Antibiotic resistance is a consequence of biased and exaggerated antibiotic treatments in both humans and animals and has recently been subject of wide-ranging community concern . Lack ofIntensive farming technologies for food animals broadly imply the use of antibiotics as therapeutic means, thus trying to reduce the economic and health impact of infectious diseases by diminishing morbidity and mortality. Nevertheless, the spread of antibiotic resistant and MDR bacteria from animal farming to the broader environment may cause diseases in humans, livestock, and wildlife .Research was conducted to clarify the transfer mechanisms of multi drug resistant (MDR) bacteria from farmed animals/food products to humans due to continuously increasing emergence of resistance. The variable potential for innate antibiotic resistance in the soil was also described based on geo-chemical conditions, while bacterio-plankton tolerance to antibiotics in heavy metal polluted areas was highlighted, suggesting the selective importance of pollution in maintaining and spreading antibiotic resistance .Reciprocal relationships that exist between resistant and potentially pathogenic bacteria and their habitat or broader environment need to be precisely defined to allow the development and implementation of preventive and control measures with highest benefits for humans, animals and the environment. A solid connection can be established between the amounts of antimicrobials used and the increase of numbers of bacterial species resistant to them, above the presence of antimicrobial resistance in pristine sources before introduction of antimicrobials in medical and/or farming practice .This Research Topic aimed at updating research results on antibiotic resistance, its emergence and persistence, horizontal transfer of antibiotic resistance genes, rapid diagnosis of multi antibiotic resistance, its prevention and control, and its connections to environmental factors  as well as the influence of farming and sewage water management, wildlife and its conservation, and others, to have a comprehensive view of the importance of the often disregarded environmental niche in increasing virulence of pathogenic bacteria.In this special e-collection there are 18 papers covering the above mentioned aspects.The presence, persistence and technological influences on antimicrobial resistance in domestic animals were the most tackled subjects . Numerous categories of animals from farmed species  companion animals , and also wildlife  inhabiting terrestrial and aquatic environments were monitored for the presence of multidrug resistant microbiome. Comprehensive studies of bacteriome resistance in various environments were also published.Bordetella bronchiseptica and Escherichia coli need close monitoring for their antimicrobial resistance gene profile. The resistance profile found in B. bronchiseptica in pigs from China, one of the largest pork producers in the world, was highly variable, but including percentages as high as 83.98 to ampicillin, very commonly used in animal therapy. Over 90% of the isolates were positive to the five virulence factor encoding genes examined, representing a reason for major consumer health concern . Similarly, other researchers  found mcr resistance genes to colistin, a last resort antibiotic to fight the infections with Enterobacteriaceae in MCRPE (mcr positive E. coli) isolates also showing MDR and connection to E. coli ETEC (enterotoxigenic) pathotype shared by human and animal hosts.Swine industry is a continuously developing economic sector, while there is a constant need and demand for meat and meet products by consumers. Nevertheless, pigs are hosts for numerous zoonotic pathogens, including ported bacteria, whose increasing antimicrobial resistance support their pathogenicity and aggressivenes and thus, their survival in the habitat. Therefore, ubiquitous bacteria such as E. coli strains originating from non-organic chickens, raised in low-income communities harbor antibiotic resistant genes found in multidrug-resistant and extended-spectrum beta-lactamase (ESBL) phenotypes, which could eventually colonize the human gut of bird contacts or consumers . In dairy cow herds, mastitis is maybe the most economically impacting disease caused by a variety of agents, with a rapidly changing etiology, frequently involving antibiotic resistant agents, therefore the phenotypic and molecular analysis of Candida krusei, a yeast collected from mastitis cases provided valuable information for disease control, indicating that drug-resistance was relying on mutations of the ERG11 gene .Further, it has been proven that Lastauskiene et al.). Experiments aiming at investigating the horizontal transfer of antimicrobial and arsenic resistance genes have provided positive evidence of this between certain bacteria, such as Rheinheimera spp. and E. coli, suggesting a permanent monitoring of antibiotic/arsenic resistance profile of the bacteriome to reduce or avoid the spread of gene pollutants .Farming aquatic animals became a widespread practice lately, following the trend of increased protein need for feeding the planet. Due to specific use of antibiotics for microbial disease control, fish farms not only represent a possible source for antimicrobial resistance for consumers but also impact on the environment health, by the location of the ponds either down- or upstream the rivers, thus showing an potentially enhanced multidirectional spread of this resistance. A study carried out in Southern Lithuania, envisaging the simultaneous presence of heavy metal pollution and antimicrobial resistance in the sediment of fish ponds, indicated that in spite of the heavy metal  levels which did not exceed the maximum allowable concentrations and antibiotic residues  present in low amounts or below the detectable limit, the resistance determinants identified  create risks to human hosts by potential transfer .Similarly, the identification of increase in the CTX-M type ESBL producing Enterococcus spp. and Pseudomonas spp., while interestingly, Klebsiella spp., Proteus spp. or Enterobacter spp. seemed to be the most resistant of Enterobacteriacea , when compared to the otherwise MDR ESBL E. coli, as indicated by other researchers . Nevertheless, Pseudomonas spp. of canine origin seemed to also be resistant (72.7–100%) to antimicrobials linezolid (LZD) and tigecycline (TGC) efficient in fighting with pan-drug resistant bacteria isolated from humans (Kim and Kim).Several studies mention the MDR or pan-drug resistance in companion animals such as dogs, cats and horses. An extended research of clinical cases in the Iberian peninsula provides an overview of the bacteria most frequently found in dogs and cats and also their resistance profile to antimicrobials, indicating the highest antimicrobial resistance in Staphylococcus aureus, non-hemolytic E. coli, and C. albicans) and also the antimicrobial resistance genes to the latter . Further, such birds could, through their interactions and lifestyle, close a loop of antimicrobial resistance in their closer or further environment.A quite widespread category of companion or hobby birds are racing pigeons. Their close contact with humans during feeding, handling and competitions creates the premises for transfer of multidrug resistant bacteria or yeasts , hospital environment could provide an appropriate environment for the persistence of antimicrobial resistance, not only through the patients seen but also on the contact surfaces. Such a study carried out in an equine hospital consulting local and international patients revealed the presence of multidrug resistant, host-versatile Salmonella typhimurium on human and patient contact surfaces, which led back to the significance of biosecurity measures implemented at all times to preserve patient and personnel safety .As already mentioned  and Geoffroy's cats (Leopardus Geoffroyi) from the Brazilian Pampa, with resistance percentages as high as 94 or 72.6 to rifampicin, one of the most potent broad spectrum antibiotics, and erythromycin, respectively. This phaenomenon was supported by the identified resistance genes (tetM/tetL and msrC/ermB) along with virulence genes , standing most probably for human interference in the pampa habitat .Wildlife, out of direct connection with antibiotic therapy, has been disregarded as a link in the antibiotic resistance transfer chain. Recent research has proven the presence and high incidence (66%) of enterococci in the feces of wild foxes .The marine ecosystem is not spared of antimicrobial resistance, the investigation of marine mammals and costal environment providing valuable information on another direction of antimicrobial resistance spread. As such, the identification of 66.6% MDR of the total mecC-positive and mecC-negative types, with possible human origin of the mecC-MRSA including the typically human “immune evasion cluster” (IEC) .A broader study comparing MRSA and MSSA from various animal sources and different environments disclosed clear differences between Bandyopadhyay and Samanta).A review of the perspectives on antimicrobial resistance at the level middle and low income countries, with special reference to the COVID period, brings forward a pertinent analysis of the antibiotic types toward which the resistance is augmented, the most frequent fields of activity and host species, representing important links within the antimicrobial resistance chain as well as multi-level and multi-actor mitigation strategies  during a study which included probiotic feed additives/silage inoculants. Tests carried out on their antibiotic susceptibility/resistance indicated the resistance to aminoglycosides and tetracyclines mainly (26%). Therefore, the authors suggested as a safety criterion the preliminary resistance analysis of the strains of Lactobacillus and Pediococcus to ensure their appropriate effects. Moreover, the analysis for resistance genes in a non-pathogenic bacteria such as Bifidobacterium animalis subsp. lactis revealed the presence of tet(W) (tetracyclin resistance gene) in 41 of 44 examined strains, but being a part of the ancient resistome, is different from other species and possesses a very low transfer risk .The food chain represents another potential route for spreading the antimicrobial resistance from farm to fork. Further, the beneficial effects of lactic acid bacteria have been recognized and given attention since decades. Nevertheless, such strains could serve as vehicle for spreading antimicrobial resistance as indicated (In conclusion, the data gathered in the studies and reviews mentioned before provide beneficial information, which, without being exhaustive, offer a valuable insight in the complex matter of antimicrobial resistance and its transmission chain, leaving room for the intriguing and still undiscovered interaction of humans, animals and environment with the aim of preserving One Health.Both authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


