Survival Benefit of Chemotherapy According to 21-Gene Recurrence Score in Young Women with Breast Cancer.

BACKGROUND: Initial trials evaluating Oncotype DX, reported as a recurrence score (RS) from 0 to 100, were not powered to evaluate overall survival, and premenopausal women were underrepresented. The purpose of this study was to explore the benefit of chemotherapy according to RS among younger women eligible for oncotype testing. METHODS: Women aged 40-50, diagnosed with HR-positive, HER2-negative breast cancer between 2010 and 2017 were selected from the National Cancer Database (NCBD). Patients were grouped by age, RS, nodal status, and chemotherapy receipt. Kaplan-Meier curves were used to compare unadjusted overall survival (OS) between the groups, and log-rank tests were used to test for a difference between groups. Cox proportional hazards models were used to examine the association between select factors and OS. RESULTS: A total of 15,422 patients met inclusion criteria, 45.3% of whom received chemotherapy. Median follow-up time was 66.4 (50.6-86.6) months. Patients who received chemotherapy were more likely to have higher-stage and higher-grade tumors, tumors that were PR-negative, and have higher RS (p < 0.001 for all). RS was prognostic for OS regardless of nodal status. After adjustment, chemotherapy was associated with a significant improvement in OS only in the pN1 RS 31-50 subgroup (p = 0.02). CONCLUSIONS: RS retains its prognostic value in younger patients with early stage HR-positive, HER2-negative breast cancer. Chemotherapy survival benefit was limited to patients aged 40-50 with pN1 disease and RS of 31-50. Therefore, chemotherapy decision-making should be especially preference-sensitive in women aged 40-50 with intermediate RS, where it may not provide a survival benefit for many women.

Implementing routine communication about costs of cancer treatment: perspectives of providers, patients, and caregivers.

OBJECTIVES: Rising costs in oncology care often impact patients and families directly, making communication about costs and financial impacts of treatment crucial. Cost expenditures could offer opportunities for estimation and prediction, affording personalized conversations about financial impact. We sought to explore providers', patients', and caregivers' preferences towards implementing communication about cost, including when, how, and by whom such information might be provided. METHODS: We conducted semi-structured phone interviews with a diverse population including 12 oncology providers, 12 patients, and 8 patient caregivers (N = 32). The constant comparative method was used to identify mutually agreed upon themes. RESULTS: Participant groups differed in their concerns surrounding cost communication, namely whether they want to receive this information and how such information might impact provider and patient treatment decisions. All participants agreed that oncology providers should not be leading cost conversations. Patients and caregivers identified social workers or financial advisors as most equipped to communicate about cost. Participants emphasized timely cost conversations, ideally around the time of diagnosis. Participants favored various metrics of financial impact beyond overall costs of care including disability, days lost from work, and out-of-pocket expenses. CONCLUSION: Cost transparency should be incorporated into usual care; however, there are several challenges to making cost conversations a part of everyday practice. Patients and family members need resources related to cost to aid in decision-making and those delivering cost information should have competency in oncology, financial advisement, and patient-centered care.

Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.

OBJECTIVE: Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA. METHODS: We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls. In addition, we studied the effects of CAM-3003, an anti-GM-CSFR antibody in a collagen induced arthritis model of RA in DBA/1 mice. The pharmacokinetic profile of CAM-3003 was studied in naïve CD1(ICR) mice (see online supplement) and used to interpret the results of the pharmacodynamic studies in BALB/c mice. RESULTS: GM-CSFRα was expressed by CD68 positive and CD163 positive macrophages in the synovium, and there was a significant increase in GM-CSFRα positive cells in patients in patients with RA as well as patients with PsA compared with patients with osteoarthritis and healthy controls. In the collagen induced arthritis model there was a dose dependent reduction of clinical arthritis scores and the number of F4/80 positive macrophages in the inflamed synovium after CAM-3003 treatment. In BALB/c mice CAM-3003 inhibited recombinant GM-CSF mediated margination of peripheral blood monocytes and neutrophils. CONCLUSIONS: The findings support the ongoing development of therapies aimed at interfering with GM-CSF or its receptor in various forms of arthritis, such as RA and PsA.

Application and feasibility of systemic lupus erythematosus reproductive health care quality indicators at a public urban rheumatology clinic.

