A case of cutaneous necrosis due to intra-articular hyaluronic acid and treated with hyaluronidase.

A 66-year-old woman presented to the hospital with cutaneous necrosis of her right ankle and foot. Her symptoms began immediately after an intra-articular injection of hyaluronic acid for ankle osteoarthritis, which was performed 6 days before. Histopathology showed an intra-vascular hyaluronic acid embolus. The initial treatment approach was conservative, but the patient's clinical state degraded. She was thus treated with sub-cutaneous hyaluronidase, the enzyme that degrades hyaluronic acid, which yielded a moderate improvement even though it was administered 22 days after the initial hyaluronic acid injection. Although hyaluronic acid embolism and subsequent cutaneous necrosis are well-known complications of dermal fillers, there are few reported cases of embolism following intra-articular injection. To our knowledge, this is the first time hyaluronidase has been used in this setting.

Identification of genetic variants associated with skeletal muscle function deficit in childhood acute lymphoblastic leukemia survivors.

Background: Although 80% of childhood acute lymphoblastic leukemia (ALL) cases are cured with current treatment protocols, exposure to chemotherapeutics or radiation therapy during a vulnerable period of child development has been associated with a high frequency of late adverse effects (LAE). Previous observations suggest important skeletal muscle size, density and function deficits in ALL survivors. Purpose: Given that only a fraction of all patients will suffer from this particular complication, we investigated whether it could be predicted by genetic markers.  Patients and methods: We analysed associations between skeletal muscle force (Fmax) and power (Pmax) and germline genetic variants from 1039 genes derived through whole-exome sequencing. Top-ranking association signals retained after correction for multiple testing were confirmed through genotyping, and further analysed through stratified analyses and multivariate models.  Results: Our results show that skeletal muscle function deficit is associated with two common single nucleotide polymorphisms (SNPs) (rs2001616DUOX2, P=0.0002 (Pmax) and rs41270041ADAMTS4, P=0.02 (Fmax)) and two rare ones located in the ALOX15 gene (P=0.001 (Pmax)). These associations were further modulated by sex, body mass index and risk groups, which reflected glucocorticoid dose and radiation therapy (P≤0.02).  Conclusion: Occurrence of muscle function deficit in childhood ALL is thus strongly modulated by variations in the DUOX2, ADAMTS4 and ALOX15 genes, which could lead to personalized prevention strategies in childhood ALL survivors.

Identification of a single-nucleotide polymorphism within CDH2 gene associated with bone morbidity in childhood acute lymphoblastic leukemia survivors.

Aim: To identify genetic markers associated with late treatment-related skeletal morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). Patients & methods: To this end, we measured the association between reduction in bone mineral density or vertebral fractures prevalence and variants from 1039 genes derived through whole exome sequencing in 242 childhood ALL survivors. Top-ranking variants were confirmed through genotyping, and further explored with stratified analyses and multivariable models. Results: The minor allele of rs1944294 in CDH2 gene was associated with bone geometrical parameter, trabecular cross-sectional area (p = 0.001). The association was modulated by radiation therapy (p = 0.001) and post-treatment time (p = 0.0002). Conclusion: The variant in CDH2 gene is a potential novel risk factor of bone morbidity in survivors of childhood ALL.

Stability of laser-assisted in situ keratomileusis (LASIK) at altitude.

BACKGROUND: The U.S. Air Force approved laser-assisted in situ keratomileusis (LASIK) for aircrew in May 2007. Relative to photorefractive keratectomy (PRK), LASIK potentially offers a more rapid return to flight status; however, there are concerns regarding corneal stability at altitude after surgery. Studies have shown that hypoxia induces a myopic shift in LASIK eyes. Mountaineers treated with LASIK have similarly reported decreased distance acuity when climbing above 22,000 ft (6706 m). We evaluated visual and refractive stability after LASIK under conditions simulating an operational aviation mission. METHODS: There were 24 eyes of 12 active duty subjects that were examined 1 or more months after LASIK. Measurements of high and low contrast visual acuity, keratometry, and refractive error were performed at ground level after a 2-h oxygen pre-breathe and repeated after 30 min of exposure to conditions simulating 35,000 ft (10,668 m) using a hypobaric chamber. A within subject, repeated measures t-test was used to compare findings at altitude to ground level. RESULTS: LASIK eyes demonstrated no clinically or statistically significant changes at altitude relative to ground level for the four parameters studied. No eyes showed more than +/-0.25 D of change on keratometry and none had a myopic shift greater than 0.25 D. CONCLUSION: LASIK eyes exposed to extreme altitudes under operational conditions, where the exposure is limited to 30 min or less, are expected to remain stable.

Beyond 20/20: new clinical methods to quantify vision performance.

