Use of Race-Specific Equations in Pulmonary Function Tests Impedes Potential Eligibility for Care and Treatment of Pulmonary Fibrosis.

RATIONALE: The use of race-specific reference values to evaluate pulmonary function has long been embedded into clinical practice; however, there is a growing consensus that this practice may be inappropriate and that use of race-neutral equations should be adopted to improve access to healthcare. OBJECTIVES: To evaluate if using race-neutral equations to assess percent predicted forced vital capacity (FVC%pred) impacts eligibility for clinical trials, antifibrotic therapy and referral for lung transplantation in Black, Hispanic/Latino, and White patients with interstitial lung disease (ILD) Methods: FVC%pred values for patients from the Pulmonary Fibrosis Foundation Patient Registry were calculated using race-specific (Hankinson 1999), race-agnostic (Global Lung Function Initiative [GLI]-2012), and race-neutral (GLI-2022 or GLI-Global) equations. Eligibility for ILD clinical trials (FVC%pred >45% and <90%), antifibrotic therapy (FVC%pred >55% and <82%), and lung transplantation referral (FVC%pred <70%) using GLI-2022 and GLI-2012 were compared with that of Hankinson 1999. RESULTS: Baseline characteristics were available for 1882 patients (Black, n=104; Hispanic/Latino, n=103; White, n=1675), and outcomes were evaluated in 1531 patients with FVC%pred within ±90 days of Registry enrollment (Black, n=78; Hispanic/Latino, n=72; White, n=1381). Black patients were younger at consent and more likely to be female than Hispanic/Latino or White patients. Compared with GLI-2022, Hankinson's 1999 criteria misclassified 22% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for ILD clinical trial eligibility; misclassified 21% of Black patients, 17% of Hispanic/Latino patients, and 19% of White patients for antifibrotic therapy eligibility; and misclassified 6% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for lung transplantation referral. Similar trends were observed when comparing GLI-2012 with Hankinson 1999. CONCLUSIONS: Misclassification of patients for critical interventions is highly prevalent when using Hankinson's 1999 criteria and highlights the need to consider adopting the race-neutral GLI-2022 for enhanced accuracy and more equitable representation in pulmonary healthcare. Our results make a compelling case for re-evaluating the use of race as a physiological variable and emphasize the pressing need for continuous innovation to ensure equal and optimal care for all patients, regardless of their race or ethnicity. CLINICAL TRIAL REGISTRATION: NCT02758808 Primary source of funding: This analysis was sponsored by F. Hoffmann-La Roche, Ltd./Genentech, Inc.

Acyl-CoA binding protein is required for lipid droplet degradation in the diatom Phaeodactylum tricornutum.

Diatoms (Bacillariophyceae) accumulate neutral storage lipids in lipid droplets during stress conditions, which can be rapidly degraded and recycled when optimal conditions resume. Since nutrient and light availability fluctuate in marine environments, storage lipid turnover is essential for diatom dominance of marine ecosystems. Diatoms have garnered attention for their potential to provide a sustainable source of omega-3 fatty acids. Several independent proteomic studies of lipid droplets isolated from the model oleaginous pennate diatom Phaeodactylum tricornutum have identified a previously uncharacterized protein with an acyl-CoA binding (ACB) domain, Phatrdraft_48778, here referred to as Phaeodactylum tricornutum acyl-CoA binding protein (PtACBP). We report the phenotypic effects of CRISPR-Cas9 targeted genome editing of PtACBP. ptacbp mutants were defective in lipid droplet and triacylglycerol degradation, as well as lipid and eicosapentaenoic acid synthesis, during recovery from nitrogen starvation. Transcription of genes responsible for peroxisomal ß-oxidation, triacylglycerol lipolysis, and eicosapentaenoic acid synthesis was inhibited. A lipid-binding assay using a synthetic ACB domain from PtACBP indicated preferential binding specificity toward certain polar lipids. PtACBP fused to eGFP displayed an endomembrane-like pattern, which surrounded the periphery of lipid droplets. PtACBP is likely responsible for intracellular acyl transport, affecting cell division, development, photosynthesis, and stress response. A deeper understanding of the molecular mechanisms governing storage lipid turnover will be crucial for developing diatoms and other microalgae as biotechnological cell factories.