OBJECTIVES: Quality indicators (QIs) are evidence-based processes of care designed to represent the current standard of care. Reproductive health QIs for the care of patients with systemic lupus erythematosus (SLE) have recently been developed, and examine areas such as pregnancy screening for autoantibodies, treatment of pregnancy-associated antiphospholipid syndrome, and contraceptive counseling. This study was designed to investigate our performance on these QIs and to explore potential gaps in care and demographic predictors of adherence to the QIs in a safety-net hospital. METHODS: We performed a record review of patients with a diagnosis of SLE at Denver Health Medical Center (DH) through an electronic query of existing medical records and via chart review. Data were limited to female patients between the ages of 18 and 50 who were seen between July 2006 and August 2011. RESULTS: A total of 137 female patients between the ages of 18 and 50 were identified by ICD-9 code and confirmed by chart review to have SLE. Of these, 122 patients met the updated 1997 American College of Rheumatology SLE criteria and had intact reproductive systems. Only 15 pregnancies were documented during this five-year period, and adherence to autoantibody screening was 100 percent. We did not have any patients who were pregnant and met criteria for pregnancy-associated antiphospholipid syndrome. Sixty-five patients (53%) received potentially teratogenic medications, and 30 (46%) had documented discussions about these medications' potential risk upon their initiation. Predictors of whether patients received appropriate counseling included younger age (OR 0.92, CI 0.87-0.98) and those who did not describe English as their primary language (OR 0.24, CI 0.07-0.87) in the multivariate analysis. CONCLUSIONS: We were able to detect an important gap in care regarding teratogenic medication education to SLE patients of childbearing potential in our public health academic clinic, as only one in two eligible patients had documented appropriate counseling at the initiation of a teratogenic medication.

Does vitamin D protect against respiratory viral infections?

The active form of vitamin D has effects on both innate and adaptive immune responses that may influence the outcome in many infectious diseases. Observational studies conclusively show that a low vitamin D status is associated with an increased occurrence of respiratory viral infections, which globally represent significant health and financial burdens. However, no consistent protective effects are evident in prospective clinical trials carried out to date where vitamin D was provided as a dietary supplement, except possibly in cases where the starting vitamin D status of the individual was considered deficient. Thus far, vitamin D has not been found to enhance the immune response to vaccines. The design of future prospective clinical trials assessing a role for vitamin D in respiratory viral infections requires very careful planning to avoid the uncertainties associated with the data available currently.

Technical Radiotherapy Advances - The Role of Magnetic Resonance Imaging-Guided Radiation in the Delivery of Hypofractionation.

Safe delivery of hypofractionated radiotherapy requires high levels of accuracy due to the high doses of radiation delivered per fraction. Magnetic resonance guided radiotherapy (MRgRT) represents a new treatment paradigm which allows improved visualisation of targets and organs at risk, alongside the capability to adapt the treatment plan in real time prior to treatment delivery. There are challenges to delivering hypofractionated radiotherapy with conventional image-guided radiotherapy (IGRT) techniques and MRgRT may help to improve accuracy in radiation delivery in a number of clinical and anatomical scenarios. Specifically, there is an emerging role of MRgRT in delivering stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC) due to the superior soft tissue contrast provided by Magnetic Resonance Imaging combined with the ability to accommodate variation in anatomical appearances during treatment delivery. Reported data on the use of MRgRT in LAPC and it's role in enabling dose escalation are discussed in this article. There are further potential benefits to the use of MRgRT, for example the use of functional imaging during treatment delivery and generation of synthetic computed tomography, which have previously been impractical or unachievable. The overall aim of this article is to demonstrate the utility of MRgRT in facilitating safe delivery of hypofractionated radiotherapy and to highlight ways in which it may help to overcome challenges posed by current IGRT techniques.

Report on the 1990 - 2018 John A. Burns School of Medicine Medical Student Specialty Match and Residency Position Data.

