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Respiratory neurobiology has been a lead discipline in the field of neuroscience for almost a century. Despite this, research studies on the fundamental synaptic and cellular processes underlying the generation and modulation of breathing movements suffered a significant decline during the last decade. We still believe that respiratory neurobiology is one of the most exciting and imperative fields of neuroscience. With the first white paper concerned with the central control of breathing, we want to celebrate the global importance of breathing research.

Nansi López-Valverde,1 Antonio López-Valverde,1 Rafael Gómez de Diego,2 Clara Cieza-Borrella,3 Juan M Ramírez,4 Rogelio González-Sarmiento31Dental Clinic, Department of Surgery, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain; 2Dental Clinic, Alfonso X El Sabio University, Madrid, Spain; 3Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain; 4Department of Morphological Sciences, School of Medicine, University of Córdoba, Córdoba, SpainAims: In this study we wanted to figure out if there was a correlation between OPRM1 N40D, TRPV1 I316M, TRPV1 I585V, NOS3 −786T>C and IL6 −174C>G polymorphisms and the response to locally applied articaine-epinephrine anesthetic.Methods: In this observational study, 114 oral cell samples of patients anesthetized with articaine-epinephrine (54 from men 60 from women), were collected from dental centers in Madrid (Spain). High molecular weight DNA was obtained from oral mucosa cells. The analysis of OPRM1 N40D (rs1799971), TRPV1 I316M (rs222747), TRPV1 I585V (rs8065080) and IL6 −174C>G polymorphism was performed through real-time PCR allelic discrimination using TaqMan probes. Polymorphism NOS3 −786T> C (rs2070744) was analyzed using RFLP-PCR.Results: The studied polymorphisms are involved neither in the response to the anesthetic, nor in the intensity of perceived dental pain. However, in a subset of female patients we found that TRPV1 I316M was associated with a delayed onset of anesthesia.Conclusions: There is no association among these polymorphisms and the time elapsed between the application of the anesthetic and the onset of its effect.Keywords: Pain, polymorphism, OPRM1, TRPV1, NOS3, IL6

This study was designed to identify barriers and facilitators to enrollment in public health insurance programs in immigrant adolescents and young adults. Focus groups were held in English, Spanish and Mandarin to assess barriers and facilitators to insurance enrollment. Twenty-nine students participated in the focus groups, 11 Chinese speakers, 13 English speakers and 5 Spanish speakers. They were between the ages of 18 and 24. The major factors affecting failure to enroll were lack of correct information about enrollment process and qualifications, fear of being reported to immigration, and language barriers. In general, newly arrived students had less information and many more questions. Facilitators to enrollment included perceived need for health insurance, requiring help with medical care costs, and assistance with information gathering. To increase enrollment, we suggest school-based approaches to education and enrollment, increased presence of facilitated enrollers, and increased visibility of existing informational outlets. [ABSTRACT FROM AUTHOR]

PURPOSE/OBJECTIVES: To describe how different treatments for prostate cancer affect health-related quality of life (QOL), health status, and masculinity. DESIGN: Longitudinal survey design with descriptive, correlational, and comparative elements. SETTING: A tertiary medical center and associated clinics in a suburban community in the Southwestern United States. SAMPLE: 185 men with localized prostate cancer were enrolled from five treatment groups: watchful waiting (n = 30), surgery (n = 59), conventional radiation (n = 25), proton-beam radiation (n = 24), and a combination of conventional radiation and proton-beam radiation or mixed-beam radiation (n = 47). At six months, 163 remained on the study; at 12 months, 154 remained: and at 18 months, 153 remained. The average age was 68 years, and 82% of the men were white. METHODS: Men were enrolled at treatment and given a questionnaire with a self-addressed, stamped envelope for return. Questionnaires were mailed again at 6, 12, and 18 months. MAIN RESEARCH VARIABLES: Health-related QOL health status, prostate treatment-specific symptoms, and sex-role identity. FINDINGS: No overall difference in health-related QOL or health status was found, but post-hoc analysis revealed specific differences. The differences existed in sexual functioning and gastrointestinal treatment-specific symptoms. No relationship existed between masculinity and health-related QOL. CONCLUSIONS: Health-related QOL and health status are similar regardless of type of treatment. Radiation tends to produce more gastrointestinal symptoms, and surgery tends to produce more sexual functioning symptoms. Watchful waiting is associated with poorer general health. IMPLICATIONS FOR NURSING PRACTICE: Nurses can provide specific treatment-related information to men who are faced with making treatment decisions for prostate cancer and, in consultation with the healthcare team, can select a treatment best sulted to them. [ABSTRACT FROM AUTHOR]