In dairy ruminants, mastitis represents one of the most serious health issues which can contribute to the reduction of milk production, high veterinary care costs, increased use of antibiotics, and animal culling, all of which may account for severe economic losses. Mastitis consists of the inflammation of the udder and is mainly caused by contagious and/or environmental microorganisms leading to overt clinical or sub-clinical cases. Management of mastitis in dairy ruminants faces various challenges: the resilience of high-yielding animals, poor efficacy of therapies and prevention , quality of milk, reduced availability of food and water, climate change, and difficulties in early diagnosis. These issues could provoke the interest of researchers and practitioners to suggest more affordable and effective control measures.This Research Topic is comprised of 20 articles. These include review articles, original research, and reports concerning the biology of mastitis pathogens, a comparison of several diagnostic tools, diverse prevention strategies, alternative treatments to antibiotics, and the prevalence of mastitis-causing agents.De Buck et al.). In emerging countries, different genetic strains of Staphylococcus aureus (SA) have been found in milk samples. Some of these strains are known to be adapted to dairy ruminant species but a highly diffuse one is a human-adapted strain. As all SA strains carry different antibiotic resistance genes, their isolation from milk poses important zoonotic concerns . In China Helcococcus ovis, a mastitis-causing agent in sheep, was isolated on a dairy cow farm. Four genetic strains were identified, all susceptible to the majority of antibiotics. Helcococcus ovis caused mild mastitis in a murine model when it was the only bacteria causing infection, but it caused severe mastitis when co-infecting the murine mammary gland with Trueperella pyogenes . The role of co-infection in mastitis has been poorly investigated but it reveals interesting aspects for the management and treatment of mastitis. For example, the role of a viral infection such as the Bovine Leukemia Virus (BLV), can impair the defenses in the mammary gland predisposing it to secondary bacterial infections . The knowledge of the pathogenesis of each agent could help in the management of this pathological condition for the udder. The mechanism by which SA infection impairs the milk protein synthesis by mammary epithelial cells has been investigated by Chen et al. demonstrating the involvement of mTORC1, STAT5, NF-kB, and two amino acid transporters (SLC1A3 and SLC7A5). Another aspect is the debated capability of some mastitis agents to develop biofilms that could explain their persistence in the udder, resistance to antibiotic treatments, and the presence of some chronic infections . Moreover, in small ruminants such as high milk production goats, genetics may play a role in certain histological features that increase the permeability of skin to milk (“Weeping Teats” or WT), but limited information was available regarding an increased risk of mastitis on animals with WT. Gazzola et al. demonstrated a positive association between high SCC and bacteria in milk from goats suffering from WT, but these variables were not associated with the WT condition.The study of pathogens, pathogenesis, and host-pathogen interaction could be helpful in the definition of new prevention or treatment protocols for combating mastitis. Non-Aureus Staphylococci (NAS) involves several species and strains that have become the most frequently isolated bacteria in milk. Non-Aureus Staphylococci are associated with mastitis, with variable severity of cases, and some species are considered commensal in the mammary gland. These aspects prompted the scientific community to investigate the biology, pathogenicity, epidemiology, and antibiotic resistance of bacteria member of the NAS group . Garcia et al. demonstrated the capability of this chromogenic medium to identify the main Gram-positive bacteria responsible for subclinical mastitis, with the exception of S. aureus.Dairy ruminant farming should try to develop early diagnostic tools and mastitis prevention strategies. Mastitis can occur as sub-clinical, mild clinical, or severe clinical pathological conditions. Depending on its appearance, the diagnosis could encounter difficulties. Somatic cell count (SCC) is the most widely used indicator of intra-mammary infection (IMI), but depending on the number of days in milk (DIM), cow breed, or other factors, the SCC value is sometimes inconclusive. The definition of the differential SCC (DSCC) has been proposed as a further indicator of IMI. The automated DSCC has become available recently with two instruments. Zigo et al., given the multifactorial nature of the pathological condition of mastitis, the prevention strategies should relate to the control of SCC, correct diet, proper housing and management, milking systems, drying strategies, and eventually, immunization protocols. Research in the mastitis prevention field is very dynamic and new tools are often being proposed. Kabera et al. after a comparison between selective dry cow antimicrobial treatment (SD) and blanket dry cow treatment (BD), suggested applying SD in regard to antibiotic use reduction. Bedding choice can influence mammary gland health. Fréchette et al. highlight the risk of K. pneumoniae mastitis when using recycled manure solids bedding. The efficacy of immunizing dairy ruminants against mastitis is debated, but efficacious vaccines could represent a strong defense for combating IMI. Tassi et al. describe the development of an efficacious intramammary vaccine against Mannheimia haemolytica, based on the activation of innate immune responses. Effective vaccination against mastitis is not available and the causes of the failure of this type of prevention still need to be investigated. New control strategies such as immunomodulation may be helpful for the future fight against mastitis.Despite the improvement of the technologies for the management of dairy herds and milking, combined with the amelioration of veterinary interventions, IMI still remains an important issue in the dairy industry. For this reason, measures of prevention play a pivotal role in the reduction of the risk of mastitis. As documented by Ruegg, there are very few studies that investigate the real efficacy of antibiotic treatment. In order to develop efficacious therapeutic protocols for the treatment of mastitis, it is important to evaluate several aspects such as the pathogen involved, activity spectrum, antibiotic resistance, and animal factors . Non-steroidal anti-inflammatory drugs (NSAID) alone have been proposed by Krömker et al. as an alternative treatment to antibiotics, but only in case of mild or moderate clinical mastitis AMPK/NrF2/Nf-kB signaling pathway has been suggested as a potential target for the treatment of S. aureus bovine mastitis by Arbab et al.The treatment of mastitis is based mainly on antibiotics but the widespread increase of antibiotic-resistant bacteria poses several concerns about their use and stimulates the search for new therapeutic strategies. As stated by Ali et al.), Ontario, Canada , and the prevalence of Klebsiella spp. in China . The distribution of mastitis pathogens around the world suggests the need for the application of differential strategy programs to control the disease in different countries.Mastitis control and prevention are based on continuous and accurate monitoring of the bacterial species prevalence and evaluation of their antibiotic resistance. In our collection, we included recent data about the prevalence of mastitis pathogens in Northwest Pakistan (All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The experimental data demonstrate a significant improvement in ibuprofen removal in the presence of prepared solids (20 min for PANI 900 at pH10) compared with non-catalytic processes (56 min at pH 10). Moreover, the influence of solution pH was emphasized, showing that, in the basic region, the removal rate of organic substrate is higher than in acidic or neutral range. Ozone consumption mgO3/mg ibuprofen was considerably reduced for catalytic processes  compared with the absence of catalysts (29.64). Hence, beside the ibuprofen degradation, the catalysts used are very active in the mineralization of organic substrate and/or formation of biodegradable compounds. The best removal rate of target pollutants and oxidation by-products was achieved by PANI 900, although raw polyaniline also presents important activity in the oxidation process. Therefore, it can be stated that polyaniline-based catalysts are effective in the oxidation processes.Catalytic ozonation is an important water treatment method among advanced oxidation processes (AOPs). Since the first development, catalytic ozonation has been consistently improved in terms of catalysts used and the optimization of operational parameters. The aim of this work is to compare the catalytic activity of polyaniline (PANI) and thermally treated polyaniline (PANI 900) in the catalytic ozonation of ibuprofen solutions at different pH values . Catalysts were thoroughly characterized through multiple techniques , while the oxidation process of ibuprofen solutions (100 mgL The results show that there are significant differences between the two solids, PANI and PANI 900, when there are used in the oxidation processes. Thus, PANI 900 is a more active catalyst in the degradation of ibuprofen, for all pH values, and shows a more rapid decomposition of ibuprofen in aromatic compounds and, further, an advanced mineralization of organic substrate.Catalytic ozonation is an important choice among advanced oxidation processes (AOPs) for water treatment owing to high efficiency in the removal of a large range of pollutants, including nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen. In this study, thermal and non-thermal treated polyaniline (PANI 900 and PANI) were used for the first time as catalysts for the oxidative destruction of ibuprofen using ozone as an oxidant agent. The presence of catalysts allows the elimination of the target pollutant twice as fast compared with non-catalytic processes, regardless of the pH of the aqueous solution. Moreover, the removal of remnant organic substrate was evaluated by various techniques  and it was emphasized that, in the presence of the prepared catalysts, the aqueous effluents containing ibuprofen were thoroughly purified regardless of the pH value and the high initial concentration (100 mgL


