The Impact of the Six Pillars of Lifestyle Medicine on Brain Health.

Dementia is growing exponentially worldwide. Unfortunately, the treatment available does not reverse any type of cognitive impairment. As a result, healthcare professionals are focusing on other evidence-based options, such as lifestyle medicine (LM). Current evidence demonstrates improvement in neurocognitive decline by applying the six pillars of LM, which include plant-based nutrition, physical activity, stress management, avoidance of risky substances, restorative sleep, and social connections. Plant-based nutrition has a positive impact on cognition by decreasing the risk for Alzheimer's disease (AD) with high adherence to the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND). Physical activity also might prevent neurocognitive decline by increasing fibronectin type III domain-containing protein 5 (FNDC5) and Irisin in the hippocampus, which increases energy expenditure and prolongs endurance. Additionally, higher perceived stress in adulthood and the use of risky substances such as alcohol, nicotine, and opioids are significantly associated with developing mild cognitive impairment and all-cause dementia. Furthermore, there is a positive correlation between poor sleep and social isolation with a rapid progression in cognitive decline. Lifestyle changes have a substantial impact on brain health. Therefore, the focus should always be on prevention as the primary treatment tool.

Common Sleep Disorders Affecting Older Adults.

Sleep disorders in older adults increase with aging, likely due to increased sleep latency, decreased sleep efficiency, and total sleep time. Common sleep issues include chronic insomnia, circadian rhythm sleep-wake disorders, sleep-related movement disorders, and sleep-disordered breathing. Diagnostic tools, such as a comprehensive sleep history and questionnaires, or a sleep log for more specific complaints, are commonly used. Polysomnography is not recommended as a routine test; however, it can be used for abnormal behaviors during sleep or if treatment fails. Sleep disorder management is based on the etiology and may include nonpharmacological and pharmacological alternative treatments. For example, nonpharmacological management for chronic insomnia and some sleep disorders may consist of cognitive behavioral therapy, sleep hygiene education, relaxation therapy, sleep restriction, light therapy, and stimulus control therapy. Because the quality of evidence for pharmacological treatment is poor, the medication choice should be based on shared decision-making between the practitioner and the patient, with limited prescription.

Developing a nursing dependency scoring tool for children's palliative care: the impact on hospice care.

BACKGROUND: Occupancy is commonly used to measure bed management in hospices. However, the increasing complexity of children and young people and growing dependence on technology mean that this is no longer effective. AIM: To develop a dependency tool that enables the hospice to safely and effectively manage the use of beds for planned short breaks (respite care), preserving capacity for children requiring symptom management and end-of-life care. METHODS: A comprehensive literature review and existing tools were used to inform the development of the Martin House Dependency Tool Framework. Training was provided to staff and the tool was piloted before applying it across the hospice caseload. FINDINGS: The tool has been used on 431 children (93.1% of caseload). The tool enabled consistency of assessment and more effective management of resources, due to a contemporaneous understanding of the clinical needs of those on the caseload. CONCLUSION: The tool has enabled consistent and transparent assessment of children, improving safety, effectiveness and responsiveness, and the management of the workforce and resources.

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer's Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain.

Calpains represent a family of calcium-dependent proteases participating in a multitude of functions under physiological or pathological conditions. Calpain-1 is one of the most studied members of the family, is ubiquitously distributed in organs and tissues, and has been shown to be involved in synaptic plasticity and neuroprotection in mammalian brain. Calpain-1 deletion results in a number of phenotypic alterations. While some of these alterations can be explained by the acute functions of calpain-1, the present study was directed at studying alterations in gene expression that could also account for these phenotypic modifications. RNA-seq analysis identified 354 differentially expressed genes (DEGs) in brain of calpain-1 knock-out mice, as compared to their wild-type strain. Most DEGs were classified in 10 KEGG pathways, with the highest representations in Protein Processing in Endoplasmic Reticulum, MAP kinase and Alzheimer's disease pathways. Most DEGs were down-regulated and validation of a number of these genes indicated a corresponding decreased expression of their encoded proteins. The results indicate that calpain-1 is involved in the regulation of a significant number of genes affecting multiple brain functions. They also indicate that mutations in calpain-1 are likely to be involved in a number of brain disorders.

