Mindfulness to Promote Healthy Aging in Older Adults with Mild Cognitive Impairment and their Caregivers: A Mixed Methods Feasibility and Acceptability Study

Mild cognitive impairment (MCI), thought be a precursor to dementia, is characterized by cognitive decline without functional impairment. As the population ages and the prevalence of MCI increases, non-pharmacologic interventions are needed to address well-being and disease progression in this population of older adults and their caregivers. In response to growing interest in mindfulness-based interventions (MBIs) as an adjunct to integrated care for this population, this single arm, mixed methods pilot study trialed a lightly adapted, 6-week MBI for both MCI patients and their caregivers (n=24). The intervention was feasible and acceptable in both groups. There was a trend toward improved Immediate Memory in MCI Patients and a significant improvement in their self-reported Social Functioning, but several other self-report measures lacked reliability and validity in this group. Caregivers reported increased trait mindfulness and application of mindfulness skills in daily life, as well as decreased sleep disturbance. However, Caregiver Burden did not improve. Thematic analysis showed acquisition of basic mindfulness skills in both groups, with a particular emphasis on meditation as a way for MCI patients to relax and generate positive affect. Several recommendations for future research are provided, and additional randomized controlled trials with larger sample sizes are required to replicate these findings and isolate mindfulness-specific treatment effects

Cardiovascular recovery from emotional stress: An operationalization of equanamity following mindfulness-based emotional stress

Theoretical models of mindfulness suggest that meditation may improve health, in part, by regulating stress physiology, including faster recovery of heart rate (HR) and blood pressure (SBP/DBP) after emotional stress. Furthermore, improved cardiovascular recovery (CR) may be a marker of equanimity, defined as increased acceptance of and reduced reactivity to stress. No studies have tested this hypothesis, partly because methodology for assessing CR remains controversial. Using a novel operationalization of equanimity and several methods of measuring CR, this project investigated whether (1) equanimity is associated with improved CR, (2) Mindfulness-Based Stress Reduction (MBSR) is associated with improved CR, and (3) increased equanimity following MBSR partly explains improved CR. Using a pretest-posttest repeated measures design, 56 healthy adults completed MBSR bracketed by stress testing. HR, SBP and DBP recovery were calculated using simple change scores, residualized change scores, and percent recovery. GLMs showed (1) no association between equanimity and CR, (2) improved BP recovery following MBSR, but only when CR was measured using simple change scores, and (3) that equanimity explained a small amount of the variance in BP recovery following MBSR but was not a statistically significant predictor. Results have important implications for statistical conclusions validity in stress recovery research and ultimately contradict theoretical models predicting faster physiological recovery from emotional stress following mindfulness training

“I’d Like My Eggs Frozen”: Negligent Emotional Distress Compensation for Lost Frozen Human Eggs

Assisted Reproductive Technology continues to advance and has already assisted thousands in childbearing. In 2012, the American Society for Reproductive Medicine announced that oocyte cryopreservation, or egg freezing, a form of Assisted Reproductive Technology, was no longer considered an experimental procedure. Egg freezing is growing significantly in popularity and, as a result, fertility clinics continue to prosper as more women seek their services. For many women, egg freezing gives them hope of motherhood beyond the typical childbearing age. For some, this procedure can preserve their fertility following invasive medical procedures that weaken their eggs’ viability. In March 2018, two tank failures occurred in San Francisco and Cleveland. As a result, thousands of eggs thawed and some women lost any chance they had at having biological children. In response, some women have sought legal recourse for their loss. This Note explores how reproductive material has been classified in property law and the overall limitations of emotional distress damages for property loss. The Note also discusses how eggs are most likely to be categorized as property and, as a result, how negligence damages for property loss are likely to be limited to the fair market value of the lost eggs. Finally, this Note argues that emotional distress damages for lost frozen eggs should be available to women for this property loss

