Unlocking the microbiome.

Individual species of bacteria and yeast present in the food of wild fruit flies work together to provide the nutrients needed for larval growth.

Botulinum toxin in the treatment of residual limb hyperhidrosis: A systematic review / Toxina botulínica para el tratamiento de la hiperhidrosis del miembro residual: revisión sistemática

The aim of the study was to analyze the current evidence regarding the effect of intradermal injections of botulinum toxin on residual limb hyperhidrosis. A comprehensive search of the MEDLINE and Scopus databases from inception until December 2021 was performed according to the PRISMA guidelines. The search terms used were “botulinum toxins”, “botulinum toxins, Type A”, “rimabotulinumtoxinB”, “amputees”, “amputation stumps”, “amputation” and “residual limbs”. The specific controlled vocabulary of each database was also used (e.g., MeSH). One hundred and thirty-one different studies met this search criteria and were reviewed. Two independent reviewers assessed the quality of the manuscripts. Eight studies met the inclusion criteria for this review. The results demonstrated an improvement in residual limb hyperhidrosis in all studies. Botulinum toxin A or B can be regarded as safe and effective for the treatment of residual limb hyperhidrosis, as well as improving prosthesis use and quality of life.(AU)

El objetivo de este estudio fue analizar la evidencia actual relacionada con el efecto de las inyecciones intradérmicas de toxina botulínica en la hiperhidrosis del miembro residual. Se realizó una búsqueda amplia en las bases de datos MEDLINE y Scopus desde su inicio hasta diciembre de 2021 con arreglo a las guías PRISMA. Los términos de la búsqueda utilizados fueron «botulinum toxins», «botulinum toxins, type A», «rimabotulinumtoxin B», «amputees», «amputation stumps», «amputation» y «residual limbs». También se utilizó el vocabulario controlado específico de cada base de datos (ej.: MeSH). Cumplieron estos criterios de búsqueda 131 estudios diferentes, que fueron revisados. Dos revisores independientes evaluaron la calidad de los documentos y 8 estudios cumplieron los criterios de inclusión. Los resultados demostraron la mejora de la hiperhidrosis del miembro residual en todos los estudios. La toxina botulínica A o B puede considerarse segura y efectiva para el tratamiento de la hiperhidrosis del miembro residual y mejora el uso de la prótesis y la calidad de vida.(AU)

A neurorobotics approach to behaviour selection based on human activity recognition.

Behaviour selection has been an active research topic for robotics, in particular in the field of human-robot interaction. For a robot to interact autonomously and effectively with humans, the coupling between techniques for human activity recognition and robot behaviour selection is of paramount importance. However, most approaches to date consist of deterministic associations between the recognised activities and the robot behaviours, neglecting the uncertainty inherent to sequential predictions in real-time applications. In this paper, we address this gap by presenting an initial neurorobotics model that embeds, in a simulated robot, computational models of parts of the mammalian brain that resembles neurophysiological aspects of the basal ganglia-thalamus-cortex (BG-T-C) circuit, coupled with human activity recognition techniques. A robotics simulation environment was developed for assessing the model, where a mobile robot accomplished tasks by using behaviour selection in accordance with the activity being performed by the inhabitant of an intelligent home. Initial results revealed that the initial neurorobotics model is advantageous, especially considering the coupling between the most accurate activity recognition approaches and the computational models of more complex animals.

Botulinum toxin in the treatment of residual limb hyperhidrosis: A systematic review.

The aim of the study was to analyze the current evidence regarding the effect of intradermal injections of botulinum toxin on residual limb hyperhidrosis. A comprehensive search of the MEDLINE and Scopus databases from inception until December 2021 was performed according to the PRISMA guidelines. The search terms used were "botulinum toxins", "botulinum toxins, Type A", "rimabotulinumtoxinB", "amputees", "amputation stumps", "amputation" and "residual limbs". The specific controlled vocabulary of each database was also used (e.g., MeSH). One hundred and thirty-one different studies met this search criteria and were reviewed. Two independent reviewers assessed the quality of the manuscripts. Eight studies met the inclusion criteria for this review. The results demonstrated an improvement in residual limb hyperhidrosis in all studies. Botulinum toxin A or B can be regarded as safe and effective for the treatment of residual limb hyperhidrosis, as well as improving prosthesis use and quality of life.

Polymyxin Resistance in Clinical Isolates of K. pneumoniae in Brazil: Update on Molecular Mechanisms, Clonal Dissemination and Relationship With KPC-Producing Strains.