The physician shortage is expected to worsen both in Hawai'i and nationally, with primary care remaining the most needed medical specialty. The University of Hawai'i John A. Burns School of Medicine (JABSOM) plays a critical role in physician workforce development through its undergraduate (Medical School) and graduate medical education (Residency) programs. This report summarizes the Residency match results of all JABSOM Medical School graduates, their trends over time, and the total number of positions available in the JABSOM Residency programs between 1990 and 2018. Overall, 1652 JABSOM Medical School graduates successfully matched into Residency between 1990-2018. There was a negative trend of JABSOM Medical School graduates matching into all 3 primary care Residency programs during this reporting period. The total number of JABSOM Residency positions decreased during the study period, while there was an increase in the number of primary care JABSOM Residency positions. Alignment of the increasing JABSOM Medical School class size with the available JABSOM Residency positions in Hawai'i will be an important health workforce development strategy going forward.

Update on the Impact of the University of Hawai'i Family Medicine Residency Program on the Family Physician Workforce in Hawai'i.

This study updates the previously-reported impact of the University of Hawai'i Family Medicine Residency Program (UHFMRP) on the state of Hawai'i family physician workforce. This study is a retrospective examination of all UHFMRP graduates from the program between 1996 and 2020. Graduate data regarding country or state of medical school, allopathic versus osteopathic training, current clinical practice, zip code of current clinical practice, current board certification, and current fellowship status were recorded between May and July 2020. Overall, 146 UHFMRP graduates completed the program between 1996 and 2020. Currently, 126 UHFMRP graduates have active medical licenses, with 121 graduates (96%, n=126) practicing in the United States, of whom 83 (69%, n=121) are practicing in Hawai'i. Of the 83 UHFMRP graduates practicing in Hawai'i, 67 graduates (81%, n=83) practice on O'ahu. UHFMRP graduates with active medical licenses in Hawai'i represent 23% (83 of 364) of the entire current family physician workforce in Hawai'i. The UHFMRP continues to make an impact on the Hawai'i State family physician workforce, and the retention rate of graduates in Hawai'i has remained relatively stable since 1996.

A Comparative Analysis of the Place of Death of Older Adults in Hawai'i, 2003-2018.

Studies from around the world have found that the preferred place of death is at home. Although desired, the ability to die at home requires personal, social, and structural factors to be in place. In the United States, between 2003 and 2017, there were decreased hospital and nursing facility deaths and increased home and hospice facility deaths. This study aims to determine whether a change in the place of death in those greater than 65 years of age in Hawai'i is similar to the overall United States data and if these changes in place of death are similar across islands/counties in the state of Hawai'i. Data from the Centers for Disease Control and Prevention database were analyzed for natural deaths between 2003 and 2018 in Hawai'i. Between 2003 and 2018, there were 120 115 natural deaths in Hawai'i, with a decrease in the overall percentage of deaths in hospitals from 53% in 2003 to 33% in 2018. During the same period, home deaths increased from 23% to 33%, and nursing facility deaths increased from 14% to 16%. This study found that the change in the place of death in those greater than 65 years in Hawai'i is similar to the overall United States data as a whole, but not within individual Hawai'i counties.

The Role of a 6-Month Primary Care Mentorship Program on Medical Student Residency Specialty.

in the State of Hawai'i, and the shortage is expected to worsen in the coming years. During the 2015-2016 academic year, a 6-month Primary Care Mentorship Program (PCMP) for first-year medical students was launched at the John A. Burns School of Medicine (JABSOM). This study sought to determine (1) whether participation in a PCMP as a first-year medical student correlates with an increased likelihood of matching into a primary care graduate medical education (GME) residency specialty, (2) whether the PCMP medical student participants developed lasting mentorship relationships with their assigned mentor, and (3) whether a PCMP is a worthwhile endeavor for medical schools to incorporate into their structured undergraduate medical education curriculum. Mentees were surveyed before and after the PCMP and after the residency Match. Overall, 105 (36%) of the 288 students in the JABSOM classes of 2019-2022 have applied to participate in the PCMP. Seventeen (85%) of the 20 JABSOM class of 2019 PCMP mentees completed the post-Match reflection survey. The study found as follows: (1) participation in a 6-month PCMP as a first-year medical student does not correlate with an increased likelihood of matching into a primary care GME residency specialty, (2) 7 (41%) participants did continue their mentorship relationship following completion of the PCMP, and (3) overwhelmingly positive qualitative feedback from mentees and the number of mentees who did establish lasting mentorship relationships suggest a PCMP is a worthwhile endeavor for medical schools to implement.

