Phytoplankton optical fingerprint libraries for development of phytoplankton ocean color satellite products.

Phytoplankton respond to physical and hydrographic forcing on time and space scales up to and including those relevant to climate change. Quantifying changes in phytoplankton communities over these scales is essential for predicting ocean food resources, occurrences of harmful algal blooms, and carbon and other elemental cycles, among other predictions. However, one of the best tools for quantifying phytoplankton communities across relevant time and space scales, ocean color sensors, is constrained by its own spectral capabilities and availability of adequately vetted and relevant optical models. To address this later shortcoming, greater than fifty strains of phytoplankton, from a range of taxonomic lineages, geographic locations, and time in culture, alone and in mixtures, were grown to exponential and/or stationary phase for determination of hyperspectral UV-VIS absorption coefficients, multi-angle and multi-spectral backscatter coefficients, volume scattering functions, particle size distributions, pigment content, and fluorescence. The aim of this publication is to share these measurements to expedite their utilization in the development of new optical models for the next generation of ocean color satellites.

Impact of Growth Phase, Pigment Adaptation, and Climate Change Conditions on the Cellular Pigment and Carbon Content of Fifty-One Phytoplankton Isolates.

Owing to their importance in aquatic ecosystems, the demand for models that estimate phytoplankton biomass and community composition in the global ocean has increased over the last decade. Moreover, the impacts of climate change, including elevated carbon dioxide (CO2 ), increased stratification, and warmer sea surface temperatures, will likely shape phytoplankton community composition in the global ocean. Chemotaxonomic methods are useful for modeling phytoplankton community composition from marker pigments normalized to chlorophyll a (Chl a). However, photosynthetic pigments, particularly Chl a, are sensitive to nutrient and light conditions. Cellular carbon is less sensitive, so using carbon biomass instead may provide an alternative approach. To this end, cellular pigment and carbon concentrations were measured in 51 strains of globally relevant, cultured phytoplankton. Pigment-to-Chl a and pigment-to-carbon ratios were computed for each strain. For 25 strains, measurements were taken during two growth phases. While some differences between growth phases were observed, they did not exceed within-class differences. Multiple strains of Amphidinium carterae, Ditylum brightwellii and Heterosigma akashiwo were measured to determine whether time in culture influenced pigment and carbon composition. No appreciable trends in cellular pigment or carbon content were observed. Lastly, the potential impact of climate change conditions on the pigment ratios was assessed using a multistressor experiment that included increased mean light, temperature, and elevated pCO2 on three species: Thalassiosira oceanica, Ostreococcus lucimarinus, and Synechococcus. The largest differences were observed in the pigment-to-carbon ratios, while the marker pigments largely covaried with Chl a. The implications of these observations to chemotaxonomic applications are discussed.

Neurological manifestations as primary presentation of COVID-19 in hospitalized patients.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. METHODS: We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. RESULTS: Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. CONCLUSION: Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

One-step enzymatic modification of RNA 3' termini using polymerase θ.

Site-specific modification of synthetic and cellular RNA such as with specific nucleobases, fluorophores and attachment chemistries is important for a variety of basic and applied research applications. However, simple and efficient methods to modify RNA such as at the 3' terminus with specific nucleobases or nucleotide analogs conjugated to various chemical moieties are lacking. Here, we develop and characterize a one-step enzymatic method to modify RNA 3' termini using recombinant human polymerase theta (Polθ). We demonstrate that Polθ efficiently adds 30-50 2'-deoxyribonucleotides to the 3' terminus of RNA molecules of various lengths and sequences, and extends RNA 3' termini with an assortment of 2'-deoxy and 2',3'-dideoxy ribonucleotide analogs containing functional chemistries, such as high affinity attachment moieties and fluorophores. In contrast to Polθ, terminal deoxynucleotidyl transferase (TdT) is unable to use RNA as a substrate altogether. Overall, Polθ shows a strong preference for adding deoxyribonucleotides to RNA, but can also add ribonucleotides with relatively high efficiency in particular sequence contexts. We anticipate that this unique activity of Polθ will become invaluable for applications requiring 3' terminal modification of RNA and potentially enzymatic synthesis of RNA.

Identification of a Small Interface between the Methyltransferase and RNA Polymerase of NS5 that is Essential for Zika Virus Replication.