The control of the respiratory rhythm and airway motor activity is essential for life. Accumulating evidence indicates that the postinspiratory complex (PiCo) is crucial for generating behaviors that occur during the postinspiratory phase, including expiratory laryngeal activity and swallowing. Located in the ventromedial medulla, PiCo is defined by neurons co-expressing two neurotransmitter markers (ChAT and Vglut2/Slc17a6). Here, we mapped the input-output connections of these neurons using viral tracers and intersectional viral-genetic tools. PiCo neurons were specifically targeted by focal injection of a doubly conditional Cre- and FlpO-dependent AAV8 viral marker (AAV8-Con/Fon-TVA-mCherry) into the left PiCo of adult Chat Cre/wt : Vglut2 FlpO/wt mice, for anterograde axonal tracing. These experiments revealed projections to various brain regions, including the Cu, nucleus of the solitary tract (NTS), Amb, X, XII, Sp5, RMg, intermediate reticular nucleus (IRt), lateral reticular nucleus (LRt), pre-Bötzinger complex (preBötC), contralateral PiCo, laterodorsal tegmental nucleus (LDTg), pedunculopontine tegmental nucleus (PPTg), periaqueductal gray matter (PAG), Kölliker-Fuse (KF), PB, and external cortex of the inferior colliculus (ECIC). A rabies virus (RV) retrograde transsynaptic approach was taken with EnvA-pseudotyped G-deleted (RV-SAD-G-GFP) to similarly target PiCo neurons in Chat Cre/wt : Vglut2 FlpO/wt mice, following prior injections of helper AAVs (a mixture of AAV-Ef1a-Con/Fon oG and viral vector AAV8-Con/Fon-TVA-mCherry). This combined approach revealed prominent synaptic inputs to PiCo neurons from NTS, IRt, and A1/C1. Although PiCo neurons project axons to the contralateral PiCo area, this approach did not detect direct contralateral connections. We suggest that PiCo serves as a critical integration site, projecting and receiving neuronal connections implicated in breathing, arousal, swallowing, and autonomic regulation., (© 2024 Wiley Periodicals LLC.)

The purpose of this study is to gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Whole Genome Sequencing (WGS) was performed on 144 infants that succumbed to SUID, and 573 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Variants of interest were identified in 88 genes, in 64.6% of our cohort. Seventy-three of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders and in two genes associated with immunological function. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria. Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Parkinson's disease (PD) is a chronic neurodegenerative disorder affecting the motor system, with non-classic symptoms such as sleep disturbances and respiratory dysfunctions. These issues reflect a complex pathophysiological interaction that severely impacts quality of life. Using a 6-hydroxydopamine (6-OHDA) mouse model of PD, we investigated these connections by analyzing sleep patterns and respiratory parameters during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Our findings revealed altered breathing, including reduced respiratory frequency and increased apneas during both NREM and REM. To address these abnormalities, we employed chemogenetic stimulation of cholinergic neurons in the laterodorsal tegmental nucleus (LDTg), a key region for sleep-wake regulation and respiratory modulation. This intervention normalized respiratory function. These results highlight the critical role of LDTg cholinergic neurons in the coordinating sleep and breathing, suggesting that targeting these neurons could offer a therapeutic strategy for managing PD-related respiratory complications., Competing Interests: The authors declare no competing interests. The illustrations and graphical abstract were partially created with BioRender.com., (© 2024 The Author(s).)