BACE inhibitor treatment of mice induces hyperactivity in a Seizure-related gene 6 family dependent manner without altering learning and memory.

BACE inhibitors, which decrease BACE1 (ß-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer's disease. Clinical trials using BACE inhibitors have reported a lack of positive effect on patient symptoms and, in some cases, have led to increased adverse events, cognitive worsening and hippocampal atrophy. A potential drawback of this strategy is the effect of BACE inhibition on other BACE1 substrates such as Seizure-related gene 6 (Sez6) family proteins which are known to have a role in neuronal function. Mice were treated with an in-diet BACE inhibitor for 4-8 weeks to achieve a clinically-relevant level of amyloid-ß40 reduction in the brain. Mice underwent behavioural testing and postmortem analysis of dendritic spine number and morphology with Golgi-Cox staining. Sez6 family triple knockout mice were tested alongside wild-type mice to identify whether any effects of the treatment were due to altered cleavage of Sez6 family proteins. Wild-type mice treated with BACE inhibitor displayed hyperactivity on the elevated open field, as indicated by greater distance travelled, but this effect was not observed in treated Sez6 triple knockout mice. BACE inhibitor treatment did not lead to significant changes in spatial or fear learning, reference memory, cognitive flexibility or anxiety in mice as assessed by the Morris water maze, context fear conditioning, or light-dark box tests. Chronic BACE inhibitor treatment reduced the density of mushroom-type spines in the somatosensory cortex, regardless of genotype, but did not affect steady-state dendritic spine density or morphology in the CA1 region of the hippocampus. Chronic BACE inhibition for 1-2 months in mice led to increased locomotor output but did not alter memory or cognitive flexibility. While the mechanism underlying the treatment-induced hyperactivity is unknown, the absence of this response in Sez6 triple knockout mice indicates that blocking ectodomain shedding of Sez6 family proteins is a contributing factor. In contrast, the decrease in mature spine density in cortical neurons was not attributable to lack of shed Sez6 family protein ectodomains. Therefore, other BACE1 substrates are implicated in this effect and, potentially, in the cognitive decline in longer-term chronically treated patients.

The Distribution and Possible Roles of Small Cardioactive Peptide in the Nudibranch Melibe leonina.

The neuropeptide small cardioactive peptide (SCP) plays an integrative role in exciting various motor programs involved in feeding and locomotion in a number of gastropod species. In this study, immunohistochemistry, using monoclonal antibodies against SCPB, was used to localize SCPB-like-immunoreactive neurons in the central nervous system, and map their connections to various tissues, in the nudibranch, Melibe leonina. Approximately 28-36 SCPB-like-immunoreactive neurons were identified in the M. leonina brain, as well as one large neuron in each of the buccal ganglia. The neuropil of the pedal ganglia contained the most SCPB-like-immunoreactive varicosities, although only a small portion of these were due to SCPB-like-immunoreactive neurons in the same ganglion. This suggests that much of the SCPB-like immunoreactivity in the neuropil of the pedal ganglia was from neurons in other ganglia that projected through the pedal-pedal connectives or the connectives from the cerebral and pleural ganglia. We also observed extensive SCPB innervation along the length of the esophagus. Therefore, we investigated the impact of SCPB on locomotion in intact animals, as well as peristaltic contractions of the isolated esophagus. Injection of intact animals with SCPB at night led to a significant increase in crawling and swimming, compared to control animals injected with saline. Furthermore, perfusion of isolated brains with SCPB initiated expression of the swim motor program. Application of SCPB to the isolated quiescent esophagus initiated rhythmic peristaltic contractions, and this occurred in preparations both with and without the buccal ganglia being attached. All these data, taken together, suggest that SCPB could be released at night to arouse animals and enhance the expression of both feeding and swimming motor programs in M. leonina.

