Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

Microbiota and the Volatile Profile of Avian Nests Associate with Each Other and with the Intensity of Parasitism.

Bacteria have been suggested as being partially responsible for avian-nest odours and, thus, volatiles from their metabolism could influence the intensity of selection pressures due to parasites detecting olfactory cues of their hosts. Here, we tested this hypothesis by exploring intra- and interspecific variability in microbial environments, volatile profiles, and intensity of ectoparasitism by Carnus hemapterus in nests of ten avian species. As expected, we found that (i) alpha and beta diversity of microbial and volatile profiles associated to each other. Moreover, (ii) alpha diversity of bacteria and volatiles of nest environment, as well as some particular bacteria and volatiles, associated with intensity of parasitism at early and late stage of the nestling period. Finally, (iii) alpha diversity of the nest microbiota, as well as some particular bacteria and volatiles, was correlated to fledging success. When considering them together, the results support the expected links between microbial environment and nest odours in different bird species, and between microbial environment and both ectoparasitism intensity and fledging success. Relative abundances of particular volatiles and bacteria predicted ectoparasitism and/or fledging success. Future research should prioritize experimental approaches directed to determine the role of bacteria and volatiles in the outcomes of host-ectoparasite interactions.

Autoimmune inner ear disease associated with antiphospholipid antibodies.

OBJECTIVES: The percentage of autoimmune diseases in Western countries is approximately 8% of the total population. Despite numerous studies indicating an increase in prevalence and incidence over the past two decades, autoimmune vestibular disorders seem to be underdiagnosed, primarily due to the lack of a definitive test capable of identifying the specific antigen of the inner ear. Autoimmune inner ear disease (AIED) is defined as a rapidly progressive and often fluctuating bilateral neurosensorial hearing loss that develops over a period of weeks or months. AIED can affect only the inner ear or be part of systemic diseases such as granulomatosis with polyangiitis, Cogan's syndrome, systemic lupus erythematosus, polyarteritis nodosa, or relapsing polychondritis, among others. Our main objective was to conduct a study on the presence of antiphospholipid antibodies (aPL) in patients with AIED seen in a specialised clinic. METHODS: We designed an observational retrospective study in which we selected patients from a total group of 55 with AIED referred to the Autoimmune Diseases Clinic, those with confirmed positivity for antiphospholipid antibodies, and described their clinical, analytical, and epidemiological characteristics. RESULTS: We found a prevalence of 29% positivity for antiphospholipid antibodies, with lupus anticoagulant (LA) being the most frequently detected, followed by anticardiolipin (aCL) and anti-beta2 glycoprotein (anti-B2GP). Double positivity was observed in 25% of patients. The main clinical manifestations were bilateral hearing loss, vestibular symptoms, and tinnitus. Only 25% of patients experienced audiometric improvement during the course of the disease. CONCLUSIONS: We emphasise the importance of identifying the presence of aPL in AIED, enabling the establishment of appropriate and specific therapeutic management to prevent audiometric deterioration.

Net costs of breast cancer in Colombia: a cost-of-illness study based on administrative claims databases.

BACKGROUND: Breast Cancer (BC) is associated with substantial costs of healthcare; however, real-world data regarding these costs in Colombia is scarce. The contributory regime provides healthcare services to formal workers and their dependents and covers almost half of the population in Colombia. This study aims to describe the net costs of healthcare in women with BC covered by the contributory regime in Colombia in 2019 from the perspective of the Colombian Health System. METHODS: The main data source was the Capitation Sufficiency Database, an administrative database that contains patient-level data on consumption of services included in the National Formulary (PBS, in Spanish Plan de Beneficios en Salud). Data on consumption of services not included in the PBS (non-PBS) were calculated using aggregated data from MIPRES database. All direct costs incurred by prevalent cases of BC, from January 1 to December 31, 2019, were included in the analysis. The net costs of the disease were estimated by multiplying the marginal cost and the expected number of cases with BC by region and age group. Marginal costs were defined as the costs of services delivered to patients with BC after subtracting the expected costs of health services due to age, comorbidity burden or region of residence. To calculate these costs, we used Propensity Score Matching in the main analysis. All costs were expressed in 2019 international dollars. Productivity losses, transportation expenses, and caregiving costs were not included. RESULTS: A total of 46,148 patients with BC were identified. Total net costs were $387 million (95% CI $377 to $396 million), 60% associated with non-PBS services. Marginal costs were $8,366 (95% Confidence Interval $8,170 to $8,573), with substantial variations between regions age groups (from $3,919 for older patients in the Amazonia region to $10,070 for younger patients in the Pacific region). The costs for PBS services were higher for ambulatory services and for patients who died during 2020. CONCLUSIONS: BC imposes a substantial economic burden for the Colombian Health System with important variations in net costs between regions and age groups. Patients near death and ambulatory services were associated with higher costs of healthcare.