PRAME expression in cutaneous melanoma does not correlate with disease-specific survival.

BACKGROUND: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67. METHODS: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index. RESULTS: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64). CONCLUSION: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.

Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients-a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy.

PURPOSE: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed. METHODS: Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. RESULTS: We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028). CONCLUSION: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Association between cervical artery dissection and spinal manipulative therapy -a medicare claims analysis.

BACKGROUND: Cervical artery dissection and subsequent ischemic stroke is the most serious safety concern associated with cervical spinal manipulation. METHODS: We evaluated the association between cervical spinal manipulation and cervical artery dissection among older Medicare beneficiaries in the United States. We employed case-control and case-crossover designs in the analysis of claims data for individuals aged 65+, continuously enrolled in Medicare Part A (covering hospitalizations) and Part B (covering outpatient encounters) for at least two consecutive years during 2007-2015. The primary exposure was cervical spinal manipulation; the secondary exposure was a clinical encounter for evaluation and management for neck pain or headache. We created a 3-level categorical variable, (1) any cervical spinal manipulation, 2) evaluation and management but no cervical spinal manipulation and (3) neither cervical spinal manipulation nor evaluation and management. The primary outcomes were occurrence of cervical artery dissection, either (1) vertebral artery dissection or (2) carotid artery dissection. The cases had a new primary diagnosis on at least one inpatient hospital claim or primary/secondary diagnosis for outpatient claims on at least two separate days. Cases were compared to 3 different control groups: (1) matched population controls having at least one claim in the same year as the case; (2) ischemic stroke controls without cervical artery dissection; and (3) case-crossover analysis comparing cases to themselves in the time period 6-7 months prior to their cervical artery dissection. We made each comparison across three different time frames: up to (1) 7 days; (2) 14 days; and (3) 30 days prior to index event. RESULTS: The odds of cervical spinal manipulation versus evaluation and management did not significantly differ between vertebral artery dissection cases and any of the control groups at any of the timepoints (ORs 0.84 to 1.88; p > 0.05). Results for carotid artery dissection cases were similar. CONCLUSION: Among Medicare beneficiaries aged 65 and older who received cervical spinal manipulation, the risk of cervical artery dissection is no greater than that among control groups.

Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

Water hardness alleviates the stress response caused by waterborne zinc in goldfish Carassius auratus.

In this study, the combined effect of waterborne Zn and water hardness on the stress response in the goldfish Carassius auratus was investigated. Goldfish were exposed to Zn concentrations of 0.5, 1.0, and 3.0 mg/L and water hardness of 90, 270, and 450 mg/L CaCO3 for 1, 3, 7, and 14 d. After exposure, it was determined that higher the Zn concentration, the more obvious the stress response. However, the stress response reduced with increasing water hardness. An increase in the Zn concentration caused stress responses in fish according to the increase in the mRNA expressions of corticotropin-releasing hormone and adrenocorticotropic hormone and cortisol level in the hypothalamus-pituitary-interrenal axis. The expression of these factors was the highest on day 7 and decreased on day 14. Furthermore, to evaluate the stress change in the liver tissue, we analyzed alanine aminotransferase, aspartate aminotransferase, and heat shock protein 70 concentrations to determine the damage caused by Zn and the change in water hardness. Immunohistochemistry staining for Na+/K+-ATPase in the gills showed that the gill activity was inhibited by Zn, and an increase in water hardness could improve Na+/K+-ATPase. In conclusion, we found that increasing water hardness is a successful method to reduce the stress response in goldfish caused by Zn.

Water Hardness Can Reduce the Accumulation and Oxidative Stress of Zinc in Goldfish, Carassius auratus.