El neuropéptido pequeño péptido cardioactivo (SCP) juega un rol integrativo en inducir varios programas motores involucrados en la alimentación y locomoción de varias especies de gasterópodos. En este estudio se usó inmunohistoquímica con anticuerpos contra SCPB para localizar y describir la conectividad de neuronas con inmunoreacción semejante al SCPB en el sistema nervioso central del nudibranquio Melibe leonina. Identificamos entre 28 y 36 neuronas en el cerebro de M. leonina con inmunoreacción semejantes al SCPB, además de una neurona grande en cada ganglio bucal. El neuropilo del ganglio pedal contiene la mayor cantidad de varicosidades neuronales con inmunoreacción semejante al SCPB aunque sólo una fracción pequeña de éstas provenían de neuronas en el mismo ganglio. Esto sugiere que gran parte de la inmunoreacción semejante al SCPB en el neuropilo del ganglio pedal tienen su origen en neuronas en otros ganglios que enviaron sus proyecciones a través de los conectivos entre los ganglios pedales, o provenientes de los ganglios cerebral o pleural. Observamos además extensa inervación con immunoreacción semejante al SCPB a lo largo del esófago. Por lo tanto investigamos el impacto de SCPB en la locomoción de animales intactos, así también como las contracciones peristálticas en preparaciones de esófagos aislados. Inyecciones nocturnas de SCPB en animales intactos resultó en in incremento significante en rastreo y nado comparado con animales inyectados con soluciones salinas. Más aún, perfusión de cerebros aislados con SCPB inició programas de programas motores de nado. La aplicación de SCPB a preparaciones aisladas de esófagos inactivos inició contracciones peristálticas rítmicas, lo cual ocurrió igualmente en preparaciones con conexiones con el ganglio bucal presentes o ausentes. Tomados en conjunto, nuestros datos sugieren que SCPB podría ser liberado de forma nocturna para despertar los animales y aumentar la expresión de programas motores de alimentación y locomoción en M. leonina.

Magnetic flux transport on the sun.

Although most of the magnetic flux observed on the sun originates in the low-latitude sunspot belts, this flux is gradually dispersed over a much wider range of latitudes by supergranular convective motions and meridional circulation. Numerical simulations show how these transport processes interact over the 11-year sunspot cycle to produce a strong "topknot" polar field, whose existence near sunspot minimum is suggested by the observed strength of the interplanetary magnetic field and by the observed areal extent of polar coronal holes. The required rates of diffusion and flow are consistent with the decay rates of active regions and with the rotational properties of the large-scale solar magnetic field.

Enhancing resilience and self-efficacy in the parents of children with disabilities and complex health needs.

AIM: The principal aim of this study was to develop, pilot and evaluate an intervention intended to support the development of resilience and self-efficacy in parents of children with disabilities or complex health needs. BACKGROUND: Previous research has found that families often experience physical, social and emotional stress in the context of living with and caring for their disabled child. The literature indicates that a key factor in determining how well the parents of these children cope with their situation may be how resilient and self-efficacious they are. METHODS: A total of 16 parents of children with complex needs and disabilities were engaged in a series of guided conversations delivered during six contact visits with nurse co-researchers (community children's nurses who had received an intensive three-day preparation programme). The conversations, which were supported with additional material that was designed specifically for use in the study, were based around four key themes: emotional coping, practical coping, support networks and 'you and your child'. The impact of the intervention was evaluated using both qualitative and quantitative measures. FINDINGS: When interviewed, parents reported increased self-belief and self-confidence and indicated that they felt better supported and stronger as a result of the intervention. This was consistent with the quantitative evaluation which identified significant improvements on scores for active coping and self-blame on the brief COPE inventory scale and for empathy and understanding and self-acceptance on the TOPSE scale. Scores on the self-report distress thermometer demonstrated a significant reduction in self-reported distress scores at the end of the intervention period.

The "Blown Pupil": Imminent Death or Harmless Contamination?

Acute anisocoria and unilateral mydriasis is physically alarming to patients and diagnostically worrisome to clinicians. We report the case of a 14-year-old girl who presented to the pediatric emergency department with acute anisocoria and unilateral mydriasis after contacting an Angel's trumpet plant and who had complete resolution of symptoms four days following eye contamination. The Angel's trumpet plant contains three active components which can result in mydriasis: hycosamine, atropine, and scopolamine. The three active components occur in different parts of the plant, including on the small glandular hairs that cover the entire plant. This likely explains why even brief contact with the plant can result in unintentional contamination of the eye and in mydriasis. It is critical when obtaining a history from a patient with such a presentation to ask explicitly about any contact with plants prior to onset of symptoms. Although eye contamination with the Angel's trumpet plant is self-limited and resolves within a week, the appearance of a persistently unilateral mydriatic eye can be alarming to patients and clinicians, which too often results in an unnecessary, costly workup.