Volatiles of symbiotic bacterial origin explain ectoparasitism and fledging success of hoopoes.

BACKGROUND: Some parasites use olfactory cues to detect their hosts and, since bacterial symbionts are partially responsible for animal odours, they could influence host parasitism. By autoclaving nest materials of hoopoe (Upupa epops) nests before reproduction started, we explored the hypothetical links between host-associated bacteria, volatiles and parasitism. During the nestling stage, we (i) estimated the level of ectoparasitism by chewing lice (Suborder Mallophaga) in adult hoopoe females and by Carnus haemapterus flies in nestlings, and (ii) characterized microbial communities and volatile profiles of nest environments (nest material and nest cavity, respectively) and uropygial secretions. RESULTS: Experimental nests had less diverse bacterial communities and more diverse volatile profiles than control nests, while occupants experienced lower intensity of parasitism in experimental than in control nests. The experiment also affected beta diversity of the microbial communities of nest material and of the volatiles of the nestling uropygial secretions. Moreover, microbial communities of uropygial secretions and of nest materials covaried with their volatile profiles, while the volatile profile of the bird secretions explained nest volatile profile. Finally, a subset of the volatiles and bacteria detected in the nest material and uropygial secretions were associated with the ectoparasitism intensity of both adult females and nestlings, and with fledging success. CONCLUSIONS: These results show that a component of animal odours is linked with the microbial communities of the host and its reproductive environment, and emphasize that the associations between bacteria, ectoparasitism and reproductive success are partially mediated by volatiles of bacterial origin. Future work should focus on mechanisms underlying the detected patterns.

Operative Management of Y-Shaped Metatarsal with Biphalangeal Sixth Toe.

BACKGROUND: In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported. Treatment of the complete deformity will prevent further foot and gait disorders. OBJECTIVE: To identify literature relevant to the operative management of Y-shaped metatarsal with biphalangeal sixth toe and related skin and wound care to improve surgical treatment protocols from a clinical experience perspective. DATA SOURCES: The authors searched several electronic databases in December 2022 for articles related to postaxial polysyndactyly in the feet and polymetatarsia. Databases searched included PubMed, SciELO, ScienceDirect, Cochrane Database of Systematic Reviews, and Google Scholar gray literature. STUDY SELECTION: Two independent researchers conducted the searches and read the article titles and abstracts. Studies were included if they were narrative reviews, case studies, or observational studies; written in English or Spanish; and published between 2012 and 2022. Nonhuman studies were excluded. Studies that met the inclusion criteria were fully evaluated. Disagreements between reviewers were resolved by consensus, and when there was no consensus, a senior researcher was consulted. DATA EXTRACTION: The following data were extracted from the included studies using a standardized form: author and year of publication, study type, number of participants, sex, polydactyly location, polymetatarsia, type of polydactyly, participants' history of hereditary associated diseases or malformations, treatment, removal criteria, and timing of surgery. DATA SYNTHESIS: Authors evaluated 11 studies of postaxial polydactyly that included a total of 153 participants (64 men, 89 women). They also document their clinical experience with a surgical technique used in cases of bilateral postaxial polydactyly of the foot with a Y-shaped metatarsal with biphalangeal sixth toe. CONCLUSIONS: Surgical correction with lateral removal of the sixth toe is a resolutive treatment to improve the functionality of the foot, its aesthetic appearance, and the patient's quality of life. Case-specific treatment should be applied and tailored to meet the individual needs. The biomechanics of gait and shoe problems in these patients improve with surgical treatment, without presenting secondary aesthetic problems in skin care.