The authors present a case of cholesteatoma of external auditory canal (CEAC) with extensive invasion of mastoid; ossicle chain and tympanic membrane remained intact. The only symptom was chronic otorrhea. Diagnosis was based on clinical elements and CT scan was used to measure pathology and program surgery. Treatment was modified radical mastoidectomy associated with meatoplasty. Due to the insidious character of CEAC and the proximity with important structures of the external auditory canal, it must be always considered in differential diagnosis for lesions of external auditory canal. This case report intended to review clinical and surgical aspects of treatment of CEAC and present our approach in a case with severe lesions. Cholesteatoma of the external auditory canal (CEAC) is a rare condition affecting especially elderly people. The progress of the disease is slow and the symptoms are not too evident. This leads to late diagnosis, with progressive bone lysis affecting important circumjacent structuresThe authors present a case of CEAC with extensive invasion of the mastoid, exposing the lateral sinus and the dura. Hearing acuity and structures of the tympanic cavity were unaffected.We discuss the possible causes and treatment of choice.In clinical practice of ear diseases, cholesteatoma occurs on the tympanum-mastoid segment. It rarely originates from the external auditory canal (EAC), whose incidence is about 0.1-0.5% in new patients with ear problemsIn 1850In CEAC, lateral epithelium desquamation is affected. Keratin debris are blocked, causing local erosion and bone lysis, which can be severeDiagnosis is made through physical examination. There is otalgia, otorrhea, hearing acuity is unaffected; otoscopy shows an intact tympanic membrane and erosion on a distinct spot of the external auditory canalDifferential diagnosis for CEAC should include necrotizing external otitis, tumors and KO. The latter is more frequent in young adults presenting severe otalgia and bilateral sensorial hearing loss. Differently from CEAC, which usually affects older patients, KO is unilateral, there is otorrhea, chronic pain and hearing acuity is preserved. In KO, the EAC has a keratin plug; otoscopy, following keratin plug removal, shows stenosis, redness and granulation tissue. In CEAC, there is an epidermal diverticulum on the lowest part of the canal, with epidermal debris and otorrhea; the other parts of the EAC are normalThe treatment of CEAC may be clinical or surgical. The former is carried out through local flushing and topic antibiotics. The latter is through resection of the cholesteatoma and necrotic boneClinical treatment is indicated whenever the lesion is limited and there is no otalgia, in cases that surgery is contraindicated, in patients refusing surgical procedures and, when observation without treatment is an option to evaluate progressionSurgical treatment is indicated in the following situations: chronic pain (despite treatment), frequent infection , facial palsy or chronic dizziness, progression during follow-up, involvement of hypotympanum, jugular or mastoid (showed in CT scans), diabetes mellitus or immunosuppression Patient A. F., male, 59 years old. Visited the otorhinolaryngological outpatient facility showing otorrhea, otalgia and ear fullness on the right for ten (10) years. Otoscopy on his right ear showed epidermal debris in the canal. Following debris removal, the tympanic membrane was intact, and there was severe erosion of the posteroinferior quadrant of the EAC. Otoscopy of the left ear was normal. Bilateral pure tone audiometry was normal.We suspected of CEAC and requested a CT scan of temporal bones. CT scan showed erosion of the posterior wall of the EAC, mastoid involvement and exposure of the lateral sinus and meninges .Figure 1Transoperative observation revealed erosion of the entire posterior wall of the EAC, except for a thin bone band close to the tympanic ring . The tymWe conducted modified radical mastoidectomy type I plus meatoplasty. The patient showed good outcomes and normal hearing, without recurrences, in a postoperative period of two years.CEAC, due to its slow and insidious progression, may severely affect structures of the middle ear at the time of presentation. In our case report, the lesion was severe at first presentation, and we were not able to visualize its limits through otoscopy. CT studies were important to determine the severity of the disease and involvement of other structures; therefore, CT scan is indicated whenever CEAC is suspected.The disease had possibly appeared spontaneously, since the patient did not have any predisposing factor to develop CEAC.Mastoid invasion is one of the indications for surgery. After the patient agreed to undergo surgery, we performed modified radical mastoidectomy and wide meatoplasty; thus, we could achieve good control of the cavity during the postoperative period.We were able to preserve the tympanic cavity and its structures; therefore, the surgical procedure was able to cure and preserve the patient's hearing acuity. It is worth mentioning that, in spite of the increased progression of the disease, there was no involvement of the facial nerve, inner ear or nerves emerging from the jugular foramen.Otorhinolaryngologists must suspect of CEAC in cases of chronic otorrhea and intact tympanic membrane. After diagnosis of CEAC, CT scans of the temporal bone must be performed in all patients to evaluate the real severity of the disease and involvement of circumjacent structures . In most cases, the treatment of choice is surgery, whose main purpose is to eradicate the lesion and, if possible, preserve the patient's hearing acuity. The modified radical mastoidectomy is the most common surgical procedure carried out in these cases.


Unilateral spatial neglect (USN) is a frequent repercussion of a cerebrovascular accident, typically a stroke. USN patients fail to orient their attention to the contralesional side to detect auditory, visual, and somatosensory stimuli, as well as to collect and purposely use this information. Traditional methods for USN assessment and rehabilitation include paper-and-pencil procedures, which address cognitive functions as isolated from other aspects of patients’ functioning within a real-life context. This might compromise the ecological validity of these procedures and limit their generalizability; moreover, USN evaluation and treatment currently lacks a gold standard. The field of technology has provided several promising tools that have been integrated within the clinical practice; over the years, a “first wave” has promoted computerized methods, which cannot provide an ecological and realistic environment and tasks. Thus, a “second wave” has fostered the implementation of virtual reality (VR) devices that, with different degrees of immersiveness, induce a sense of presence and allow patients to actively interact within the life-like setting. The present paper provides an updated, comprehensive picture of VR devices in the assessment and rehabilitation of USN, building on the review of Pedroli et al. (2015). The present paper analyzes the methodological and technological aspects of the studies selected, considering the issue of usability and ecological validity of virtual environments and tasks. Despite the technological advancement, the studies in this field lack methodological rigor as well as a proper evaluation of VR usability and should improve the ecological validity of VR-based assessment and rehabilitation of USN. A cerebrovascular accident, such as stroke, represents an urgent public health issue and patients surviving this catastrophic acute event must deal with life-long motor and cognitive disabilities. This could restrict patients’ participation to social activities, providing them and their caregivers a relevant psychological burden  cancellation tests, that require patients to detect specific targets among numerous other distractors, employing stimuli such as lines Albert, , lettersRehabilitative interventions for USN patients usually fall under two broad categories of behavioral approaches  capable of providing a safe, standardized, and more realistic virtual environment that simulates complex daily situations, directly involving patients and engaging them to purposely interact within it Slater, . These cGiven the importance of VR devices for assessment and rehabilitation, particularly within the field of USN, a review of the most recent technological advancements is needed to have a comprehensive state-of-the-art and to provide future directions for researchers. Therefore, the present review aims at updating the previous work of Pedroli et al.  and to pThe present review builds on and updates the previous work by Pedroli et al. , followiA computer-based search strategy for relevant publications was performed considering several databases, specifically PsycINFO, Web of Science (Web of Knowledge), PubMed/Medline. In line with the previous work of Pedroli et al. , the seaThe flowchart of the review is shown in Fig. The field of USN assessment could benefit from more ecological devices capable of detecting this condition more precisely, to overcome the lack of sensitivity, specificity, and ecological validity of paper-and-pencil tests. Over the past five years, several studies have integrated VR-based devices in USN assessment, either digitalizing traditional neuropsychological tests or developing new paradigms. A total of 15 studies was selected; six studies employed non-immersive technologies  Neglect App card dealing task, which recreates a digitalized version of the card dealing task , for improving the quality of unilateral visual neglect and excluding possible confounding errors deriving from a manual correction of the paper-and-pencil test , either in a simple scene  or in a complex scene , receiving auditory feedback afterward. In the absence of the target, patients were asked to wait for the next trial. On the other hand, the navigation task required patients to navigate toward the target using the joystick, following the most straightforward pathway possible. The VR-based assessment was preceded by a practice trial for patients to get acquainted with the procedure and neuropsychological measures were collected  employing the BTS NIRVANA system  and a Another digital adaptation of a traditional rehabilitation method, such as prism adaptation (PA) has been tested in an exploratory, prospective randomized controlled study by Cogné et al. . A thoroFive studies employed HMDs as a rehabilitative tool for USN. As previously mentioned, OKS has proved as an effective rehabilitative intervention for left hemispatial neglect, training patients to either look at or pay attention to stimuli placed in their left (neglected) hemispace  as well  space around it. It integrates the many bodily representations, such as the sentient body, the spatial body, or the active body . The present work outlines that the greater diffusion of non-immersive and fully immersive devices, integrating traditional assessment and rehabilitation methods, provides a more ecological context and exploits motion-tracking systems. Furthermore, the present review has considered whether the virtual environments and the stimuli employed in the assessment and rehabilitation of USN could be considered ecological, compared to the papers considered in the previous work of Pedroli et al. . DespiteElisa Pedroli created the original methodology of the study. Literature search results found by the first author (Silvia Cavedoni) were shared with the review co-authors  for individual selection of papers in order to reduce bias, and disagreements were resolved through consensus. Silvia Cavedoni wrote the first draft of the manuscript and all authors critically reviewed previous versions. All authors read and approved the final manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