We investigated the changes in toxicity stress in goldfish, Carassius auratus, under exposure to different concentrations of Zn and water hardness for 14 days. We analyzed the changes in water hardness and Zn accumulation after exposure. To investigate the stress levels, the expression of metallothionein, caspase-3 activity, NO activity, and total antioxidant capacity were detected. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were also performed to measure apoptosis in the liver. The results showed that compared to the control group, a more significant difference in the accumulation of Zn in body stress markers (metallothionein, caspase-3 activity, NO activity, and total antioxidant capacity) were observed with increasing Zn concentration and exposure time. Notably, at the same Zn concentration and exposure time, lower stress levels were discovered in the samples under harder water conditions. Finally, the TUNEL assay showed that Zn accumulation caused apoptosis and high water hardness could reduce the apoptosis. In conclusion, we found that high water hardness can influence the absorption of Zn, and alleviating the hardness levels can reduce the toxicity stress caused by Zn.

PRAME expression in melanocytic lesions of the nail.

BACKGROUND: Subungual melanoma can be diagnostically challenging. We evaluated the potential of PReferentially expressed Antigen for MElanoma (PRAME) immunoreactivity for differentiating benign from malignant nail melanocytic lesions. METHODS: Sixty cases were identified (10 invasive melanomas, 8 melanomas in situ, 14 nevi, 12 cases of lentigo, and 16 of melanocytic activation). Percentage of PRAME-positive melanocytes was evaluated as follows: 0 no staining, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. A combined score of both percentage and intensity was also evaluated. RESULTS: The difference in PRAME expression between malignant and benign lesions was statistically significant (p < 0.0001). The degree of PRAME expression significantly correlated with patients' age and clinical size. When based on percentage score, 61.1% of melanomas showed a 4+ score, 16.7% showed a 3+ score, 11.1% showed a 1+ score, and 11.1% was negative; 69.0% of the benign lesions was negative, 23.8% showed a 1+ score, 4.8% showed a 2+ score, and 2.4% showed a 4+ score. When the cutoff value for malignancy decreased from 4+ to 3+, the sensitivity increased from 61.1% to 77.8%, while specificity remained 97.6%. Combined score results were similar. CONCLUSIONS: PRAME is a relatively sensitive and highly specific marker in differentiating benign from malignant nail melanocytic lesions. However, correlation with morphology is imperative.

CEO Overconfidence and Corporate Innovation Outcomes: Evidence From China.

This study examines how chief executive officer (CEO) overconfidence can influence the quantity, quality and direction of corporate innovation using Chinese firms for the period 2009-2016. Our results suggest that overall, CEO overconfidence has a positive impact on firm innovation productivity. Furthermore, this effect is significant for Chinese non-SOEs but not for Chinese SOEs. Specifically, an overconfident CEO can facilitate firm innovation in new technological areas but not in the firm's existing areas. Additionally, we find that internal controls can regulate the relationship between CEO overconfidence and innovation. Interestingly, when the internal control level is too high or too low, the correlation between CEO overconfidence and innovation productivity is not significant.

Geriatric All-Terrain Vehicle Trauma: An Unhelmeted and Severely Injured Population.

BACKGROUND: All-terrain vehicle (ATV) use is widespread, however, little is known about injury patterns and outcomes in geriatric patients. We hypothesized that geriatric patients would have distinct and more severe injuries than non-geriatric adults after ATV trauma. METHODS: A retrospective cohort study was performed using the National Trauma Databank comparing non-geriatric (18-64) and geriatric adults (≥65) presenting after ATV trauma at Level 1 and 2 trauma centers from 2011 to 2015. Demographic, admission, and outcomes data were collected, including injury severity score (ISS), abbreviated injury scale (AIS) score, discharge disposition, and mortality. We performed univariate statistical tests between cohorts and multiple logistic regression models to assess for risk factors associated with severe injury (ISS>15) and mortality. RESULTS: 23,568 ATV trauma patients were identified, of whom 1,954 (8.3%) were geriatric. Geriatric patients had higher rates of severe injury(29.2 v 22.5%,p<0.0001), and thoracic (55.2 v 37.8%,p<0.0001) and spine (31.5 v 26.0%,p<0.0001) injuries, but lower rates of abdominal injuries (14.6 v 17.9%,p<0.001) as compared to non-geriatric adults. Geriatric patients had overall lower head injury rates (39.2 v 42.1%,p=0.01), but more severe head injuries (AIS>3) (36.2 vs 30.2%,p<0.001). Helmet use was significantly lower in geriatric patients (12.0 v 22.8%,p<0.0001). On multivariate analysis age increased the odds for both severe injury (OR 1.50, 95% CI 1.31-1.72, p<0.0001) and mortality (OR 5.07, 95% CI 3.42-7.50, p<0.0001). CONCLUSIONS: While severe injury and mortality after ATV trauma occurred in all adults, geriatric adults suffered distinct injury patterns and were at greater risk for severe injury and mortality.

