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The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of Toxoplasma relies on its swift dissemination to the central nervous system through a 'Trojan Horse' mechanism using infected leukocytes as carriers. Previous work found TgWIP, a protein secreted from Toxoplasma, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with Toxoplasma exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with Toxoplasma expressing a mutant TgWIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a TgWIP-Shp1/2 dependent manner. Collectively, the data uncover a molecular mechanism by which TgWIP modulates the migration dynamics of infected DCs in vitro.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

The glassy-winged sharpshooter, Homalodisca vitripennis Germar, is an invasive xylem-feeding leafhopper with a devastating economic impact on California agriculture through transmission of the plant pathogen, Xylella fastidiosa. While studies have focused on X. fastidiosa or known symbionts of H. vitripennis, little work has been done at the scale of the microbiome (the bacterial community) or mycobiome (the fungal community). Here, we characterize the mycobiome and the microbiome of H. vitripennis across Southern California and explore correlations with captivity and host insecticide resistance status. Using high-throughput sequencing of the ribosomal internal transcribed spacer 1 region and the 16S rRNA gene to profile the mycobiome and microbiome, respectively, we found that while the H. vitripennis mycobiome significantly varied across Southern California, the microbiome did not. We also observed a significant difference in both the mycobiome and microbiome between captive and wild H. vitripennis. Finally, we found that the mycobiome, but not the microbiome, was correlated with insecticide resistance status in wild H. vitripennis. This study serves as a foundational look at the H. vitripennis mycobiome and microbiome across Southern California. Future work should explore the putative link between microbes and insecticide resistance status and investigate whether microbial communities should be considered in H. vitripennis management practices. IMPORTANCE The glassy-winged sharpshooter is an invasive leafhopper that feeds on the xylem of plants and transmits the devastating pathogen, Xylella fastidiosa, resulting in significant economic damage to California's agricultural system. While studies have focused on this pathogen or obligate symbionts of the glassy-winged sharpshooter, there is limited knowledge of the bacterial and fungal communities that make up its microbiome and mycobiome. To address this knowledge gap, we explored the composition of the mycobiome and the microbiome of the glassy-winged sharpshooter across Southern California and identified differences associated with geography, captivity, and host insecticide resistance status. Understanding sources of variation in the microbial communities associated with the glassy-winged sharpshooter is an important consideration for developing management strategies to control this invasive insect. This study is a first step toward understanding the role microbes may play in the glassy-winged sharpshooter's resistance to insecticides.

Persian walnut is a drought-sensitive species with considerable genetic variation in the photosynthesis and water use efficiency of its populations, which is largely unexplored. Here, we aimed to elucidate changes in the efficiency of photosynthesis and water content using a diverse panel of 60 walnut families which were submitted to a progressive drought for 24 days, followed by two weeks of re-watering. Severe water-withholding reduced leaf relative water content (RWC) by 20%, net photosynthetic rate (Pn) by 50%, stomatal conductance (gs) by 60%, intercellular CO2 concentration (Ci) by 30%, and transpiration rate (Tr) by 50%, but improved water use efficiency (WUE) by 25%. Severe water-withholding also inhibited photosystem II functionality as indicated by reduced quantum yield of intersystem electron transport (φEo) and transfer of electrons per reaction center (ET0/RC), also enhanced accumulation of QA (VJ) resulted in the reduction of the photosynthetic performance (PIABS) and maximal quantum yield of PSII (FV/FM); while elevated quantum yield of energy dissipation (φDo), energy fluxes for absorption (ABS/RC) and dissipated energy flux (DI0/RC) in walnut families. Cluster analysis classified families into three main groups (tolerant, moderately tolerant, and sensitive), with the tolerant group from dry climates exhibiting lesser alterations in assessed parameters than the other groups. Multivariate analysis of phenotypic data demonstrated that RWC and biophysical parameters related to the chlorophyll fluorescence such as FV/FM, φEo, φDo, PIABS, ABS/RC, ET0/RC, and DI0/RC represent fast, robust and non-destructive biomarkers for walnut performance under drought stress. Finally, phenotype-environment association analysis showed significant correlation of some photosynthetic traits with geoclimatic factors, suggesting a key role of climate and geography in the adaptation of walnut to its habitat conditions.

Objective- To identify and assess whether three major risk factors that due to differential access to flexible resources might help explain disparities in the spread of COVID-19 across communities with different socioeconomic status, including socioeconomic inequalities in social distancing, the potential risk of interpersonal interactions, and access to testing.MethodsAnalysis uses ZIP code level weekly COVID-19 new cases, weekly population movement flows, weekly close-contact index, and weekly COVID-19 testing sites in Southern California from March 2020 to April 2021, merged with the U.S. census data to measure ZIP code level socioeconomic status and cofounders. This study first develops the measures for social distancing, the potential risk of interactions, and access to testing. Then we employ a spatial lag regression model to quantify the contributions of those factors to weekly COVID-19 case growth.ResultsResults identify that, during the first COVID-19 wave, new case growth of the low-income group is two times higher than that of the high-income group. The COVID-19 case disparity widens to four times in the second COVID-19 wave. We also observed significant disparities in social distancing, the potential risk of interactions, and access to testing among communities with different socioeconomic status. In addition, all of them contribute to the disparities of COVID-19 incidences. Among them, the potential risk of interactions is the most important contributor, whereas testing accessibility contributes least. We also found that close-contact is a more effective measure of social distancing than population movements in examining the spread of COVID-19.Conclusion- This study answers critically unaddressed questions about health disparities in the spread of COVID-19 by assessing factors that might explain why the spread is different in different groups.

Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the DMD gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs. The adeno-associated virus (AAV) vector is the leading gene delivery system for addressing genetic neuromuscular diseases. Since the gene encoding the full-length dystrophin protein exceeds the packaging capacity of a single AAV vector, gene replacement therapy based on AAV-delivery of shortened, yet, functional microdystrophin genes has emerged as a promising treatment. This article seeks to explain the rationale for use of the accelerated approval pathway to advance AAV microdystrophin gene therapy for DMD. Specifically, we provide support for the use of microdystrophin expression as a surrogate endpoint that could be used in clinical trials to support accelerated approval.