For cancer patients, many different reasons can cause financial burdens and economic threads. Sociodemographic factors, rural/remote location and income are known determinants for these vulnerable groups. This economic vulnerability is related to the reduced utilization of cancer care and the impact on outcome. Financial burden has been reported in many countries throughout the world and needs to be addressed as part of the sufficient quality of cancer care.Within healthcare systems in all countries, vulnerable groups of patients can be identified and are characterized by the reduced utilization of available healthcare. Many different reasons can be attributed to this observation, summarized as implementation barriers involving acceptance, accessibility, affordability, acceptability and quality of care. For many patients, cancer care is specifically associated with the occurrence of vulnerability due to the complex disease, very different target groups and delivery situations  as well as cost-intensive care. Sociodemographic factors, such as educational level, rural/remote location and income, are known determinants for these vulnerable groups. However, different forms of financial burdens likely influence this vulnerability in cancer care delivery in a distinct manner. In a narrative review, these socioeconomic challenges are summarized regarding their occurrence and consequences to current cancer care. Overall, besides direct costs such as for treatment, many facets of indirect costs including survivorship costs for the cancer patients and their social environment need to be considered regarding the impact on vulnerability, treatment compliance and abundance. In addition, individual cancer-related financial burden might also affect the society due to the loss of productivity and workforce availability. Healthcare providers are requested to address this vulnerability during the treatment of cancer patients. Currently, worldwide, 17.5 million cancer cases and 8.7 million deaths occur. During the last decade, their incidence raised by 33%, with population aging contributing 16%, population growth contributing 13% and changes in age-specific rates contributing 4%  will becIn a recent review, Yong et al.  concludeCancer patients can experience financial difficulties even within a publicly funded healthcare system . These pN = 139). The remaining papers (N = 81) were divided into a group containing quantitative or qualitative research data (N = 33) and publications focusing on non-empirical approaches (N = 48). In addition, secondary literature (N = 28) was used to supplement specific aspects of financial consequences . These publications were screened regarding the relationship to the UHC criteria, and papers without relation to cancer care and economic burden were eliminated  and indirect involvement . The qualitative and quantitative research data are summarized in Some investigations addressed, in part, economic consequences for the society, such as the loss of the workforce and the costs for outcomes . For example, the costs and cost-effectiveness of treating childhood cancers in LMICs  in termsThe affordability of cancer care has to be considered from two different perspectives: (A) the individual financial burden of the patients and their families due to cancer diagnosis and (B) the GDP-related affordability of cancer care for the society, which is mainly translated into limited availability of the respective resources. Financial consequences could arise due to the costs of treatment and the consequences of cancer.Financial burden is a phenomenon that has been reported in many countries, contributing to the affordability of cancer care. For example, in the US, it was identified in about 50% of patients with cancer , and aboOverall, the SES appears to seriously determine the affordability and related consequences for cancer patients. The respective predictors of worse financial burdens were the lack of health insurance, lower income, unemployment and younger age at cancer diagnosis ,50. For However, the published evidence targeting the economic perspective of LMICs is biased towards costs incurred by the healthcare sector, and direct nonmedical as well as indirect costs were often not included . TherefoBesides the availability of healthcare resources, the socioeconomic determinants of healthcare usage can vary between regions, such as between African and Latin American LIMCs, due to the limited accessibility of required specialties . Older aAll stages of cancers, from prevention and early detections up to advanced cancer stages, appear to be at risk for financial burdens . These bSimilarly, higher rates of treatment-related late effects and second primary malignancies , as wellThe financial framework and the public and clinical facets of global cancer care appear to intensively interfere with the implementation of prevention and the early detection of cancer  and thusDespite worldwide efforts for HPV primary screening , the impMany countries have limited healthcare resources that can be made available for nationwide prevention programs, contributing to economic, political and societal instabilities. As a result of affordable national screening programs, the individual financial burden due to cancer will not only positively affect the direct costs of the prevention but will also improve indirect economic burdens, as described above .The individual SES of cancer patients is intensively related to their acceptance of care, which is not limited to immediate clinical aspects. For example, perceived financial vulnerability appears as a determinant for insufficient perceptions of environmental and psychosocial cancer risk factors embedded in social and cultural contexts . DispariBesides the direct costs for cancer patients, their social environment also faces financial burdens due to the care for the involved person. Since, in most healthcare systems, this thread is not covered or even systematically addressed by insurance, etc., the extent of resulting consequences for cancer treatment and outcome have rarely been investigated so far. Social and economic deficits due to family-based caregiving for patients with cancer may include lifestyle disruption, less socializing, greater out-of-pocket payment and lost productivity costs . Female Pediatric cancer-induced financial distress and its adverse effects on parents is well documented . The ecoThe financial distress can likely induce cost-coping strategies at the individual level that interfere with treatment acceptance and compliance . In addiCancer care usage in LMICs and, at least in part, in vulnerable groups in HIC is unevenly distributed throughout the different clinical specialties. For example, barriers to access, including inequalities in financial protection (mainly out-of-pocket payment), remain a fundamental challenge to providing surgical care or histopathological diagnostics . InnovatFor countries with limited economic resources for cancer care, various strategies have been recommended to provide the best care under the given conditions considering the existing financial framework (mainly targeting affordability and availability). Low-tech treatment protocols, such as switching from complex surgery to radiotherapy  or the uThese differences in diagnostic and treatment options, as determined by the given economic framework, are not limited to clinical availability but are furthermore related to participation in clinical research and access to innovation, respectively, due to financial limitations in these countries ,96. For Recognition cost of care discussions between the patient and physician as an important component of high-quality care;The provision of educational and support tools for cancer care providers promoting effective cost-related communication;Resource development to include the cost awareness of cancer care as part of shared decision making.More than a decade ago, the American Society of Clinical Oncology (ASCO) published their Guidance Statement on the Cost of Cancer Care, reflecting the increasing costs and financial burdens of cancer care, with a special focus towards the most vulnerable group, the cancer patients ,98. The The identification and active targeting of vulnerable groups for cancer that are still outside the existing cancer care structures but should be addressed for improved prognosis and outcome.However, these requests are based on an existing patient–physician relationship and require that cancer patients have already found their way to cancer care. Therefore, the needs should be supplemented by bullet points related to public health challenges, such as for prevention and early detection:The recognition of different levels and reasons for financial or socioeconomical vulnerability as part of individual medical history.Furthermore, numerous factors related to indirect costs for cancer care and determinants of financial vulnerability need to be considered:The various aspects of the SES of cancer patients appear to be the most important determinants of their individual vulnerability regarding the affordability, accessibility and acceptability of cancer care. The same factors intensively affect the financial burden of these patient groups, resulting in the worsening of their cancer care coverage. In addition, disease-related reasons and public aspects can influence the financial burden and vulnerability of cancer patients .Targeting vulnerable groups and their financial burden requires structured and comparable reporting of the entire cancer care processes. Usually, financial burden, economic hazards and related threads are solely investigated and discussed from the individual perspective of the cancer patients and sometimes of their social environment. However, there are additional economic effects on the society which are mainly out of focus when investigating cancer care. Reduced workforce availability, lower employment rates and premature retirement, among others, which are related to the direct cancer patients and their caregivers, may have negative consequences for a nation’s economy.Non-communicable diseases, especially cancer, impose a substantial and growing global impact on families and impoverishment in all continents and at all income levels. The true extent, however, remains difficult to analyze due to the heterogeneity across existing studies in terms of the populations studied, the determinants considered, the outcomes reported and the measures employed. The impact that is exerted on the patients themselves, their families and their perspectives is likely to be underestimated. Important (socio)economic domains, such as indirect financial burden, economic handling and relief strategies and the inclusion of marginalized and vulnerable people who do not seek healthcare due to financial reasons, are underrepresented in the literature. Given the scarcity of information on specific regions, further research is required to estimate the impact of cancer diagnoses on households/families and impoverishment in LMICs, especially the Middle Eastern, African and Latin American regions . HoweverThe vulnerability of cancer patients due to financial burden and economic impact can be determined by various factors differing in certain subgroups, regions or countries. Similarly, the resulting consequences, such as treatment compliance, abandonment, the acceptance of care, impaired QoL, etc., depend on the specific environment of each cancer patient. This requires setting the right incentives to motivate all participating groups, including patients, healthcare providers, healthcare politicians and the society ,100, andResearch on cancer prevention, detection and management with a focus on vulnerable groups should not be limited to their specific risk factors, carcinogens and interactions between genetic and environmental factors, among other clinical and epidemiological topics ; rather,