Reducing dermal exposure to agrochemical carcinogens using a fluorescent dye-based intervention among subsistence farmers in rural Honduras.

BACKGROUND: Occupational exposure to agrochemicals, some of which are known or suspected carcinogens, is a major health hazard for subsistence agricultural workers and their families. These impacts are more prevalent in low-and-middle income countries (LMIC) due to weak regulations, lack of awareness of the risks of contamination, predominant use of handheld backpack style spraying equipment, general lack of personal protective equipment (PPE), and low literacy about proper agrochemical application techniques. Reducing exposure to agrochemicals was identified as a paramount concern by rural Hondurans working with a community-engaged research initiative. Fluorescent tracer dyes have been described as a means of visualizing and quantifying dermal exposure to agricultural chemicals, and exposure models adapted for LMIC have been developed previously. Tracer dyes have also been used in educational simulations to promote pesticide safety. However, studies evaluating the effectiveness of these educational dye interventions in reducing future exposure have been lacking. AIM: To evaluate whether observing one's own chemical contamination after applying agrochemicals changed the amount of occupational dermal exposure during a subsequent chemical application. METHODS: We employed a multi-modal community intervention in a rural village in Honduras that incorporated chemical safety education and use of a fluorescent tracer dye during pesticide application on two consecutive occasions, and compared dermal exposure between the intervention group (previous dye experience and safety education, n = 6) and the control group (safety education only, n = 7). RESULTS: Mean total visual score (TVS) of the tracer dye, which accounts for both extent and intensity of whole-body contamination, was lower among those who had previously experienced the dye intervention (mean TVS = 41.3) than among participants who were dye-naïve (mean TVS = 78.4), with a difference between means of -37.10 (95% CI [-66.26, -7.95], p = 0.02). Stratifying by body part, contamination was significantly lower for the anterior left lower extremity and bilateral feet for the dye-experienced group vs. dye-naïve, with most other segments showing a trend toward decreased contamination as well. CONCLUSION: Participants who had previously experienced the dye intervention were significantly less contaminated than the dye-naïve control group during a subsequent spraying event. The findings of this small pilot study suggest that a multi-modal, community-based approach that utilizes fluorescence-augmented contamination for individualized learning (FACIL) may be effective in reducing dermal exposure to carcinogenic agrochemicals among subsistence farmers in Honduras and other LMIC.

Geriatric Snowmobile Trauma: Longer Courses After Similar Injuries.

BACKGROUND: Snowmobiling is a popular activity that leads to geriatric trauma admissions; however, this unique trauma population is not well characterized. We aimed to compare the injury burden and outcomes for geriatric versus nongeriatric adults injured riding snowmobiles. MATERIALS AND METHODS: A retrospective cohort study was performed using the National Trauma Databank comparing nongeriatric (18-64) and geriatric adults (≥65) presenting after snowmobile-related trauma at level 1 and 2 trauma centers from 2011 to 2015. Demographic, admission, injury, and outcome data were collected and compared. A multivariate logistic regression model assessed for risk factors associated with severe injury (Injury Severity Score >15). Analysis was also performed using chi square, analysis of variance, and Kruskal-Wallis testing. RESULTS: A total of 2471 adult patients with snowmobile trauma were identified; 122 (4.9%) were geriatric. Rates of severe injury (Injury Severity Score >15) were similar between groups, 27.5% in geriatric patients and 22.5% in nongeriatric adults (P = 0.2). Geriatric patients experienced higher rates of lower extremity injury (50.4 versus 40.3%, P = 0.03), neck injury (4.1 versus 1.4%, P = 0.02), and severe spine injury (20.6 versus 7.0%, P = 0.004). Geriatric patients had longer hospitalizations (5 versus 3 d, P < 0.0001), rates of discharge to a facility (36.8% versus 12%, P < 0.0001), and higher mortality (4.1 versus 0.6%, P < 0.0001). Geriatric age did not independently increase the risk for severe injury. CONCLUSIONS: Geriatric age was not a significant predictor of severe injury after snowmobile trauma; however, geriatric patients suffered unique injuries, had longer hospitalizations, had higher rates of discharge to a facility, and had higher mortality. Tailored geriatric care may improve outcomes in this unique sport-related trauma population.

