The Power of Advocacy in Global Neurosurgery.

Advocacy, one of the five domains of global neurosurgery, represents a powerful avenue to influence public policy to expand access to safe, timely, and affordable neurosurgical care. In this manuscript, we characterize advocacy in global neurosurgery, describe specific neurosurgeon-led initiatives, and delineate how neurosurgeons can become involved in global neurosurgery advocacy efforts. Advocacy in global neurosurgery involves working together in organized neurosurgery with organizations focused on clinical provisions, training, and policy initiatives. Effective advocacy uses a data-driven approach with myriad facilitators, including collaboration and approach strategies for sharing information and a variety of contextual, ideological, and practical barriers. The main action fronts for global neurosurgery include identifying needs, broadening access, and assuring quality. Neurosurgery-led initiatives transforming public policy have occurred on regional and global scales and accelerated since 2019. Folate fortification of staple foods to prevent neural tube defects represents a recent and notably successful area of advocacy and remains in progress. Neurosurgeons who aspire to become involved in advocacy efforts must obtain competencies and skills distinct from, yet complementary to, the traditional neurosurgical training curriculum.

An Efficient Extraction Method Allowing the Genetic Evaluation of Host DNA from Samples Collected for Virus Infection Diagnosis in Viral Transport Medium.

Introduction: During the COVID-19 pandemic, an extraordinary number of nasopharyngeal secretion samples inoculated in viral transport medium (VTM) were collected and analyzed to detect SARS-CoV-2 infection. In addition to viral detection, those samples can also be a source of host genomic material, providing excellent opportunities for biobanking and research. Objective: To describe a simple, in-house-developed DNA extraction method to obtain high yield and quality genomic DNA from VTM samples for host genetic analysis and assess its relative efficiency by comparing its yield and suitability to downstream applications to two different commercial DNA extraction kits. Methods: In this study, 13 VTM samples were processed by two commercial silica-based kits and compared with an in-House-developed protocol for host DNA extraction. An additional 452 samples were processed by the in-House method. The quantity and quality of the differentially extracted DNA samples were assessed by Qubit and spectrophotometric measurements. The suitability of extracted samples for downstream applications was tested by polymerase chain reaction (PCR) amplification followed by amplicon sequencing and allelic discrimination in real-time PCR. Results: The in-House method provided greater median DNA yield (0.81 µg), being significantly different from the PureLink® method (0.14 µg, p < 0.001), but not from the QIAamp® method (0.47 µg, p = 0.980). Overall satisfactory results in DNA concentrations and purity, in addition to cost, were observed using the in-House method, whose samples were able to produce clear amplification in PCR and sequencing reads, as well as effective allelic discrimination in real-time PCR TaqMan® assay. Conclusion: The described in-House method proved to be suitable and economically viable for genomic DNA extraction from VTM samples for biobanking purposes. These results are extremely valuable for the study of the COVID-19 pandemic and other emergent infectious diseases, allowing host genetic studies to be performed in samples initially collected for diagnosis.

La actividad física en la gestión de la obesidad en adultos: una ponencia de Exercise and Sport Science Australia / Physical activity in the management of obesity in adults: A position statement from Exercise and Sport Science Australia / Atividade física no controle da obesidade em adultos: um documento da Exercise and Sport Science Australia