We describe a rare case of acute mania in the setting of autoimmune adrenalitis. A 41-year-old male with no previous psychiatric diagnoses presented with impulsivity, grandiosity, delusions of telepathy, and hyperreligiosity following a previous hospitalization for an acute adrenal crisis and 2 subsequent days of low-dose corticosteroid treatment. Workups for encephalopathy and lupus cerebritis were negative, raising concern that this presentation might represent steroid-induced psychosis. However, discontinuation of corticosteroids for 5 days did not resolve the patient's manic episode, suggesting that his clinical presentation was more likely new onset of a primary mood disorder or a psychiatric manifestation of adrenal insufficiency itself. The decision was made to restart corticosteroid treatment for the patient's primary adrenal insufficiency (formerly known as Addison disease), coupled with administration of both risperidone and valproate for mania and psychosis. Over the following 2 weeks, the patient's manic symptoms resolved, and he was discharged home. His final diagnosis was acute mania secondary to autoimmune adrenalitis. Although acute mania in adrenal insufficiency is quite rare, clinicians should be aware of the range of psychiatric manifestations associated with Addison disease so that they can pursue the optimal course of both medical and psychiatric treatment for these patients.

SN 2018aoz is a Type Ia SN with a B-band plateau and excess emission in infant-phase light curves ≲1 day after the first light, evidencing an over-density of surface iron-peak elements as shown in our previous study. Here, we advance the constraints on the nature and origin of SN 2018aoz based on its evolution until the nebular phase. Near-peak spectroscopic features show that the SN is intermediate between two subtypes of normal Type Ia: core normal and broad line. The excess emission may be attributable to the radioactive decay of surface iron-peak elements as well as the interaction of ejecta with either the binary companion or a small torus of circumstellar material. Nebular-phase limits on Hα and He i favor a white dwarf companion, consistent with the small companion size constrained by the low early SN luminosity, while the absence of [O i] and He i disfavors a violent merger of the progenitor. Of the two main explosion mechanisms proposed to explain the distribution of surface iron-peak elements in SN 2018aoz, the asymmetric Chandrasekhar-mass explosion is less consistent with the progenitor constraints and the observed blueshifts of nebular-phase [Fe ii] and [Ni ii]. The helium-shell double-detonation explosion is compatible with the observed lack of C spectral features, but current 1D models are incompatible with the infant-phase excess emission, B max - V max color, and weak strength of nebular-phase [Ca ii]. Although the explosion processes of SN 2018aoz still need to be more precisely understood, the same processes could produce a significant fraction of Type Ia SNe that appear to be normal after ∼1 day.

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

The glassy-winged sharpshooter, Homalodisca vitripennis Germar, is an invasive xylem-feeding leafhopper with a devastating economic impact on California agriculture through transmission of the plant pathogen, Xylella fastidiosa . While studies have focused on X. fastidiosa or known symbionts of H. vitripennis , little work has been done at the scale of the microbiome (the bacterial community) or mycobiome (the fungal community). Here we characterize the mycobiome and the microbiome of H. vitripennis across Southern California and explore correlations with captivity and host insecticide-resistance status. Using high-throughput sequencing of the ribosomal internal transcribed spacer (ITS1) region and the 16S rRNA gene to profile the mycobiome and microbiome, respectively, we found that while the H. vitripennis mycobiome significantly varied across Southern California, the microbiome did not. We also observed a significant difference in both the mycobiome and microbiome between captive and wild H. vitripennis . Finally, we found that the mycobiome, but not the microbiome, was correlated with insecticide-resistance status in wild H. vitripennis . This study serves as a foundational look at the H. vitripennis mycobiome and microbiome across Southern California. Future work should explore the putative link between microbes and insecticide-resistance status and investigate whether microbial communities should be considered in H. vitripennis management practices.

PurposePrimary spinal infections (PSIs) are a group of infectious diseases characterized by inflammation of the end plate-disk unit or its surroundings. PSI is considered more prevalent and aggressive among patients with chronic immunocompromised states. Association of PSIs, immunocompromising cancers, and hemoglobinopathies has not been systematically analyzed. We conducted a systematic review to study characteristics, clinical presentation, and mortality of patients with PSI in the setting of hematologic disease.MethodsA systematic literature search in PubMed, Web of Science, and Scopus was conducted in April 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included retrospective case series and individual case reports.ResultsOn careful review, 28 articles published between 1970 and 2022 were selected. These studies featured 29 patients who met inclusion criteria (mean age 29 years, age range 1.5 to 67 years; 63.3% male). Lumbar infection was the most common location (65.5%), with Salmonella (24.1%) as the main causative microorganism. Neurologic compromise was present in 41% of patients, and surgical intervention occurred in 48.3%. Average antibiotic duration was 13 weeks. The postoperative complication rate was 21.4%, with a mortality of 6.9%.ConclusionPSI in patients with hematologic disease, while having shorter periods to diagnosis, presents increased rates of neurologic deficit, surgical intervention, and complications.

BackgroundChronic back pain (CBP) is a condition that places a considerable burden on society, with several million people affected in the United States alone. Treatment options to address this problem and relieve CBP are constantly evolving, and one of the most promising treatment modalities for CBP that is refractory to conservative treatment options is endoscopic rhizotomy (ER).MethodsA thorough search of the PubMed (MEDLINE) database was conducted to assess the full progression of ER from its earliest uses to present day in a historical narrative review of ER, with treatment of facetogenic pain as a model pathology.ResultsER allows for direct visualization and ablation of sensory branches of the dorsal ramus to provide pain relief in up to 80% of patients faced with refractory CBP. This technique has been built upon since the early 20th century, and the novel endoscopic approach continues to gain popularity among physicians. Benefits of ER include superior postoperative median pain-free duration compared with traditional percutaneous radiofrequency ablation, as well as direct visualization of regional anatomy. Patient selection criteria for the procedure and a modest list of contraindications allow the use of ER as a viable treatment option for a significant population of patients suffering from CBP. Potential barriers to ER include high cost of the procedure, longer intraoperative time, and expensive proprietary equipment.ConclusionsER is an effective treatment for refractory CBP with notable advantages. As the technology and popularity of this procedure progress, improvements in the cost, training, and intraoperative time may make it a favorable alternative to the current standard of care.