Functional divergence of diacylglycerol acyltransferases in the unicellular green alga Haematococcus pluvialis.

Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the final committed step in triacylglycerol biosynthesis in eukaryotes. In microalgae, the copy number of DGAT genes is extraordinarily expanded, yet the functions of many DGATs remain largely unknown. This study revealed that microalgal DGAT can function as a lysophosphatidic acyltransferase (LPAAT) both in vitro and in vivo while losing its original function as DGAT. Among the five DGAT-encoding genes identified and cloned from the green microalga Haematococcus pluvialis, four encoded HpDGATs that showed triacylglycerol synthase activities in yeast functional complementation analyses; the exception was one of the type II DGAT encoding genes, HpDGTT2. The hydrophobic recombinant HpDGTT2 protein was purified in soluble form and was found to function as a LPAAT via enzymatic assay. Introducing this gene into the green microalga Chlamydomonas reinhardtii led to retarded cellular growth, enlarged cell size, and enhanced triacylglycerol accumulation, identical to the phenotypes of transgenic strains overexpressing CrLPAAT. This study provides a framework for dissecting uncharacterized DGATs, and could pave the way to decrypting the structure-function relationship of this large group of enzymes that are critical to lipid biosynthesis.

Aberrant expression of HMB45 and negative PRAME expression in halo nevi.

BACKGROUND: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). METHODS: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. RESULTS: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. CONCLUSION: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.

Geriatric Skiers: Active But Still at Risk, a National Trauma Data Bank Study.

BACKGROUND: Downhill skiing accounts for a large portion of geriatric sport-related trauma. We assessed the national burden of geriatric versus nongeriatric ski trauma. MATERIALS AND METHODS: Adults presenting to level 1/2 trauma centers after ski-associated injuries from 2011 to 2015 were identified from the National Trauma Data Bank by ICD-9 code. We compared demographics, injury patterns, and outcomes between geriatric (age ≥65 y) and nongeriatric adult skiers (age 18-64 y). A multiple regression analysis assessed for risk factors associated with severe injury (Injury Severity Score >15). RESULTS: We identified 3255 adult ski trauma patients, and 16.7% (543) were geriatric. Mean ages for nongeriatric versus geriatric skiers were 40.8 and 72.1 y, respectively. Geriatric skiers more often suffered head (36.7 versus 24.3%, P < 0.0001), severe head (abbreviated injury scale score >3, 49.0 versus 31.5%, P < 0.0001) and thorax injuries (22.2 versus 18.1%, P = 0.03) as compared with nongeriatric skiers. Geriatric skiers were also more often admitted to the ICU (26.5 versus 14.9%, P < 0.0001), discharged to a facility (26.7 versus 11.6%, P < 0.0001), and suffered higher mortality rates (1.3 versus 0.4%, P = 0.004). Independent risk factors for severe injury included being male (OR: 1.68, CI: 1.22-2.31), helmeted (OR: 1.41, CI: 1.07-1.85), and having comorbidities (OR: 1.37, CI: 1.05-1.80). Geriatric age was not independently associated with severe injury. CONCLUSIONS: At level 1/2 trauma centers, geriatric age in ski trauma victims was associated with unique injury patterns, higher acuity, increased rates of facility care at discharge, and higher mortality as compared with nongeriatric skiers. Our findings indicate the need for specialized care after high impact geriatric ski trauma.

Identification and Biotechnical Potential of a Gcn5-Related N-Acetyltransferase Gene in Enhancing Microalgal Biomass and Starch Production.