Uneven response of phytoplankton-bacteria coupling under Saharan dust pulse and ultraviolet radiation in the south-western Mediterranean Sea.

The microbial carbon (C) flux in the ocean is a key functional process governed by the excretion of organic carbon by phytoplankton (EOC) and heterotrophic bacterial carbon demand (BCD). Ultraviolet radiation (UVR) levels in upper mixed layers and increasing atmospheric dust deposition from arid regions may alter the degree of coupling in the phytoplankton-bacteria relationship (measured as BCD:EOC ratio) with consequences for the C-flux through these compartments in marine oligotrophic ecosystem. Firstly, we performed a field study across the south-western (SW) Mediterranean Sea to assess the degree of coupling (BCD:EOC) and how it may be related to metabolic balance (total primary production: community respiration; PPT:CR). Secondly, we conducted a microcosm experiment in two contrasting areas (heterotrophic nearshore and autotrophic open sea) to test the impact of UVR and dust interaction on microbial C flux. In the field study, we found that BCD was not satisfied by EOC (i.e., BCD:EOC >1; uncoupled phytoplankton-bacteria relationship). BCD:EOC ratio was negatively related to PPT:CR ratio across the SW Mediterranean Sea. A spatial pattern emerged, i.e. in autotrophic open sea stations uncoupling was less severe (BCD:EOC ranged 1-2), whereas heterotrophic nearshore stations uncoupling was more severe (BCD:EOC > 2). In the experimental study, in the seawater both enriched with dust and under UVR, BCD:EOC ratio decreased by stimulating autotrophic processes (particulate primary production (PPP) and EOC) in the heterotrophic nearshore area, whereas BCD:EOC increased by stimulating heterotrophic processes [heterotrophic bacterial production (HBP), bacterial growth efficiency (BGE), bacterial respiration (BR)] in the autotrophic open sea. Our results show that this spatial pattern could be reversed under future UVR × Dust scenario. Overall, the impact of greater dust deposition and higher UVR levels will alter the phytoplankton-bacteria C-flux with consequences for the productivity of both communities, their standing stocks, and ultimately, the ecosystem's metabolic balance at the sea surface.

SEOM-GEINO clinical guidelines for grade 2 gliomas (2023).

The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.

3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas.

BACKGROUND: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using 3 main classes and a total of 5 subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320. METHODS: All patients with at least 1 available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation. RESULTS: Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A, and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%), and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (P = .061). All class 1 patients (2/2), 75% of class 2 patients (3/4), and only 10% of class 3 patients (1/10) had clinical benefit. CONCLUSIONS: Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Winged resistance: Storks and gulls increase carriage of antibiotic resistance by shifting from paddy fields to landfills.

Waterbirds are vectors for the dissemination of antimicrobial resistance across environments, with some species increasingly reliant on highly anthropized habitats for feeding. However, data on the impact of their feeding habits on the carriage of antibiotic resistance genes (ARGs) are still scarce. To fill this gap, we examined the microbiota (16S rRNA amplicon gene sequencing) and the prevalence of ARG (high-throughput qPCR of 47 genes) in faeces from white storks (Ciconia ciconia) and lesser black-backed gulls (Larus fuscus) feeding in highly (landfill) and less (paddy fields) polluted habitats. Faecal bacterial richness and diversity were higher in gulls feeding upon landfills and showed a greater abundance of potential pathogens, such as Staphylococcus. In contrast, faecal bacterial communities from storks were similar regardless of habitat preferences, maybe due to a less intense habitat use compared to gulls. In addition, birds feeding in the landfill carried a higher burden of ARGs compared to the surrounding soil and surface waters. Network analysis revealed strong correlations between ARGs and potential pathogens, particularly between tetM (resistance to tetracyclines), blaCMY (beta-lactam resistance), sul1 (sulfonamide resistance) and members of the genera Streptococcus, Peptostreptococcus, and Peptoclostridium. Our work demonstrates how transitioning from paddy fields to landfills fosters the carriage of ARGs and potential pathogens in the bird gut, shedding light on the ecological role of these avian vectors in antimicrobial resistance dissemination.

