorted normal epicardial development, reduced the number of invasive WT1/RALDH2-positive EPDCs, and provoked anomalies in the coronary vessels, the ventricular myocardium, and the AV cushions. We suggest that the proper development of ventricular myocardium is dependent on the invasion of undifferentiated, WT1-positive, retinoic acid-synthesizing EPDCs. Furthermore, we propose that an interaction between EPDCs and endocardial (derived) cells is imperative for correct development of the AV cushions. Key Words: cardiac development; EPDCs; epicardium; RALDH2; WT1.

Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the main cause of human brucellosis. B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with an N-formyl-perosamine O-polysaccharide (O-PS) that is absent in the rough LPS of B. ovis. Their control and eradication require vaccination, but B. melitensis Rev 1, the only vaccine available, triggers anti-O-PS antibodies that interfere in the S-brucellae serodiagnosis. Since eradication and serological surveillance of the zoonotic species are priorities, Rev 1 is banned once B. melitensis is eradicated or where it never existed, hampering B. ovis control and eradication. To develop a B. ovis specific vaccine, we investigated three Brucella live vaccine candidates lacking N-formyl-perosamine O-PS: Bov::CAΔwadB (CO 2 -independent B. ovis with truncated LPS core oligosaccharide); Rev1::wbdRΔwbkC (carrying N-acetylated O-PS); and H38ΔwbkF (B. melitensis rough mutant with intact LPS core). After confirming their attenuation and protection against B. ovis in mice, were tested in rams for efficacy. H38ΔwbkF yielded similar protection to Rev 1 against B. ovis but Bov::CAΔwadB and Rev1::wbdRΔwbkC conferred no or poor protection, respectively. All H38ΔwbkF vaccinated rams developed a protracted antibody response in ELISA and immunoprecipitation B. ovis diagnostic tests. In contrast, all remained negative in Rose Bengal and complement fixation tests used routinely for B. melitensis diagnosis, though some became positive in S-LPS ELISA owing to LPS core epitope reactivity. Thus, H38ΔwbkF is an interesting candidate for the immunoprophylaxis of B. ovis in B. melitensis-free areas., (© 2022. The Author(s).)

Lactide-valerolactone copolymers have potential application in the packaging sector. Different copolymers were synthesized, and the kinetics of the copolymerization reactions and the microstructure of the copolymers were analysed. Lactide showed higher reactivity than valerolactone which leads to composition drift through the reaction. Thermal, mechanical and barrier properties of the selected copolymers were studied. Overall, the incorporation of valerolactone results in copolymers with higher ductility than poly(lactide) with intermediate water and oxygen permeability which makes these materials appropriate candidates for use in the packaging sector.

Bovine brucellosis induces abortion in cows, produces important economic losses, and causes a widely distributed zoonosis. Its eradication was achieved in several countries after sustained vaccination with the live attenuated Brucella abortus S19 vaccine, in combination with the slaughtering of serologically positive animals. S19 induces antibodies against the smooth lipopolysaccharide (S-LPS), making difficult the differentiation of infected from vaccinated bovines. We developed an S19 strain constitutively expressing the green fluorescent protein (S19-GFP) coded in chromosome II. The S19-GFP displays similar biological characteristics and immunogenic and protective efficacies in mice to the parental S19 strain. S19-GFP can be distinguished from S19 and B. abortus field strains by fluorescence and multiplex PCR. Twenty-five heifers were vaccinated withS19-GFP (5×109 CFU) by the subcutaneous or conjunctival routes and some boosted with GFP seven weeks thereafter. Immunized animals were followed up for over three years and tested for anti-S-LPS antibodies by both the Rose Bengal test and a competitive ELISA. Anti-GFP antibodies were detected by an indirect ELISA and Western blotting. In most cases, anti-S-LPS antibodies preceded for several weeks those against GFP. The anti-GFP antibody response was higher in the GFP boosted than in the non-boosted animals. In all cases, the anti-GFP antibodies persisted longer, or at least as long, as those against S-LPS. The drawbacks and potential advantages of using the S19-GFP vaccine for identifying vaccinated animals in infected environments are discussed., Competing Interests: The authors have declared that no competing interests exist.