The applications of microalgae biomass have been widely studied worldwide. The classical processes used in outdoor cultivations of microalgae, in closed or open photobioreactors, occur in the presence of bacteria. Understanding how communication between cells occurs through quorum sensing and evaluating co-cultures allows the production of microalgae and cyanobacteria to be positively impacted by bacteria, in order to guarantee safety and profitability in the production process. In addition, the definition of the effects that occur during an interaction, promotes insights to improve the production of biomolecules, and to develop innovative products. This review presents the interactions between microalgae and bacteria, including compounds exchanges and communication, and addresses the development of new pharmaceutical, cosmetic and food bioproducts from microalgae based on these evaluations, such as prebiotics, vegan skincare products, antimicrobial compounds, and culture media with animal free protein for producing vaccines and other biopharmaceutical products. The use of microalgae as raw biomass or in biotechnological platforms is in line with the fulfillment of the 2030 Agenda related to the Sustainable Development Goals (SDGs). The annual production of microalgae is estimated to be up to 19,000 tons per year . AccordiDunaliella, mainly for obtaining β-carotene, Haematococcus, as a source of astaxanthin, as well as Chlorella and Arthrospira used as food additives [Considering the biocompounds produced by microalgae, carotenoids and polyunsaturated fatty acids have high added value, with an essential demand for naturally synthesized carotenoids, in global markets . The mosdditives . In addidditives . Althougdditives , effortsdditives . Therefodditives .There is little information available on microalgae bioproducts and their applications in the literature, mainly referring to uses in nutraceutical, cosmetical, pharmaceutical, and the food industry . BiologiIt is essential to evaluate microalgae-bacteria interactions to foresee the behavior of the consortia system, allowing adjustments in the operational conditions for successful microalgae production. Existing co-culture articles focus on the cultivation process, especially algal growth ,9,12, an2 [2 can attain inhibitory levels [In 1958, an Italian researcher named Luigi Provasoli suggested that bacteria could improve algae growth . It is k2 . In micry levels .For the production of microalgae in non-axenic conditions, it is necessary to ensure that the bacterium, which is present in the cultivation of the microalgae, does not present any toxicity to the latter. In addition, the concentration of bacteria must be maintained below a maximum threshold, promoting microalgae growth and preventing competition for nutrients . The envThe environmental conditions also determine the species present in the cultivation and, consequently, the type of interaction between microorganisms. For example, microalgae growth in extreme salinity avoids competition and contamination with less halotolerant organisms ,26.Dunaliella salina culture was obtained, but fungal contaminants were observed [It is known that the physiological changes mediated by bacteria and microalgae include increases in algae growth, flocculation, and a change in lipid content . Besidesobserved .The knowledge about possible interactions between bacteria and algae allows the control of the mechanisms that support mutualistic interactions, which can improve the development of bioprocesses with increased algae biomass and production of biocompounds such as carotenoids, lipids, and carbohydrates with high added value . Also, tQuorum sensing (QS) is a phenomenon of communication between microorganisms through the release and detection of small signaling molecules that accumulate in their surroundings as a function of cell-density . Cell-toThere are several QS communication systems, and the most well-known mechanisms are described in bacteria. QS is usually based on the production, secretion and detection of low molecular weight signaling biomolecules commonly referred to as autoinducers (AI). Quorum sensing plays essential roles in regulating gene expression and modulating complex processes such as virulence, symbiosis, production of bacteriocins, sporulation, conjugation, bioluminescence, motility, and biofilm formation, among others .Signaling molecules vary according to each bacterial group. In Proteobacteria, AI molecules belong to the group of acylated homoserine lactones (AHLs), initially known as autoinducer-1 (AI-1). AHL molecules vary in size and substitutions in the carbon chain, creating specificity in the communication within the species level. However, it is known that AHL molecules from one species can be detected by homologous signaling receptors present across different bacterial species . AutoindEscherichia coli and humans through the host-derived adrenergic signals norepinephrine and epinephrine that activate bacterial responses, meanwhile, the bacterial signaling molecules collectively known as autoinducer 3 (AI-3) have been shown to exert immunological effects in human tissues [Microbial communication through signaling molecules has been intensively investigated, and two-way interactions between bacteria and other organisms have been reported across different fields of study. For instance, Kim and collaborators (2020) described a type of interkingdom communication between  tissues . Studies tissues . Similar tissues ,34. Some tissues .Asterionellopsis glacialis by symbiotic bacteria of the Roseobacter group through inhibition of motility and improvement of biofilm formation, which likely enhanced the capacity of the bacteria to attach to the diatom microalgae. Interestingly, diatoms may also interfere with bacterial motility by producing QS mimics, such as rosmarinic acid, which may contribute to bacterial attachment [Fei and collaborators (2020) have shown that QS signals enabled the colonization of the phycosphere of the diatom tachment . Seymourtachment .Chlorophyta sp. by 86%, but algal biomass was slightly reduced [Chlorella sorokiniana, there was an improvement in algae biomass productivity by 2.25 times, as well as significant increases in the lipid and protein content, as well as in the harvest efficiency [Quorum sensing molecules (QSMs) extracted from wastewater microbial consortiums increased the production of lipid content by the microalgae  reduced . The autficiency . The supMicroalgae can produce amino acids such as tryptophan, a precursor for auxin biosynthesis in bacteria, promoting mutualistic interactions ,40.The ubiquitous sulfur-containing dimethylsulfoniopropionate (DMSP) is a compound produced by phytoplankton , they arOn the other hand, QS signals may exert an algaecide effect in some microalgae. Dow (2021) has discussed the role of some signaling molecules such as alkyl-quinolones and tetramic acid (a spontaneous rearrangement of 3-oxo-AHLs) to inhibit photosynthesis , as well as being able to interrupt important cell cycle and metabolic activities in microalgae . Segev eBacterial-produced QS inhibitors are suitable and efficient candidates to block the biological functions of QS microalgae, as they control algal blooms in water bodies so as to decrease concentrations of toxic species and prevent the harmful effects of toxins .According to Zhang et al. (2020), bacterial QS signals are detected by microalgae that have developed several mechanisms to respond positively or negatively to these signals, which can be symbiotic or algaecide signals, depending on the species associations performed .The co-cultures of bacterium and algae may be effective in detoxifying inorganic and organic pollutants and removing nutrients from wastewater if compared to the activity of these microorganisms individually. Photosynthesis by cyanobacteria and eukaryotic algae provides oxygen, an essential factor for heterotrophic bacteria that degrade pollutants. Sequentially, the bacteria help the photoautotrophic growth of the collaborators, furnishing carbon dioxide and stimulating factors  and decr2 coming from industrial processes, like distilleries , cement industry (CO2 from burning of energy source and CaCO3 decomposition), energy industry (CO2 from burning of energy source) as well as from aerobic and anaerobic treatment of wastewaters, as a carbon source to produce microalgae biomass. Simultaneously, the oxygen produced by phytoplankton may support the necessity of aerobic processes in these industries. The oxygen produced by microalgae could be used in an integrated process involving aerobic depuration of wastewaters, with a production of bacteria which could be used in different applications, like agricultural inoculants, among others, depending on the species of microorganism cultivated [This relationship is interesting because microalgae can be part of a circular economy, since it allows the use of COltivated .Although several species of bacteria have a beneficial effect on algae growth, some bacterial species may also inhibit microalgae by producing extracellular algaecide compounds . This inKordia algicida secretes an algaecide protease that hinders the growth of several diatomaceous marine species [Acinetobacter sp. was inoculated in the exponential phase, a substantial drop in the growth of Botryococcus braunii was observed. This bacterium, which presented a negative interaction with B. braunii, produces AHL signaling molecules involved in bacterial quorum sensing, which were found in the non-axenic culture of microalgae [Some bacteria can induce the lysis of microalgal cells. For instance, the  species . Bacteri species . For inscroalgae .From these considerations, it is important to evaluate the environmental conditions of the processes where the presence of undesirable bacteria is minimized and preferentially suppressed to maximize the microalgal growth. Otherwise, favoring beneficial bacteria within an appropriate threshold is also a determinant for optimizing microalgae growth.Tetraselmis is a phytoplankton species that controls bacterial diseases in fish, inhibiting the growth of bacteria such as Aeromonas hydrophila, Aeromonas salmonicida strains NG and LL, Lactobacillus sp., Serratia liquefaciens, Staphylococcus epidermidis, Vibrio anguillarum, Vibro salmonicida, and Yersinia ruckeri type I [In contrast, i type I . This inNormally, non-pathogenic bacteria from several species have been found in microalgae cultivations with beneficial effects on their growth.Alteromonas and Muricauda allowed the most significant accumulation of Dunaliella biomass due to the increase in the availability of nitrogen for microalgae. However, more research is needed to understand the mechanisms behind these interactions [It has been shown that bacteria may modify the growth of phytoplankton, accumulating biomass and increasing cell productivity, which is of particular interest for industrial production. The bacteria of the genera ractions .Chlorella prototecoides in synthetic wastewater media in co-culture with Brevundimonas diminuta with light intensities of 75 and 130 μmol photons m−2s−1, the μ values in non-axenic conditions were at least five times higher than in cultivations without co-culture. Thus, under these conditions, the addition of Brevundimonas diminuta was able to provide higher growth rates of C. protothecoides with more efficient nutrient removal [In the cultivation of  removal .Achromobacter sp. produces IAA, which promotes the growth of Haematococcus pluvialis, with an increase in chlorophyll and cell concentrations [2 in the medium, preventing this gas from reaching an inhibitory concentration. As a consequence of higher microalgae growth in co-culture with bacteria, there is a