ObjectiveFew prospective studies have assessed whether individuals with subclinical thyroid dysfunction are more likely to develop diabetes, with conflicting results. In this study, we conducted a systematic review of the literature and an individual participant data analysis of multiple prospective cohorts to investigate the association between subclinical thyroid dysfunction and incident diabetes.MethodsWe performed a systematic review of the literature in Medline, Embase, and the Cochrane Library from inception to February 11, 2022. A two-stage individual participant data analysis was conducted to compare participants with subclinical hypothyroidism and subclinical hyperthyroidism vs euthyroidism at baseline and the adjusted risk of developing diabetes at follow-up.ResultsAmong 61 178 adults from 18 studies, 49% were females, mean age was 58 years, and mean follow-up time was 8.2 years. At the last available follow-up, there was no association between subclinical hypothyroidism and incidence of diabetes (odds ratio (OR) = 1.02, 95% CI: 0.88-1.17, I2 = 0%) or subclinical hyperthyroidism and incidence of diabetes (OR = 1.03, 95% CI: 0.82-1.30, I2 = 0%), in age- and sex-adjusted analyses. Time-to-event analysis showed similar results (hazard ratio for subclinical hypothyroidism: 0.98, 95% CI: 0.87-1.11; hazard ratio for subclinical hyperthyroidism: 1.07, 95% CI: 0.88-1.29). The results were robust in all sub-group and sensitivity analyses.ConclusionsThis is the largest systematic review and individual participant data analysis to date investigating the prospective association between subclinical thyroid dysfunction and diabetes. We did not find an association between subclinical thyroid dysfunction and incident diabetes. Our results do not support screening patients with subclinical thyroid dysfunction for diabetes.Significance statementEvidence is conflicting regarding whether an association exists between subclinical thyroid dysfunction and incident diabetes. We therefore aimed to investigate whether individuals with subclinical thyroid dysfunction are more prone to develop diabetes in the long run as compared to euthyroid individuals. We included data from 18 international cohort studies with 61 178 adults and a mean follow-up time of 8.2 years. We did not find an association between subclinical hypothyroidism or subclinical hyperthyroidism at baseline and incident diabetes at follow-up. Our results have clinical implications as they neither support screening patients with subclinical thyroid dysfunction for diabetes nor treating them in the hope of preventing diabetes in the future.

Similar to other cropping systems, few walnut cultivars are used as scion in commercial production. Germplasm collections can be used to diversify cultivar options and hold potential for improving crop productivity, disease resistance and stress tolerance. In this study, we explored the anatomical and biochemical bases of photosynthetic capacity and response to water stress in 11 Juglans regia accessions in the U.S. department of agriculture, agricultural research service (USDA-ARS) National Clonal Germplasm. Net assimilation rate (An ) differed significantly among accessions and was greater in lower latitudes coincident with higher stomatal and mesophyll conductances, leaf thickness, mesophyll porosity, gas-phase diffusion, leaf nitrogen and lower leaf mass and stomatal density. High CO2 -saturated assimilation rates led to increases in An under diffusional and biochemical limitations. Greater An was found in lower-latitude accessions native to climates with more frost-free days, greater precipitation seasonality and lower temperature seasonality. As expected, water stress consistently impaired photosynthesis with the highest % reductions in lower-latitude accessions (A3, A5 and A9), which had the highest An under well-watered conditions. However, An for A3 and A5 remained among the highest under dehydration. J. regia accessions, which have leaf structural traits and biochemistry that enhance photosynthesis, could be used as commercial scions or breeding parents to enhance productivity.

BackgroundAs evidence continues to accumulate regarding the multi-organ dysfunction associated with Parkinson's disease (PD), it is still unclear as to whether PD increases the risk of hematological pathology. In this study, the authors investigate the association between PD and hematological pathology risk factors.MethodsThis retrospective cohort analysis was conducted using 8 years of the National Readmission Database. All individuals diagnosed with PD were queried at the time of primary admission. Readmissions, complications, and risk factors were analyzed at 30-, 90-, 180-, and 300-day intervals. Statistical analysis included multivariate Gaussian-fitted modeling using age, sex, comorbidities, and discharge weights as covariates. Coefficients of model variables were exponentiated and interpreted as odds ratios.ResultsThe database query yielded 1,765,800 PD patients (mean age: 76.3 ± 10.4; 44.1% female). Rates of percutaneous blood transfusion in readmitted patients at 30, 90, 180, and 300 days were found to be 8.7%, 8.6%, 8.3%, and 8.3% respectively. Those with anti-parkinsonism medication side effects at the primary admission had increased rates of gastrointestinal (GI) hemorrhage (OR: 1.02; 95%CI: 1.01-1.03, p

Introduction and importanceDegenerative lumbar scoliosis is a prominent cause of adult spinal deformity with an increasing prevalence as the population ages. This pathology is associated with debilitating symptoms, including radicular back pain and lower extremity claudication. Surgical realignment of the spine and restoration of sagittal imbalance can reduce low back pain. Chronic sacroiliac dysfunction commonly causes low back radicular pain. We present a complicated case where stereotactic navigation facilitated an extensive fusion and decompression procedure for adult spinal deformity in an obese patient with multiple prior surgeries for scoliosis and sacroiliac joint pathology.Case presentationA 69-year-old, obese female with scoliosis refractory to multiple interventions presented with severe, radicular lower back pain. On examination of the right lower extremity (RLE), she had mild weakness (3/5 strength) and reduced sensation to light touch over its anterolateral aspect (dermatome L4). She was unable to perform single leg stance or tandem walk. Imaging revealed moderate mid-lumbar levoscoliosis, severe degenerative disc disease and facet hypertrophy changes in the setting of prior multilevel lumbar fusion, and consecutive nerve root impingement between L1 and L5 (worst at L3-4). DEXA scan was consistent with osteoporosis. The patient underwent lumbar laminectomy with posterior fusion of T10-ilium, transforaminal lumbar interbody fusion, osteotomy, and decompression using stereotactic navigation. The presence of SI titanium dowels from her previous SI fusion procedure posed a challenge with respect to achieving pelvic fixation.Clinical discussionIliac screw placement is a critical adjunctive to lumbosacral fusion, notably for prevention of pseudoarthrosis; however, patients with prior SI fusion may present a biomechanical challenge to surgeons due to obstruction of the surgical site. The O-arm neuronavigation system was successfully used to bypass this obstruction and provide sacroiliac fixation in this procedure.ConclusionStereotactic navigation (The O-arm Surgical Imaging System) can effectively be used to circumvent prior SI fusion in osteoporotic bone.

IntroductionSurgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage.MethodsElectrodes were placed according to a hypothesis derived from noninvasive monitoring techniques in adult patients with long term epilepsy. Seizure onset was not clearly localized at the end of the invasive monitoring period in ten patients, and additional electrodes were placed based on a new hypothesis that incorporated data from the invasive monitoring period.ResultsSuccessful localization was achieved in nine patients. There were no complications with adding additional electrodes. At final follow up, four patients were seizure free while four others had at least a 50% reduction in seizures after undergoing surgical intervention.ConclusionSeizure foci were localized safely in 90% of adult patients with long term epilepsy after implanting additional electrodes and expanding coverage. Patients undergoing invasive monitoring without clear localization should have additional electrodes placed to expand monitoring coverage as it is safe and effective.

BackgroundPyogenic spinal infections (PSIs) are a group of uncommon but serious infectious diseases that are characterized by inflammation of the endplate-disc unit. PSIs are considered more prevalent and aggressive among patients with chronic immunocompromised states. Association between PSIs and liver disease has not been systematically analyzed. The authors performed a systematic review to study baseline characteristics, clinical presentation, and mortality of patients with PSI in the setting of chronic liver disease.ObservationsThe authors presented the case of a 72-year-old female patient with chronic liver disease who presented with severe low back pain and bilateral lower weakness. Imaging studies showed T10-11 spondylodiscitis. The patient received decompression and fusion surgery with partial neurological improvement. The authors performed a systematic literature search of spondylodiscitis and liver disease, and eight published articles met the studies inclusion and exclusion criteria. These studies featured a total of 144 patients, of whom 129 met inclusion criteria (mean age, 60.5 years, range 40 to 83 years; 62% males). Lumbar infection was the most common report (67%), with Staphylococcus aureus (48%) as the main causative microorganism. Neurological compromise was present in 69% of patients. Surgical intervention occurred in 70.5% of patients, and the average duration of antibiotic treatment was 69.4 days. Postoperative complication rate was 28.5%, with a 30- and 90-day mortality of 17.2% and 24.8%, respectively.LessonsPyogenic spondylodiscitis in patients with liver disease was associated with a high rate of neurological compromise, postoperative complications, and mortality.

BackgroundPrimary spinal infections (PSIs) are a group of uncommon but serious infectious diseases that are characterized by inflammation of the endplate-disc unit. Pediatric spinal infection is rare and challenging to diagnose due to vague presenting symptoms. Most cases are conservatively managed with surgery rarely indicated. The authors performed a systematic review to study the baseline characteristics, clinical presentation, and outcomes of pediatric patients with PSIs who underwent surgical treatment.ObservationsPSI in pediatric patients might behave differently in terms of epidemiology, clinical presentation, and outcomes when compared with nonpediatric patients. Overall, PSI ultimately managed surgically in pediatric patients is associated with a high rate of localized pain, neurological compromise, and treatment failure when compared with nonsurgically managed pediatric spinal infections.LessonsPSIs managed surgically in the pediatric population were found to be caused by Mycobacterium tuberculosis in 74.4% of cases and were associated with higher rates of localized pain, neurological compromise, and treatment failure than nonsurgically managed pediatric spinal infections. Thoracic involvement (71.8%) in the spinal infection was reported most commonly in our review. When omitting the cases involving M. tuberculosis infection, it was revealed that 50% of the pediatric cases involved infection in the cervical region, suggesting increased severity and disease course of cervical spinal infections in the pediatric population. Surgical treatment is indicated only in cases of severe neurological compromise and treatment failure.

BackgroundPrimary spinal infections (PSIs) are a group of uncommon but serious infectious diseases considered more prevalent and aggressive among patients with chronic immunocompromised states. Association of PSI and solid organ transplant has not been systematically analyzed. The authors performed a systematic review analyzing clinical presentation and mortality of patients with PSI in the setting of solid organ transplant.ObservationsPSIs in patients with immunosuppressive therapy, such as those with solid organ transplant, may behave differently in terms of epidemiology, clinical presentation, and outcomes compared with nonimmunosuppressed patients. Overall PSI in solid organ transplant patients is associated with a high rate of neurological compromise, postoperative complications, and mortality.LessonsAccurate diagnosis and appropriate treatment of PSI require a multidisciplinary effort. Localized pain is the most frequently reported symptom associated with PSI. As opposed to PSI in patients without transplant, inflammatory and infectious markers such as white blood cells and C-reactive protein are often not elevated. Furthermore, the causative microorganism profile varies significantly when compared to pyogenic spinal infection in patients without transplant. Aspergillus species was responsible for spondylodiscitis in transplant patients in more than 50% of cases, and the incidence of Aspergillus infection is projected to rise in the coming years.

Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total resection with adjuvant chemotherapy or radiotherapy. The current body of literature is largely inconclusive regarding the overall benefit of adjuvant chemo- or radiotherapy. However, it is known that both are associated with conditions that lower the quality of life in children who undergo those treatments. Chemotherapy is often associated with nausea, emesis, significant fatigue, immunosuppression, and alopecia. While radiotherapy can be effective for achieving local control, it is associated with late effects such as endocrine dysfunction, secondary malignancy, and neurocognitive decline. Advancements in radiotherapy grant both an increase in lifetime survival and an increased lifetime for survivors to contend with these late effects. In this review, the authors examined all the published literature, analyzing the results of clinical trials, case series, and technical notes on patients undergoing radiotherapy for the treatment of tumors of the central nervous system with a focus on neurocognitive decline and survival outcomes.

Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B-band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B − V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions.