Microalgae are promising feedstocks for starch production, which are precursors for bioenergy and chemicals manufacturing. Though starch biosynthesis has been intensively studied in the green alga Chlamydomonas reinhardtii, regulatory mechanisms governing starch metabolism in this model species have remained largely unknown to date. We proposed that altering triacylglycerol (TAG) biosynthesis may trigger intrinsic regulatory pathways governing starch metabolism. In accordance with the hypothesis, it was observed in this study that overexpression of the plastidial lysophosphatidic acid acyltransferase gene (i.e. LPAAT1) in C. reinhardtii significantly enhanced TAG biosynthesis under nitrogen (N)-replete conditions, whereas the starch biosynthesis was enhanced in turn under N depletion. By the exploitation of transcriptomics analysis, a putative regulatory gene coding Gcn5-related N-acetyltransferase (GNAT19) was identified, which was up-regulated by 11-12 times in the CrLPAAT1 OE lines. Overexpression of the cloned full-length CrGNAT19 cDNA led to significant increase in the starch content of C. reinhardtii cells grown under both N-replete and N-depleted conditions, which was up to 4 times and 26.7% higher than that of the empty vector control, respectively. Moreover, the biomass yield of the CrGNAT19 OE lines reached 1.5 g L-1 after 2 days under N-depleted conditions, 72% higher than that of the empty vector control (0.87 g L-1). Overall, the yield of starch increased by 118.5% in CrGNAT19 OE lines compared to that of the control. This study revealed the great biotechnical potentials of an unprecedented GNAT19 gene in enhancing microalgal starch and biomass production.

The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).

PURPOSE: To assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: A retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death. RESULTS: Among 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; p<0.001). Risk of death from bladder cancer did not differ significantly by low (cumulative incidence [CIn] 8.4% [95% CI 6.5-10.9) at 5 years) vs. high-intensity surveillance (CIn 9.1% [95% CI 7.4-11.2) at 5 years, p = 0.61). Low vs. high-intensity surveillance was not associated with increased risk of bladder cancer death among patients with Ta (CIn 5.7% vs. 8.2% at 5 years p = 0.24) or T1 disease at diagnosis (CIn 10.2% vs. 9.1% at 5 years, p = 0.58). Among patients with Ta disease, low-intensity surveillance was associated with decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (CIn 19.3% vs. 31.3% at 5 years, p = 0.002). CONCLUSIONS: Patients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC.

Neonatal early onset sepsis in Middle Eastern countries: a systematic review.

BACKGROUND: Early onset neonatal sepsis (EOS) accounts for a significant portion of neonatal mortality, which accounts for 46% of global under five child mortality. OBJECTIVE: This systematic review studies the bacterial aetiology of EOS in the Middle East, susceptibility patterns to recommended empirical antibiotic therapy and whether this differs between high-income and middle-income countries in the region. METHODS: Articles were collected from Medline, Web of Science, the Cochrane Library and Index Medicus for the Eastern Mediterranean Region. The articles included in our systematic review met the following criteria: published after January 2000, data relevant to the Middle East, data specific for early onset sepsis, no language restriction. Data on aetiology and susceptibility were extracted from prospective and retrospective studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. This study focused on EOS but does include data regarding neonatal late-onset sepsis antibiotic susceptibility. The data regarding coagulase-negative Staphylococcus species were excluded from final analysis, as possible contaminants. The protocol for this systematic review was registered on PROSPERO: CRD42017060662. RESULTS: 33 articles from 10 countries were included in the analysis. There were 2215 cases of culture-positive EOS, excluding coagulase-negative Staphylococcus. In middle-income countries, Klebsiella species (26%), Staphylococcus aureus (17%) and Escherichia coli (16%) were the most common pathogens, in contrast to group B Streptococcus (26%), E. coli (24%) and Klebsiella (9%) in high-income countries. Overall susceptibility to ampicillin/gentamicin and third-generation cephalosporin were 40% and 37%, respectively, in middle-income countries versus 93% and 91%, respectively, in high-income countries. CONCLUSIONS: EOS in middle-income countries was more likely to be due to Gram-negative pathogens and less likely to be susceptible to empirical antibiotic therapy. This has important public health implications regarding neonatal mortality in the Middle East region.