Characterization of cardiac arrhythmias and maternal-fetal outcomes in pregnant women: A prospective cohort study.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease is a common cause of morbidity and mortality in pregnant women. Arrhythmias are common complications during pregnancy; however, the data are limited. Our goal was to characterize the epidemiology, clinical presentation, and impact of cardiac arrhythmias on maternal-fetal outcomes. METHODS: A prospective cohort study from the Colombian Registry of Pregnancy and Cardiovascular Disease was carried out from 2016 to 2019. All patients with tachyarrhythmia or bradyarrhythmia and a minimum follow-up of six months after delivery were included. The primary outcome was a composite of cardiac events defined as pulmonary edema, symptomatic sustained arrhythmia requiring specific therapy, stroke, cardiac arrest, or maternal death. Secondary outcomes were other cardiac, neonatal, and obstetric events. RESULTS: Arrhythmias were the most common cause of referral to our dedicated cardio-obstetric clinic. A total of 92 patients were included, mean age 27±6 years; 8.7% had previous structural heart disease, and cardiology consultation was delayed in 79.4%. The most common arrhythmias were premature ventricular contractions (33%) and paroxysmal reentrant supraventricular tachycardias (15%); 11 patients (12%) had cardiac implantable electronic devices. Cardiac events occurred in 18.4% of patients, obstetric events occurred in 6.5%, and one caesarean was indicated in the context of symptomatic severe mitral stenosis. Adverse neonatal outcomes were observed in 24.3% of newborns. CONCLUSIONS: Arrhythmias were the most common cause of referral to a dedicated cardio-obstetric clinic; most had a benign course. Adverse maternal cardiovascular outcomes were significant and there was a high rate of obstetric and neonatal adverse events, underlining the importance of multidisciplinary care.

A Short-Term Evaluation of Foot Pronation Tendency in Healthy Recreational Runners.

Running is a highly physical activity, and it is related to injuries when there is an excessive pronation of the foot. This study evaluates, from a sample group of healthy recreational runners, if the foot tends to pronate after a period of running activity and when, with respect to a period of running compared to walking, evaluated during several phases: after 30, 45, and 60 min. This quasi-experimental study has been carried out on a total of 36 healthy recreational subjects. The subjects were evaluated during two different activities: running activity for a period of an hour with respect to normal walking activity. The main outcome measures were the foot posture index (FPI) and the navicular drop test (NDT), which were evaluated at p1 (the screening day), after 30 min of activity (p2), after 45 min of activity (p3), and finally after 60 min (p4) during running or walking activity. The analysis showed significant differences for the FPI and NDT variables in both groups and on both feet, comparing p1 and p4. These changes showed a significant relationship comparing p1 and p3 for the FPI variable, and for the NDT variable (p < 0.001) of the left foot and, with respect to the right foot, significance was shown to the FPI comparing the p1 and p2. A significant difference was found in the tendency to pronate the foot after a period of running compared to the same period of walking after 60 min of activity. Running produced an excessive pronation of the foot after 45 min of activity, evaluated with the FPI for both feet.

Circular and L50-like leaderless enterocins share a common ABC-transporter immunity gene.