BackgroundSurgical treatment of scoliosis includes long and invasive multi-level instrumentation and correction which may result in high rates of postoperative complications, especially in elderly patients with osteopenia or multiple comorbidities. Minimally invasive surgical options may benefit these patients.Case descriptionA 73-year-old female patient with a history of degenerative lumbar scoliosis, L4-5 pseudarthrosis, and resulting L5-S1 adjacent segment following prior unsuccessful lateral L4-5 interbody fusion presented to the clinic with severe lower back pain and lower extremity radiculopathy. The decision was made to proceed with surgical correction via a robotic-guided prone transpsoas (PTP) approach, which is a novel approach similar to lateral lumbar interbody fusion (LLIF) with the patient in a prone decubitus position. Excellent spinal alignment was achieved with no complications. On two-month follow-up, imaging revealed pedicle screws at the L3, L4, L5 levels and at the sacrum without change and continued interbody cages position with no signs or symptoms of infection.DiscussionMinimally invasive procedures have demonstrated benefit in spine surgery especially for at risk populations. The LLIF procedure has been well established for use in a wide range of spinal pathologies given its noted benefits in increasing spinal column stability through posterior fixation and indirect decompression. However, only marginal improvements in segmental lordosis are expected and there are reports of neurological complications. The PTP procedure has emerged as an alternative to LLIF for the treatment of spinopelvic pathologies. This approach enables greater improvements to spinal lordosis through single-position surgery while simultaneously reducing intraoperative repositioning and providing the known benefits of lateral interbody surgery.ConclusionOur experience suggests that the PTP approach is safe and effective because it does not require patient repositioning, easily interfaces with robotic guidance, and achieves increased lordosis gains via the prone positional effect compared to LLIF and comparable approaches.

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.

Uncovering the genetic basis of photosynthetic trait variation under drought stress is essential for breeding climate-resilient walnut cultivars. To this end, we examined photosynthetic capacity in a diverse panel of 150 walnut families (1500 seedlings) from various agro-climatic zones in their habitats and grown in a common garden experiment. Photosynthetic traits were measured under well-watered (WW), water-stressed (WS) and recovery (WR) conditions. We performed genome-wide association studies (GWAS) using three genomic datasets: genotyping by sequencing data (∼43 K SNPs) on both mother trees (MGBS) and progeny (PGBS) and the Axiom™ Juglans regia 700 K SNP array data (∼295 K SNPs) on mother trees (MArray). We identified 578 unique genomic regions linked with at least one trait in a specific treatment, 874 predicted genes that fell within 20 kb of a significant or suggestive SNP in at least two of the three GWAS datasets (MArray, MGBS, and PGBS), and 67 genes that fell within 20 kb of a significant SNP in all three GWAS datasets. Functional annotation identified several candidate pathways and genes that play crucial roles in photosynthesis, amino acid and carbohydrate metabolism, and signal transduction. Further network analysis identified 15 hub genes under WW, WS and WR conditions including GAPB, PSAN, CRR1, NTRC, DGD1, CYP38, and PETC which are involved in the photosynthetic responses. These findings shed light on possible strategies for improving walnut productivity under drought stress.

BackgroundPrior studies attempting to identify disparities in the care of patients with appendiceal (AC) or colorectal cancer (CRC) with peritoneal metastasis (PM) are limited to single-institution, highly selected patient populations. This observational cohort study sought to identify factors associated with specialty care for Medicare beneficiaries with AC/CRC-PM.Materials and methodsPatients >65 years old in the United States diagnosed with AC/CRC and isolated PM were identified within the Medicare Standard Analytic File (2013-2017). Mixed-effects analyses assessed patient factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and outpatient consultation with a peritoneal surface malignancy (PSM) surgeon, and Cox proportional-hazards analysis compared 3-year overall survival (OS) between patients receiving CRS/HIPEC versus systemic therapy alone.ResultsAmong 7,653 patients, only 250 (3.3%) underwent CRS/HIPEC. Among those individuals who did not undergo CRS/HIPEC (N=7,403), only 475 (6.4%) had outpatient consultation with a PSM surgeon. Patient factors independently associated with lower odds of CRS/HIPEC and PSM surgery consultation included older age, greater comorbidity burden, higher social vulnerability index, and further distance from a PSM center (p

Dietary fiber, a nutrient derived mainly from whole grains, vegetables, fruits, and legumes, is known to confer a number of health benefits, yet most Americans consume less than half of the daily recommended amount. Convenience and affordability are key factors determining the ability of individuals to incorporate fiber-rich foods into their diet, and many Americans struggle to access, afford, and prepare foods rich in fiber. The objective of this clinical study was to test the changes in microbial community composition, human metabolomics, and general health markers of a convenient, easy to use prebiotic supplement in generally healthy young participants consuming a diet low in fiber. Twenty healthy adults participated in this randomized, placebo-controlled, double-blind, crossover study which was registered at clinicaltrials.gov as NCT03785860. During the study participants consumed 12 g of a prebiotic fiber supplement and 12 g of placebo daily as a powder mixed with water as part of their habitual diet in randomized order for 4 weeks, with a 4-week washout between treatment arms. Fecal microbial DNA was extracted and sequenced by shallow shotgun sequencing on an Illumina NovaSeq. Plasma metabolites were detected using liquid chromatography-mass spectrometry with untargeted analysis. The phylum Actinobacteria, genus Bifidobacterium, and several Bifidobacterium species (B. bifidum, B. adolescentis, B. breve, B. catenulatum, and B. longum) significantly increased after prebiotic supplementation when compared to the placebo. The abundance of genes associated with the utilization of the prebiotic fiber ingredients (sacA, xfp, xpk) and the production of acetate (poxB, ackA) significantly changed with prebiotic supplementation. Additionally, the abundance of genes associated with the prebiotic utilization (xfp, xpk), acetate production (ackA), and choline to betaine oxidation (gbsB) were significantly correlated with changes in the abundance of the genus Bifidobacterium in the prebiotic group. Plasma concentrations of the bacterially produced metabolite indolepropionate significantly increased. The results of this study demonstrate that an easy to consume, low dose (12 g) of a prebiotic powder taken daily increases the abundance of beneficial bifidobacteria and the production of health-promoting bacteria-derived metabolites in healthy individuals with a habitual low-fiber diet.Clinical trial registrationwww.clinicaltrials.gov/, identifier: NCT03785860.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.

