Quantifying the Effect of a Novel topical Hyaluronic-Acid Phosphatidylethanolamine Cream on the Epidermis

With aging, keratinocytes have diminished proliferative capacity resulting in atrophic skin with reduced barrier function. This investigation evaluates the effect of daily topical applications of a novel high-molecular weight hyaluronan cream (HA-PE) on keratinocyte renewal and epidermal thickness. Unmodified hyaluronan and HA-PE were mixed separately into a vehicle cream. Each topical formulation was applied daily onto the shaved backs of aged female C57BL6 mice. Full-thickness biopsies of treated skin were obtained for analysis of keratinocyte proliferation, keratinocyte differentiation, and local inflammation at days 1, 5, and 10 of cream application. In addition, a cardiac puncture was performed for serum C-reactive protein analysis. The HA-PE group exhibited the highest level of keratinocyte proliferation and epidermal thickness at all time points. There was no significant difference in keratinocyte differentiation or local/systemic inflammation between groups. Thus, topical HA-PE cream is a novel skin care technology that increases epidermal thickness through enhanced keratinocyte proliferation/renewal

QUANTITATIVE ASSESSMENT OF STRENGTH AND FATIGUE IN PATIENTS WITH MYASTHENIA GRAVIS

The objective of this thesis was to quantify, by direct measurement of muscle force, the strength and fatigue of patients with myasthenia gravis (MG). MG is characterized by fatigable muscle weakness resulting from impaired neuromuscular transmission. A maximal voluntary isometric contraction protocol of shoulder abductors was used in conjunction with conventional fatigue and disease severity instruments. Results from patients with (D-MG) and without. decrement (ND-MG) on repetitive nerve stimulation (RNS) were compared to controls. Patients with MG reported experiencing greater fatigue than controls. Muscle strength was the lowest in the D-MG group followed by the ND-MG group and controls, respectively. Surprisingly, normalized shoulder abduction fatigue and recovery values did not differ between patients with MG and controls. Greater experienced fatigue in MG may correspond to confounding variables such as physical inactivity. In addition, decrement upon RNS, appears to relate best to disease severity and muscle weakness but not to fatigue in this population

Radiographic Thresholds With Increased Odds of a Poor Outcome Following Distal Radius Fractures in Patients Over 65 Years Old

© 2019 Purpose: Older patients (aged older than 65 years)appear to tolerate a great degree of anatomic deformity after DRFs; however, the threshold beyond which the deformity becomes unacceptable is unknown. The purposes of this study were to identify the acceptable threshold for radiographic parameters after DRFs in patients aged over 65 years according to a patient-rated pain and disability outcome measure and to determine whether baseline activity levels influenced these parameters. Methods: A cohort of 190 older adults (aged 65 years and older)with DRF were selected from an existing prospectively collected database. The influence of specific radiographic parameters (ulnar variance, radial inclination [RI], and volar-dorsal tilt)and baseline activity levels on 1-year Patient-Rated Wrist Evaluation (PRWE)scores was investigated. The odds ratio (OR)of a poor outcome according to a 1-year PRWE (cutoff score of ≥25)at various alignment thresholds was calculated with 95% confidence intervals (CIs). Activity level (underactive vs active)was determined using the Rapid Assessment of Physical Activity survey. Results: Radiographic parameters for the cohort varied widely (mean ulnar variance, 1.9 ± 0.9 mm, range –2.4 to 8.0 mm; mean RI, 18.7°± 5.9°, range, 0.1° to 38°; and mean dorsal tilt, 4.5° ±11.9°, range –24.0° to 33.6°). Most of the cohort (n = 158, 83%)had a good outcome (mean PRWE, 14.4 ± 19.5). The OR of a poor outcome was significant for RI less than 20° (OR = 3.6; 95% CI 1.5–8.7)and dorsal tilt greater than 15° (OR = 5.3; 95% CI, 1.0–27.8). Malalignment on radiographs and a poor outcome according to PRWE were not significantly different in the underactive versus active subpopulations. Conclusions: This study provides alignment cutoffs that best discriminate adverse pain and disability patient outcomes after DRF in a cohort aged more than 65 years. This information can be used to counsel older patients about their increased likelihood of a poor outcome with RI less than 20˚ or a dorsal tilt greater than 15°. Further research is required to examine outcomes after applying these thresholds in a prospective manner to management decision algorithms for DRF in patients aged over 65 years. Type of study/level of evidence: Prognostic II

Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis

Hyaluronan-Phosphatidylethanolamine Polymers Form Pericellular Coats on Keratinocytes and Promote Basal Keratinocyte Proliferation

Aged keratinocytes have diminished proliferative capacity and hyaluronan (HA) cell coats, which are losses that contribute to atrophic skin characterized by reduced barrier and repair functions. We formulated HA-phospholipid (phosphatidylethanolamine, HA-PE) polymers that form pericellular coats around cultured dermal fibroblasts independently of CD44 or RHAMM display. We investigated the ability of these HA-PE polymers to penetrate into aged mouse skin and restore epidermal function in vivo. Topically applied Alexa647-HA-PE penetrated into the epidermis and dermis, where it associated with both keratinocytes and fibroblasts. In contrast, Alexa647-HA was largely retained in the outer cornified layer of the epidermis and quantification of fluorescence confirmed that significantly more Alexa647-HA-PE penetrated into and was retained within the epidermis than Alexa647-HA. Multiple topical applications of HA-PE to shaved mouse skin significantly stimulated basal keratinocyte proliferation and epidermal thickness compared to HA or vehicle cream alone. HA-PE had no detectable effect on keratinocyte differentiation and did not promote local or systemic inflammation. These effects of HA-PE polymers are similar to those reported for endogenous epidermal HA in youthful skin and show that topical application of HA-PE polymers can restore some of the impaired functions of aged epidermis

Do all hemochromatosis patients have the same origin? A pilot study of mitochondrial DNA and Y-DNA

BACKGROUND: Mitochondrial DNA (mtDNA) and Y-DNA analysis have been widely used to predict ancestral origin. Genetic anthropologists predict that human civilizations may have originated in central Africa one to two million years previously. Primary iron overload is not a common diagnosis among indigenous people of northern Africa, but hereditary hemochromatosis is present in approximately one in 200 people in northern Europe. MtDNA analysis has the potential to determine whether contemporary hemochromatosis patients have an ancient ancestral linkage