In Brazil, the production of KPC-type carbapenemases in Enterobacteriales is endemic, leading to widespread use of polymyxins. In the present study, 502 Klebsiella pneumoniae isolates were evaluated for resistance to polymyxins, their genetic determinants and clonality, in addition to the presence of carbapenem resistance genes and evaluation of antimicrobial resistance. Resistance to colistin (polymyxin E) was evaluated through initial selection on EMB agar containing 4% colistin sulfate, followed by Minimal Inhibitory Concentration (MIC) determination by broth microdilution. The susceptibility to 17 antimicrobials was assessed by disk diffusion. The presence of blaKPC, blaNDM and blaOXA-48-like carbapenemases was investigated by phenotypic methods and conventional PCR. Molecular typing was performed by PFGE and MLST. Allelic variants of the mcr gene were screened by PCR and chromosomal mutations in the pmrA, pmrB, phoP, phoQ and mgrB genes were investigated by sequencing. Our work showed a colistin resistance frequency of 29.5% (n = 148/502) in K. pneumoniae isolates. Colistin MICs from 4 to >128 µg/mL were identified (MIC50 = 64 µg/mL; MIC90 >128 µg/mL). All isolates were considered MDR, with the lowest resistance rates observed for amikacin (34.4%), and 19.6% of the isolates were resistant to all tested antimicrobials. The blaKPC gene was identified in 77% of the isolates, in consonance with the high rate of resistance to polymyxins related to its use as a therapeutic alternative. Through XbaI-PFGE, 51 pulsotypes were identified. MLST showed 21 STs, with ST437, ST258 and ST11 (CC11) being the most prevalent, and two new STs were determined: ST4868 and ST4869. The mcr-1 gene was identified in 3 K. pneumoniae isolates. Missense mutations in chromosomal genes were identified, as well as insertion sequences in mgrB. Furthermore, the identification of chromosomal mutations in K. pneumoniae isolates belonging from CC11 ensures its success as a high-risk epidemic clone in Brazil and worldwide.

Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1-positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

Neuro4PD: An Initial Neurorobotics Model of Parkinson's Disease.

In this work, we present the first steps toward the creation of a new neurorobotics model of Parkinson's Disease (PD) that embeds, for the first time in a real robot, a well-established computational model of PD. PD mostly affects the modulation of movement in humans. The number of people suffering from this neurodegenerative disease is set to double in the next 15 years and there is still no cure. With the new model we were capable to further explore the dynamics of the disease using a humanoid robot. Results show that the embedded model under both conditions, healthy and parkinsonian, was capable of performing a simple behavioural task with different levels of motor disturbance. We believe that this neurorobotics model is a stepping stone to the development of more sophisticated models that could eventually test and inform new PD therapies and help to reduce and replace animals in research.

Bioactive small molecules produced by the human gut microbiome modulate Vibrio cholerae sessile and planktonic lifestyles.

Humans live in symbiosis with a diverse community of microorganisms, which has evolved to carry out many specific tasks that benefit the host, including protection against invading pathogens. Within the chemical diversity of the gastrointestinal tract, small molecules likely constitute chemical cues for the communication between the microbiota and pathogens. Therefore, we sought to investigate if molecules produced by the human gut microbiota show biological activity against the human pathogen Vibrio cholerae. To probe the effects of the gut metabolome on V. cholerae, we investigated its response to small-molecule extracts from human feces, from a complex bacterial community cultivated in vitro, and from culture supernatants of Enterocloster citroniae, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. Using RNA sequencing, we determined the impact of the human gut metabolome on V. cholerae global gene expression. Among the genes downregulated in the presence of the fecal extract, the most overrepresented functional category was cell motility, which accounted for 39% of repressed genes. Repression of V. cholerae motility by the fecal extract was confirmed phenotypically, and E. citroniae extracts reproduced this phenotype. A complex in vitro microbial community led to increased motility, as did extracts from B. vulgatus, a species present in this community. Accordingly, mucin penetration was also repressed by fecal and E. citroniae extracts, suggesting that the phenotypes observed may have implications for host colonization. Together with previous studies, this work shows that small molecules from the gut metabolome may have a widespread, significant impact on microbe-microbe interactions established in the gut environment.

The role of two-component regulatory systems in environmental sensing and virulence in Salmonella.