BackgroundHomalodisca vitripennis Germar, the glassy-winged sharpshooter, is an invasive insect in California and a critical threat to agriculture through its transmission of the plant pathogen, Xylella fastidiosa. Quarantine, broad-spectrum insecticides, and biological control have been used for population management of H. vitripennis since its invasion and subsequent proliferation throughout California. Recently wide-spread neonicotinoid resistance has been detected in populations of H. vitripennis in the southern portions of California's Central Valley. In order to better understand potential mechanisms of H. vitripennis neonicotinoid resistance, we performed RNA sequencing on wild-caught insecticide-resistant and relatively susceptible sharpshooters to profile their transcriptome and population structure.ResultsWe identified 81 differentially expressed genes with higher expression in resistant individuals. The significant largest differentially expressed candidate gene linked to resistance status was a cytochrome P450 gene with similarity to CYP6A9. Furthermore, we observed an over-enrichment of GO terms representing functions supportive of roles in resistance mechanisms (cytochrome P450s, M13 peptidases, and cuticle structural proteins). Finally, we saw no evidence of broad-scale population structure, perhaps due to H. vitripennis' relatively recent introduction to California or due to the relatively small geographic scale investigated here.ConclusionsIn this work, we characterized the transcriptome of insecticide-resistant and susceptible H. vitripennis and identified candidate genes that may be involved in resistance mechanisms for this species. Future work should seek to build on the transcriptome profiling performed here to confirm the role of the identified genes, particularly the cytochrome P450, in resistance in H. vitripennis. We hope this work helps aid future population management strategies for this and other species with growing insecticide resistance.

BackgroundAnkylosing spondylitis (AS) is a chronic, progressive, inflammatory disease of the spine and SI joints. Diagnostic criteria and treatments have continued to evolve, necessitating a historical compendium of AS and its management. This paper aims to review the historical context underlying the discovery of AS, as well as the major diagnostic and therapeutic discoveries in the last two centuries.MethodsA scoping review of the literature pertaining to AS was performed via the Pubmed, Scopus, and Web of Science databases. Future directions of AS treatments were assessed by querying the clinicaltrials.gov website.ResultsThe history of AS can be traced as far back as ancient Egypt (as evidenced by the discovery of its presence in ancient Egyptian mummies) to the late 20th century, when the inherited nature of AS was linked to a genetic factor, HLA-B27. Each discovery made throughout the years led to further investigations into the pathophysiology, diagnosis, and treatment of AS. The criteria to differentiate AS from rheumatoid arthritis were first reported in 1893. Since then, diagnostic criteria for AS have undergone a series of changes before the present-day diagnostic criteria for AS were ultimately determined in 2009 by the Assessment of Spondyloarthritis International Society.ConclusionAs the pathophysiology of AS is better understood, healthcare providers are able to diagnose and treat the condition more effectively. In particular, earlier diagnosis and multiple treatment options have facilitated efficient and more effective treatment.

Although hypothermia has shown to protect against ischemic and traumatic neuronal death, its potential role in neurologic recovery following traumatic spinal cord injury (TSCI) remains incompletely understood. Herein, we systematically review the safety and efficacy of hypothermia therapy for TSCI. The English medical literature was reviewed using PRISMA guidelines to identify preclinical and clinical studies examining the safety and efficacy of hypothermia following TSCI. Fifty-seven articles met full-text review criteria, of which twenty-eight were included. The main outcomes of interest were neurological recovery and postoperative complications. Among the 24 preclinical studies, both systemic and local hypothermia significantly improved neurologic recovery. In aggregate, the 4 clinical studies enrolled 60 patients for treatment, with 35 receiving systemic hypothermia and 25 local hypothermia. The most frequent complications were respiratory in nature. No patients suffered neurologic deterioration because of hypothermia treatment. Rates of American Spinal Injury Association (AIS) grade conversion after systemic hypothermia (35.5%) were higher when compared to multiple SCI database control studies (26.1%). However, no statistical conclusions could be drawn regarding the efficacy of hypothermia in humans. These limited clinical trials show promise and suggest therapeutic hypothermia to be safe in TSCI patients, though its effect on neurological recovery remains unclear. The preclinical literature supports the efficacy of hypothermia after TSCI. Further clinical trials are warranted to conclusively determine the effects of hypothermia on neurological recovery as well as the ideal means of administration necessary for achieving efficacy in TSCI.

CRISPR/Cas9 technology enables the extension of genetic techniques into insect pests previously refractory to genetic analysis. We report the establishment of genetic analysis in the glassy-winged sharpshooter (GWSS), Homalodisca vitripennis, which is a significant leafhopper pest of agriculture in California. We use a novel and simple approach of embryo microinjection in situ on the host plant and obtain high frequency mutagenesis, in excess of 55%, of the cinnabar and white eye pigmentation loci. Through pair matings, we obtained 100% transmission of w and cn alleles to the G3 generation and also established that both genes are located on autosomes. Our analysis of wing phenotype revealed an unexpected discovery of the participation of pteridine pigments in wing and wing-vein coloration, indicating a role for these pigments beyond eye color. We used amplicon sequencing to examine the extent of off-target mutagenesis in adults arising from injected eggs, which was found to be negligible or non-existent. Our data show that GWSS can be easily developed as a genetic model system for the Hemiptera, enabling the study of traits that contribute to the success of invasive pests and vectors of plant pathogens. This will facilitate novel genetic control strategies.

Stomata allow CO2 uptake by leaves for photosynthetic assimilation at the cost of water vapor loss to the atmosphere. The opening and closing of stomata in response to fluctuations in light intensity regulate CO2 and water fluxes and are essential for maintaining water-use efficiency (WUE). However, a little is known about the genetic basis for natural variation in stomatal movement, especially in C4 crops. This is partly because the stomatal response to a change in light intensity is difficult to measure at the scale required for association studies. Here, we used high-throughput thermal imaging to bypass the phenotyping bottleneck and assess 10 traits describing stomatal conductance (gs) before, during and after a stepwise decrease in light intensity for a diversity panel of 659 sorghum (Sorghum bicolor) accessions. Results from thermal imaging significantly correlated with photosynthetic gas exchange measurements. gs traits varied substantially across the population and were moderately heritable (h2 up to 0.72). An integrated genome-wide and transcriptome-wide association study identified candidate genes putatively driving variation in stomatal conductance traits. Of the 239 unique candidate genes identified with the greatest confidence, 77 were putative orthologs of Arabidopsis (Arabidopsis thaliana) genes related to functions implicated in WUE, including stomatal opening/closing (24 genes), stomatal/epidermal cell development (35 genes), leaf/vasculature development (12 genes), or chlorophyll metabolism/photosynthesis (8 genes). These findings demonstrate an approach to finding genotype-to-phenotype relationships for a challenging trait as well as candidate genes for further investigation of the genetic basis of WUE in a model C4 grass for bioenergy, food, and forage production.