On structural studies of high-density potassium and sodium

The alkali elements at ambient conditions are well described by the nearly-free electron (NFE) model, yet show a remarkable departure from this “simple” behaviour with increasing pressure. Low-symmetry complex structures are observed in all, and anomalous melting has been observed in lithium (Li), sodium (Na), rubidium (Rb), and caesium (Cs). In this Thesis, static and dynamic compression techniques have been used to investigate the high-pressure high-temperature behaviour of the alkali elements potassium (K) and Na. Utilising diamond anvil pressure cells and external resistive heating, both in-air and in-vacuum, the melting curve of K has been determined to 24 GPa and 750 K, and is found to be remarkably similar to that of Na, but strikingly different to that reported previously. Furthermore, there is some evidence to suggest that a change in the compressibility of liquid-K occurs at lower pressures than the solid-solid phase transitions, perhaps indicating structural transitions occurring in the liquid phase, similar to those in the underlying solid. This could suggest a mechanism to explain the anomalous melting behaviour observed. Previous ab initio computational studies indicate that the unusual melting curve of Na arises due to structural and electronic transitions occurring in the liquid, mirroring those found in the underlying solid at higher pressures. The discovery that the melting curve of K is very similar to that of Na suggests that the same physical phenomena predicted for Na could be responsible for the high-pressure melting behaviour observed in K. The tI19 phase of K, observed above 20 GPa at 300 K, is a composite incommensurate host-guest structure consisting of 1D chains of guest atoms surrounded by a tetragonal host framework. Along the unique c-axis, the host and guest are incommensurate with each other. During the melting studies described above, it was observed that with increasing temperature, the weaker-bonded guest chains become more disordered while the host structure remains unchanged. To investigate and characterise this order-disorder transition, in situ synchrotron X-ray diffraction studies were conducted on single-crystal and quasi-single crystal samples of tI19-K. An order-disorder phase line has been mapped out to 50 GPa and 650 K. Perhaps the most striking departure from NFE behaviour in the alkali elements is observed in Na at pressures above 200 GPa where it transforms to a transparent electrical insulator. This phase is a so-called elemental “electride”, which may be thought of as being pseudo-ionically bonded. Electrides are predicted to exist in many elements, but at pressures far beyond the current capabilities of static pressure techniques. Utilising laser-driven quasi-isentropic compression techniques, dynamic compression experiments were performed on Na to see if it is possible to observe this electride phase under the timescales of dynamic compression experiment (ns). Optical velocimetry and reflectivity of the sample were measured directly to determine pressure and monitor the on-set of the transparent phase, respectively

Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke

Aims: Cerebral small vessel disease (SVD) causes a fifth of all strokes plus diffuse brain damage leading to cognitive decline, physical disabilities and dementia. The aetiology and pathogenesis of SVD are unknown, but largely attributed to hypertension or microatheroma. Methods: We used the spontaneously hypertensive stroke-prone rat (SHRSP), the closest spontaneous experimental model of human SVD, and age-matched control rats kept under identical, non-salt-loaded conditions, to perform a blinded analysis of mRNA microarray, qRT-PCRand pathway analysis in two brain regions (frontal and midcoronal) commonly affected by SVD in the SHRSP at age five, 16 and 21 weeks. Results: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats. All were present at age 5 weeks thus pre-dating blood pressure elevation. ‘Neurological’ and ‘inflammatory’ pathways were more affected than ‘vascular’ functional pathways. Conclusions: This set of defects, although individually modest, when acting in combination could explain the SHRSP's susceptibility to microvascular and brain injury, compared with control rats. Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD

Characterization of microtubule-associated protein tau isoforms and Alzheimer’s disease-like pathology in normal sheep (Ovis aries):Relevance to their potential as a model of Alzheimer’s disease

Alzheimer’s disease is a chronic neurodegenerative disease that accounts for up to 80% of all dementias. Characterised by deteriorations of memory and cognitive function, the key neuropathological features are accumulations of β-amyloid and hyperphosphorylated tau, as ‘plaques’ and ‘tangles’, respectively. Despite extensive study, however, the exact mechanism underlying aggregate formation in Alzheimer’s disease remains elusive, as does the contribution of these aggregates to disease progression. Importantly, a recent evaluation of current Alzheimer’s disease animal models suggested that rodent models are not able to fully recapitulate the pathological intricacies of the disease as it occurs in humans. Therefore, increasing attention is being paid to species that might make good alternatives to rodents for studying the molecular pathology of Alzheimer’s disease. The sheep (Ovis aries) is one such species, although to date, there have been few molecular studies relating to Alzheimer’s disease in sheep. Here, we investigated the Alzheimer’s disease relevant histopathological characteristics of 22 sheep, using anti-β-amyloid (Abcam 12267 and mOC64) and phosphorylation specific anti-tau (AT8 and S396) antibodies. We identified numerous intraneuronal aggregates of both β-amyloid and tau that are consistent with early Alzheimer’s disease-like pathology. We confirmed the expression of two 3-repeat (1N3R, 2N3R) and two 4-repeat (1N4R, 2N4R) tau isoforms in the ovine brain, which result from the alternative splicing of two tau exons. Finally, we investigated the phosphorylation status of the serine396 residue in 30 sheep, and report that the phosphorylation of this residue begins in sheep aged as young as 2 years. Together, these data show that sheep exhibit naturally occurring β-amyloid and tau pathologies, that reflect those that occur in the early stages of Alzheimer’s disease. This is an important step towards the validation of the sheep as a feasible large animal species in which to model Alzheimer’s disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04572-z