Resumen Esta ponencia examina las evidencias para la actividad física en la pérdida de peso y de adiposidad, la prevención del aumento de peso y la adiposidad, así como la recuperación de peso en adultos, y provee orientación sobre las implicaciones para los profesionales del ejercicio. La evidencia de la investigación indica que se requieren > 150 minutos, pero preferiblemente 300 minutos por semana de actividad aeróbica de intensidad al menos moderada para prevenir el aumento de peso y adiposidad, y al menos el extremo superior de esta gama de actividad para prevenir la recuperación de peso después de la pérdida de peso. Para que la pérdida de peso y adiposidad total sea significativa, se requiere un mínimo de 300 a 400 minutos por semana de actividad aeróbica de intensidad, al menos, moderada. La evidencia en torno al volumen de actividad física aeróbica requerida para reducir la adiposidad central está surgiendo, y las investigaciones apuntan a que puede ser sustancialmente menor que la que se requiere para la pérdida de peso. El impacto de la actividad física de alta intensidad y el ejercicio de resistencia para la gestión del peso es incierto. Durante las consultas para la gestión del peso, los profesionales en ejercicio deben aconsejar que se pueden lograr beneficios para la salud metabólica y cardiovascular por medio de la actividad física a cualquier peso, e independientemente del cambio de peso.

Abstract This Position Statement examines the evidence for physical activity in weight and adiposity loss, prevention of weight and adiposity gain, and in weight regain in adults, and provides guidance on implications for exercise practitioners. Research evidence indicates that >150 min but preferably 300 min per week of aerobic activity of at least moderate intensity is required to prevent weight and adiposity gain, and at least the upper end of this range of activity to prevent weight regain after weight loss. For meaningful weight and total adiposity loss, a minimum of 300-420 min per week of aerobic activity of at least moderate intensity is required. The evidence around the volume of aerobic physical activity required to reduce central adiposity is emerging, and research suggests that it may be substantially less than that required for weight loss. The impact of high-intensity physical activity and resistance exercise for weight management is uncertain. During consultations for weight management, exercise practitioners should advise that metabolic and cardiovascular health benefits can be achieved with physical activity at any weight, and irrespective of weight change.

Resumo Este documento examina as evidências da atividade física na perda de peso e adiposidade, na prevenção do ganho de peso e adiposidade e na recuperação de peso em adultos, e fornece orientações sobre as implicações para os profissionais do exercício físico. As evidências da pesquisa indicam que são necessários mais de 150 minutos, mas preferencialmente 300 minutos por semana de atividade aeróbica de intensidade moderada para evitar o ganho de peso e adiposidade, e pelo menos o extremo superior dessa gama de atividade para evitar o ganho de peso após a perda de peso. É necessário um mínimo de 300 a 400 minutos por semana de atividade aeróbica de intensidade moderada para uma perda significativa de peso e adiposidade total. Estão surgindo evidências sobre a quantidade de atividade física aeróbica necessária para reduzir a adiposidade central, e pesquisas sugerem que ela pode ser substancialmente menor do que a necessária para a perda de peso. O impacto da atividade física de alta intensidade e dos exercícios de resistência no controle de peso é incerto. Durante as consultas de controle de peso, os profissionais do exercício físico devem informar que os benefícios metabólicos e cardiovasculares à saúde podem ser obtidos por meio da atividade física em qualquer peso, independentemente da mudança de peso.

Costs and Consequences of a Novel Emergency Department Sepsis Diagnostic Test: The IntelliSep Index.

Sepsis causes 270,000 deaths and costs $38 billion annually in the United States. Most cases of sepsis present in the emergency department (ED), where rapid diagnosis remains challenging. The IntelliSep Index (ISI) is a novel diagnostic test that analyzes characteristics of WBC structure and provides a reliable early signal for sepsis. This study performs a cost-consequence analysis of the ISI relative to procalcitonin for early sepsis diagnosis in the ED. PERSPECTIVE: U.S. healthcare system. SETTING: Community hospital ED. METHODS: A decision tree analysis was performed comparing ISI with procalcitonin. Model parameters included prevalence of sepsis, sensitivity and specificity of diagnostic tests (both ISI and procalcitonin), costs of hospitalization, and mortality rate stratified by diagnostic test result. Mortality and prevalence of sepsis were estimated from best available literature. Costs were estimated based on an analysis of a large, national discharge dataset, and adjusted to 2018 U.S. dollars. Outcomes included expected costs and survival. RESULTS: Assuming a confirmed sepsis prevalence of 16.9% (adjudicated to Sepsis-3), the ISI strategy had an expected cost per patient of $3,849 and expected survival rate of 95.08%, whereas the procalcitonin strategy had an expected cost of $4,656 per patient and an expected survival of 94.98%. ISI was both less costly and more effective than procalcitonin, primarily because of fewer false-negative results. These results were robust in sensitivity analyses. CONCLUSIONS: ISI was both less costly and more effective in preventing mortality than procalcitonin, primarily because of fewer false-negative results. The ISI may provide health systems with a higher-value diagnostic test in ED sepsis evaluation. Additional work is needed to validate these results in clinical practice.