The spread of Zika virus (ZIKV) has caused an international health emergency due to its ability to cause microcephaly in infants. Yet, our knowledge of how ZIKV replicates at the molecular level is limited. For example, how the non-structural protein 5 (NS5) performs replication, and in particular whether the N-terminal methytransferase (MTase) domain is essential for the function of the C-terminal RNA-dependent RNA polymerase (RdRp) remains unclear. In contrast to previous reports, we find that MTase is absolutely essential for all activities of RdRp in vitro. For instance, the MTase domain confers stability onto the RdRp elongation complex (EC) and and is required for de novo RNA synthesis and nucleotide incorporation by RdRp. Finally, structure function analyses identify key conserved residues at the MTase-RdRp interface that specifically activate RdRp elongation and are essential for ZIKV replication in Huh-7.5 cells. These data demonstrate the requirement for the MTase-RdRp interface in ZIKV replication and identify a specific site within this region as a potential site for therapeutic development.

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis.

Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis.

Evaluating the Change in Medical Marijuana Dispensary Locations in Los Angeles Following the Passage of Local Legislation.

In May 2013, Los Angeles voters approved Proposition D, a regulatory measure that set zoning restrictions and capped the number of dispensaries at those that opened before 2007. Specifically, Proposition D stated that only 135 dispensaries were allowed to be in operation and set zoning restrictions prohibiting dispensaries from operating in certain areas. We first assessed whether the legislation changed the physical availability of medical marijuana via dispensaries in Los Angeles. We then used two data points 1 year prior to and 1 year following the implementation of Proposition D to determine if the locations of where the dispensaries are located changed after the enactment of Proposition D. Using a cross-sectional, ecological design, we investigated the change in dispensaries from 2012 to 2014 for Census tracts within the city of Los Angeles (N = 1000). We analyzed data using spatial error regression models that included controls for spatial autocorrelation due to the spatial structure of the data. We found that while the total number of dispensaries in Los Angeles remained largely unchanged, the spatial distribution of dispensaries did change in meaningful ways. Census tracts with more dispensaries in 2014 were significantly and positively associated with the proportion of African American residents and negatively associated with the percent of area that was commercially zoned. In other words, dispensaries opened in areas with a higher proportion of Black residents and closed in Census tract areas that had a higher percentage of commercially zoned land. Findings from this study highlight the importance of continuously regulating dispensary locations. Results suggest that likely as a result of changing regulations, dispensaries may be attempting to conceal their presence and locate in areas that will not advocate against their presence.

An Alternative to Residential Neighborhoods: An Exploratory Study of how Activity Spaces and Perception of Neighborhood Social Processes relate to Maladaptive Parenting.

BACKGROUND: The environments where parents spend time, such as at work, at their child's school, or with friends and family, may exert a greater influence on their parenting behaviors than the residential neighborhoods where they live. These environments, termed activity spaces, provide individualized information about the where parents go, offering a more detailed understanding of the environmental risks and resources to which parents are exposed. OBJECTIVE: This study conducts a preliminary examination of how neighborhood context, social processes, and individual activity spaces are related to a variety of parenting practices. METHODS: Data were collected from 42 parents via door-to-door surveys in one neighborhood area. Survey participants provided information about punitive and non-punitive parenting practices, the locations where they conducted daily living activities, social supports, and neighborhood social processes. OLS regression procedures were used to examine covariates related to the size of parent activity spaces. Negative binomial models assessed how activity spaces were related to four punitive and five non-punitive parenting practices. RESULTS: With regards to size of parents' activity spaces, male caregivers and those with a local (within neighborhood) primary support member had larger activity spaces. Size of a parent's activity space is negatively related to use of punitive parenting, but generally not related to non-punitive parenting behaviors. CONCLUSIONS: These findings suggest social workers should assess where parents spend their time and get socially isolated parents involved in activities that could result in less use of punitive parenting.

Assessing Sample Bias among Venue-Based Respondents at Medical Marijuana Dispensaries.