Background: Disproportionate fear of contracting COVID-19 (coronaphobia) may result in inappropriate use of preventive measures that could, in turn, result in severe harm to the patient., Objective: To describe a patient with subacute parkinsonism and cognitive dysfunction and magnetic resonance imaging (MRI) evidence of bilateral deep white matter and basal ganglia damage., Case Presentation: A 56-year-old female presented with a 4-week history of insomnia, cognitive decline, and parkinsonism. Brain MRI revealed a bilateral lesion of both globus pallidus, deep white matter, and cerebellar hemispheres. Her son reported that, for the previous month, she had been cleaning her facial mask three times a day with a pure methanol solution as a disinfectant due to an intense fear of acquiring COVID-19. Previously, she had used 97% isopropyl alcohol and had inadvertently switched to methanol. After the exposure ended, she slowly improved but 4 months later she remains severely disabled., Conclusions: The repeated exposure to methanol vapor, the MRI findings, and the absence of other etiologies for her cognitive and parkinsonian features led to the diagnosis of chronic methanol intoxication with severe central nervous system damage. Misinformation is a likely contributory factor to such scenario. Efforts should be made by the scientific community to educate the general public on avoiding self-damaging behaviors as a result of coronaphobia., (© 2021 European Academy of Neurology.)

The brucellae are facultative intracellular bacteria with a cell envelope rich in phosphatidylcholine (PC). PC is abundant in eukaryotes but rare in prokaryotes, and it has been proposed that Brucella uses PC to mimic eukaryotic-like features and avoid innate immune responses in the host. Two PC synthesis pathways are known in prokaryotes: the PmtA-catalyzed trimethylation of phosphatidylethanolamine and the direct linkage of choline to CDP-diacylglycerol catalyzed by the PC synthase Pcs. Previous studies have reported that B. abortus and B. melitensis possess non-functional PmtAs and that PC is synthesized exclusively via Pcs in these strains. A putative choline transporter ChoXWV has also been linked to PC synthesis in B. abortus . Here, we report that Pcs and Pmt pathways are active in B. suis biovar 2 and that a bioinformatics analysis of Brucella genomes suggests that PmtA is only inactivated in B. abortus and B. melitensis strains. We also show that ChoXWV is active in B. suis biovar 2 and conserved in all brucellae except B. canis and B. inopinata. Unexpectedly, the experimentally verified ChoXWV dysfunction in B. canis did not abrogate PC synthesis in a PmtA-deficient mutant, which suggests the presence of an unknown mechanism for obtaining choline for the Pcs pathway in Brucella . We also found that ChoXWV dysfunction did not cause attenuation in B. suis biovar 2. The results of these studies are discussed with respect to the proposed role of PC in Brucella virulence and how differential use of the Pmt and Pcs pathways may influence the interactions of these bacteria with their mammalian hosts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aragón-Aranda, Palacios-Chaves, Salvador-Bescós, de Miguel, Muñoz, Vences-Guzmán, Zúñiga-Ripa, Lázaro-Antón, Sohlenkamp, Moriyón, Iriarte and Conde-Álvarez.)

The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner-Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites. [ABSTRACT FROM AUTHOR]

Background: An increasing number of neurologic problems are being described in coronavirus disease 2019 (COVID-19) disease, but their frequency and type have not been defined. In this study, we sought to determine the extent of neurologic manifestations of COVID-19 in a prospective series of unselected patients admitted to the general medicine wards of our hospitals due to COVID-19 and who were examined by a team of neurologists., Methods: Eight neurologists provided medical attention to patients hospitalized for COVID-19 to provide medical support to other hospital units tasked with the care of an increasingly larger influx of patients with COVID-19. A series of 100 consecutive, unselected patients were evaluated systematically, including a questionnaire that collected medical information derived from the initial examination and the medical history., Results: Eighty-eight percent of the patients had 1 neurologic manifestation associated with COVID-19 during hospitalization. Most common were anosmia-dysgeusia and headache (44% each), myalgias (43%), and dizziness (36%). Less frequent were encephalopathy (8%), syncope (7%), seizures (2%), and ischemic stroke during the period of hospitalization (2%). Anosmia and headache associated with younger patients with less severe disease, and both were associated with each other and with serum inflammatory markers. Encephalopathy was associated with fever and syncope and with markers of inflammation., Conclusions: Neurologic disturbances are common in patients with COVID-19, particularly if patients are evaluated by neurologists. There is a wide variety of neurologic conditions, some of them severe, in the spectrum of COVID-19 disease that will benefit from an evaluation by practicing neurologists., (© 2020 American Academy of Neurology.)