Is Santaniella a ranunculid? Reassessment of this enigmatic fossil angiosperm from the Lower Cretaceous (Aptian, Crato Konservat-Lagerstätte, Brazil) provides a new interpretation.

PREMISE: The Lower Cretaceous Crato Konservat-Lagerstätte (CKL) preserves a rich flora that includes early angiosperms from northern Gondwana. From this area, the recently described fossil genus Santaniella was interpreted as a ranunculid (presumably Ranunculaceae). However, based on our examination of an additional specimen and a new phylogenetic analysis, we offer an alternative interpretation. METHODS: The new fossil was collected from an active quarry for paving stones in the state of Ceará, northeastern Brazil. We assessed support for alternative phylogenetic hypotheses using a combined analysis of morphological data and DNA sequence data using Bayesian inference. We used a consensus network to visualize the posterior distribution of trees, and we used RoguePlot to illustrate the support for alternative positions on a scaffold tree. RESULTS: The new material includes a flower-like structure not present in the original material and also includes follicles preserved at early stages of development. The flower-like structure is a compact terminal cluster of elliptical sterile laminar organs surrounding internal filamentous structures that occur on flexuous axes. Phylogenetic analyses did not support the fossil placement among eudicots. Instead, Santaniella appears to belong in the magnoliid clade. CONCLUSIONS: The presence of seeds in a marginal-linear placentation and enclosed in a follicle supports the fossil as an angiosperm. However, even though most characters are clearly recognizable, its combination of characters does not provide strong support for a close relationship to any extant order of flowering plants. Its position in the magnoliid clade is intriguing and, based on plicate carpels, it is definitely a mesangiosperm.

The Rise of the Expert Patient in Cancer: From Backseat Passenger to Co-navigator.

PURPOSE: Patients who have cancer have leveraged the Internet to gain a better understanding of their disease and connect across geographic boundaries with others facing the same challenges. Online cancer communities have developed into resources that highlight new research and evolving care pathways. Combined with increasing health literacy and social media, they have enabled some patients to become experts in their cancer. This combination of empowerment and expertise describes the new "e-patients." METHODS: We reviewed the literature to identify key areas where expert e-patients have directly participated in advancing cancer medicine, as well as opportunities available to those who wish to become more involved in research advocacy. RESULTS: E-patients are widely acknowledged as key stakeholders in oncology by clinicians, researchers, cancer centers, government agencies, and nonprofits. Their input is vital for informing cancer care delivery, developing and launching research initiatives, creating care guidelines and pathways, and formulating policy. CONCLUSION: Expert e-patients play an expanded role in their own care and in larger conversations regarding practice, research, and policy. Clinicians can engage e-patients as partners in cancer care as we work together towards improving health care access and outcomes for people with cancer.

Mycobacterium leprae Infection in a Wild Nine-Banded Armadillo, Nuevo León, Mexico.

Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and are implicated in the zoonotic transmission of leprosy in the United States. In Mexico, the existence of such a reservoir remains to be characterized. We describe a wild armadillo infected by M. leprae in the state of Nuevo León, Mexico.

A eudicot leaf from the Lower Cretaceous (Aptian, Araripe Basin) Crato Konservat-Lagerstätte.