Venue-based sampling is the identification of, and outreach to, locations visited by the population of interest for the purpose of collecting data. The method is frequently used to reach specific populations, commonly referred to as "hidden populations." Medical marijuana users represent a hidden population of persons who use marijuana for medicinal purposes. We examine whether venue-based procedures introduce selection or non-respondent bias into the study. The venue based sampling procedures employed for the UCLA Medical Marijuana Study used a two-stage, venue-based sampling approach. First, analyses were conducted to assess potential bias within dispensaries that agreed to participate in the surveys. Secondly, analyses were conducted to examine differences among patrons who responded to surveys. Overall, selection bias was generally absent among study results. Results also illuminated the minimal respondent bias observed among the survey respondents. Results suggest that the use of dispensaries to access and survey medical marijuana users is a viable option to gather patient information that adequately represents the greater population of medical marijuana users in Los Angeles. Thus, recommendations and conclusions based on findings from venue-based studies of medical marijuana users at dispensary sites serve to impartially inform meaningful research.

Examining the locations of medical marijuana dispensaries in Los Angeles.

INTRODUCTION AND AIMS: Little is known about the spatial distribution of medical marijuana dispensaries, particularly whether or not sites are disproportionately located in minority or communities with younger populations. This paper will assess if there is a relationship between medical marijuana dispensaries and neighbourhood characteristics. DESIGN AND METHODS: This study used an ecological, cross-sectional design of 1000 census tracts from Los Angeles city in 2012 to explore the relationship between neighbourhood sociodemographics, structural features of neighbourhoods and density of medical marijuana dispensaries. Locations of dispensaries were obtained through a premise survey of all listed dispensaries. Data on neighbourhood characteristics were obtained from Geolytics. The study used Bayesian conditionally autoregressive models that include controls for spatial heterogeneity to analyse the data. RESULTS: Findings show that dispensaries are located in areas that allow for commercial establishments. Results indicate a positive relationship between dispensaries and percent commercially zoned, areas with highway ramp access, density of on- and off-premise alcohol outlets and percent Hispanic residents. DISCUSSION AND CONCLUSIONS: In sum, the findings suggest that, likely because of zoning regulations, dispensaries were located in primarily commercially zoned areas with greater road access (as measured by the presence of highway ramps). Given that areas with higher densities of dispensaries also have higher densities of alcohol outlets, future work should examine how this co-location affects neighbourhood problems such as crime and violence. [Thomas C, Freisthler B. Examining the locations of medical marijuana dispensaries in Los Angeles. Drug Alcohol Rev 2016;35:334-337].

Robotic-assisted resection of an intrapericardial bronchogenic cyst.

The advantages of robotic-assisted surgery have been well described and include improved three-dimensional visualization, increased precision of dissection, and the absence of tremor. These characteristics are particularly useful in the mediastinal dissection of major vascular structures. We present a case of an intrapericardial bronchogenic cyst resected with robotic assistance. Bronchogenic cysts are congenital thoracic anomalies that typically occur in the mediastinum or lung parenchyma, and occasionally within the pericardium. Historically a sternotomy was required for complete resection, although a thoracoscopic approach has now been widely adopted. We report the resection of an intrapericardial bronchogenic cyst utilizing a robotic-assisted thoracoscopic approach and a review of the literature regarding the incidence, diagnosis, and management of this rare condition.

Granular cell atypical fibroxanthoma: case report and review of the literature.

We present a case of granular cell atypical fibroxanthoma of the scalp. The neoplasm occurred as a tender nodule on the frontal scalp of an 82-year-old Caucasian man. Histology demonstrated a diffuse proliferation of atypical epithelioid cells with abundant granular cytoplasm. Many of the cells had large irregular nuclei and atypical mitotic figures were present. Immunohistochemical stains were positive for CD68 and procollagen 1 and negative for cytokeratin, HMB-45 and S-100 protein. The granular cell phenotype has been observed in other cutaneous neoplasms including granular cell tumors, dermatofibromas, dermatofibrosarcoma protuberans, fibrous papules, basal cell carcinomas, leiomyosarcomas, angiosarcomas and primitive polypoid granular cell tumors. We discuss the differential diagnosis and review the previously reported cases of this rare variant of atypical fibroxanthoma.

Cytophagic and S-100 protein immunoreactive myeloid leukemia cutis.

