Analysis of Nonweightbearing MRI Fat Pad Thickness Under Central Metatarsals in Patients With and Without Metatarsalgia.

BACKGROUND: Metatarsalgia is a common diagnosis for patients with forefoot pain. Many have proposed metatarsal fat pad atrophy is a cause of metatarsalgia and therefore have suggested fat grafting instead of distal metatarsal osteotomies to treat metatarsalgia. For fat grafting to be a viable treatment, fat pad atrophy should correlate with metatarsalgia. This study looked to determine the relationship between metatarsal fat pad thickness and metatarsalgia and the correlation between metatarsal fat pad thickness and patient-reported outcomes. METHODS: We conducted a retrospective review of patients with metatarsalgia and those with foot or ankle osteoarthritis who had a nonweightbearing MRI performed between February 1, 2021, and March 1, 2023. Data collected included demographics, PROMIS scores, metatarsal fat pad thickness in the second and third rays of the affected foot, and thinnest area on coronal section, measured on MRI. Student t test was used to compare continuous variables, whereas the χ2 test was used to compare categorical variables. Multivariable linear regression models were used to control for potential confounding factors. RESULTS: A total of 112 patients were included in this study. Patients with metatarsalgia were significantly more likely to have a lower body mass index (29.3 vs 32.0, P = .03) than patients with osteoarthritis, but this finding was not present when controlling for confounding variables. We found no significant difference in fat pad thickness between patients with metatarsalgia vs patients with foot or ankle osteoarthritis (P = .43). We found no correlation between metatarsal fat pad thickness and pain interference (P = .59), physical function (P = .64), or mobility (P = .94) PROMIS scores. CONCLUSION: In this retrospective comparative study of a relatively small cohort we found no significant difference in metatarsal fat pad thickness for patients with metatarsalgia vs patients with foot and ankle osteoarthritis based on nonweightbearing MRI, and no association between metatarsal fat pad thickness and patient-reported outcomes. LEVEL OF EVIDENCE: Level III, case control study.

Alteration of genetic recombination and double-strand break repair in human cells by progerin expression.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare autosomal, dominant genetic condition characterized by many features of accelerated aging. On average, children with HGPS live to about fourteen years of age. The syndrome is commonly caused by a point mutation in the LMNA gene which normally codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The LMNA mutation alters splicing, leading to production of a truncated, farnesylated form of lamin A referred to as "progerin." Progerin is also expressed at very low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs), suggesting corruption of DNA repair. In this work, we investigated the influence of progerin expression on DSB repair in the human genome at the nucleotide level. We used a model system that involves a reporter DNA substrate inserted in the genome of cultured human cells. A DSB could be induced within the substrate through exogenous expression of endonuclease I-SceI, and DSB repair events occurring via either homologous recombination (HR) or nonhomologous end-joining (NHEJ) were recoverable. Additionally, spontaneous HR events were recoverable in the absence of artificial DSB induction. We compared DSB repair and spontaneous HR in cells overexpressing progerin versus cells expressing no progerin. We report that overexpression of progerin correlated with an increase in DSB repair via NHEJ relative to HR, as well as an increased fraction of HR events occurring via gene conversion. Progerin also engendered an apparent increase in spontaneous HR events, with a highly significant shift toward gene conversion events, and an increase in DNA amplification events. Such influences of progerin on DNA transactions may impact genome stability and contribute to aging.

Inactivation of Listeria monocytogenes on Hot-smoked Salmon by the Interaction of Heat and Smoke or Liquid Smoke †.

L. monocytogenes was inoculated onto the surface of brined salmon steaks and heat processed in a commercial smokehouse to simulate a hot process for preparing smoked fish. The minimum temperature required for inactivation of L. monocytogenes was 153°F (67.2°C) when generated smoke was applied throughout the entire process. When generated smoke was added only during the last half of the process, L. monocytogenes was recovered from steaks heated to temperatures as high as 176°F (80.0°C). When smoke was not applied during the process, L. monocytogenes survived on steaks heated to internal temperatures between 131°F and 181°F (55.0 to 82.8°C) but was not isolated from steaks heated above 181°F (82.8°C). When liquid smoke CharSol C-l0 was applied as a full-strength (100%) dip before processing, L. monocytogenes was inactivated in samples processed at temperatures as low as 138°F (58.9°C). When liquid smoke l0-Poly or CharSol C-l0 was applied at a concentration of 50%, the lethal temperature was increased to the range of 145 to 150°F (62.8 to 65.6°C). With further dilution of C-l0 to 25% and 10% the inactivation temperatures increased to 156°F (68.9°C) and 163°F (72.8°C). A full-strength dip of CharOil, the oil-soluble fraction of CharSol C-l0, was less effective, and L. monocytogenes survived in salmon steaks processed to an internal temperature of 166°F (74.4°C), the highest temperature tested with this liquid smoke. This study provides evidence that heat alone is not reliable for inactivation of L. monocytogenes during the hot-smoking process. The proper stage and duration of smoke application or proper composition and concentration of liquid smoke in combination with heat are critical for inactivation of the organism.