Adaptation to environments with constant fluctuations imposes challenges that are only overcome with sophisticated strategies that allow bacteria to perceive environmental conditions and develop an appropriate response. The gastrointestinal environment is a complex ecosystem that is home to trillions of microorganisms. Termed microbiota, this microbial ensemble plays important roles in host health and provides colonization resistance against pathogens, although pathogens have evolved strategies to circumvent this barrier. Among the strategies used by bacteria to monitor their environment, one of the most important are the sensing and signalling machineries of two-component systems (TCSs), which play relevant roles in the behaviour of all bacteria. Salmonella enterica is no exception, and here we present our current understanding of how this important human pathogen uses TCSs as an integral part of its lifestyle. We describe important aspects of these systems, such as the stimuli and responses involved, the processes regulated, and their roles in virulence. We also dissect the genomic organization of histidine kinases and response regulators, as well as the input and output domains for each TCS. Lastly, we explore how these systems may be promising targets for the development of antivirulence therapeutics to combat antibiotic-resistant infections.

Metabolic profiles of multidrug resistant and extensively drug resistant Mycobacterium tuberculosis unveiled by metabolomics.

Although treatable with antibiotics, tuberculosis is a leading cause of death. Mycobacterium tuberculosis antibiotic resistance is becoming increasingly common and disease control is challenging. Conventional drug susceptibility testing takes weeks to produce results, and treatment is often initiated empirically. Therefore, new methods to determine drug susceptibility profiles are urgent. Here, we used mass-spectrometry-based metabolomics to characterize the metabolic landscape of drug-susceptible (DS), multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis. Direct infusion mass spectrometry data showed that DS, MDR, and XDR strains have distinct metabolic profiles, which can be used to predict drug susceptibility and resistance. This was later confirmed by Ultra-High-Performance Liquid Chromatography and High-Resolution Mass Spectrometry, where we found that levels of ions presumptively identified as isoleucine, proline, hercynine, betaine, and pantothenic acid varied significantly between strains with different drug susceptibility profiles. We then confirmed the identification of proline and isoleucine and determined their absolute concentrations in bacterial extracts, and found significantly higher levels of these amino acids in DS strains, as compared to drug-resistant strains (combined MDR and XDR strains). Our results advance the current understanding of the effect of drug resistance on bacterial metabolism and open avenues for the detection of drug resistance biomarkers.

A multimetric approach to evaluate offshore mussel aquaculture effects on the taxonomical and functional diversity of macrobenthic communities.

A multimetric approach was used to detect structural, compositional, and functional shifts in the underlying macrobenthic communities of an offshore mussel (Mytilus galloprovincialis) farm in a Portuguese Aquaculture Production Area. Sampling stations distributed inside and outside this area were used to evaluate sediment descriptors and macrobenthic samples collected before (April and September 2010) and after (June and September 2014) the initiation of mussel farming. Sediment fine fraction, organic matter content, and trace element concentrations were found to increase with depth, independently from the mussel farm. Moreover, the structure and composition of the macrobenthic communities were likewise structured by depth. Turnover was the dominant temporal and spatial pattern of beta diversity for all communities. Furthermore, the functional diversity of these communities was unaffected by the mussel farm. These results suggested that an offshore profile allowed hydrodynamic conditions to weaken the impact of mussel farming and highlighted the importance of conducting an integrative multimetric analysis when studying aquaculture impacts on benthic communities.

Solitary fibrous tumor of the kidney: a report of two cases / Tumor fibroso solitário do rim: relato de dois casos

ABSTRACT Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, composed of monotonous spindle cells, intermingled with collagen fibers. Kidney location is sporadic, with few reports in literature. We present two cases of 40- and 48-year-old males, one with incidental detection of a peripheral mass; another with hilar lesion perceived following investigation of hematuria. Both revealed a spindle-cell proliferation, without mitosis and necrosis. Immunohistochemical studies: positivity for CD34, CD99 and B-cell lymphoma 2 (Bcl-2). No sign of disease were evident nine and five months after surgery, respectively. SFT is mostly benign, but can show malignant behavior. Morphologic and immunohistochemical characteristics are essential for diagnosis.

RESUMEN Tumor fibroso solitario (TFS) es una neoplasia mesenquimal infrecuente de células fusiformes monótonas, separadas por bandas de colágeno. Localización renal es poco habitual, con escasos casos descriptos. Reportamos dos casos de pacientes masculinos, de 40 e 48 anos, el uno con detección incidental de masaperiférica; el otro con lesión hiliar descubierta en la investigación de hematuria. Los dos revelaronproliferación fusocelular sin necrosis ni mitosis. Inmunohistoquímica: positividad para CD34, CD99 y linfoma de células B2 (Bcl-2). No hay evidencia de recidiva a los nueve y cinco meses de la cirugía, respectivamente. TFS es, por lo general, benigno, pero puede revelar comportamiento agresivo. Características morfológicas y inmunohistoquímicas son esencialespara el diagnóstico.