Myeloid leukemia cutis (LC) is the cutaneous involvement by neoplastic leukocytes of the myeloid series. Myeloid LC may occur de novo or concurrently with acute myeloid leukemias, chronic myeloid leukemias, other myeloproliferative disorders or myelodysplastic syndromes. We describe an unusual case of cytophagic S-100 protein immunoreactive leukemia cutis presenting in an 87-year-old woman without prior history of myeloid leukemia or other hematologic disorders. We outline key histologic and immunohistochemical features that aide in the diagnosis of LC. The presence of cytophagocytosis on histologic examination, a phenomenon more commonly associated with lymphoid rather than myeloid malignancies, provided a clue to the possibility of a malignant process. The atypical myeloid infiltrate showed S-100 protein positivity, an unusual finding that may be seen in LC. Although not commonly reported in LC, the presence of S-100 protein positivity and cytophagocytosis should not lead to the premature exclusion of LC as a possible diagnosis until a thorough clinical, histologic and immunohistochemical evaluation is performed. In addition, the presence of cytophagocytosis has been shown to have prognostic significance for patients with myeloid leukemia.

Cutaneous malignant peripheral nerve sheath tumors.

Cutaneous malignant peripheral nerve sheath tumors (MPNSTs) are rare entities compared with their deep soft tissue counterparts. We describe two cases of cutaneous MPNSTs. The first case, occurring in a 27-year-old woman with neurofibromatosis I, presented with recent growth of a pre-existing nodule on her back. A biopsy showed a densely cellular area within a conventional neurofibroma composed of atypical, hyperchromatic epithelioid and spindled cells with frequent mitotic figures (MFs). The second case presented in an 88-year-old man with no stigmata of neurofibromatosis as a rapidly growing subcutaneous tumor of the right calf. A biopsy showed a diffuse neurofibroma that abruptly transitioned to a densely cellular proliferation of hyperchromatic atypical spindled cells arranged in short fascicles with frequent MFs. The diagnosis of MPNST was rendered in both cases. MPNSTs of the dermis and subcutis are rare sarcomas. They can occur as sporadic tumors or in the setting of neurofibromatosis. They are often associated with pre-existing neurofibromas. Increase in size of pre-existing neurofibromas is an indication for biopsy. Recognition of the cellular atypia, increased cellularity and mitotic activity is key to the diagnosis.

Adult-derived stem cells and their potential for use in tissue repair and molecular medicine.

This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast-like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6-hydroxydopamine-lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult-derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.

The cost of psoriasis therapies: considerations for therapy selection.

PURPOSE: The purpose of this article is to provide a review of the cost of psoriasis therapies from two sources as well as compare the average wholesale price (AWP), as listed in the 2003 Drug Topics Red Book to that of a popular Internet pharmacy. METHODS: Prices of therapies were obtained two ways: the AWP was recorded from the 2003 Drug Topics Red Book. A range and average price per gram (or mL) were calculated based on the smallest size or quantity available. In addition, a price comparison was made to values as they were reported online at drugstore.com. Monthly cost estimates were based on average systemic dosing and for topicals, 18 g/month (for 1% body surface area [BSA] involvement). RESULTS: The prices of psoriatic treatment medications vary considerably--from the relatively inexpensive topical corticosteroids to the more costly biologic therapies. In the category of corticosteroids, a trend was evident between the overall price per gram of each class and the potency of each class. Class I and VI corticosteroids had an average price per gram (or mL) of dollars 2.08 (dollars 37/month/1% BSA) and dollars 0.86 (dollars 15/month/1% BSA), respectively. Nonsteroidal topical treatments had an average price per gram (or mL) dollars 2.18 (dollars 39/month/1% BSA). Systemic therapies have a wide range of costs. The total monthly expense, based on estimated average dosing, was calculated for methotrexate, acitretin, and cyclosporine and were dollars 78.60, dollars 400.50, and dollars 735.00, respectively. Biologic therapies designed for continuous use cost roughly dollars 1,300/month. DISCUSSION: There are numerous treatment options for psoriasis with a wide range of costs. In addition to significant challenges from a scientific perspective, psoriasis treatment is further complicated by the cost of the numerous medications. Prices reported in the AWP were similar in many instances to those listed at an Internet pharmacy. Many considerations should go into therapy selection for psoriasis and a comprehensive approach that includes cost will likely provide the best patient care.