Reduced Levels of Brain-Derived Neurotrophic Factor Affect Body Weight, Brain Weight and Behavior.

Neurotrophins, which belong to the family of growth factors, not only play crucial roles during development but are also involved in many processes in the postnatal brain. One representative of neurotrophins is brain-derived neurotrophic factor (BDNF). BDNF plays a role in the regulation of body weight and neuronal plasticity and is, therefore, also involved in processes associated with learning and memory formation. Many of the studies on BDNF have been carried out using BDNF-deficient mice. Unfortunately, homozygous deletion of BDNF is lethal in the early postnatal stage, so heterozygous BDNF-deficient mice are often studied. Another possibility is the use of conditional BDNF-deficient mice in which the expression of BDNF is strongly downregulated in some brain cells, for example, in the neurons of the central nervous system, but the expression of BDNF in other cells in the brain is unchanged. To further reduce BDNF expression, we crossed heterozygous BDNF-deficient mice with mice carrying a deletion of BDNF in neurofilament L-positive neurons. These offspring are viable, and the animals with a strong reduction in BDNF in the brain show a strongly increased body weight, which is accompanied by a reduction in brain weight. In addition, these animals show behavioral abnormalities, particularly with regard to locomotion.

Testing the Preliminary Validity of a Multidimensional Framework for Studying the Effects of Cancer Health Literacy on Cancer Screening Behaviors among Diverse Populations.

The objective of this study was to evaluate the applicability of a multidimensional framework to explore factors associated with cancer literacy and its effects on receiving cancer screenings among diverse populations. Based on the conceptual framework, we developed and pilot-tested the Multidimensional Cancer Literacy Questionnaire (MCLQ) among 1500 individuals (African Americans, Latinos and Whites) in Louisiana. Exploratory factor analysis was used to identify the MCLQ underlying structure and predominant factors explaining each of the dimensions in the model. A total of 82 items (explaining 67% of the total variance) in the MCLQ were grouped into 20 factors associated with three key dimensions related to cancer literacy. Preliminary validity of the MCLQ was supported: Cronbach alpha for the scale score was 0.89 and internal consistency reliability coefficients for each factor were all above 0.67. The Facilitators Domain included five factors (28 items) that may positively influence individuals to have early-detection cancer screenings. The Barriers Domain included seven factors (26 items) explaining aspects that may negatively influence individuals to have cancer screenings. The Cultural Domain included eight factors (28 items) related to aspects that influence positively or negatively individuals' perceptions regarding cancer as a disease, screenings and treatments. A multidimensional framework to study cancer literacy, including cultural attitudes, beliefs and practices, as well as facilitators and barriers, among diverse populations, will increase understanding of factors influencing individuals' approach to cancer prevention and screening. Results will inform further testing of the multidimensional framework and questionnaire.

Outcomes Following Orbital Floor Fractures in the Elderly.

BACKGROUND: Orbital floor fractures in the elderly are controversial, with varying guidelines on indications for operative and nonoperative management. Morbidity includes changes to ocular position, inferior rectus muscle injury, and damage to the neurovascular bundle as it traverses the orbital floor. Across all facial fractures, the elderly are less frequently operated on, albeit longer hospital stays and more probably ICU admission. This study's purpose is to describe our experience with orbital floor fractures and the role of operative versus nonoperative management in the context of patient age. METHODS: Retrospective review of orbital floor fracture coronal and sagittal CT images between 2015 and 2018 in those aged 20 to 40 (controls) or over 65 (cases). Patients were excluded if imaging revealed additional complex fractures of the upper third of the face or the midface. RESULTS: Twenty-five subjects met inclusion criteria for the elderly cohort (mean age of 79.4 years) compared to 48 subjects included in the control cohort (mean age 29.9). In the elderly population the most common mechanisms of injury were mechanical fall (72%) and syncope (8%), compared to assault (69%) and MVC (13%) in the controls. Two elderly patients (8%) required operative repair of their injury, whereas fourteen had surgery (29%) in the control cohort. Overall, the mean elderly fracture size was 3.19 cm (SD 1.18) and the mean control fracture size was 2.83 cm (SD 1.67) (P = 0.37). Within the elderly group, the mean fracture size for those who underwent surgery was 3.5 cm compared to 3.2 cm in those treated non-operatively (P = 0.27). Within the control group, the mean fracture size for those who underwent surgery was 2.9 cm compared to 2.8 cm in those treated non-operatively (P = 0.25). CONCLUSIONS: Orbital floor fractures in the elderly do not require operative intervention in most instances for management.