RESUMO Tumor fibroso solitário (TFS) é uma neoplasia mesenquimatosa rara composta por células fusiformes monótonas, intercaladas por fibras de colágeno. Localização renal é incomum, com escassos casos descritos. Relatamos dois casos do gênero masculino, com 40 e 48 anos, um com detecção incidental de massa periférica; outro com lesão hilar descoberta na sequência de investigação por hematúria. Ambos revelaram proliferação fusocelular sem mitoses nem necrose. Imuno-histoquímica: positividade para CD34, CD99 e linfoma de células B2 (Bcl-2). Não há evidência de recidiva nove e cinco meses após cirurgia, respetivamente. TFS é maioritariamente benigno, mas pode revelar comportamento agressivo. Características morfológicas e imuno-histoquímicas são essenciais para o diagnóstico.

Integrated analysis of ethionamide resistance loci in Mycobacterium tuberculosis clinical isolates.

Tuberculosis patients taking second line drugs such as ethionamide (ETH) have often experienced previous treatment failure and usually have a complex history of disease and treatment that can span decades. Mutations in the ETH activating enzyme, EthA, confer resistance through undescribed mechanisms. To explore the impact of EthA mutations on ETH resistance, data from a total of 160 ETHR isolates was analysed. The most frequently mutated positions are within regions that display sequence conservation with the active site of OTEMO, another FAD-containing NADH-binding Baeyer-Villiger monooxygenase (BVMO), or with the sugar binding site of galectin-4N. Additionally, to look at a possible role of EthR on ETH resistance we purified an EthR mutant identified in a clinical isolate, F110L, and found it to bind the ethA-ethR intergenic region with higher affinity than the wild type regulator in gel shift assays. The ability of cyclic di-GMP to enhance DNA binding is maintained in the EthR mutant. To our knowledge, this is the first ETH resistance study that combines sequence and resistance data of clinical isolates with functional and structural information.

Extraction of Small Molecules from Fecal Samples and Testingof Their Activity on Microbial Physiology.

The human body is colonized by vast communities of microbes, collectively known as microbiota, or microbiome. Although microbes colonize every surface of our bodies that is exposed to the external environment, the biggest collection of microbes colonizing humans and other mammals can be found in the gastrointestinal tract. Given the fact that the human gut is colonized by several hundred microbial species, our group hypothesized that the chemical diversity of this environment should be significant, and that many of the molecules present in that environment would have important signaling roles. Therefore, we devised a protocol to extract these molecules from human feces and test their signaling properties. Potentially bioactive extracts can be tested through addition to culture medium and analyses of bacterial growth and gene expression, among other properties. The protocol described herein provides an easy and rapid method for the extraction and testing of metabolites from fecal samples using Salmonella enterica as a model organism. This protocol can also be adapted to the extraction of small molecules from other matrices, such as cultured mammalian cells, tissues, body fluids, and axenic microbial cultures, and the resulting extracts can be tested against various microbial species.

The last frontier: Coupling technological developments with scientific challenges to improve hazard assessment of deep-sea mining.

The growing economic interest in the exploitation of mineral resources on deep-ocean beds, including those in the vicinity of sensitive-rich habitats such as hydrothermal vents, raise a mounting concern about the damage that such actions might originate to these poorly-know ecosystems, which represent millions of years of evolution and adaptations to extreme environmental conditions. It has been suggested that mining may cause a major impact on vent ecosystems and other deep-sea areas. Yet, the scale and the nature of such impacts are unknown at present. Hence, building upon currently available scientific information it is crucial to develop new cost-effective technologies embedded into rigorous operating frameworks. The forward-thinking provided here will assist in the development of new technologies and tools to address the major challenges associated with deep sea-mining; technologies for in situ and ex situ observation and data acquisition, biogeochemical processes, hazard assessment of deep-sea mining to marine organisms and development of modeling tools in support of risk assessment scenarios. These technological developments are vital to validate a responsible and sustainable exploitation of the deep-sea mineral resources, based on the precautionary principle.

Detection of mycobacterial infection in non-human primates using the Xpert MTB/RIF molecular assay.