Swallowing, both nutritive and non-nutritive, is highly dysfunctional in children with Leigh Syndrome (LS) and contributes to the need for both gastrostomy and tracheostomy tube placement. Without these interventions aspiration of food, liquid, and mucus occur resulting in repeated bouts of respiratory infection. No study has investigated whether mouse models of LS, a neurometabolic disorder, exhibit dysfunctions in neuromuscular activity of swallow and breathing integration. We used a genetic mouse model of LS in which the NDUFS4 gene is knocked out (KO) specifically in Vglut2 or Gad2 neurons. We found increased variability of the swallow motor pattern, disruption in breathing regeneration post swallow, and water-induced apneas only in Vglut2 KO mice. These physiological changes likely contribute to weight loss and premature death seen in this mouse model. Following chronic hypoxia (CH) exposure, swallow motor pattern, breathing regeneration, weight, and life expectancy were not changed in the Vglut2-Ndufs4-KO CH mice compared to control, indicating a rescue of phenotypes. These findings show that like patients with LS, Ndufs4 mouse models of LS exhibit swallow impairments as well as swallow-breathing dyscoordination alongside the other phenotypic traits described in previous studies. Understanding this aspect of LS will open roads for the development of future more efficacious therapeutic intervention for this illness., Competing Interests: Competing Interest Statement: The authors declare no conflict of interest.

Importance: Rates of maternal obesity are increasing in the US. Although obesity is a well-documented risk factor for numerous poor pregnancy outcomes, it is not currently a recognized risk factor for sudden unexpected infant death (SUID)., Objective: To determine whether maternal obesity is a risk factor for SUID and the proportion of SUID cases attributable to maternal obesity., Design, Setting, and Participants: This was a US nationwide cohort study using Centers for Disease Control and Prevention National Center for Health Statistics linked birth-infant death records for birth cohorts in 2015 through 2019. All US live births for the study years occurring at 28 weeks' gestation or later from complete reporting areas were eligible; SUID cases were deaths occurring at 7 to 364 days after birth with International Statistical Classification of Diseases, Tenth Revision cause of death code R95 (sudden infant death syndrome), R99 (ill-defined and unknown causes), or W75 (accidental suffocation and strangulation in bed). Data were analyzed from October 1 through November 15, 2023., Exposure: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared)., Main Outcome and Measure: SUID., Results: Of 18 857 694 live births eligible for analysis (median [IQR] age: maternal, 29 [9] years; paternal, 31 [9] years; gestational, 39 [2] weeks), 16 545 died of SUID (SUID rate, 0.88/1000 live births). After confounder adjustment, compared with mothers with normal BMI (BMI 18.5-24.9), infants born to mothers with obesity had a higher SUID risk that increased with increasing obesity severity. Infants of mothers with class I obesity (BMI 30.0-34.9) were at increased SUID risk (adjusted odds ratio [aOR], 1.10; 95% CI, 1.05-1.16); with class II obesity (BMI 35.0-39.9), a higher risk (aOR, 1.20; 95% CI, 1.13-1.27); and class III obesity (BMI ≥40.0), an even higher risk (aOR, 1.39; 95% CI, 1.31-1.47). A generalized additive model showed that increased BMI was monotonically associated with increased SUID risk, with an acceleration of risk for BMIs greater than approximately 25 to 30. Approximately 5.4% of SUID cases were attributable to maternal obesity., Conclusions and Relevance: The findings suggest that infants born to mothers with obesity are at increased risk of SUID, with a dose-dependent association between increasing maternal BMI and SUID risk. Maternal obesity should be added to the list of known risk factors for SUID. With maternal obesity rates increasing, research should identify potential causal mechanisms for this association.