Soil-borne plant pathogens represent a serious threat that undermines commercial walnut (Juglans regia) production worldwide. Crown gall, caused by Agrobacterium tumefaciens, and Phytophthora root and crown rots, caused by various Phytophthora spp., are among the most devastating walnut soil-borne diseases. A recognized strategy to combat soil-borne diseases is adoption of resistant rootstocks. Here, resistance to A. tumefaciens, P. cinnamomi, and P. pini is mapped in the genome of Juglans microcarpa, a North American wild relative of cultivated walnut. Half-sib J. microcarpa mother trees DJUG 31.01 and DJUG 31.09 were crossed with J. regia cv. Serr, producing 353 and 400 hybrids, respectively. Clonally propagated hybrids were genotyped by sequencing to construct genetic maps for the two populations and challenged with the three pathogens. Resistance to each of the three pathogens was mapped as a major QTL on the long arm of J. microcarpa chromosome 4D and was associated with the same haplotype, designated as haplotype b, raising the possibility that the two mother trees were heterozygous for a single Mendelian gene conferring resistance to all three pathogens. The deployment of this haplotype in rootstock breeding will facilitate breeding of a walnut rootstock resistant to both crown gall and Phytophthora root and crown rots.

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.

ObjectiveTo study the impact of demographic factors on management of traumatic injury to the lumbar spine and postoperative complication rates.MethodsData was obtained from the National Inpatient Sample (NIS) between 2010-2014. International Classification of Diseases, 9th revision, Clinical Modification codes identified patients diagnosed with lumbar fractures or dislocations due to trauma. A series of multivariate regression models determined whether demographic variables predicted rates of complication and revision surgery.ResultsA total of 38,249 patients were identified. Female patients were less likely to receive surgery and to receive a fusion when undergoing surgery, had higher complication rates, and more likely to undergo revision surgery. Medicare and Medicaid patients were less likely to receive surgical management for lumbar spine trauma and less likely to receive a fusion when operated on. Additionally, we found significant differences in surgical management and postoperative complication rates based on race, insurance type, hospital teaching status, and geography.ConclusionSubstantial differences in the surgical management of traumatic injury to the lumbar spine, including postoperative complications, among individuals of demographic factors such as age, sex, race, primary insurance, hospital teaching status, and geographic region suggest the need for further studies to understand how patient demographics influence management and complications for traumatic injury to the lumbar spine.

Sorghum (Sorghum bicolor) is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is studied as a feedstock for biofuel and forage. Mechanistic modeling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping to discover genotype-to-phenotype associations remains a bottleneck in understanding the mechanistic basis for natural variation in gs and iWUE. This study addressed multiple methodological limitations. Optical tomography and a machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were the subject of genome-wide association study and transcriptome-wide association study across 869 field-grown biomass sorghum accessions. The ratio of intracellular to ambient CO2 was genetically correlated with SD, SLA, gs, and biomass production. Plasticity in SD and SLA was interrelated with each other and with productivity across wet and dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population validated associations between DNA sequence variation or RNA transcript abundance and trait variation. A total of 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose Arabidopsis (Arabidopsis thaliana) putative orthologs have functions related to stomatal or leaf development and leaf gas exchange, as well as genes with nonsynonymous/missense variants. These advances in methodology and knowledge will facilitate improving C4 crop WUE.

BackgroundChordomas are rare malignant neoplasms that develop from the primitive notochord with < 5% of the tumors occurring in pediatric patients younger than the age of 20. Of these pediatric chordomas, those affecting the craniocervical junction (C1-C2) are even more rare; therefore, parameters for surgical management of these pediatric tumors are not well characterized.ObservationsIn this case, a 3-year-old male was found to have a clival chordoma on imaging with extension to the craniocervical junction resulting in spinal cord compression. Endoscopic-assisted transoral transclival approach for clival tumor resection was performed first. As a second stage, the patient underwent a left-sided far lateral craniotomy and cervical laminectomy for resection of the skull base chordoma and instrumented fusion of the occiput to C3. He made excellent improvements in strength and dexterity during rehab and was discharged after 3 weeks.LessonsIn pediatric patients with chordoma with extension to the craniocervical junction and spinal cord compression, decompression with additional occipito-cervical fusion appears to offer a good clinical outcome. Fusion performed as a separate surgery before or at the same time as the initial tumor resection surgery may lead to better outcomes.

Autumn and winter Santa Ana wind (SAW)-driven wildfires play a substantial role in area burned and societal losses in southern California. Temperature during the event and antecedent precipitation in the week or month prior play a minor role in determining area burned. Burning is dependent on wind intensity and number of human-ignited fires. Over 75% of all SAW events generate no fires; rather, fires during a SAW event are dependent on a fire being ignited. Models explained 40 to 50% of area burned, with number of ignitions being the strongest variable. One hundred percent of SAW fires were human caused, and in the past decade, powerline failures have been the dominant cause. Future fire losses can be reduced by greater emphasis on maintenance of utility lines and attention to planning urban growth in ways that reduce the potential for powerline ignitions.

The primary goal of the unrelated population HLA diversity (UPHD) component of the 17th International HLA and Immunogenetics Workshop was to characterize HLA alleles at maximum allelic-resolution in worldwide populations and re-evaluate patterns of HLA diversity across populations. The UPHD project included HLA genotype and sequence data, generated by various next-generation sequencing methods, from 4,240 individuals collated from 12 different countries. Population data included well-defined large datasets from the USA and smaller samples from Europe, Australia, and Western Asia. Allele and haplotype frequencies varied across populations from distant geographical regions. HLA genetic diversity estimated at 2- and 4-field allelic resolution revealed that diversity at the majority of loci, particularly for European-descent populations, was lower at the 2-field resolution. Several common alleles with identical protein sequences differing only by intronic substitutions were found in distinct haplotypes, revealing a more detailed characterization of linkage between variants within the HLA region. The examination of coding and non-coding nucleotide variation revealed many examples in which almost complete biunivocal relations between common alleles at different loci were observed resulting in higher linkage disequilibrium. Our reference data of HLA profiles characterized at maximum resolution from many populations is useful for anthropological studies, unrelated donor searches, transplantation, and disease association studies.

