Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.

Mouse and human immune responses share neutralization epitopes of HAstV-VA1.

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in human astroviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient's immunotherapy. In agreement with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, suggesting that both mouse and human antibody responses target shared neutralization epitopes. The isolated Nt-MAbs reported in this work will help to characterize the functional domains of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1. IMPORTANCE: Human astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. In this work high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1 were isolated and characterized. The proposed binding sites for these antibodies and for neutralizing antibodies against classical HAstVs suggest that there are at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will help to define the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

Outcomes after chimeric antigen receptor T-cell therapy across large B-cell lymphoma subtypes.

Not available.

Amyloid precursor protein induces reactive astrogliosis.

AIM: Astrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis. METHODS: We investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors. RESULTS: Overexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI. CONCLUSIONS: The APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.

Fistula espontánea de LCR como manifestación de la hipertensión intracraneal idiopática / Spontaneous CSF fistula as manifestation of idiopathic intracranial hypertension

Introducción: La fistula espontanea de líquido cefalorraquídeo (LCR) de origen desconocido, es una afección poco frecuente cuya etiología se relaciona cada vez más con la hipertensión intracraneal idiopática (HII). Este estudio trata de concienciar que no deben considerase como 2 procesos distintos, sino que las fistulas pueden ser una forma de inicio, requiriendo un estudio y tratamiento posterior. Se describen las técnicas de reparación, así como el estudio de la HII. Resultados: Se trataron 8 pacientes, 5 mujeres y 3 varones, con edades comprendidas entre 46 y 72 años, con diagnóstico de fistula espontánea de LCR, 4 nasales y 4 óticas a los que se le sometió a tratamiento quirúrgico. Tras la reparación se realizó un estudio diagnóstico para la HII mediante RMN y angio-RM, presentando en todos los casos una estenosis de seno venoso transverso. Los valores de presión intracraneal obtenidos mediante punción lumbar mostraron valores de 20mmHg o superiores. Todos los pacientes fueron diagnosticados de HII. El seguimiento a un año no reveló ninguna recidiva de las fistulas, manteniendo un control de la HII. Conclusión: A pesar de su escasa frecuencia tanto de las fistulas craneales de LCR como de la HII, debe considerarse una asociación de ambas afecciones continuando el estudio y vigilancia de estos pacientes tras el cierre de la fístula.(AU)

Introduction: Spontaneous cerebrospinal fluid (CSF) fistula, of unknown origin, is a rare condition whose etiology is increasingly related to idiopathic intracranial hypertension (IIH). This study tries to raise awareness that they should not be considered as two different processes, but that fistulas can be a form of debut, requiring a study and subsequent treatment. Repair techniques are described, as well as the study of IIH. Results: We treated eight patients, five women and three men, aged between 46 and 72 years, with a diagnosis of spontaneous CSF fistula, four nasal and four otics who underwent surgical treatment. After repair, a diagnostic study was performed for IIH by MRI and angio-MRI, presenting in all cases a transverse venous sinus stenosis. The intracranial pressure values obtained by lumbar puncture showed values of 20mmHg or higher. All patients were diagnosed with IIH. The one-year follow-up did not reveal any recurrence of the fistulas, maintaining a control of the IIH. Conclusion: Despite their low frequency of both cranial CSF fistula and IIH, an association of both conditions should be considered by continuing the study and surveillance of these patients after fistula closure.(AU)

Whole genome assembly and annotation of the King Angelfish (Holacanthus passer) gives insight into the evolution of marine fishes of the Tropical Eastern Pacific.

Holacanthus angelfishes are some of the most iconic marine fishes of the Tropical Eastern Pacific (TEP). However, very limited genomic resources currently exist for the genus. In this study we: (i) assembled and annotated the nuclear genome of the King Angelfish (Holacanthus passer), and (ii) examined the demographic history of H. passer in the TEP. We generated 43.8 Gb of ONT and 97.3 Gb Illumina reads representing 75× and 167× coverage, respectively. The final genome assembly size was 583 Mb with a contig N50 of 5.7 Mb, which captured 97.5% of the complete Actinoterygii Benchmarking Universal Single-Copy Orthologs (BUSCOs). Repetitive elements accounted for 5.09% of the genome, and 33,889 protein-coding genes were predicted, of which 22,984 were functionally annotated. Our demographic analysis suggests that population expansions of H. passer occurred prior to the last glacial maximum (LGM) and were more likely shaped by events associated with the closure of the Isthmus of Panama. This result is surprising, given that most rapid population expansions in both freshwater and marine organisms have been reported to occur globally after the LGM. Overall, this annotated genome assembly provides a novel molecular resource to study the evolution of Holacanthus angelfishes, while facilitating research into local adaptation, speciation, and introgression in marine fishes.

