Parkeraagaard4765

β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by β-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the β-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of β-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates β-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway.

Descriptive Psychometrics Study OBJECTIVES Neurogenic lower urinary tract dysfunction (NLUTD), or "neurogenic bladder" is a common and disruptive condition for individuals with spinal cord injury (SCI) and disease (including multiple sclerosis, MS). Our team has developed patient-centered instruments of urinary symptoms specific to patients with NLUTD, across bladder management methods. Validity evidence is needed to support the use of two new instruments, Urinary Symptom Questionnaires for people with Neurogenic Bladder (USQNB) for those who manage their bladder with indwelling catheters (IDC), or who void (V).

Online surveys completed by individuals in the United States with NLUTD due to either SCI or MS who manage their bladder with indwelling catheters (SCI, n = 306; MS, n = 8), or by voiding (SCI, n = 103; MS, n = 383). A total of n = 381 USQNB-IDC respondents (five control groups), and 351 USQNB-V respondents (four control groups), contributed to our convergent and divergent validity evidence.

Data were collected online to estimate key aspects of psychometric validity (content, reflection of the construct to be measured; face, recognizability of the contents as representing the construct to be measured; structural, the extent to which the instrument captures recognizable dimensions of the construct to be measured). Divergent and convergent validity evidence was derived from multiple control groups, while evidence of criterion validity was derived from attribution of each item to their experience "with a UTI".

Evidence of face, content, criterion, convergent, and divergent validity was compiled for each instrument.

The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.

The instruments demonstrate adequate, multi-dimensional, validity evidence to recommend their use for decision-making by patients, clinicians, and researchers.

This is a prospective validation study.

The neurogenic bowel dysfunction (NBD) score is a widely used symptom-based questionnaire evaluating bowel dysfunction and its impact on quality of life (QoL) in spinal cord-injured patients. This study aimed to translate and validate a Dutch-language NBD score in patientswith SCI.

Patientswith SCI visiting the urology department or general practitioner (GP) in Rotterdam, the Netherlands.

Standardized guidelines were followed for the translation and validation process of the NBD score. Adult patientswith SCI visiting our urology department were asked to participate by filling in a set of questionnaires the NBD score, the Fecal Incontinence Quality of Life scale (FIQL), the Fecal Incontinence Severity Index (FISI), and the European Quality of life 5-Dimension 3-Level questionnaire (EQ-5D-3L) at baseline and 1-2 weeks afterward. A control group recruited at a GP office completed the questionnaires once. The following measurement properties were evaluated content v evaluation and research purposes.Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD). In animals, voluntary alcohol consumption increases DRD3 expression, and pharmacological blockade of DRD3s attenuates alcohol self-administration and reinstatement of alcohol seeking. However, these findings have yet to be translated in humans. This study used positron emission tomography (PET) and [11C]-(+)-PHNO to compare receptor levels in several dopamine D2 receptor (DRD2) and DRD3 regions of interest between AUD subjects in early abstinence (n = 17; 6.59 ± 4.14 days of abstinence) and healthy controls (n = 18). We recruited non-treatment seeking subjects meeting DSM-5 criteria for AUD. We examined the relationship between DRD2/3 levels and both alcohol craving and alcohol motivation/wanting, using a cue reactivity procedure and an intravenous alcohol self-administration (IVASA) paradigm, respectively. [11C]-(+)-PHNO binding levels in AUD subjects were significantly lower than binding in HCs when looking at all DRD2/3 ROIs jointly (Wilk's Λ = .58, F(6,28) =3.33, p = 0.013, η2p = 0.42), however there were no region-specific differences. Binding values demonstrate -12.3% and -16.1% lower [11C]-(+)-PHNO binding in the SMST and SN respectively, though these differences did not withstand Bonferroni corrections. There was a positive association between [11C]-(+)-PHNO binding in the SN (almost exclusively reflective of DRD3) and alpha (lower values reflect higher alcohol demand) in the APT after Bonferroni corrections (r = 0.66, p = 0.0080). This demonstrates that AUD subjects with lower DRD3 levels in the SN exhibit increased demand for alcohol. These results replicate previous findings demonstrating reduced DRD2/3 levels while also supporting a lack of DRD3 upregulation and potential downregulation in early abstinent AUD. Furthermore, the finding that binding in the SN is associated with alcohol demand warrants further examination.

The decision to pursue chronic mechanical ventilation involves a complex mix of clinical and social considerations. Understanding the medical indications to pursue tracheostomy would reduce the ambiguity for both providers and families and facilitate focus on appropriate clinical goals.

To describe potential indications to pursue tracheostomy and chronic mechanical ventilation in infants with severe BPD (sBPD).

We surveyed centers participating in the Children's Hospitals Neonatal Consortium to describe their approach to proceed with tracheostomy in infants with sBPD. We requested a single representative response per institution. Question types were fixed form and free text responses.

The response rate was high (31/34, 91%). Tracheostomy was strongly considered when airway malacia was present, PCO

 ≥ 76-85 mmHg, FiO

 ≥ 0.60, PEEP ≥ 9-11 cm H

O, respiratory rate ≥ 61-70 breaths/min, PMA ≥ 44 weeks, and weight <10th %ile at 44 weeks PMA.

Understanding the range of indications utilized by high level NICUs around the country to pursue a tracheostomy in an infant with sBPD is one step toward standardizing consensus indications for tracheostomy in the future.

Understanding the range of indications utilized by high level NICUs around the country to pursue a tracheostomy in an infant with sBPD is one step toward standardizing consensus indications for tracheostomy in the future.

Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization.

Fecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3-4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing.

Preterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. read more The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after stion.

The initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode. Our study provides new evidence regarding the early gut colonization patterns in preterm infants. Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.

Indoor air pollution is associated with adverse health effects; however, few studies exist studying indoor air pollution on the Navajo Nation in the southwest U.S., a community with high rates of respiratory disease.

Indoor PM

concentration was evaluated in 26 homes on the Navajo Nation using real-time PM

monitors. Household risk factors and daily activities were evaluated with three metrics of indoor PM

time-weighted average (TWA), 90th percentile of concentration, and daily minutes exceeding 100 μg/m

. A questionnaire and recall sheet were used to record baseline household characteristics and daily activities.

The median TWA, 90th percentile, and daily minutes exceeding 100 μg/m

were 7.9 μg/m

, 14.0 μg/m



and 17 min, respectively. TWAs tended to be higher in autumn and in houses that used fuel the previous day. Other characteristics associated with elevated PM exposure in all metrics included overcrowded houses, nonmobile houses, and houses with current smokers, pets, and longer cooking time.

Some residents of the Navajo Nation have higher risk of exposure to indoor air pollution by Environmental Protection Agency (EPA) standards. Efforts to identify the causes and associations with adverse health effects are needed to ensure that exposure to risks and possible health impacts are mitigated.

Some residents of the Navajo Nation have higher risk of exposure to indoor air pollution by Environmental Protection Agency (EPA) standards. Efforts to identify the causes and associations with adverse health effects are needed to ensure that exposure to risks and possible health impacts are mitigated.