PREMISE: The Crato Konservat-Lagerstätte in Brazil preserves an exceptionally rich assemblage of plant macrofossils from the Early Cretaceous (late Aptian), including rare early angiosperm fossils related to Nymphaeales, monocots, and magnoliids, and a variety of angiosperms of uncertain affinities. Macrofossils of eudicot angiosperms have not been described previously, despite the presence of tricolpate pollen. We describe a fossil leaf with morphology characteristic of eudicot angiosperms. METHODS: The fossil was collected from a quarry in the Lower Cretaceous (late Aptian) Crato Formation of northeastern Brazil in the state of Ceará. We compared the leaf architecture with that of ferns, gymnosperms, and similar living and fossil angiosperms. RESULTS: The leaf of Baderadea pinnatissecta gen. et sp. nov. is simple and petiolate, with leaf architecture similar to that of some herbaceous Ranunculales. The blade is 5 cm long and the margin is untoothed and twice pinnately lobed with narrow lobes (pinnatisect). The primary vein framework is pinnate and there are multiple orders of reticulate venation. CONCLUSIONS: The combination of characters preserved in the fossil supports the interpretation that B. pinnatissecta was an herbaceous eudicot similar to some members of Ranunculales and distinguished from other lobate Aptian angiosperms by leaf shape, presence of multiple orders of reticulate venation, and the absence of glandular teeth. The presence of eudicots in the flora of the Crato was already supported by pollen; the discovery of macrofossils like these provides additional information about their morphology and ecological role in low-latitude Early Cretaceous plant communities.

Impact of COVID-19 on Neurosurgery in Brazil's Health System: The Reality of a Developing Country Affected by the Pandemic.

BACKGROUND: The coronavirus disease identified in 2019 (COVID-19) pandemic changed neurosurgery protocols to provide ongoing care for patients while ensuring the safety of health care workers. In Brazil, the rapid spread of the disease led to new challenges in the health system. Neurooncology practice was one of the most affected by the pandemic due to restricted elective procedures and new triage protocols. We aim to characterize the impact of the pandemic on neurosurgery in Brazil. METHODS: We analyzed 112 different types of neurosurgical procedures, with special detail in 11 neurooncology procedures, listed in the Brazilian Hospital Information System records in the DATASUS database between February and July 2019 and the same period in 2020. Linear regression and paired t-test analyses were performed and considered statistically significant at P < 0.05. RESULTS: There was an overall decrease of 21.5% (28,858 cases) in all neurosurgical procedures, impacting patients needing elective procedures (-42.46%) more than emergency surgery (-5.93%). Neurooncology procedures decreased by 14.89%. Nonetheless, the mortality rate during hospitalization increased by 21.26%. Linear regression analysis in hospitalizations (Slope = 0.9912 ± 0.07431; CI [95%] = 0.8231-1.159) and total cost (Slope = 1.03 ± 0.03501; CI [95%] = 0.9511-1.109) in the 11 different types of neurooncology procedures showed a P < 0.0001. The mean cost per type of procedure showed an 11.59% increase (P = 0.0172) between 2019 and 2020. CONCLUSIONS: The COVID-19 pandemic has increased mortality, decreased hospitalizations, and therefore decreased overall costs, despite increased costs per procedure for a variety of neurosurgical procedures. Our study serves as a stark example of the effect of the pandemic on neurosurgical care in settings of limited resources and access to care.