higher removal of nutrients from the cultivation medium, which is particularly important in the tertiary treatment of wastewater since nitrogen and phosphorus are constituents of the microalgae biomass. In a study using synthetic wastewater with a semi-continuous process, the immobilized consortium of Chlorella vulgaris and Azospirillum brasilense led to an increase in the uptake of ammonium by culture [C. sorokiniana are signaling molecules that may be used by A. brasilense to synthesize and secrete another signaling molecule, indole-3-acetic acid, which promotes microalgae growth. The occurrence of signaling compounds, such as thiamine and tryptophan in the exudates of Chlorella sorokiniana, supports the mutualistic interaction of this photosynthetic microorganism with A. brasilense [A substantial promotion in the growth of phytoplankton has been described because the bacterium produces indole-3-acetic acid (IAA) . The Achtrations . In fact culture . Thiaminasilense .C. vulgaris was grown with Bacillus pumilus, it was found that the bacterium fixed nitrogen from the atmosphere producing ammonia, a nitrogen form that promoted the growth of the microalga [In a study where icroalga . It is aicroalga , which iChlorella vulgaris was also grown with four bacterial strains that may promote its growth: Flavobacterium, Hypomonas, Rhizobium, and Sphingomonas for 24 days, obtaining higher growth of the microalgae in co-culture with these bacteria (cell concentrations up to 3.31 g L−1) compared to the control (1.30 g L−1) [Rhizobium in the culture of B. braunii, led to an increase (approximately 50%) in the growth of this microalga. This positive interaction between B. braunii and Rhizobium sp. indicates the viability of using these bacteria as inoculum in large-scale cultures for producing microalgae biomass [0 g L−1) . The add0 g L−1) . Rivas e biomass .One of the most discussed topics in this area is the increase in algal biomass in non-axenic strains. Efforts are required to evaluate the behavior of each microalga species, mainly in relation to bacteria isolated in different places of the world, which give different environmental conditions, concerning parameters such as temperature, light cycles, and water source. Additional attempts regarding this topic include (i) the concentration of a bacterium species or mix of bacteria species present in the cultivation of microalgae in different proportions, (ii) supplementation of different compounds in the medium to support the bacterium growth aiming to favor the microalgae growth; and (iii) evaluation of bacterial extracts in culture medium for microalgae growth.Microalgae may increase bacterial activity by secreting extracellular molecules such as lipids, proteins, and nucleic acids that serve as nutrients for bacterial growth. In this sense, dead microalgae cells can also provide nutrients for the growth of bacterial cells .Halomonas, that supply cobalamin for the microalgae Amphidinium operculatum [Pseudomonas sp., on the other hand, produced a glycoprotein that performed as a growth factor for Asterionella glacialis [Chlorella sp was shown to be improved due to the release of riboflavin by E. coli [Croft et al. (2005) showed that vitamin B12 is an important molecule in algae metabolism, the main cofactor for methionine synthase, which depends on vitamin B12. They also observed that cobalamin auxotrophy had appeared numerous times throughout evolution processes, probably related to the presence or absence of vitamin B12-dependent enzymes. An example of this symbiosis is the case of bacteria of the genus rculatum . Pseudomlacialis . In anot E. coli . MoreoveStreptomyces produced a respiratory inhibitor known as antimycin A (AA) that acts as mediator of Fe (III) in the halotolerant algae D. salina. AA forms fat-soluble complexes with Fe (III) that are absorbed and used by algae. Several species of phytoplankton can use bacterial siderophores as a source of Fe and at least one species of Dunaliella, D. bardawil, uses bacterial factors to improve iron acquisition. However, D. salina is unlikely to use AA as a mediator of Fe (III) in its natural habitat because Streptomyces species are not common in hypersaline environments characteristic of D. salina. The most likely interpretation of the results is that AA functions as an artificial mediator of Fe (III), forming Fe (III) -AA, which is a fat-soluble and stable complex that penetrates through the cell membrane and can be used directly by the cells, increasing Fe (III) bioavailability. Similar captures have been demonstrated for the use of organic lipophilic complexes of Cu and Ni ions by aquatic organisms [One study showed that rganisms .The knowledge of nutrients demanded by microalgae and bacteria is essential to optimize their cell growth. The metabolomic approach may be a valuable tool for better understanding the interaction between these organisms, thus providing useful information to maximize the cell growth and production of metabolites by them. In fact, in co-cultures of microalgae and bacteria, the metabolomic study allows to detect the secretion of substances, such as vitamins, which are produced by one of these microorganisms and are essential for the other one.Chlorella vulgaris cultivated in consortium with bacteria where it was detected the presence of Hyphomonas sp., Flavobacterium sp., Sphingomonas sp, and Rhizobium sp., with a significant increase in the proportion of palmitic (C16:0) and oleic (C18:1) acids if compared with results obtained with axenic cultivation [Some studies have reported that the interaction with bacteria can also change the lipid content, especially the fatty acids of microalgae. Cho et al. (2015) reported an increase of 20% in triacylglycerols in tivation .Rhizobium sp. KB10 with B. braunii increased algae growth by nine times and improved the oleate content, used to produce biodiesel [Rhizobium 10II in the cultivation of Ankistrodesmus sp. strain SP2-15 increased by 30% the chlorophyll content in the microalgae biomass, and the lipid productivity was up to 112 g.m−2d−1 on the sixth day of cultivation [Chlamydomonas reinhardtii with Bradyrhizobium japonicum improved the growth of the microalgae by 3.9 times, reaching lipid contents 26% higher and increasing Fe-hydrogenase activity and H2 production [The association of iodiesel . Inoculativation . The co-oduction .In addition to the possibility of increasing the production of fatty acids for producing biodiesel, widely explored in the literature, it is interesting to conduct efforts in studies regarding the effect of several bacteria on the production of carotenoids by microalgae that produce these metabolites, which are used in food, cosmetics, and medicines. Although the classic forms to stimulate the synthesis of carotenoids are related to the exposition of the cells to a stress condition , there iScenedesmus obliquus and the bacterial strains Diaphorobacter sp. and Acidovorax facilis positively influence the amount of microalgae biomass, and lipid production. Compared with the biomass of the axenic strain, the biomass of the co-culture of selected strains increased such cellular fraction by 3.5–24.8%. In addition, it was found that the bacteria adhered directly to the cell surface of S. obliquus, changing the concentration and composition of Extracellular Polymeric Substances (EPS) [Studies demonstrated that the cultivation of es (EPS) .Chlamydomonas reinhardtii CC-849 and Azotobacter chroococcum, under nitrogen deprivation, increased both the cell growth and the quantity of lipid in the microalga if compared with axenic microalga, which was attributed to the modulation of gene expression that regulates fatty acid metabolism. Such an increase in the lipid content of microalga was accomplished by a decrease in protein content [The consortium of  content . ConcernThe activity of bio-flocculant depends on the growth phase of the bacteria, being enzymatic activities related to the formation of bio-flocculants observed during the stationary growth phase. Although the production of bacterial bio-flocculant is beneficial for improving the formation of large flakes of microalgae and bacteria, the additional cost related to the carbon source required for the growth of these bacteria still remains a challenge , which ePaenibacillus polymyxa exhibited high efficiency for the flocculation of C. vulgaris and Scenedesmus sp. [Exopolysaccharides and pyruvic and uronic acids are important for cell adhesion. In addition, factors such as the sources of nitrogen and carbon and the ratio between these two elements influence the production of bio-flocculants. The bio-flocculant produced by the smus sp. .Flavobacterium, Terrimonas, and Sphingobacterium and their extracellular polymeric substances may help to increase the flocculating activity of algae such as C. vulgaris, resulting in sedimentable flakes [Bacteria such as e flakes .Flocculation helps in the processes of microalgae biomass harvest, and the study of interactions between bacteria and microalgae which promote at the same time improvement of the microalgae growth and their flocculation, mainly at the end of the cultivation, could diminish the overall production cost. Therefore, depending on the use of the microalgae biomass, efforts need to be made to improve the production of non-toxic bio-flocculants at the end of cultivation, by the addition of bacteria that promote microalgae aggregation at the end of cultivation, or even by the addition of substances that increase the content of such components in the cells at this period.2 and the production of exopolysaccharides by microalgae can increase the bacterial growth rate, as CO2 and the production of growth-promoting substances by bacteria can improve microalgae growth. However, bacteria and microalgae may produce substances that hinder the growth of the other co-immobilized organism. Besides, the increase in pH and oxygen concentration in the medium, due to photosynthetic activity, can reduce bacterial growth in the system with the co-immobilization of bacteria and algae [Microalgae are part of the organisms attached to filters in wastewater treatment plants, where the wastewater percolates during the treatment process. In these filters, enzymes or whole cells may be immobilized, including microalgae cells, which serve to obtain more biomass and for removing macronutrients since the production of oxygen by the algae improves the aerobic degradation of these substances. Moreover, the consumption of COnd algae .C. vulgaris co-immobilized with the bacterium Azospirillum brasilense strain Cd did not increase the growth compared with axenic C. vulgaris culture, but nitrogen uptake per cell improved. The initial ammonium concentration affects its uptake by immobilized cells of Chlorella vulgaris alone, but not when this photosynthetic microorganism is co-immobilized with A. brasilense. Nitrogen uptake depends more on the number of Chlorella vulgaris cells than on the initial concentration of nitrogen [Chlorella spp. with Azospirillum brasilense promoted the starch consumption in Chlorella spp. This phenomenon may occur because the bacteria produce indole-3-acetic acid (IAA), inducing cell growth of Chlorella spp. [When the nitrogen source was nitrate instead of ammonium, nitrogen . On the lla spp. ,60. It iConsidering the information on the interaction of microalgae and bacteria, besides the high potential of using microalgal