Microbes live within complex communities of interacting populations, either free-living in waters and soils or symbionts of animals and plants. Their interactions include the production of antimicrobial peptides (bacteriocins) to antagonize competitors, and these producers must carry their own immunity gene for self-protection. Whether other coexisting populations are sensitive or resistant to the bacteriocin producer will be key for the population dynamics within the microbial community. The immunity gene frequently consists of an ABC transporter to repel its own bacteriocin but rarely protects against a nonrelated bacteriocin. A case where this cross-resistance occurs mediated by a shared ABC transporter has been shown between enterocins MR10A/B and AS-48. The first is an L50-like leaderless enterocin, while AS-48 is a circular enterocin. In addition, L50-like enterocins such as MR10A/B have been found in E. faecalis and E. faecium, but AS-48 appears only in E. faecalis. Thus, using the ABC transporter of the enterocin MR10A/B gene cluster of Enterococcus faecalis MRR10-3 as a cross-resistance model, we aimed to unravel to what extent a particular ABC transporter can be shared across multiple bacteriocinogenic bacterial populations. To this end, we screened the MR10A/B-ABC transporters in available microbial genomes and analyzed their sequence homologies and distribution. Overall, our main findings are as follows: (i) the MR10A/B-ABC transporter is associated with multiple enterocin gene clusters; (ii) the different enterocins associated with this transporter have a saposin-like fold in common; (iii) the Mr10E component of the transporter is more conserved within its associated enterocin, while the Mr10FGH components are more conserved within the carrying species. This is the least known component of the transporter, but it has shown the greatest specificity to its corresponding enterocin. Bacteriocins are now being investigated as an alternative to antibiotics; hence, the wider or narrower distribution of the particular immunity gene should be taken into account for clinical applications to avoid the selection of resistant strains. Further research will be needed to investigate the mechanistic interactions between the Mr10E transporter component and the bacteriocin as well as the specific ecological and evolutionary mechanisms involved in the spread of the immunity transporter across multiple bacteriocins.

Comparison of Resorbable and Non-Resorbable Osteosynthesis Material in Hallux Surgery: A Systematic Review.

There are various pathologies that involve the hallux, among which hallux valgus is the most common. When conservative treatment fails, it is necessary to resort to a surgical approach. The fixation elements for osteotomies in the hallux are usually composed of metallic materials; however, today, there are numerous resorbable materials that offer numerous advantages over conventional materials. In this article, the objective is to analyze the scientific evidence through the systematic analysis of the existing literature in relation to the effectiveness of resorbable versus non-resorbable osteosynthesis material in the surgical correction of hallux deformities and compare the complications as well as the patient satisfaction and quality of life between both fixation methods. A systematic review of the literature available in the PubMed, EMBASE, Web of Science and Scopus databases and 10 studies were included. The documents were chosen following the eligibility and exclusion criteria, including experimental and observational studies evaluated with the Jadad and Newcastle-Ottawa methodological quality scale, respectively. Data were extracted from valid studies for the review, and the variables functionality, pain, angular corrections, complications, satisfaction and quality of life were observed. In conclusion, there is limited scientific evidence regarding the effectiveness of resorbable versus non-resorbable osteosynthesis material in the surgical correction of hallux deformities. All observed variables are similar regardless of the surgical technique and osteosynthesis material used.

Lactiplantibacillus paraplantarum BPF2 and Pediococcus acidilactici ST6, Two Bacteriocinogenic Isolated Strains from Andalusian Spontaneous Fermented Sausages.

Traditional spontaneously fermented foods are well known for their sensory and safety properties, which is mainly due to their indigenous microflora. Within this group of food, Mediterranean dry-cured sausages stand out as a significant source of lactic-acid bacterial strains (LAB) with biotechnological properties, such as their antimicrobial activity. The aim of this study was to investigate the biodiversity of antagonistic LAB strains from different Andalusian traditional sausages, such as salchichón and chorizo. First, a screening was carried out focusing on the antimicrobial activity against foodborne pathogens, such as Listeria monocytogenes, Escherichia coli, Clostridium perfringens, and Staphylococcus aureus, selecting two strains due to their higher antibiosis properties, both in agar and liquid media. These bacteria were identified as Lactiplantibacillus paraplantarum BPF2 and Pediococcus acidilactici ST6. In addition, genomic studies confirmed the presence of certain structural genes related to the production of bacteriocins. Finally, the culture supernatants of both strains were purified and analyzed by LC-MS/MS, obtaining the relative molecular mass and the amino acid sequence and identifying the peptides as the bacteriocins Pediocin-PA and Leucocin K. In conclusion, genomes and antimicrobial substances of P. acidilactici ST6, a Pediocin-PA producer, and Lpb. paraplantarum BPF2, a Leucocin K producer, isolated from Andalusian salchichón and chorizo, respectively, are presented in this work. Although further studies are required, these strains could be used alone or in combination as starters or protective cultures for the food industry.

The vestibular system: Contributions of Lorente de Nó.