Brucella species cause brucellosis, a worldwide extended zoonosis. The brucellae are related to free-living and plant-associated α2- Proteobacteria and, since they multiply within host cells, their metabolism probably reflects this adaptation. To investigate this, we used the rodent-associated Brucella suis biovar 5, which in contrast to the ruminant-associated Brucella abortus and Brucella melitensis and other B. suis biovars, is fast-growing and conserves the ancestral Entner-Doudoroff pathway (EDP) present in the plant-associated relatives. We constructed mutants in Edd (glucose-6-phosphate dehydratase; first EDP step), PpdK (pyruvate phosphate dikinase; phosphoenolpyruvate ⇌ pyruvate), and Pyk (pyruvate kinase; phosphoenolpyruvate → pyruvate). In a chemically defined medium with glucose as the only C source, the Edd mutant showed reduced growth rates and the triple Edd-PpdK-Pyk mutant did not grow. Moreover, the triple mutant was also unable to grow on ribose or xylose. Therefore, B. suis biovar 5 sugar catabolism proceeds through both the Pentose Phosphate shunt and EDP, and EDP absence and exclusive use of the shunt could explain at least in part the comparatively reduced growth rates of B. melitensis and B. abortus . The triple Edd-PpdK-Pyk mutant was not attenuated in mice. Thus, although an anabolic use is likely, this suggests that hexose/pentose catabolism to pyruvate is not essential for B. suis biovar 5 multiplication within host cells, a hypothesis consistent with the lack of classical glycolysis in all Brucella species and of EDP in B. melitensis and B. abortus . These results and those of previous works suggest that within cells, the brucellae use mostly 3 and 4 C substrates fed into anaplerotic pathways and only a limited supply of 5 and 6 C sugars, thus favoring the EDP loss observed in some species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lázaro-Antón, de Miguel, Barbier, Conde-Álvarez, Muñoz, Letesson, Iriarte, Moriyón and Zúñiga-Ripa.)

Background: COVID-19 disease affects the nervous system and led to an increase in neurological consults for patients at admission and through the period of hospitalization during the peak of the pandemic., Methods: Patients with clinical and laboratory diagnosis of COVID-19 that required a neurologic consultation or those who presented with neurological problems on admission that led to a diagnosis of SARS-CoV-2 infection during a 2-month period at the peak of the pandemic were included in this study. Demographic and clinical variables were analyzed., Results: Thirty-five patients were included. The presenting neurologic manifestations on admission led to the diagnosis of COVID-19 in 14 patients (40%). The most common reasons for consultation during the hospitalization period were stroke (11), encephalopathy (7), seizures (6), and neuropathies (5) followed by a miscellaneous of syncope (2), migraine (1), anosmia (1), critical illness myopathy (1), and exacerbation of residual dysarthria (1). The most common neurological disturbances were associated with severe disease except for neuropathies. Patients with encephalopathies and seizures had markedly increased D-dimer and ferritin values, even higher than stroke patients. RT-PCR was performed in 8 CSF samples and was negative in all of them., Conclusion: Neurological disturbances represent a significant and severe burden in COVID-19 patients, and they can be the presenting condition that leads to the diagnosis of the viral infection in a high percentage of patients. Evidence of direct viral mechanisms was scarce, but the pathogenesis of the diverse manifestations remains enigmatic.