biomass as a source of carbohydrates or fatty acids for energy production, food, cosmetic, and pharmaceutical industries, one could develop products in which microalgae, or their components could be used to confer special properties to them .Dunaliella salina and non-axenic strains of Chlorella vulgaris [Considering that bacteria and microalgae are rich in valuable organic compounds, and considering the related well-succeeded co-culture between these organisms, their extract could improve their growth. In this approach, Carvalho et al. (2021) developed a bacterial extract to promote the cultivation of microalgae, providing important nutrients for their growth. This extract allows greater growth in axenic and non-axenic strains of vulgaris . Otherwivulgaris .Arthrospira on bacteria in the intestine, increasing the growth rate of Lactobacillus, thus supporting the function of the digestive tract and being used as a prebiotic [Chlorella vulgaris and Arthrospira platensis as they increased the in vitro growth of beneficial bacteria such as Bifidobacterium animalis and Lactobacillus casei, thus acting as prebiotics [Saccharina and Laminaria, were recognized as dietary fibers with prebiotic properties [It is possible to develop foods based on the interactions between microalgae and bacteria, such as those that are not digestible, to beneficially affect the host by stimulating proliferation or activity of populations of beneficial bacteria in the intestine. There was a positive effect of rebiotic . For exaebiotics . In addioperties ,75. Consoperties  or safetoperties .Arthrospira platensis (APL95) led to a hypolipidemic effect if compared with high-fat diet without supplementation of the extract (HFD). In fact, the total cholesterol and triglycerides were 120.2% and 27.8% higher in HFD than in APL95 diet. APL95 diet also had a protective effect on liver in rats treated with high-fat diet. Concerning gut microbiota, APL95 diet promoted an increase in beneficial bacteria, such as Alloprevotella, Araprevotella, Barnesiella, Porphyromonadaceae and Prevotella as well as a decrease in undesired microorganisms, including Clostridium XVIII, Olsenella, Phascolarctobacterium, Romboutsi and Turicibacter. Therefore, APL95 diet could be used as a new adjunctive therapy and functional food to regulate the intestinal microbiota in diabetic and obese people [High-fat diet of rats supplemented with 95% ethanol extract of e people .Tetraselmis chuii (T), Phaeodactylum tricornutum (P) and Bacillus subtilis (B), simple or combined, showing morphological changes and significant signs of intestinal damage. The diets applied to fish led to a decrease in the bacterial diversity in the intestinal microbiota. Only diets containing Bacillus subtilis resulted in a significant reduction in the height of the microvilli. Moreover, fish fed with experimental diets showed different signs of edema and inflammation, and the authors concluded that such effects could compromise fish body homeostasis [Cerezuela et al. (2012) carried out in vivo studies of experimental diets with eostasis . These fPorphyridium sp. in a proportion of 5% and 10% of its standard diet led to a reduction of 11% and 28% in the level of serum cholesterol, respectively, accomplished by a reduction of 10% in consumption of food, without any loss in production of eggs if compared to the control. Moreover, when microalgae biomass was included in the diet, egg yolks presented a tendency to have lower levels of cholesterol (by 10%), higher levels of linolenic (by 29%) and arachidonic acids (by 24%). Their color became darker as a result of the higher levels of carotenoids (2.4 times more with chicken fed with 5% supplement), thus encouraging the development of feed for chickens with polyunsaturated fatty acids and dietary fibers [Concerning strict biochemical findings, studies show that chickens fed with microalgae y fibers . Accordiy fibers . Considey fibers .It is worth mentioning that metabolomic studies could evaluate the compounds produced by intestinal bacteria in a diet containing microalgae and/or their extracts, being an important field to be considered in further research. For these studies, it could be used in vitro models or even in vivo evaluation, employing microalgae biomass . Such studies can provide information for the development of healthier processed foods, in which the incorporation of microalgae biomass could improve the consumer’s health, not only furnishing beneficial nutrients but also increasing the beneficial microorganisms in the gut.The growing need for obtaining safe products by bioprocesses has made microalgae a sustainable source for new products. Currently, microbial sources are the best available on the market to replace implemented entities .Chlorella vulgaris, Arthrospira, and Nostoc when growing in the presence of radiation. These biomolecules can help to protect against the oxidative process of oil in formulations, especially in emulsions with a large quantity of oily phase, as they have antioxidant activities [Several secondary metabolites produced by algae are known to benefit the skin. Algae cells are naturally exposed to oxidative stress, which makes them develop efficient protection systems against radicals and reactive oxygen species, producing biomolecules that may act in cosmetics against the damaging effects of UV radiation, promoting the same action of inorganic filters and organic agents currently commercialized. There is an increase in the production of carotenoids and chlorophyll by tivities . Such prArthrospira platensis extracts, which are abundant in free fatty acids, was verified. The nanocarriers based on copper alginate loaded with extract, were able to inhibit the formation of biofilms from one and two species of Cutibacterium acnes, but did not inhibit preformed biofilms. Nanovectorized extracts reduced the growth of Candida albicans biofilms, as well as preformed biofilms [Due to the fact that biofilm is related to infections, particularly due to the low susceptibility of microorganisms to traditional antimicrobial agents, microalgae may be explored seeking an innovation to solve this problem. The antibiofilm activity of biofilms .Proteins are molecules currently present in large amounts in microalgae and they can be used as alternatives to proteins from plants and animals in cosmetic formulations, which opens a large research field with high industrial potential. Polysaccharides and carotenoids are other macromolecules present in microalgae with high potential to be used in cosmetic formulations. Such compounds can act on the cosmetic formulation, changing their properties, protecting and or stabilizing them. These molecules can also act in skin, avoiding its water loss and/or nourishing it.Considering that cosmetic formulations are destined to several uses, the change of the source of raw material can, in addition to the change in formulations properties, affect the conservation of the formulations and the microbiota of the skin. Research demonstrates that the levels of sebum and hydration are essential factors for the diversity of the skin’s microbiota, differing according to age and skin groups with acne . This fiChlamydomonas reinhardtii as a drug delivery system. These modified microalgae masked vancomycin thanks to an insertion of a photocleavable binder on the cell surface, and the antibiotic was released in a controlled way, under exposure to ultraviolet light (340–400 nm). This technique was tested on Bacillus subtilis, successfully resulting in growth inhibition of this bacterium [Currently, resistant strains are gaining attention in the treatment of bacterial infections . Therefoacterium . Microalacterium . Thus, tAlthough the presence of pathogenic bacteria has not been reported in microalgae cultures, the production of antibiotics by microalgae could contribute to the biological safety of the obtained biomass.Dunaliella salina extract can inhibit the growth of opportunistic bacteria such as E. coli and Pseudomonas aeruginosa. In liquid medium, the growth of these two bacteria was delayed by 263% and 20%, respectively. Conversely, this same extract did not affect the growth of Klebsiella pneumoniae, Enterococcus sp., and Staphylococcus aureus, demonstrating the specificity in the action of the whole cell extract [The antioxidant activity of  extract .Chlorella vulgaris showed antibacterial activity against Salmonella Typhi, a Gram-negative bacterium, the causative agent of enteric fever, infectious diarrhea, and sepsis in humans, in addition to E. coli and P. aeruginosa ATCC 29212. The antimicrobial activity of Chlorella vulgaris was found to control Gram-positive bacteria such as Bacillus subtilis, Enterococcus faecalis ATCC 29212, Streptococcus pyogenes ATCC 12344, and Staphylococcus aureus ATCC 25923 [It was found that the extracts of fatty acid mixture from CC 25923 .Chlamydomonas reinhardtii inhibiting bacterial aggregation of Escherichia coli, leaving the bacteria vulnerable to predation [There was a report in the literature of the alga redation . In addiChlamydomonas reinhardtii against Bacillus subtilis, Streptococcus sp., Neisseria mucosa and E. coli, validated the antibacterial activity in vitro, and showed that they can prevent biofilm formation and eradicate pre-formed biofilms [Extracts were prepared from 225 microalgae, containing polyunsaturated fatty acids with antibacterial and antibiofilm properties . Vishwakbiofilms .Processes based on interaction of microalgae and bacteria are recognized as a renewable and sustainable technology, in compliance with current economic and low-carbon guidelines for environmental protection and resource recovery. Consortium-based technologies are expected to be viable for the current microalgae industry. Nevertheless, more research is required with an in-depth evaluation of the mechanisms of interaction between these microorganisms, as well as large-scale cultures for biotechnological application in actual conditions .In nature, regardless of the environmental condition, microalgae and bacteria interact through communication by quorum sensing, which may change the metabolism of both organisms. The understanding of the interaction between different species of bacteria and microalgae may highlight the production of new molecules by microalgae and even improve the production of already known molecules. Moreover, the knowledge of the structure of these molecules and their actions on other organisms, including bacteria, indicates that the use of extracts or purified molecules from microalgae can be useful in the development of health, food, and cosmetic products, as well as in the development of nutritional ingredients for culture media. Efforts are necessary to develop such useful products, increasing the world microalgae demand, and contributing to the sustainable production of industrial products.As future perspectives, we can indicate (i) isolation of new antibiotic biomolecules from microalgae and carry out computational studies; (ii) development of pharmacotechnical formulations for pre-clinical studies; (iii) development of dermatological formulations for the treatment of acne; (iv) development of skincare creams and/or gels; (v) development of microalgae-based prebiotic juices for bowel regulation; (vi) development of specific culture media for the growth of heterotrophic microorganisms, mainly focusing on vaccines and biopharmaceuticals.