Unraveling the Mechanisms Underlying Irregularities in Inspiratory Rhythm Generation in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder anatomically characterized by a progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). Much less known, yet clinically very important, are the detrimental effects on breathing associated with this disease. Consistent with the human pathophysiology, the 6-hydroxydopamine hydrochloride (6-OHDA) rodent model of PD shows reduced respiratory frequency (fR) and NK1r-immunoreactivity in the pre-Bötzinger complex (preBötC) and PHOX2B+ neurons in the retrotrapezoid nucleus (RTN). To unravel mechanisms that underlie bradypnea in PD, we employed a transgenic approach to label or stimulate specific neuron populations in various respiratory-related brainstem regions. PD mice were characterized by a pronounced decreased number of putatively rhythmically active excitatory neurons in the preBötC and adjacent ventral respiratory column (VRC). Specifically, the number of Dbx1 and Vglut2 neurons was reduced by 47.6% and 17.3%, respectively. By contrast, inhibitory Vgat+ neurons in the VRC, as well as neurons in other respiratory-related brainstem regions, showed relatively minimal or no signs of neuronal loss. Consistent with these anatomic observations, optogenetic experiments identified deficits in respiratory function that were specific to manipulations of excitatory (Dbx1/Vglut2) neurons in the preBötC. We conclude that the decreased number of this critical population of respiratory neurons is an important contributor to the development of irregularities in inspiratory rhythm generation in this mouse model of PD.SIGNIFICANCE STATEMENT We found a decreased number of a specific population of medullary neurons which contributes to breathing abnormalities in a mouse model of Parkinson's disease (PD).

Fossil evidence from South America for the diversification of Cunoniaceae by the earliest Palaeocene.

BACKGROUND AND AIMS: Cunoniaceae are woody plants with a distribution that suggests a complex history of Gondwanan vicariance, long-distance dispersal, diversification and extinction. Only four out of ~27 genera in Cunoniaceae are native to South America today, but the discovery of extinct species from Argentine Patagonia is providing new information about the history of this family in South America. METHODS: We describe fossil flowers collected from early Danian (early Palaeocene, ~64 Mya) deposits of the Salamanca Formation. We compare them with similar flowers from extant and extinct species using published literature and herbarium specimens. We used simultaneous analysis of morphology and available chloroplast DNA sequences (trnL-F, rbcL, matK, trnH-psbA) to determine the probable relationship of these fossils to living Cunoniaceae and the co-occurring fossil species Lacinipetalum spectabilum. KEY RESULTS: Cunoniantha bicarpellata gen. et sp. nov. is the second species of Cunoniaceae to be recognized among the flowers preserved in the Salamanca Formation. Cunoniantha flowers are pentamerous and complete, the anthers contain in situ pollen, and the gynoecium is bicarpellate and syncarpous with two free styles. Phylogenetic analysis indicates that Cunoniantha belongs to crown-group Cunoniaceae among the core Cunoniaceae clade, although it does not have obvious affinity with any tribe. Lacinipetalum spectabilum, also from the Salamanca Formation, belongs to the Cunoniaceae crown group as well, but close to tribe Schizomerieae. CONCLUSIONS: Our findings highlight the importance of West Gondwana in the evolution of Cunoniaceae during the early Palaeogene. The co-occurrence of C. bicarpellata and L. spectabilum, belonging to different clades within Cunoniaceae, indicates that the diversification of crown-group Cunoniaceae was under way by 64 Mya.

Could natural products modulate early inflammatory responses, preventing acute respiratory distress syndrome in COVID-19-confirmed patients?

BACKGROUND: The ARDS (Acute Respiratory Distress Syndrome) is a severe respiratory syndrome that was recently associated as the main death cause in the COVID-19 pandemic outbreak. Hence, in order to prevent ARDS, the pulmonary function maintenance has been the target of several pharmacological approaches. However, there is a lack of reports regarding the use of effective pharmaceutical active natural products (PANPs) for early treatment and prevention of COVID-19-related ARDS. Therefore, the aim of this work was to conduct a systematic review regarding the PANPs that could be further studied as alternatives to prevent ARDS. Consequently, this work can pave the way to spread the use of PANPs on the prevention of ARDS in COVID-19-confirmed or -suspected patients. METHODS: The search strategy included scientific studies published in English from 2015 to 2020 that promoted the elucidation of anti-inflammatory pathways targeting ARDS by in vitro and/or in vivo experiments using PANPs. Then, 74 studies regarding PANPs, able to maintain or improve the pulmonary function, were reported. CONCLUSIONS: The PANPs may present different pulmonary anti-inflammatory pathways, wherein (i) reduction/attenuation of pro-inflammatory cytokines, (ii) increase of the anti-inflammatory mediators' levels, (iii) pulmonary edema inhibition and (iv) attenuation of lung injury were the most observed biological effects of such products in in vitro experiments or in clinical studies. Finally, this work highlighted the PANPs with promising potential to be used on respiratory syndromes, allowing their possible use as alternative treatment at the prevention of ARDS in COVID-19-infected or -suspected patients.