BACKGROUND: Rafael Lorente de Nó was a neuroscientist that worked alongside two of the giants of Medicine, the Nobel Prize winners Cajal and Bárány. OBJECTIVE: To describe the contributions of Lorente de Nó to vestibular neuroscience. METHODS: Detailed review of the publications of Lorente de Nó and analysis of the archives from Junta para Ampliación de Estudios e Investigaciones Científicas at Residencia de Estudiantes (Madrid, Spain), Casa de Salud Valdecilla at Hospital Universitario Marqués de Valdecilla (Santander, Spain), Becker Medical Library at Washington University (St. Louis, MO, USA), Rockefeller Archive Center (Sleepy Hollow, New York, NY, USA), Archivo Fernando de Castro (Madrid, Spain), Biblioteca Nacional de España (Madrid, Spain) and Legado Cajal at Instituto Cajal (Madrid, Spain). Most of this material is unpublished and includes over a hundred letters to or from Lorente. RESULTS: Lorente de Nó made a substantial contribution to our understanding of the vestibular system. Amongst these, he meticulously detailed the course of the vestibular nerve and its central projections. He described the vestibulo-ocular reflex as the consequence of an integration of the various nuclei and connections across the vestibular system, rather than a simple three-neuron arc. He also highlighted the role of the reticular formation in the generation of the fast phase of the nystagmus. CONCLUSIONS: Lorente de Nó was a pioneer of modern neuro-otology, having made outstanding contributions to vestibular neuroscience, forging novel discoveries that still burn true today.

The Importance of Cajal's and Lorente de Nó's Neuroscience to the Birth of Cybernetics.

The beginnings of cybernetics were marked by the publication of two papers in 1943. In the first one, Rosenblueth, Wiener, and Bigelow claimed that purposeful behavior is a circular process controlled by negative feedback. In the second seminal paper, McCulloch and Pitts proposed that neurons are interconnected working as logical operators. Both articles raised human-machine analogies and mathematically formulated cognitive mechanisms. These ideas ignited the interest of von Neumann, who was developing the first stored-program computer. Thus, after a preliminary meeting in 1945, a series of meetings were held between 1946 and 1953. The role of the Spanish neurophysiologist Rafael Lorente de Nó in the beginnings of cybernetics is attested not only by his participation in the core members of these Macy conferences but also for his previous description of reverberating circuits formed by a closed chain of internuncial neurons. This was the first neurobiologic demonstration of a feedback loop. Most researchers considered the central nervous system as a mere reflex organ until then; nevertheless, he demonstrated a self-sustained central activity in the nervous system, supporting the idea of self-regulating mechanisms as a key concept not just in machines but also in the brain.

Pediatric Palliative Care at Home: A Prospective Study on Subcutaneous Drug Administration.

CONTEXT: The subcutaneous route is a useful alternative for drug administration in palliative care. Although there is scientific evidence on its use in adult patients, the literature in pediatric palliative care is almost nonexistent. OBJECTIVES: To describe the experience of a pediatric palliative care unit (PPCU) with in-home subcutaneous drug administration symptom control. METHODS: Prospective observational study of patients receiving home-based subcutaneous treatment administered as part of a PPCU treatment regimen over 16 months. Analysis includes demographic and clinical variables and treatment received. RESULTS: Fifty-four different subcutaneous lines were inserted in the 15 patients included, mainly in the thigh (85.2%). The median time of needle in situ was 5.5 days (range: 1-36 days). A single drug was administered in 55.7% of treatments. The most frequently used drugs were morphine chloride (82%) and midazolam (55.7%). Continuous subcutaneous infusion was the predominant administration route (96.7%), with infusion rates oscillating between 0.1 mL/h and 1.5 mL/h. A statistically significant relationship was found between the maximum infusion rate and induration onset. Of the 54 lines placed, 29 (53.7%) had an associated complication requiring line removal. The primary cause for removal was insertion-site induration (46.3%). Subcutaneous lines were mainly used to manage pain, dyspnea, and epileptic seizures. CONCLUSION: In the pediatric palliative care patients studied, the subcutaneous route is most frequently used for administering morphine and midazolam in continuous infusion. The main complication was induration, especially with longer dwell times or higher infusion rates. However, further studies are required to optimize management and prevent complications.