Background: Since the first confirmed case of the Novel Coronavirus Disease 2019 (COVID-19) in Nigeria, the pandemic has become a major public health challenge, affecting different sectors of the country. While Nigeria is battling to control the spread of COVID-19, the eruption of new cholera cases has put additional pressure on the strained healthcare system.Evidence: We showed how the overwhelming focus on COVID-19 has jeopardized key cholera containment measures such as disease surveillance, risk communication, and case management.Policy Options and Recommendations: We recommend provision and universal access to safe water and sanitation as key cholera preventive and control measures. However, these are resources that developing countries including Nigeria find rather challenging to provide. We also proposed the implementation of well-coordinated multi-sectoral interventions that involve strengthening disease surveillance including access to safe drinking water, vaccines, and treatment, especially in vulnerable communities.Conclusion: This policy brief provides evidence for policymakers, which if acted upon, will foster sustainable solutions to the lingering cholera outbreaks in Nigeria. There are roughly 2.9 million cases of cholera each year, resulting in approximately 95,000 deaths worldwide, mainly in low and middle-income countries . Since tCoronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) was first identified in 2019 in Hubei Province in China . On the Amid the COVID-19 pandemic, seven African countries including Nigeria reported cholera outbreaks , which fThis paper aimed to discuss efforts in the fight against cholera and the challenges faced in response to the cholera outbreak amidst COVID-19 in Nigeria. Thus, providing evidence for policymakers to take action and foster sustainable solutions.The first series of cholera outbreaks in Nigeria was reported between 1970 and 1990 [Cholera is an acute diarrheal infection caused by the consumption of food or water contaminated with the bacterium Vibrio cholera. The WHO has highlighted the provision of safe water and sanitation as important preventive and control measures . These aIn Nigeria, the centerpiece of cholera prevention and control has been Water, Sanitation, and Hygiene (WASH) approaches, surveillance, risk communication, and case management. In 2018, National Cholera Hotspot Prioritization Survey and Risk Assessment led to the identification of 105 Local Government Areas (LGAs) as Cholera Hotspot Locations .In addition, a 5 years National Strategic Plan of Action for Cholera Control was established to promote coordinated control and prevention of cholera in the country. An important component of the plan is to reduce cholera morbidity and mortality by 67% by the year 2023, which constitutes a commitment toward meeting the global target of eliminating cholera by 2030 . GearingIn response to the sudden increase in the number of cholera cases in April 2021, the National Cholera Emergency Operations Center (EOC) was activated on the 22nd of June 2021. This led to the distribution of Rapid Response Teams to states affected by the outbreak . Also, tAs with other countries across the world, Nigeria is trying to revamp its health system to control the third wave of the COVID-19 pandemic. However, the sudden outbreak of cholera has further worsened the fragile health system. As of December 19, 2021, a total of 109,189 suspected cholera cases and 3,604 cholera-related deaths were reported across the 32 states and the Federal Capital Territory . ChildreWhile the focus is on the COVID-19 pandemic, cholera cases are silently increasing and could become a bigger threat in a country with an underserved healthcare system. This situation coupled with the interruption of humanitarian aid, inefficient human capacity , ongoingIn June 2021, following an escalating cholera outbreak across the country, the NCDC launched the National Cholera Emergency Operations Center (EOC), response techniques include the deployment of Rapid Response Teams (RRT) to help stem the outbreak at the local level, distribute medical supplies and update risk communication . While tThe direction of the health workforce towards containing issues caused by COVID-19 has created a huge deficit of ineffective surveillance and control of cholera outbreaks. According to the World Bank, the health workforce density in Nigeria is approximately 4 doctors per 10,000 patients and 16.1 midwives and nurses per 10,000 patients . This isThe emergence of COVID-19 has threatened a surge in the spread and treatment of diseases endemic to Nigeria, such as cholera, Lassa fever, and meningitis, making them more transmissible and more lethal. On 20th May 2020, a total of 99 countries reported the suspension of immunization activities including oral cholera vaccines .Although COVID-19 has highlighted the importance of vaccines, the current increase in cholera cases in Nigeria is due to the disruption of the cholera vaccination campaign including key cholera control components such as disease surveillance and risk communication . This isIn 2019, approximately 29% of Nigerians lack access to basic drinking water services, 38.1% without access to improved sanitation facilities, and 80% without access to basic handwashing facilities . AdditioThe WHO highlighted the provision of safe water and sanitation as important preventive and control measures against cholera outbreaks . HoweverCholera remains one of the major public health challenges in Nigeria, and the recurrent outbreak has shown us the weakness of our healthcare systems. Based on available evidence and international best practices as indicated in policies of WHO, UNICEF, and CDC, the following recommendations should be adopted to mitigate the spread of the cholera outbreak in Nigeria:There is a need to adopt a well-coordinated multi-sectoral approach to cholera prevention in Nigeria. This will help to identify and strengthen the connections between government agencies, bilateral and multilateral development partners, and non-governmental organizations (NGOs) whose activities help to lower the risk of cholera and promote prevention at the local and national levels. A well-coordinated cholera prevention and control strategy should be developed and implemented by the Nigerian government, and it should include robust disease surveillance as well as free and compulsory vaccination. This will aid in the early detection of cholera outbreaks, targeted prevention strategy, and partnership with state governments and non-governmental organizations (NGOs). Furthermore, the collaboration will include ministries of environment and water boards to ensure proper sanitation, sewage management, and adequate supply of clean water. If implemented, this recommendation will assist in preventing Cholera outbreaks in Nigeria, particularly during pandemics such as COVID-19. There will, however, be challenges, including funding issues, improper implementation, and corruption across various sectors.While stool cultures are the most popular method for confirming cholera cases in Nigeria, rapid diagnostic test kits should be promoted once an outbreak has begun to quickly identify suspected cases, select candidate samples for stool cultures, and track epidemiological data. To achieve this, the government should empower and train the health personnel that is the closest to people such as those in community pharmacies, primary healthcare centers, and patent medicine stores to carry out rapid diagnostic tests. The recommendation may be challenged by laws governing health practices but the official Gazette granting a waiver will be sufficient to solve this problem. Therefore, the government in Nigeria should be prompt to increase the number of healthcare facilities particularly, primary and comprehensive healthcare centers at least within a reach of 1 km square. This will drastically reduce the case fatality rate (the CFR) and the spreading of the cholera infection in an outbreak.2, especially in vulnerable communities. Also, chlorination of drinking water supplies has proven to be an effective means of preventing infectious diseases. Therefore, drinking water must be treated at the source, at points of collection or at the household level. Data on cholera surveillance must be shared with the WASH, this will timely activation of rapid response techniques.COVID-19 has highlighted the importance of WASH programs in controlling the spread of infectious diseases including cholera. Therefore, there is a need to strengthen policies and programs that promote WASH and waste management practices including the provision of public convenience toilets and latrines to combat open defecation. In addition, there should be at least one safe drinking water facility in every radius of 1 kmThere is a need to strengthen community engagement to ensure timely reports and control of cholera outbreaks at local, state, and national levels. This can be done by increasing awareness on social media and billboards in public spaces, reorienting people through the National Orientation Agency (NOA), and educating the public about disease management and prevention in local languages through radio stations. Also, advocacy should be made to the government and policy makers to provide monitoring and evaluation units to checkmate the success of the programs and compliance with the policies on tackling and preventing cholera outbreaks across Nigeria.Eliminating cholera in at least 20 countries by the year 2030 is a global target. Although Nigeria has shown commitment to achieving this goal, the sudden surge in cholera cases amidst the COVID-19 pandemic has further shown the need for preparedness and reform in the healthcare system in Nigeria. It is therefore important for policymakers to evaluate the current health system status to build resilient institutions against future disease outbreaks. There is a need for the government to take the lead in implementing coordinated multi-sectoral interventions that promote universal access to safe drinking water, sanitation, and hygiene infrastructure.