A new species of freshwater mussel in the genus Popenaias Frierson, 1927, from the Gulf coastal rivers of central Mexico (Bivalvia: Unionida: Unionidae) with comments on the genus.

The Gulf coastal drainages of central Mexico are a faunal transition zone between North and South America and harbor a unique assemblage of freshwater mussels (Bivalvia: Unionida). However, little information is available regarding the taxonomy, distribution, and evolutionary history of the Mexican mussel fauna due to limited sampling over the last 100 years. To address these knowledge gaps, we evaluated species-level diversity in the genus Popenaias Frierson, 1927, in Mexican Gulf coastal drainages as part of a larger effort to inform conservation efforts for members of this genus both in Mexico and the United States of America. Based on our analyses, we describe Popenaias berezai n. sp. from the Río Valles of the Río Pánuco basin, San Luis Potosí, Mexico. We also provide presumptive distributional range, phylogenetic structure, and molecular and morphological diagnoses of the new species and provide comments on the other species currently in Popenaias. Our findings highlight the high levels of endemism among freshwater mussels in Mexican Gulf coastal drainages and will help guide impending conservation actions for P. popeii, which is listed as "endangered" in the United States.

Protein Profiling of Extracellular Vesicles Associated With Cisplatin Resistance in Lung Cancer.

BACKGROUND/AIM: Extracellular vesicles (EVs) can mediate drug resistance within the tumor microenvironment by delivering bioactive molecules, including proteins. Here, we performed a comparative proteomic analysis of EVs secreted by A549 lung cancer cells and their cisplatin-resistant counterparts in order to identify proteins involved in drug resistance. MATERIALS AND METHODS: Cells were co-cultivated using a transwell system to evaluate EV exchange. EVs were isolated by ultracentrifugation and analyzed using microscopy and nanoparticle tracking. EV proteome was analyzed by mass spectrometry. RESULTS: EV-mediated communication was observed between co-cultured A549 and A549/CDDP cells. EVs isolated from both cells were mainly exosome-like structures. Extracellular matrix components, cell adhesion proteins, complement factors, histones, proteasome subunits and membrane transporters were found enriched in the EVs released by cisplatin-resistant cells. CONCLUSION: Proteins identified in this work may have a relevant role in modulating the chemosensitivity of the recipient cells and could represent useful biomarkers to monitor cisplatin response in lung cancer.

A Bibliographic Analysis of the Most Cited Articles in Global Neurosurgery.

OBJECTIVE: Global neurosurgery is the practice of neurosurgery with the primary purpose of delivering timely, safe, and affordable neurosurgical care to all who need it. The aim of this study is to identify the most frequently cited articles in global neurosurgery through a bibliographic review to characterize articles and trends around this growing topic. METHODS: The top most-cited articles in global neurosurgery were determined by searching the Web of Science database using a priori search terms. Articles with at least 5 citations were selected, and there were no time period or language restrictions. The data were extracted from each included article and all characteristics were summarized. RESULTS: A total of 932 articles were identified using the search terms; 69 articles fulfilled inclusion criteria and 17 articles were selected that had more than 5 citations. The articles' number of citations ranged from 6 to 98 for the most-cited article. Authors from, or affiliated with, 14 countries contributed to the 17 articles, and the country that had the greatest representation was the United States. The main topic discussed was surgical capacity, the second topic was the treatment of different neurosurgical conditions, and volunteerism was the third topic. CONCLUSIONS: There is currently a deficit in both the amount of literature surrounding the topic of global neurosurgery and how much that literature is cited. Developing innovative ways to increase academic productivity within, or in collaboration with, low-middle income countries is essential to contribute to global neurosurgery.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