In the antibiotic resistance era, utilizing understudied sources for novel antimicrobials or antivirulence agents can provide new advances against antimicrobial resistant pathogens. In this study, we aimed to investigate antibacterial and antibiofilm activities of Posidonia oceanica (L.) Delile against Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 and several S. aureus clinical isolates obtained from medical devices, including patient urinary catheters and breast implant infections, with varying antibiotic recalcitrance profiles. The ethanolic and methanolic extracts from P. oceanica rhizome exhibited significant antibacterial activity against E. faecalis and S. aureus , as well as drug resistant S. aureus clinical isolates. Furthermore, significant antibiofilm activity was observed against S. aureus and E. faecalis treated with ER, MR 1 , and MR 2 . P. oceanica extracts also exhibited synergistic antimicrobial activity with ciprofloxacin against E. faecalis, sensitizing E. faecalis to a lower ciprofloxacin concentration. Collectively, our data demonstrate the selective antibacterial and antibiofilm activity of the extracts of P. oceanica against Gram-positive bacteria and clinical isolates along with potentiation of current antibiotics, which suggests that P. oceanica can be further investigated as a potential source for novel therapeutic options in the treatment of drug resistant bacterial infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Noonan Syndrome with Multiple Lentigines (NSML-formerly known as LEOPARD syndrome) is a rare autosomal dominant condition that usually exhibits cardiac involvement with hypertrophic cardiomyopathy (HCM). Here we present a case of a NSML patient with an unusual and patchy cardiac hypertrophy distribution., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Every year over 200,000 motorcyclists are killed globally. One poorly understood risk factor for motorcycle crashes is the role of motorcyclists' ability to hear traffic and other sounds around them in all directions. Most motorcycle helmets protect the head and permit vision in the forward direction, but they impair the wearer's ability to hear. This study evaluated user perceptions of Protective Helmet with Earpieces Equipped, a novel system that affixes technology onto existing motorcycle helmets to allow motorcyclists to better hear the surrounding environment in all directions., Methods: 59 Colombian traffic police agents who rode motorcycles daily completed self-report surveys about their traditional motorcycle helmet, used a Protective Helmet with Earpieces Equipped helmet for two months, and then completed a follow-up survey. We tested two hypotheses: (a) at follow-up compared to baseline, motorcyclists would report decreases in perceived safety, comfort, and ability to detect sounds with their traditional helmet, as well as increased fatigue and stress from motorcycling with their traditional helmet, and (b) at follow-up, motorcyclists would report high perceived safety and perceived importance of hearing traffic sounds in all directions while motorcycling. Wilcoxon signed-rank test evaluated hypotheses., Results: Participants rated perceived safety while using their traditional helmet to be significantly lower after using the Protective Helmet with Earpieces Equipped compared to before using it (Z=-3.5, p less than .001). There were no changes in other variables assessed. Following use of the new helmet, participants reported greatly improved safety (M=4.56, SD=0.54, where 4=safer and 5=substantially safer) and perceived the importance of hearing traffic sounds in all directions as high., Conclusions: Improved auditory perception could increase motorcyclist safety. Participating traffic agents felt the Protective Helmet with the Earpieces Equipped greatly improved their ability to hear and improved their motorcycling safety. Perceived safety while using their traditional helmet decreased following use of the alternative.

Insulator-based electrokinetically driven microfluidic devices stimulated with direct current (DC) voltages are an attractive solution for particle separation, concentration, or isolation. However, to design successful particle manipulation protocols, it is mandatory to know the mobilities of electroosmosis, and linear and nonlinear electrophoresis of the microchannel/liquid/particle system. Several techniques exist to characterize the mobilities of electroosmosis and linear electrophoresis. However, only one method to characterize the mobility of nonlinear electrophoresis has been thoroughly assessed, which generally requires DC voltages larger than 1000 V and measuring particle velocity in a straight microchannel. Under such conditions, Joule heating, electrolysis, and the DC power source cost become a concern. Also, measuring particle velocity at high voltages is noisy, limiting characterization quality. Here we present a protocol-tested on 2 μm polystyrene particles-for characterizing the mobility of nonlinear electrophoresis of the liquid/particle system using a DC voltage of only 30 V and visual inspection of particle dynamics in a microchannel featuring insulating obstacles. Multiphysics numerical modelling was used to guide microchannel design and to correlate particle location during an experiment with electric field intensity. The method was validated against the conventional characterization protocol, exhibiting excellent agreement while significantly reducing measurement noise and experimental complexity.

Background: Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2)., Objective: Presenting real-world effectiveness data for darvadstrocel in a Spanish population., Design: Observational retrospective cohort study with prospective data gathering., Settings: The study was conducted at 14 institutions in Spain., Patients: From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery., Interventions: Darvadstrocel treatment., Main Outcome Measures: Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment., Results: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported., Limitations: Retrospective nature of the study., Conclusions: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract ., Uso De Darvadstrocel Terapia Con Clulas Madre Alognicas Para Fstula En Enfermedad De Crohn En La Prctica Clnica Real El Proyecto Nacional Para Implementar De Clulas Madre Mesenquimales Para El Tratamiento De La Fstula De Crohn Perianal El Estudio Prime: ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco )., (Copyright © The ASCRS 2024.)