Tuberculosis is a major public health concern, and diagnostic strategies applied to animal populations are scarce. As part of ongoing efforts to control tuberculosis dissemination at our animal facility, two non-human primates (NHP, Saimiri sciureus) presenting cutaneous lesions were examined for mycobacterial infection. Both animals tested positive for acid-fast bacilli and Mycobacterium tuberculosis using a molecular assay (IS6110 PCR). Animals were euthanized and several samples were tested for M. tuberculosis using the Xpert MTB/RIF assay. Many samples were positive for M. tuberculosis and rifampicin resistance, and some produced mycobacterial growth. Oral swabs from cage mates were then tested with Xpert MTB/RIF, and the majority tested positive for M. tuberculosis and rifampicin resistance, and produced growth in culture. To our knowledge, this is the first report of multidrug-resistant mycobacterial infection in NHP. Additionally, our data shows that the Xpert MTB/RIF assay can be useful as a screening tool for tuberculosis infection in NHP.

Repression of Salmonella Host Cell Invasion by Aromatic Small Molecules from the Human Fecal Metabolome.

The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of hilA, the gene encoding the master regulator of invasion genes in Salmonella We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of hilA expression and of invasion of cultured host cells by Salmonella Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule.IMPORTANCE Microbes constantly sense and adapt to their environment. Often, this is achieved through the production and sensing of small extracellular molecules. The human body is colonized by complex communities of microbes, and, given their biological and chemical diversity, these ecosystems represent a platform where the production and sensing of molecules occur. In previous work, we showed that small molecules produced by microbes from the human gut can significantly impair the virulence of the enteric pathogen Salmonella enterica Here, we describe a specific compound from the human gut that produces this same effect. The results from this work not only shed light on an important biological phenomenon occurring in our bodies but also may represent an opportunity to develop drugs that can target these small-molecule interactions to protect us from enteric infections and other diseases.

Abnormal mortality of octopus after a storm water event: Accumulated lead and lead isotopes as fingerprints.

Octopus vulgaris is a sedentary organism that inhabits coastal waters being exposed to anthropogenic compounds. Lead concentration in coastal environments reflects many processes and activities namely weathering, industrial and domestic discharges, and atmospheric deposition. Since lead isotopic composition is little affected by kinetic processes occurring between source and sink, its signature has been used to identify different Pb sources. After a short-term heavy rainfall, hundreds of octopus appeared dead in two Portuguese coastal areas. Histopathology and Pb levels and its stable isotopes were determined in tissues, such as digestive gland, of stranded octopus and compared to alive specimens, sediments and runoff material from the same areas. Histology results showed severe damage in stranded octopus tissues suggesting that death was probably associated to multiple organ failure linked to hypertrophy and exudates input. In addition, Pb in stranded specimens reach concentrations up to one order of magnitude above the levels reported for alive octopus. Pb isotopic signatures in stranded organisms were closer to runoff material pointing to a similar origin of Pb. In summary, the results in this study showed that a short-term runoff event might change abruptly the salinity leading to the disruption of the osmoregulation function of octopus and consequently leading to its death. The analyses of stable isotopic Pb signature in octopus tissues corroborate these results and points to a change in the Pb source due to runoff after the storm water event. Pb stable isotopes in octopus proved to be an adequate tool to confirm the cause of death and linking it to the environment conditions.

A compact remediation system for the treatment of groundwater contaminated with BTEX and TPH.

Gas stations constitute important point sources of soil and groundwater pollution. The leaking of hydrocarbons into the soil is a significant environment issue due to the wide-ranging occurrence of leaks and the high levels and toxicity of pollutants involved in the contamination of groundwater for human use. This study introduces a compact system developed to treat groundwater contaminated with benzene, toluene, ethyl benzene, and xylenes (BTEX) and total petroleum hydrocarbon (TPH) leaked from gas station tanks. The system comprises three units: (1) suction and volatilization of volatile organic compounds (VOCs), (2) aeration tank (to remove volatile organic substances), and (3) an adsorption packed-bed filter (activated carbon (AC) and rice husk ash, 50% each, to remove TPH). Contaminated groundwater was characterized in a pilot study and in the field. Levels of BTEX and of TPH decreased by 96% with an 8-h retention time. The results obtained show that the remediation system is highly efficient and yielded water that met the discharge standards defined in the Brazilian legislation, that is, maximum benzene, toluene, and xylene levels of 5, 170, and 300 µg/L, respectively.

Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar therapeutic antibodies.

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.