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This genetic blistering disease is the result of mutations in COL7A1 , which encodes type VII collagen. Topical HSV-1 gene therapy delivering COL7A1 resulted in greater wound healing at 6 months than placebo.

Abstract Background Deficits in auditory processing are seen in patients with schizophrenia. Evidence implicates altered auditory cortical dendritic developments, such as reduced dendritic arborization, contribute to these symptoms. Increased Kalirin, a protein critical in dendritic morphogenesis, is seen in postmortem auditory cortical samples of patients with schizophrenia, and the resulting impaired signaling is thought to contribute to functional deficits. Our group recently established that a missense gain of function mutation in the Kalirin gene, P2255T (KAL-PT), leads to decreased auditory cortical dendritic length and complexity in 12-, but not 4-week old mice. However, it is unclear whether these contribute to auditory sensory impairments. Here, using the gap-induced pre-pulse inhibition of startle response test (gap-PPI), we examined whether KAL-PT mice exhibit behavioral deficits compared to wild-type animals (WT), and whether the deficits are specific to the auditory domain. Methods 4- and 12-week old mice were tested for gap-PPI through insertion of silent gaps (1, 2, 4, 7, 10, 20, 40, 100, and 250 ms) within a 70 dB white noise prior to the presentation of a 105 dB startle stimulus. Startle response was defined as the maximum force applied by the mouse to the apparatus. Data were analyzed using factorial repeated measures analysis of variance with genotype as between-subject factors and gap duration as within-subject factors. One-sample t-tests for each gap duration were analyzed for PPI above threshold (i.e. 0%). Data were expressed as mean ± SD, and p < 0.05 was considered statistically significant. Results Surprisingly, results indicated a significant main effect of genotype in the 4- (p=0.049), but not 12-week old mice (p=0.651). One-sample t-tests demonstrated 4-week old WT were able to discriminate the gap stimulus at 10 ms (p=0.020), whereas 4-week KAL-PT detected gap at 40 ms (p=0.017). For 12-week old animals WT were able to discriminate the gap stimulus at 7 ms (p=0.031), while KAL-PT detected gap at 20 ms (p=0.011). Discussion We suspect that 4-week KAL-PT may have molecular abnormalities not yet identified that led to gap PPI deficits without altering auditory cortex morphology. These alterations were either insufficient to produce long lasting impairments in auditory sensory processing, as evident in the lack of gap-PPI deficits within the 12-week KAL-PT, or possibly led to compensatory mechanisms that resulted in aberrant dendritic growth. Alternatively, the Kalirin mutation itself may drive both the behavioral deficits seen in the 4-week old animals, and the morphological changes in the 12-week old mice, via independent mechanisms, with the resulting changes in dendritic architecture normalizing gap-PPI. Clinically, our results suggest that, without additional insults, the KAL-PT mutation alone may be insufficient for the development of auditory processing deficits despite changes in neuronal morphology. Identification of functional changes within these neuronal populations may help elucidate the mechanisms by which Kalirin alters neuronal activities, and offer insights into the role this protein plays in the pathophysiology of schizophrenia.

PurposeThe main objective of Repro-Can-OPEN Study Part 2 is to learn more about oncofertility practices in optimum resource settings to provide a roadmap to establish oncofertility best practice models.MethodsAs an extrapolation for oncofertility best practice models in optimum resource settings, we surveyed 25 leading and well-resourced oncofertility centers and institutions from the USA, Europe, Australia, and Japan. The survey included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer.ResultsAll surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed three major characteristics of oncofertility practice in optimum resource settings: (1) strong utilization of sperm freezing, egg freezing, embryo freezing, ovarian tissue freezing, gonadal shielding, and fractionation of chemo- and radiotherapy; (2) promising utilization of GnRH analogs, oophoropexy, testicular tissue freezing, and oocyte in vitro maturation (IVM); and (3) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, in vitro spermatogenesis, and stem cell reproductive technology as they are still in preclinical or early clinical research settings. Proper technical and ethical concerns should be considered when offering advanced and experimental oncofertility options to patients.ConclusionsOur Repro-Can-OPEN Study Part 2 proposed installing specific oncofertility programs for common cancers in optimum resource settings as an extrapolation for best practice models. This will provide efficient oncofertility edification and modeling to oncofertility teams and related healthcare providers around the globe and help them offer the best care possible to their patients.