OBJECTIVE: To describe the design, the sensitivity, and the application of new methods to quantify visual performance. METHODS: The super vision test-night vision goggle (SVT-NVG) is a new clinical letter chart that measures high- and low-contrast vision under daytime and simulated night conditions. The cone contrast test (CCT) is a computer-based color test that readily diagnoses type and severity of color deficiency. RESULTS: The SVT-NVG reveals subtle decrements from normal not detected by standard visual acuity. The CCT shows 100% sensitivity for the detection of hereditary red or green color deficiency and reveals acquired deficiency as an early sign of disease. CONCLUSIONS: The SVT-NVG and CCT provide rapid, sensitive indices of color and spatial vision potentially linkable to real-world operational demands.

Why preoperative acuity predicts postoperative acuity in wavefront-guided LASIK.

PURPOSE: To critically evaluate the following clinical wisdom regarding custom (wavefront-guided) laser in situ keratomileusis (LASIK) that subjects with better-than-average best-corrected visual acuity (BCVA) before surgery have a greater risk of losing BCVA postoperatively than do subjects with worse-than-average BCVA before surgery. METHODS: High contrast BCVA was measured once before and 3 months after custom LASIK in one eye of 79 subjects. Preoperative spherical equivalent refractive error ranged between -1.00 and -10.38 D. The sample was divided into one of two subsamples: eyes that had better-than-average preoperative BCVA (<-0.11 logMAR) and eyes that had average or worse-than-average preoperative BCVA (≥-0.11 logMAR). Controls were implemented for retinal magnification and for the statistical phenomenon of regression to the mean of the preoperative acuity measurement. RESULTS: On average, for the entire sample, moving the correction from the spectacle plane to the corneal plane increased letter acuity 4.7% (1 letter, 0.02 logMAR). For each subsample, the percentage regression to the mean was 57.24%. After correcting for magnification effects and regression to the mean, eyes with better-than-average preoperative acuity had a small but significant gain in acuity (∼1 letter, p = 0.040) that was nearly identical to the gain for eyes with worse-than-average preoperative acuity (∼1.5 letters, p = 0.002). CONCLUSIONS: Custom LASIK produced a statistically significant gain in visual acuity after correction for magnification effects. Dividing the sample into two subsamples based on preoperative acuity confirmed the common clinical observation that eyes with better-than-average acuity tend to remain the same or lose acuity, whereas eyes with worse-than-average acuity tend to gain acuity. However, when only one acuity measurement is taken at a single time point and the sample is subsampled nonrandomly, this clinical observation is due to a statistical artifact (regression to the mean) and is not attributable to the surgery.

The tubulin homologue FtsZ contributes to cell elongation by guiding cell wall precursor synthesis in Caulobacter crescentus.

The tubulin homologue FtsZ is well known for its essential function in bacterial cell division. Here, we show that in Caulobacter crescentus, FtsZ also plays a major role in cell elongation by spatially regulating the location of MurG, which produces the essential lipid II peptidoglycan cell wall precursor. The early assembly of FtsZ into a highly mobile ring-like structure during cell elongation is quickly followed by the recruitment of MurG and a major redirection of peptidoglycan precursor synthesis to the midcell region. These FtsZ-dependent events occur well before cell constriction and contribute to cell elongation. In the absence of FtsZ, MurG fails to accumulate near midcell and cell elongation proceeds unperturbed in appearance by insertion of peptidoglycan material along the entire sidewalls. Evidence suggests that bacteria use both a FtsZ-independent and a FtsZ-dependent mode of peptidoglycan synthesis to elongate, the importance of each mode depending on the timing of FtsZ assembly during elongation.

Mycobacteriophage Bxb1 integrates into the Mycobacterium smegmatis groEL1 gene.

Mycobacteriophage Bxb1 is a temperate phage of Mycobacterium smegmatis and forms stable lysogens in which the Bxb1 genome is integrated into the host chromosome. Bxb1 encodes an integrase of the large serine recombinase family that catalyses integration and excision of the Bxb1 genome. We show here that Bxb1 integrates into a chromosomal attB site located within the 3' end of the groEL1 gene such that integration results in alteration of the C-terminal 21 amino acid residues. An integration-proficient plasmid vector containing the Bxb1 integrase gene and flanking DNA sequences efficiently transforms M. smegmatis via integration at attB. Bxb1-integrated recombinants are stable and fully compatible with L5 integration vectors. Strand exchange occurs within an 8 bp common core sequence present in attB and within an attP site situated immediately upstream of the phage integrase gene. Establishment of a defined in vitro system for Bxb1 integration shows that recombination occurs efficiently without requirement for high-energy cofactors, divalent metals, DNA supercoiling or additional proteins.