Previous studies have found that maximum quantum yield of CO2 assimilation (Φ CO2,max,app) declines in lower canopies of maize and miscanthus, a maladaptive response to self-shading. These observations were limited to single genotypes, leaving it unclear whether the maladaptive shade response is a general property of this C4 grass tribe, the Andropogoneae. We explored the generality of this maladaptation by testing the hypothesis that erect leaf forms (erectophiles), which allow more light into the lower canopy, suffer less of a decline in photosynthetic efficiency than drooping leaf (planophile) forms. On average, Φ CO2,max,app declined 27% in lower canopy leaves across 35 accessions, but the decline was over twice as great in planophiles than in erectophiles. The loss of photosynthetic efficiency involved a decoupling between electron transport and assimilation. This was not associated with increased bundle sheath leakage, based on 13C measurements. In both planophiles and erectophiles, shaded leaves had greater leaf absorptivity and lower activities of key C4 enzymes than sun leaves. The erectophile form is considered more productive because it allows a more effective distribution of light through the canopy to support photosynthesis. We show that in sorghum, it provides a second benefit, maintenance of higher Φ CO2,max,app to support efficient use of that light resource.

Benthic animals profoundly influence the cycling and storage of carbon and other elements in marine systems, particularly in coastal sediments. Recent climate change has altered the distribution and abundance of many seafloor taxa and modified the vertical exchange of materials between ocean and sediment layers. Here, we examine how climate change could alter animal-mediated biogeochemical cycling in ocean sediments. The fossil record shows repeated major responses from the benthos during mass extinctions and global carbon perturbations, including reduced diversity, dominance of simple trace fossils, decreased burrow size and bioturbation intensity, and nonrandom extinction of trophic groups. The broad dispersal capacity of many extant benthic species facilitates poleward shifts corresponding to their environmental niche as overlying water warms. Evidence suggests that locally persistent populations will likely respond to environmental shifts through either failure to respond or genetic adaptation rather than via phenotypic plasticity. Regional and global ocean models insufficiently integrate changes in benthic biological activity and their feedbacks on sedimentary biogeochemical processes. The emergence of bioturbation, ventilation, and seafloor-habitat maps and progress in our mechanistic understanding of organism–sediment interactions enable incorporation of potential effects of climate change on benthic macrofaunal mediation of elemental cycles into regional and global ocean biogeochemical models.

Benthic animals profoundly influence the cycling and storage of carbon and other elements in marine systems, particularly in coastal sediments. Recent climate change has altered the distribution and abundance of many seafloor taxa and modified the vertical exchange of materials between ocean and sediment layers. Here, we examine how climate change could alter animal-mediated biogeochemical cycling in ocean sediments. The fossil record shows repeated major responses from the benthos during mass extinctions and global carbon perturbations, including reduced diversity, dominance of simple trace fossils, decreased burrow size and bioturbation intensity, and nonrandom extinction of trophic groups. The broad dispersal capacity of many extant benthic species facilitates poleward shifts corresponding to their environmental niche as overlying water warms. Evidence suggests that locally persistent populations will likely respond to environmental shifts through either failure to respond or genetic adaptation rather than via phenotypic plasticity. Regional and global ocean models insufficiently integrate changes in benthic biological activity and their feedbacks on sedimentary biogeochemical processes. The emergence of bioturbation, ventilation, and seafloor-habitat maps and progress in our mechanistic understanding of organism–sediment interactions enable incorporation of potential effects of climate change on benthic macrofaunal mediation of elemental cycles into regional and global ocean biogeochemical models.

Sacroiliac (SI) joint pathology is a newly appreciated contributor to lower back pain. Sacroiliac joint fusion (SIJF) has grown rapidly in popularity in association with the advent of minimally-invasive surgical techniques. This has led to an explosion of new medical devices used for SIJF. The objective of this article is to outline clinical trends, summarize the current data, and categorize novel devices for SIJF. Trends in SI joint pathology and fusion were obtained via the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample (NIS) database and Web of Science. To review literature on devices for SIJF, PubMed was searched using the Boolean phrase "sacroiliac joint AND (fusion OR arthrodesis)" since 2010. To establish a list of SIJF devices not represented in the literature, searches were performed on the FDA 510(k), premarket approval, and de novo databases, as well as Google and LinkedIn. Literature review yielded 11 FDA-approved devices for minimally invasive SIJF. Database query yielded an additional 22 devices for a total of 33 devices. Twenty-one devices used the lateral transiliac approach, six posterior allograft approach, three posterolateral approach, and three combined the lateral transiliac and posterolateral approaches. The evidence for the lateral transiliac approach is the most robust. Many novel devices have been developed for minimally invasive SIJF over the past 10 years. Further randomized comparative trials are warranted to evaluate different surgical approaches and novel devices at this time.

Optical manipulations of genetically defined cell types have generated significant insights into the dynamics of neural circuits. While optogenetic activation has been relatively straightforward, rapid and reversible synaptic inhibition has proven more elusive. Here, we leveraged the natural ability of inhibitory presynaptic GPCRs to suppress synaptic transmission and characterize parapinopsin (PPO) as a GPCR-based opsin for terminal inhibition. PPO is a photoswitchable opsin that couples to Gi/o signaling cascades and is rapidly activated by pulsed blue light, switched off with amber light, and effective for repeated, prolonged, and reversible inhibition. PPO rapidly and reversibly inhibits glutamate, GABA, and dopamine release at presynaptic terminals. Furthermore, PPO alters reward behaviors in a time-locked and reversible manner in vivo. These results demonstrate that PPO fills a significant gap in the neuroscience toolkit for rapid and reversible synaptic inhibition and has broad utility for spatiotemporal control of inhibitory GPCR signaling cascades.