Gene Therapy With RALA/iNOS Composite Nanoparticles Significantly Enhances Survival In A Model Of Metastatic Prostate Cancer

Abstract Background Recent approvals of gene therapies by the FDA and the EMA for treatment of inherited disorders have further opened the door for assessment of nucleic acid pharmaceuticals for clinical usage. Arising from the presence of damaged or inappropriate DNA, cancer is a condition particularly suitable for genetic intervention. The RALA peptide has been shown to be a potent non-viral delivery platform for nucleic acids. This study examines the use of RALA to deliver a plasmid encoding inducible nitric oxide synthase (iNOS) as an anti-cancer treatment. Methods The physiochemical properties of the RALA/DNA nanoparticles were characterized via dynamic light scattering and transmission electron microscopy. The nanoparticles were labelled with fluorophores and tracked over time using confocal microscopy with orthogonal sections to determine cellular location. In vitro studies were employed to determine functionality of the nanoparticles both for pEGFP-N1 and CMV-iNOS. Nanoparticles were injected intravenously into C57/BL6 mice with blood and serum samples analysed for immune response. PC3-luc2M cells were injected into the left ventricle of SCID mice followed by treatment with RALA/CMV-iNOS nanoparticles to evaluate the tumour response in a metastatic model of prostate cancer. Results Functional cationic nanoparticles were produced with gene expression in PC-3 prostate cancer cells. Furthermore, repeated administrations of RALA/DNA nanoparticles into immunocompetent mice did not produce any immunological response: neutralization of the vector or release of inflammatory mediators. RALA/CMV-iNOS reduced the clonogenicity of PC-3 cells in vitro, and in an in vivo model of prostate cancer metastasis, systemically delivered RALA/CMV-iNOS significantly improved the survival of mice. Conclusion These studies further validate RALA as a genetic cargo delivery vehicle and iNOS as a potent therapy for the treatment of cancer

Anthropometric and physical characteristics of english academy rugby league players.

The purpose of the present study was to evaluate the anthropometric and physical characteristics of English academy rugby league players by annual-age category (under 16s-under 20s) and between backs and forwards. Data were collected on 133 academy players over a 6-year period (resulting in a total of 257 assessments). Player assessments comprised of anthropometric (height, body mass, sum of 4 skinfolds) and physical (vertical jump, 10- and 20-m sprint, estimated V[Combining Dot Above]O2max via the yo-yo intermittent recovery test level 1, absolute 1 repetition maximum [1RM], and relative squat, bench press, and prone row) measures. Univariate analysis of variance demonstrated significant (p ≤ 0.05) increases in height, body mass, vertical jump, absolute, and relative strength measures across the 5 annual-age categories (e.g., body mass: under 16s = 75.2 ± 11.1, under 20s = 88.9 ± 8.5 kg; vertical jump: under 16s = 45.7 ± 5.2, under 20s = 52.8 ± 5.4 cm; 1RM bench press: under 16s = 73.9 ± 13.2, under 20s = 114.3 ± 15.3 kg). Independent t-tests identified significant (p ≤ 0.05) differences between backs and forwards for anthropometric (e.g., under 16s body mass: backs = 68.4 ± 8.6, forwards = 80.9 ± 9.7 kg) and physical (e.g., under 19s 20-m sprint: backs = 3.04 ± 0.08, forwards = 3.14 ± 0.12s; under 18s relative squat: backs = 1.65 ± 0.18, forwards = 1.51 ± 0.17 kg·kg) characteristics that were dependent on the age category and measure assessed. Findings highlight that anthropometric and physical characteristics develop across annual-age categories and between backs and forwards in academy rugby league players. These findings provide comparative data for such populations and support the need to monitor player development in junior rugby league players