Nociceptin/orphanin FQ modulates energy homeostasis through inhibition of neurotransmission at VMN SF-1/ARC POMC synapses in a sex- and diet-dependent manner.

BACKGROUND: Orphanin FQ (aka nociceptin; N/OFQ) binds to its nociceptin opioid peptide (NOP) receptor expressed in proopiomelanocortin (POMC) neurons within the arcuate nucleus (ARC), a critical anorexigenic component of the hypothalamic energy balance circuitry. It inhibits POMC neurons by modifying neuronal excitability both pre- and postsynaptically. We tested the hypothesis that N/OFQ inhibits neurotransmission at synapses involving steroidogenic factor (SF)-1 neurons in the ventromedial nucleus (VMN) and ARC POMC neurons in a sex- and diet-dependent fashion. METHODS: Electrophysiological recordings were done in intact male and in cycling and ovariectomized female NR5A1-Cre and eGFP-POMC mice. Energy homeostasis was assessed in wildtype animals following intra-ARC injections of N/OFQ or its saline vehicle. RESULTS: N/OFQ (1 µM) decreased light-evoked excitatory postsynaptic current (leEPSC) amplitude more so in males than in diestrus or proestrus females, which was further accentuated in high-fat diet (HFD)-fed males. N/OFQ elicited a more robust outward current and increase in conductance in males than in diestrus, proestrus, and estrus females. These pleiotropic actions of N/OFQ were abrogated by the NOP receptor antagonist BAN ORL-24 (10 µM). In ovariectomized female eGFP-POMC mice, 17ß-estradiol (E2; 100 nM) attenuated the N/OFQ-induced postsynaptic response. SF-1 neurons from NR5A1-Cre mice also displayed a robust N/OFQ-induced outward current and increase in conductance that was sexually differentiated and suppressed by E2. Finally, intra-ARC injections of N/OFQ increased energy intake and decreased energy expenditure, which was further potentiated by exposure to HFD and diminished by estradiol benzoate (20 µg/kg; s.c.). CONCLUSION: These findings show that males are more responsive to the pleiotropic actions of N/OFQ at anorexigenic VMN SF-1/ARC POMC synapses, and this responsiveness can be further enhanced under conditions of diet-induced obesity/insulin resistance.

Systematic Review and Meta-Analysis: Serum Infliximab Levels During Maintenance Therapy and Outcomes in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: A number of observational studies have reported an association between serum levels of infliximab [IFX] at various thresholds, and clinical outcomes in inflammatory bowel disease [IBD]. This association has not previously been systematically analysed. METHODS: Systematic review of studies that reported serum infliximab levels according to outcomes in IBD. Primary outcome was clinical remission, and secondary outcomes included endoscopic remission, C-reactive protein [CRP] levels, and colectomy. Meta-analysis of raw data was performed where appropriate. A quality assessment was also undertaken. RESULTS: A total of 22 studies met the inclusion criteria, including 3483 patients; 12 studies reported IFX levels in a manner suitable for determining effect estimates. During maintenance therapy, patients in clinical remission had significantly higher mean trough IFX levels than patients not in remission: 3.1 µg/ml versus 0.9 µg/ml. The standardised mean difference in serum IFX levels between groups was 0.6 µg/ml (95% confidence interval [CI] 0.4-0.9, p = 0.0002]. Patients with an IFX level > 2 µg/ml were more likely to be in clinical remission (risk ratio [RR] 2.9, 95% CI 1.8-4.7, p < 0.001], or achieve endoscopic remission [RR 3, 95% CI 1.4-6.5, p = 0.004] than patients with levels < 2 µg/ml. CONCLUSIONS: There is a significant difference between serum infliximab levels in patients with IBD in remission, compared with those who relapse. A trough threshold during maintenance > 2 µg/ml is associated with a greater probability of clinical remission and mucosal healing.