OBJECTIVES: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence. STUDY DESIGN: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development. RESULTS: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions. CONCLUSIONS: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental. TRIAL REGISTRATION: clinicaltrials.gov: NCT00747396.

"My Patient Was Diagnosed With Nontargetable Advanced Non-Small Cell Lung Cancer. What Now?" Diagnosis and Initial Treatment Options for Newly Diagnosed Patients With Advanced NSCLC.

Although lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide, the rate at which Americans are dying from lung cancer is declining. Improving survival can be explained, in large part, by a growing understanding of the heterogeneous biology of non-small cell lung cancer (NSCLC) as well as recent successes of novel therapeutic strategies more effective and tolerable than platinum-based chemotherapy. We now recognize distinct subtypes of NSCLC, defined by molecular profiling and immunohistochemistry, with different treatment algorithms, including targeted small molecular inhibitors and immunotherapy for each. Both biomarker selection and preferred frontline strategies continue to evolve rapidly, making it difficult for many practitioners to keep up. In this review, we will first describe the recommended initial workup for a patient with advanced or metastatic NSCLC in 2018; next, we present an algorithm to aid oncologists in the selection of the most appropriate therapy for treatment-naive patients with NSCLC, and finally, we offer a look into future treatment options through a discussion of ongoing clinical trials.

Cruel Carousel: The Grim Grind of "Compassionate" Dialysis.

In this graphic narrative, a clinician illustrates an experience of caring for an undocumented patient suffering from end-stage renal disease (ESRD). Cruel Carousel tells one of the stories that most profoundly shaped the author's own views on health care for undocumented immigrants. Graphic narrative was chosen to tell this story because words alone couldn't capture the patient's experience or the author's distress about what happened to him.

Fossil moonseeds from the Paleogene of West Gondwana (Patagonia, Argentina).

PREMISE OF THE STUDY: The fossil record is critical for testing biogeographic hypotheses. Menispermaceae (moonseeds) are a widespread family with a rich fossil record and alternative hypotheses related to their origin and diversification. The family is well-represented in Cenozoic deposits of the northern hemisphere, but the record in the southern hemisphere is sparse. Filling in the southern record of moonseeds will improve our ability to evaluate alternative biogeographic hypotheses. METHODS: Fossils were collected from the Salamanca (early Paleocene, Danian) and the Huitrera (early Eocene, Ypresian) formations in Chubut Province, Argentina. We photographed them using light microscopy, epifluorescence, and scanning electron microscopy and compared the fossils with similar extant and fossil Menispermaceae using herbarium specimens and published literature. KEY RESULTS: We describe fossil leaves and endocarps attributed to Menispermaceae from Argentinean Patagonia. The leaves are identified to the family, and the endocarps are further identified to the tribe Cissampelideae. The Salamancan endocarp is assigned to the extant genus Stephania. These fossils significantly expand the known range of Menispermaceae in South America, and they include the oldest (ca. 64 Ma) unequivocal evidence of the family worldwide. CONCLUSIONS: Our findings highlight the importance of West Gondwana in the evolution of Menispermaceae during the Paleogene. Currently, the fossil record does not discern between a Laurasian or Gondwanan origin; however, it does demonstrate that Menispermaceae grew well outside the tropics by the early Paleocene. The endocarps' affinity with Cissampelideae suggests that diversification of the family was well underway by the earliest Paleocene.