Miami Transplant Institute

BackgroundThe cafeteria diet (CAFD) model has been used to mimic the Western‐style “junk food” eating pattern, inducing obesity in rodents. As the dietary composition varies across studies, we developed a CAFD model based on commonly consumed Brazilian ultra‐processed foods to evaluate its effect on weight gain, metabolic parameters, and gene expression in C57BL/6 mice.MethodsForty male C57BL/6 mice were assigned to either a standard diet (SD) group or a CAFD group for 16 weeks. Biometric data, glycemic control, insulin resistance (IR), hepatic steatosis, and serum leptin and adiponectin levels were assessed. Expressions of 27 genes involved in adipocytokine signaling, inflammation, apoptosis, lipid, and glucose metabolism were analyzed using quantitative real‐time polymerase chain reaction in visceral (VAT) and subcutaneous (SAT) adipose tissues, liver, and skeletal muscle.ResultsCAFD‐fed mice exhibited significantly greater weight gain, hyperglycemia, elevated IR, and hepatic steatosis compared to SD controls. Circulating leptin and adiponectin levels increased in the CAFD group. Gene expression analysis revealed significant dysregulation in VAT (19 genes), SAT (6 genes), liver (11 genes), and muscle (4 genes) of the CAFD group, affecting pathways related to adipocytokine signaling, oxidative stress, inflammation, apoptosis, and lipid and glucose metabolism. Additionally, an increased Itgax‐to‐Llgl1 ratio in VAT of the CAFD mice indicated a phenotypic shift in macrophages from M2 to pro‐inflammatory M1.ConclusionThis CAFD model efficiently induces obesity, metabolic dysfunction, and tissue‐specific alterations in gene expression in C57BL/6 mice, supporting its use as a relevant model for studying the molecular and inflammatory mechanisms underlying diet‐induced obesity.

Centromeres ensure accurate chromosome segregation, yet their DNA evolves rapidly across eukaryotes leaving the origins of new centromere architectures unclear1-4. The brewer's yeast Saccharomyces cerevisiae exemplifies this long-standing puzzle. Its centromeres shifted ancestrally from large, repeat-rich, epigenetically specified forms to the compact, genetically defined 'point' centromeres1,5. How this transition occurred has remained unresolved6. Here we identify evolutionarily related 'proto-point' centromeres that provide a resolution to the evolutionary origins of point centromeres. Proto-point centromeres contain a single centromeric nucleosome positioned over an AT-rich core, accompanied by relaxed organization and sequence variability of flanking cis-elements. In two species, these proto-point centromeres lie within retrotransposon-derived repeat clusters, linking ancestral repeat-rich centromeres to genetically encoded ones. Comparative and phylogenetic analyses indicate that proto-point and point centromeres evolved in an ancestor with retrotransposon-rich centromeres. These results identify long-terminal-repeat retrotransposons, specifically Ty5 sequences, as the genetic substrate for point-centromere evolution and provide a mechanistic route by which an epigenetic centromere can become genetically specified. More broadly, they show how selfish elements can be co-opted to perform essential chromosomal functions.

Cutaneous squamous cell carcinoma has a propensity for perineural invasion. Treating perineural spread has involved surgery and adjuvant chemoradiation, and more recently, immune checkpoint inhibitors. This study aims to evaluate motor and sensory functional outcomes in patients with cranial neuropathies from perineural spread of squamous cell carcinoma, particularly those undergoing immunotherapy. This was a multicenter case series and literature review. Eighteen patients with cranial neuropathies from perineural spread had a mean age of 72.5 ± 9.7 years. Cranial nerves V and VII were most often involved. Treatments included radiotherapy (8/18; 44.4%), chemotherapy (7/18; 38.9%), and/or immunotherapy (11/18; 61.1%), with many receiving a combination of modalities (8/18; 44.4%). Of those receiving immunotherapy, 72.7% (8/11) demonstrated at least partial clinical and/or radiologic tumor response. Among those with functional outcomes documented, half had improvement in sensory/motor nerve function following immunotherapy (4/8; 50%). A literature review identified 55 articles describing 449 patients total with cranial neuropathies from squamous cell carcinoma perineural spread. Combinations of surgery, chemotherapy, and/or radiotherapy were employed, with immunotherapy used in 16 patients. From 5 patients on immunotherapy with documented functional outcomes, all demonstrated at least some improvement. Immunotherapy plays an evolving role in managing advanced squamous cell carcinoma. Functional improvements in cranial neuropathy were demonstrated in 50% of patients receiving treatment with immunotherapy at a mean of 32.6 months of follow-up. This may hold important implications for the timing of surgical intervention, particularly in the case of cranial nerves V and VII palsies.

The aims of this pilot study were to determine whether (1) a modified version of the Robinson-Ho Skin Type Color Bar would identify early, subtle skin tone variations in patients with dark skin tones because of injury, and (2) if the tool was reliable between clinicians. This was a prospective, observational cohort study in a surgical intensive care/acute care unit located in an urban, academic hospital. Patients who were ≥18 years old without a skin injury, but with a confirmed dark skin tone based on the modified Robinson-Ho Skin Type Color Bar, were included in the pilot study. The first aim could not be supported because of the lack of patients who developed subtle skin tone changes indicative of a skin injury. Two patients developed a skin injury (deep tissue pressure injury, trauma). These wounds did not manifest as subtle changes, therefore rendering the tool ineffective for these cases. The second aim was supported as inter-rater reliability of the Robinson-Ho Skin Type Color Bar showed moderate agreement between multiple raters. It was also noted that race/ethnicity was not an objective marker for determining skin tone per the tool. Although the modified Robinson-Ho Skin Type Color Bar was not an effective method to detect subtle skin tone changes indicative of injury because of the 2 wounds that did occur, it was reliable to use between multiple users. The tool also served as an objective marker for determining baseline skin tone.

BackgroundMultisensory Stimulation Interventions (MSI) aims to stimulate the senses such as sight, hearing, touch, taste, smell, vestibular and proprioceptive systems, which can be areas affected by dementia. Studies on MSI in the home environment, both for older adults with dementia and for their family caregivers, are scarce.MethodMSI in home environments was carried out in 8 sessions, lasting 1.5 hours and occurring weekly. The sample was allocated into two groups: Experimental and Control. The benefits of the intervention were assessed by objective outcome measures such as the Neuropsychiatric Inventory (NPI) and the Anxiety, Depression and Stress Scale (DASS‐21) through descriptive and comparative analyses considering pre‐ and post‐intervention and effect size.ResultThe sample consisted of 10 families (older adults and their family caregivers). Comparing the pre‐ and post‐intervention through the NPI, there was an improvement of great magnitude in the EG in all the variables: Total score in the NPI (d Cohen = ‐1.07), Frequency (d Cohen = ‐1.33), Intensity (d Cohen = ‐1.45), Caregiver distress (d Cohen = ‐1.06) and quantity of behaviors (d Cohen = ‐1.14). In the DASS‐21 there was an improvement in the following variables: DASS‐21 total score (Cohen's d = ‐0.65), Anxiety (Cohen's d = ‐1.05) and Stress (Cohen's d = ‐0.30), a value of p ≤0.05 was adopted.ConclusionThe MSI intervention based on the principles of Snoezelen in home environments has a positive effect on reducing the frequency and intensity of BPSD in the older adults, as well as on the caregiver distress, anxiety and stress of the caregivers regarding these behaviors.