Exploration of low-frequency allelic variants of SARS-CoV-2 genomes reveals coinfections in Mexico occurred during periods of VOCs turnover.

A total of 14 973 alleles in 29 661 sequenced samples collected between March 2021 and January 2023 by the Mexican Consortium for Genomic Surveillance (CoViGen-Mex) and collaborators were used to construct a thorough map of mutations of the Mexican SARS-CoV-2 genomic landscape containing Intra-Patient Minor Allelic Variants (IPMAVs), which are low-frequency alleles not ordinarily present in a genomic consensus sequence. This additional information proved critical in identifying putative coinfecting variants included alongside the most common variants, B.1.1.222, B.1.1.519, and variants of concern (VOCs) Alpha, Gamma, Delta, and Omicron. A total of 379 coinfection events were recorded in the dataset (a rate of 1.28 %), resulting in the first such catalogue in Mexico. The most common putative coinfections occurred during the spread of Delta or after the introduction of Omicron BA.2 and its descendants. Coinfections occurred constantly during periods of variant turnover when more than one variant shared the same niche and high infection rate was observed, which was dependent on the local variants and time. Coinfections might occur at a higher frequency than customarily reported, but they are often ignored as only the consensus sequence is reported for lineage identification.

Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response.

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and also select a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in rotaviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient's immunotherapy. In accordance with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, indicating shared neutralization epitopes between the mouse and human antibody response. The isolated Nt-MAbs reported in this work will help characterize the functional sites of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1. Importance: Human astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. This work isolated high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1. The proposed binding sites for these antibodies, together with previously reported sites for neutralizing antibodies against classical HAstVs, suggest the existence of at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will be helpful in defining the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.

Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.

Immune response to SARS-CoV-2 variants after immunization with different vaccines in Mexico.

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.

Chemical analysis of wetland plants to evaluate the bioaccumulation and metabolism of hexachlorocyclohexane (HCH).

Hexachlorocyclohexanes (HCH) belong to the banned pesticides with short-time production and use during the last century. However, the consequences of this short period are still present as persistent environmental contamination. This study represents the large lab-scale experiment focused on the HCH accumulation and metabolism in selected wetland plants (Juncus effuses, Typha latifolia, Phragmites australis) and trees (Alnus glutinosa) after the exposure to the technical mix of HCH isomers (t-HCH) or δ-HCH at three different concentration. During the three-month exposure, morphological (biomass, height, relative chlorophyll content) and physiological (photosynthetic measurements - photosynthetic rate, stomatal conductance, transpiration and dark transpiration) parameters were measured to assess the HCH effect on plant's growth. The results showed that all selected plant species supported HCH removal from the soil. The total removal efficiency was lower for the t-HCH than for δ-HCH exposure, and the best results were provided by Alnus glutinosa tree. Also, no isomer preference was observed in plants exposed to t-HCH. Most HCH remained accumulated in the root biomass, and mainly α-HCH and δ-HCH were transported to the above-ground parts due to their physicochemical properties. Simultaneously, HCH uptake and metabolization to chlorobenzenes (CB) and chlorophenols (CP) occur. Non-targeted analysis showed that CP could be conjugated to glucose and malonyl in plant tissue, and secondary plant metabolism is affected positively and negatively after exposure to t-HCH depending on plant species and chemical concentration. Luteolin, quercetin and quercetin-3-O-glucoside found common to all species showed quantitative changes due to HCH. Nevertheless, most morphological and physiological parameters were adversely affected without statistical significance. This large-scale study provides information on the fate of HCH in the soil-plant system, the suitability of selected plants and their adaptation to chemical stress for use in the phytoremediation process.

Nucleolin-RNA interaction modulates rotavirus replication.

Rotavirus infection is a leading cause of gastroenteritis in children worldwide; the genome of this virus is composed of 11 segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, in rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 6.3-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA-binding domains. Under these conditions, viral production increased by 1.5-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all 11 RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through the direct interaction with the viral RNAs by sequences forming G4 structures.IMPORTANCEViruses rely on cellular proteins to carry out their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.

Usefulness of third ventricle volumetry in patients with normal pressure hydrocephalus.

