The black-legged tick Ixodes scapularis transmits the human anaplasmosis agent, Anaplasma phagocytophilum. In this study, we show that A. phagocytophilum specifically up-regulates I. scapularis organic anion transporting polypeptide, isoatp4056 and kynurenine amino transferase (kat), a gene involved in the production of tryptophan metabolite xanthurenic acid (XA), for its survival in ticks. RNAi analysis revealed that knockdown of isoatp4056 expression had no effect on A. phagocytophilum acquisition from the murine host but affected the bacterial survival in tick cells. Knockdown of the expression of kat mRNA alone or in combination with isoatp4056 mRNA significantly affected A. phagocytophilum survival and isoatp4056 expression in tick cells. Exogenous addition of XA induces isoatp4056 expression and A. phagocytophilum burden in both tick salivary glands and tick cells. Electrophoretic mobility shift assays provide further evidence that A. phagocytophilum and XA influences isoatp4056 expression. Collectively, this study provides important novel information in understanding the interplay between molecular pathways manipulated by a rickettsial pathogen to survive in its arthropod vector.
Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.
Stem cell factor (SCF) is developmentally critical for melanocyte migration, differentiation, and survival. Recently, SCF expression in hair shaft progenitor cells has been shown to be absolutely required for the pigmentation in hair shafts, as evidenced by the complete loss of hair pigmentation in mice without SCF in these epithelial cells. Interestingly, this fully disruption of hair pigmentation only targets melanogenic mature monocytes in the upper hair bulb, but not melanocyte precursors below. This shows an important role of SCF in the determination of mature melanocytes to their destination. Here we report that the skin pigmentation in the dermis layer appears to follow the same mechanism for the distribution of dermal melanocytes. We employed multiple cell-type specific Scf knockout mice to characterize the sources and contribution of SCF to dermal pigmentation. Our results show that dermal melanocytes are also sustained by SCF. However, in contrast to hair pigmentation, dermal pigmentation appears to be supported by SCF expression in a selective population of dermal cells. This study reveals a faithful distribution of melanogenic melanocytes in distinct skin compartments guided by selective populations of SCF expressing cells. Our findings suggest that manipulation of SCF expression in the skin cells might be a potential target to manage hyper-or hypo-pigmented skin manifestations in clinic.
The aim of this study was to investigate surgical complications and localized recurrence rates of patients undergoing excision of HS lesions. Duke Enterprise Data Unified Content Explorer (DEDUCE) was queried for all patients who underwent a first-time excision of HS lesion(s) from 2006-2016. Data regarding HS medications, surgical procedures, surgical complications, and localized recurrence rates were collected and presented below. McNemars test will be used to compare the correlated recurrence rates between anatomic locations. From 2006-2016, 128 patients underwent surgical excision of HS lesions at a median age of 36.4 years (range 15.1-72.5 years). Forty-one patients (32.0%) underwent excisions of multiple locations simultaneously. Sites included the axilla, inguinal region, perianal region, vulva, mons pubis, scrotum, pannus, and inframammary region. Of 9 HS locations reviewed, the most commonly excised lesions included 100 in the axilla, 40 inguinal excisions, and 19 perianal. Surgical closure techniques included 87 primary closures (67.0%), 28 secondary closures (21.9%), 7 grafts (5.5%), and 6 flaps (4.7%). At a median follow-up time of 3.6 years (range 0.0-11.2 years), 32 patients (25%) experienced a recurrence in the region previously excised. The median time to recurrence was 1.1 year (range 0.1-7.4 years). Despite each receiving perioperative antibiotics, 7 patients (5.5%) experienced a postoperative infection, all of which were successfully managed with additional antibiotics. Other operative complications included hematoma/seroma formation in 2 patients (1.6%) and wound dehiscence in 11 patients (8.6%). Surgical excision of HS lesions is well-tolerated and produces long-term remission for the majority of patients. Given the recurrent and chronic nature of the disease, early surgical intervention should be considered in patients with significant HS-associated morbidity.
The Surveillance, Epidemiology, and End Results (SEER 18) database is the largest national registry for cancer-related patient data in the United States. Despite these advances, Black populations consistently have shown poorer survival statistics, possibly due to later stages of presentation, increased tumor aggressiveness, treatment noncompliance, among other debated causes. Our goal in this study is to look at a socioeconomic marker that may link all of these causes, namely median income level, and derive the extent of influence a patient's financial resources can have on overall survival. Study Design: Retrospective cohort study. Setting: Surveillance, Epidemiology, and End Results (SEER 18) Database, April 2015 Update. Methods: Original cases from the aforementioned database were identified, with unknown racial status cases excluded from the final dataset. Survival Data by geographical county was collected from the SEER database and correlated to US Census Bureau median income data to uncover meaningful statistical relationships. Results: Whites were found to overall fare better than Blacks for all time intervals (Year 1 to Year 5) following diagnosis, based on mean survival data (p<0.05). Blacks were noted to have higher survival rates for the same time intervals (Year 1 to Year 5) when survival statistics adjusted for income (p<0.05). Conclusion: Significance correlations were seen between income and overall survival. When race was accounted for, blacks were noted to have a higher survival rate than whites. These findings accentuate a major socioeconomic issue to address within the policy-making framework and endorse earlier intervention for underprivileged populations.
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