Corrosion threshold data of metallic materials in various operating environment of offshore wind turbine parts (tower, foundation, and nacelle/gearbox).

This paper outlines corrosion thresholds for different environmental conditions of metallic materials commonly used in the tower, foundation, and nacelle/gearbox of an offshore wind turbine. These threshold values were derived from laboratory corrosion testing employing electrochemical analysis techniques, using the media/solvents that are representative to the operating environment of those wind turbine parts, such as seawater, grease, oils/lubricants, or their combination, at room temperature and at 328K. These values can provide an indication when general/local corrosion or protective film/surface damages have occurred. They can thus be utilised for detecting and monitoring corrosion at certain locations in the wind turbine structure. The presented data have been verified and validated to ensure their repeatability and reliability by means of numerous laboratory tests in accordance to the relevant engineering test standards and an extensive literature/published data review.

The Pacific Region Indigenous Doctors Congress Medical Student Track Report.

The 2018 Pacific Region Indigenous Doctors Congress (PRIDoC) conference featured a student track curriculum that was developed by students at the John A. Burns School of Medicine. Activities were designed around the student track theme, ho'oku'ikahi, meaning "unity" or "unify," as well as the overarching conference theme 'Oi Ola Wai Honua meaning "life is better while the earth has water." Following the conference, surveys were distributed among the trainees who had participated in the student track. The survey feedback was used to evaluate the student track curriculum, as well as its execution. Learning objectives developed for the Student Track were (1) to build formal professional networks, (2) to build a knowledge economy with shared knowledge among participants, and (3) to engage in cultural experiences. Analysis of qualitative data suggest that all learning objectives were satisfactorily fulfilled through planned conference activities. The data will be used to facilitate student tracks at future PRIDoC conferences. The student track at PRIDoC aims to establish and contribute to an ever-growing international network of indigenous students that will extend into professional practice.

Prophylactic but not therapeutic activity of a monoclonal antibody that neutralizes the binding of VEGF-B to VEGFR-1 in a murine collagen-induced arthritis model.

OBJECTIVE: To assess the therapeutic potential of a mAb that neutralizes the binding of VEGF-B to VEGFR-1, to inhibit the pathogenesis of CIA in mice. METHODS: CIA was induced in C57BL6/J and DBA-1 mice by intradermal injection of chick collagen type II (CII) in adjuvant. A neutralizing VEGF-B mAb or an isotype control mAb was then administered by intraperitoneal injection twice weekly beginning either post CII booster injection but prior to or immediately following clinical disease diagnosis. RESULTS: Neutralizing VEGF-B mAb inhibited the development of CIA in C57BL6/J mice in a dose-dependent manner when administered following the CII booster injection, but prior to clinical disease diagnosis. This result was also confirmed in DBA-1 strain mice. In contrast, the neutralizing VEGF-B mAb had no measurable effect on disease severity or progression when treatment commenced from the day of clinical disease diagnosis. CONCLUSIONS: Treatment with an mAb that neutralizes the binding of VEGF-B to VEGFR-1 exhibits prophylactic but not therapeutic actions in a mouse model of RA. These data indicate that while VEGF-B/VEGFR-1 signalling is involved in the early development of arthritis it may not be required for maintenance or progression of established disease.

Semliki Forest virus strongly reduces mosquito host defence signaling.

The Alphavirus genus within the Togaviridae family contains several important mosquito-borne arboviruses. Other than the antiviral activity of RNAi, relatively little is known about alphavirus interactions with insect cell defences. Here we show that Semliki Forest virus (SFV) infection of Aedes albopictus-derived U4.4 mosquito cells reduces cellular gene expression. Activation prior to SFV infection of pathways involving STAT/IMD, but not Toll signaling reduced subsequent virus gene expression and RNA levels. These pathways are therefore not only able to mediate protective responses against bacteria but also arboviruses. However, SFV infection of mosquito cells did not result in activation of any of these pathways and suppressed their subsequent activation by other stimuli.