OBJECTIVE: To use third ventricle morphometric variables as a tool for the selection of patients with idiopathic normal pressure hydrocephalus (iNPH) who are candidates for ventriculoperitoneal shunts (VPS). MATERIAL AND METHODS: Retrospective study enrolling patients with iNPH. Katzman infusion test was performed and a Rout > 12 mmHg/mL/min was considered a positive result. The transverse diameter and the volume of the third ventricle were measured in the preoperative MRI. Postoperative improvement was assessed with the NPH score. The results were analysed with SPSS software. RESULTS: 52 patients with a mean age of 76 years were analysed. There was no difference in the diameter of the third ventricle among patients with a positive result and those with a negative result in the infusion test (12.28 vs 11.68 mm; p = 0.14). Neither were difference detected in the ventricle volume of both groups (3.6 vs 3.5cc; p = 0.66). Those patients who improved after VPS had a smaller third ventricle compared to those who did not respond after surgery (11.85 mm vs. 12.96 mm; p = 0.009). Diameter and volume of third ventricle present a significant strong correlation (Pearson correlation coefficient = 0.72; p < 0.0001). CONCLUSION: Morphometric variables of third ventricle may be useful in predicting a good response to VPS in patients with idiopathic normal pressure hydrocephalus.

Constructed wetland mesocosms improve the biodegradation of microcystin-LR and cylindrospermopsin by indigenous bacterial consortia.

Cyanobacterial blooms releasing harmful cyanotoxins, such as microcystin (MC) and cylindrospermopsin (CYN), are prominent threats to human and animal health. Constructed wetlands (CW) may be a nature-based solution for bioremediation of lake surface water containing cyanotoxins, due to its low-cost requirement of infrastructure and environmentally friendly operation. There is recent evidence that microcystin-LR (MC-LR) can efficiently be removed in CW microcosms where CYN degradation in CW is unknown. Likewise, the mechanistic background regarding cyanotoxins transformation in CW is not yet elucidated. In the present study, the objective was to compare MC-LR and CYN degradation efficiencies by two similar microbial communities obtained from CW mesocosms, by two different experiments setup: 1) in vitro batch experiment in serum bottles with an introduced CW community, and 2) degradation in CW mesocosms. In experiment 1) MC-LR and CYN were spiked at 100 µg L-1 and in experiment 2) 200 µg L-1 were spiked. Results showed that MC-LR was degraded to ≤1 µg L-1 within seven days in both experiments. However, with a markedly higher degradation rate constant in the CW mesocosms (0.18 day-1 and 0.75 day-1, respectively). No CYN removal was detected in the in vitro incubations, whereas around 50 % of the spiked CYN was removed in the CW mesocosms. The microbial community responded markedly to the cyanotoxin treatment, with the most prominent increase of bacteria affiliated with Methylophilaceae (order: Methylophilales, phylum: Proteobacteria). The results strongly indicate that CWs can develop an active microbial community capable of efficient removal of MC-LR and CYN. However, the CW operational conditions need to be optimized to achieve a full CYN degradation. To the best of our knowledge, this study is the first to report the ability of CW mesocosms to degrade CYN.

Cyanobacterial blooms in surface waters - Nature-based solutions, cyanotoxins and their biotransformation products.

Cyanobacterial blooms are expected to become more frequent and severe in surface water reservoirs due to climate change and ecosystem degradation. It is an emerging challenge that especially countries relying on surface water supplies will face. Nature-based solutions (NBS) like constructed wetlands and biofilters can be used for cyanotoxin remediation. Both technologies are reviewed and critically assessed for different types of water resources. The available information on cyanotoxins (bio)transformation products (TPs) is reviewed to point out the potential research gaps and to disclose the most reliable enzymatic degradation pathways. Knowledge gaps were found, such as information on the performance of the revised NBS in pilot and full scales, the removal processes covering different cyanotoxins (besides the most widely studied microcystin-LR), and the difficulties for real-world implementation of technologies proposed in the literature. Also, most studies focus on bacterial degradation processes while fungi have been completely overlooked. This review also presents an up-to-date overview of the transformation of cyanotoxins, where degradation product data was compiled in a unified library of 22 metabolites for microcystins (MCs), 7 for cylindrospermopsin (CYN) and 10 for nodularin (NOD), most of them reported only in a single study. Major gaps are the lack of environmentally relevant studies with TPs in pilot and full- scale treatment systems, information on TP's toxicity, as well as limited knowledge of environmentally relevant degradation pathways. NBS have the potential to mitigate cyanotoxins in recreational and irrigation waters, enabling the water-energy-food nexus and avoiding the degradability of the ecosystems.

Spontaneous CSF fistula as a manifestation of idiopathic intracranial hypertension.