Thin and Ultra-Thin Split-Thickness Skin Grafts Are Safe and Efficacious in the Burn Population.

Split-thickness skin-grafts are a mainstay of burn management. Studies suggest no benefit to using thick (0.025 inch) over standard (0.012-0.020 inch) grafts, and some support the use of thin (0.008 inch) over standard thickness. Data on the use of even thinner grafts is scarce. This study reviewed outcomes of burn patients treated with thin (0.008-0.011 inch) and ultra-thin (≤0.007 inch) grafts. Retrospective review of records from July 2012 to June 2016 included patients who sustained operative burns treated by a single surgeon. Patients were excluded for nonoperative injuries, inhalational injuries, or prolonged hospitalizations. Outcome measures were compared between thin and ultra-thin groups. One-hundred twenty-eight patients met inclusion criteria; 35 received thin split-thickness skin-grafts while 93 received ultra-thin. Cohort analysis demonstrated equivalent graft-take, time to reepithelialization, and functional outcomes. Time to donor-site healing was significantly faster in the ultra-thin cohort (P = .04). Of those with functional outcomes recorded, 88.1% had good-excellent function and 11.9% retained a limitation in function as designated in physical therapy notes. There were fewer complications overall (P = .004) and a lower incidence of hypertrophic scarring (P = .025) in the ultra-thin cohort. This study presents a single-surgeon experience with thin and ultra-thin split-thickness skin-grafts. These grafts are exhibit excellent graft-take and few complications. There was no correlation between thickness and functional outcome at the time of physical therapy discharge. Donor-site reepithelialization was faster with ultra-thin grafts, which may be important in patients with large burns and limited donor sites.

Ewing Sarcoma Presenting as a Congenital Scalp Mass.

Ewing sarcoma is a locally aggressive, highly malignant tumor most commonly seen in the skeletal system. The "Ewing family of tumors" also includes other tissue types that are not common, such as soft tissue origin classified as extraosseous Ewing sarcoma (EES) or primitive neuroendocrine origin. Age of onset most often occurs within the first 2 decades of life. Congenital presentation of EES is exceedingly rare. We report the first described case to our knowledge of congenital EES originating from the scalp.

Cancer Health Literacy and Willingness to Participate in Cancer Research and Donate Bio-Specimens.

Although it has been well documented that poor health literacy is associated with limited participation in cancer clinical trials, studies assessing the relationships between cancer health literacy (CHL) and participation in research among diverse populations are lacking. In this study, we examined the relationship between CHL and willingness to participate in cancer research and/or donate bio-specimens (WPRDB) among African Americans, Latinos, and Whites. Participants completed the Cancer Health Literacy Test and the Multidimensional Cancer Literacy Questionnaire. Total-scale and subscale scores, frequencies, means, and distributions were computed. Analyses of variance, the Bonferroni procedure, and the Holm method were used to examine significant differences among groups. Cronbach's alphas estimated scales' internal consistency reliability. Significant interactions were found between race/ethnicity, gender, and CHL on WPRDB scales and subscale scores, even after education and age were taken into account. Our study confirms that CHL plays an important role that should be considered and researched further. The majority of participants were more willing to participate in non-invasive research studies (surveys, interviews, and training) or collection of bio-specimens (saliva, check cells, urine, and blood) and in studies led by their own healthcare providers, and local hospitals and universities. However, participants were less willing to participate in more-invasive studies requiring them to take medications, undergo medical procedures or donate skin/tissues. We conclude that addressing low levels of CHL and using community-based participatory approaches to address the lack of knowledge and trust about cancer research among diverse populations may increase not only their willingness to participate in research and donate bio-specimens, but may also have a positive effect on actual participation rates.

Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas.

Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci. Digital H&E images from 20 gynecologic tract carcinosarcomas were reviewed by 22 gynecologic pathologists with a request to determine the presence or absence of an osteosarcomatous component. The 20 preselected cases included areas of classic heterologous osteosarcoma (malignant cells producing osteoid; n=10) and osteosarcoma mimics (malignant cells with admixed nonosteoid matrix; n=10). Interobserver agreement was evaluated and SATB2 scored on all 20 cases and compared with the original diagnoses. Moderate agreement (Fleiss' κ=0.483) was identified for the 22 raters scoring the 20 cases with a median sensitivity of 7/10 and a median specificity of 9/10 for the diagnosis of osteosarcoma. SATB2 showed 100% sensitivity (10/10) and 60% (6/10) specificity in discriminating classic osteosarcoma from osteosarcoma mimics. Utilizing negative SATB2 as a surrogate marker to exclude osteosarcoma, 73% (16/22) of the reviewers would have downgraded at least 1 case to not contain an osteosarcomatous component (range, 1-6 cases, median 1 case). Gynecologic pathologists demonstrate only a moderate level of agreement in the diagnosis of heterologous osteosarcoma based on morphologic grounds. In such instances, a negative SATB2 staining may assist in increasing accuracy in the diagnosis of an osteosarcomatous component.

The Effects of Molding Helmet Therapy on Spring-Mediated Cranial Vault Remodeling for Sagittal Craniosynostosis.

There is no clear consensus for the optimal treatment of sagittal craniosynostosis; however, recent studies suggest that improved neurocognitive outcomes may be obtained when surgical intervention imparts active cranial expansion or remodeling and is performed before 6 months of age. The authors consider spring-mediated cranioplasty (SMC) to optimally address these imperatives, and this is an investigation of how helmet orthoses before or after SMC affect aesthetic outcomes.The authors retrospectively evaluated patients treated with SMC and adjunct helmeting for sagittal synostosis. Patients were stratified into 4 cohorts based on helmet usage: preop, postop, both, and neither. The cephalic index (CI) was used to assess head shape changes and outcomes. Twenty-six patients met inclusion criteria: 6 (23%) had preop, 11 (42%) had postop, 4 (15%) had preop and postop, and 5 (19%) had no helmeting. Average age at surgery was 3.6 months. Overall, CI improved from a mean 69.8 to 77.9 during an average 7-month course of care. Mean preoperative change in CI showed greater improvement with preop helmet (1.3) versus not (0.0), (P = 0.029), despite similar initial CI in these cohorts (70.4 and 69.6 respectively, P = 0.69). Nonetheless, all patient cohorts regardless of helmeting status achieved similar final CIs (range 76.4-80.4; P = 0.72).In summary, preoperative molding helmet therapy leads to improved CI at the time of spring-mediated cranioplasty. However, this benefit does not necessarily translate into overall improved CI after surgery and in follow-up, calling into question the benefits of molding helmet therapy in this setting.

Detection of female lower genital tract dysplasia using orally administered 5-aminolevulinic acid induced protoporphyrin IX: a preliminary study.

OBJECTIVE: Previous studies have suggested that 5-aminolevulinic acid (ALA) may be used topically on the cervix to allow optical detection of cervical dysplasia, based on the fluorescence of protoporphyrin IX (PpIX) synthesized in situ from ALA. However, the uniformity of distribution of topically applied PpIX and the sensitivity and specificity of detection are not optimal. The current study was undertaken to demonstrate the feasibility of administering ALA by mouth (po) with the hypothesis that systemic administration might provide a more reliable diagnostic tool. METHODS: Oral ALA was administered to 14 patients with abnormal Pap smears in a dose- and time-intensity design. Institutional review board approval was obtained. A starting dose of 10 mg/kg of po ALA was administered and colposcopy was performed in 3 patients at 1 h, 3 patients at 2 h, 6 patients at 3 h, and 2 patients at 4 h. The study was written with the intent to increase the dose in 10 mg/kg increments if fluorescence was not detected; however, fluorescence was detected at the first dose level. Liver function tests were checked pre and post ALA and follow-up telephone calls were made regarding possible side effects. Both white and blue light colposcopy examinations were performed by two blinded clinicians and biopsies of all abnormal areas were performed. RESULTS: All patients tolerated po ALA well, with no systemic side effects. At the 10 mg/kg dose there was no reported nausea or photosensitivity. Optimal fluorescence was achieved at the 3-h time point, with quenching noted at the 4-h time point. Excellent absorption was documented with fluorescence of the lip demonstrated with Wood's lamp. In some cases fluorescence correlated with dysplasia on biopsy. CONCLUSION: 5-ALA given via the po route and at the dose and time period studied is well tolerated and affords fluorescence of the cervix. Future study is needed to demonstrate the successful identification of dysplastic lesions, with the ultimate goal of treating dysplasia of the lower genital tract with 5-ALA and light therapy.