INTRODUCTION: Spontaneous cerebrospinal fluid (CSF) fistula, of unknown origin, is a rare condition whose aetiology is increasingly related to idiopathic intracranial hypertension (IIH). This study tries to raise awareness that they should not be considered as two different processes, but that fistulas can be a form of debut, requiring a study and subsequent treatment. Repair techniques are described, as well as the study of HII. RESULTS: We treated 8 patients, 5 women and three men, aged between 46 and 72 years, with a diagnosis of spontaneous CSF fistula, four nasal and four otics who underwent surgical treatment. After repair, a diagnostic study was performed for IIH by MRI and Angio-MRI, presenting in all cases a transverse venous sinus stenosis. The intracranial pressure values obtained by lumbar puncture showed values of 20mm Hg or higher. All patients were diagnosed with HII. The one-year follow-up did not reveal any recurrence of the fistulas, maintaining a control of the HII. CONCLUSION: Despite their low frequency of both cranial CSF fistula and IIH, an association of both conditions should be considered by continuing the study and surveillance of these patients after fistula closure.

Combination of advanced biological systems and photocatalysis for the treatment of real hospital wastewater spiked with carbamazepine: A pilot-scale study.

Over the past few decades, the increase in dependency on healthcare facilities has led to the generation of large quantities of hospital wastewater (HWW) rich in chemical oxygen demand (COD), total suspended solids (TSS), ammonia, recalcitrant pharmaceutically active compounds (PhACs), and other disease-causing microorganisms. Conventional treatment methods often cannot effectively remove the PhACs present in wastewater. Hence, hybrid processes comprising of biological treatment and advanced oxidation processes have been used recently to treat complex wastewater. The current study explores the performance of pilot-scale treatment of real HWW (3000 L/d) spiked with carbamazepine (CBZ) using combinations of moving and stationary bed bio-reactor-sedimentation tank (MBSST), aerated horizontal flow constructed wetland (AHFCW), and photocatalysis. The combination of MBSST and AHFCW could remove 85% COD, 93% TSS, 99% ammonia, and 30% CBZ. However, when the effluent of the AHFCW was subjected to photocatalysis, an enhanced CBZ removal of around 85% was observed. Furthermore, the intermediate products (IPs) formed after the photocatalysis was also less toxic than the IPs formed during the biological processes. The results of this study indicated that the developed pilot-scale treatment unit supplemented with photocatalysis could be used effectively to treat HWW.

Biodiversity in wetland+ system: a passive solution for HCH dump effluents.

The hexachlorocyclohexane isomers (HCH) are long-banned pesticides. Even though their use has been prohibited for decades, their presence in the environment is still reported worldwide. Wetland + is a registered trademark of the remedial treatment technology consisting of an aerobic sedimentary tank, a permeable reactive barrier, a biosorption system, and an aerobic wetland. This proven method combines a reductive treatment known from PRBs with the natural wetland self-cleaning processes. The average efficiency of the system is 96.8% for chlorobenzenes (ClB) and 81.7% for HCH, during the first 12 months of the system operation. The presence of the genes encoding enzymes involved in the degradation of the HCH compounds indicates that the removal of HCH and ClB occurs not only by chemical removal but also through aerobic and anaerobic combining biodegradation. Changes in abundance and the composition of the diatom community were found to be suitable indicators of the water quality and of the impact of the Wetland + operation on the water ecosystem. The system's annual operation exhibited a markedly higher number of diatom species in the closing profiles of the Ostrovský Creek, the Wetland + effluent recipient.

SARS-CoV-2 Omicron variants BA.4 and BA.5 dominated the fifth COVID-19 epidemiological wave in Mexico.

In Mexico, the BA.4 and BA.5 Omicron variants dominated the fifth epidemic wave (summer 2022), superseding BA.2, which had circulated during the inter-wave period. The present study uses genome sequencing and statistical and phylogenetic analyses to examine these variants' abundance, distribution, and genetic diversity in Mexico from April to August 2022. Over 35 % of the sequenced genomes in this period corresponded to the BA.2 variant, 8 % to the BA.4 and 56 % to the BA.5 variant. Multiple subvariants were identified, but the most abundant, BA.2.9, BA.2.12.1, BA.5.1, BA.5.2, BA.5.2.1 and BA.4.1, circulated across the entire country, not forming geographical clusters. Contrastingly, other subvariants exhibited a geographically restricted distribution, most notably in the Southeast region, which showed a distinct subvariant dynamic. This study supports previous results showing that this region may be a significant entry point and contributed to introducing and evolving novel variants in Mexico. Furthermore, a differential distribution was observed for certain subvariants among specific States through time, which may have contributed to the overall increased diversity observed during this wave compared to the previous ones. This study highlights the importance of sustaining genomic surveillance to identify novel variants that may impact public health.