Delayed Presentation and Treatment of Sagittal Synostosis: A Case Report.

Sagittal suture synostosis (SSS), caused by premature closure of the sagittal suture of the skull, is usually diagnosed and treated in the first few months of life; delayed diagnosis can be associated with abnormalities in brain development, including raised intracranial pressure (ICP) and neurocognitive development impairments. It can also affect an individual's self-perception and self-esteem. We present a unique case of late presentation and treatment of non-syndromic sagittal synostosis in a 10-year-old. Whilst the patient and his family's main concerns were aesthetic, he also had neurobehavioural issues and needed glasses for vision. Total cranial vault remodelling was offered and successfully performed at the age of 10; this normalised his cephalic index, immediately improved vision, prevented the progression of neurobehavioural under-development and significantly improved self-esteem. This case highlights the difficulties of sagittal synostosis diagnosis, the potential consequences of delayed presentation and the success of treatment, even in an older age group.

Infection of Feral Phenotype Swine with Japanese Encephalitis Virus.

Background: Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves Culex spp. mosquitoes and Ardeid birds, with domestic pigs (Sus scrofa domestica) being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population. Although many studies have concluded that domestic pigs play an important role in the transmission cycle of JEV, and infection of humans, the role of feral pigs in the transmission of JEV remains unclear. Since domestic and feral pigs are the same species, and because feral pig populations in the United States are increasing and expanding geographically, the current study aimed to test the hypothesis that if JEV were introduced into the United States, feral pigs might play a role in the transmission cycle. Materials and Methods: Sinclair miniature pigs, that exhibit the feral phenotype, were intradermally inoculated with JEV genotype Ib. These pigs were derived from crossing miniature domestic pig with four strains of feral pigs and were used since obtaining feral swine was not possible. Results: The Sinclair miniature pigs became viremic and displayed pathological outcomes similar to those observed in domestic swine. Conclusion: Based on these findings, we conclude that in the event of JEV being introduced into the United States, feral pig populations could contribute to establishment and maintenance of a transmission cycle of JEV and could lead to the virus becoming endemic in the United States.

Health sciences library workshops in the COVID era: librarian perceptions and decision making.

Objective: We sought to determine how the COVID-19 pandemic impacted academic health sciences library workshops. We hypothesized that health sciences libraries moved workshops online during the height of the pandemic and that they continued to offer workshops virtually after restrictions were eased. Additionally, we believed that attendance increased. Methods: In March 2022, we invited 161 Association of American Health Sciences Libraries members in the US and Canada to participate in a Qualtrics survey about live workshops. Live workshops were defined as synchronous; voluntary; offered to anyone regardless of school affiliation; and not credit-bearing. Three time periods were compared, and a chi square test of association was conducted to evaluate the relationship between time period and workshop format. Results: Seventy-two of 81 respondents offered live workshops. A chi square test of association indicated a significant association between time period and primary delivery method, chi-square (4, N=206) = 136.55, p< .005. Before March 2020, 77% of respondents taught in person. During the height of the pandemic, 91% taught online and 60% noted higher attendance compared to pre-pandemic numbers. During the second half of 2021, 65% of workshops were taught online and 43% of respondents felt that attendance was higher than it was pre-pandemic. Overall workshop satisfaction was unchanged (54%) or improved (44%). Conclusion: Most health sciences librarians began offering online workshops following the onset of the COVID-19 pandemic. More than half of respondents were still teaching online in the second half of 2021. Some respondents reported increased attendance with similar levels of satisfaction.

Ascertainment of malformations in pregnancy registries: Lessons learned in the North American AED Pregnancy Registry.

BACKGROUND: Pregnancy registries, designed to assess the safety of medications and vaccines for the exposed mother and fetus, have been developed since the 1990s. Malformations present in the exposed liveborn or stillborn infant or fetuses in elective terminations are the outcome of greatest concern. The experiences of the North American AED (antiepileptic drug) Pregnancy Registry (NAAPR) can be used to identify the challenges and limitations of a pregnancy registry in identifying congenital malformations. METHODS: The NAAPR enrolls pregnant women who are taking one or more AEDs for any medical condition, but primarily to prevent seizures, and an unexposed comparison group. Participants are interviewed by clinical research coordinators (CRCs) at enrollment, later in pregnancy and postpartum. Malformations are identified in the mother's reports and her infant's medical records through age 12 weeks. A teratologist, blinded to exposure status, evaluates each potential malformation identified. RESULTS: Among 10,982 pregnancies enrolled between 1997 and 2022, 282 malformations were identified in the 9677 AED-exposed and 15 among the 1305 unexposed infants. Isolated malformations, such as cleft palate, accounted for 84% of the malformations identified. Increased frequencies of oral clefts and myelomeningocele were associated with exposure to several different AEDs. Copies of reports from many diagnostic studies were not obtained and very few pregnancy losses had autopsies. CONCLUSIONS: The evaluation of the AED-exposed infants in a pregnancy registry is indirect. Improvements rely on the rapport established with the mothers by the CRCs and the mothers' willingness to assist in obtaining information from her infants' physicians.

COVID-19 Experiences of Relatives of Nursing Home Residents.

Nursing home residents comprise a disproportionate share of coronavirus-related deaths in the United States. Additionally, lockdown restrictions disrupted residents' relationships with their family members to an unknown extent. This study explored family members' perceived family role and interactions with nursing home residents and staff during the COVID-19 pandemic. Using a qualitative descriptive approach, 10 family members were interviewed using a semi-structured guide. Interviews were audio-recorded and transcribed verbatim, and data were analyzed using Braun and Clarke's Reflexive Thematic analysis. Themes and subthemes indicated that family members accounted for residents' care in new ways, found existing relationships becoming amplified under stress, maintained connections through creative alternatives, and also felt powerless to provide care, despite their knowledge and experience. Family members increasingly relied on staff to meet residents' care needs and provide updates, and often desired to provide assistance and companionship beyond what policy permitted, representing a major opportunity for improving experiences.

Are Outcomes of Acute Meniscus Root Tear Repair Better Than Debridement or Nonoperative Management? A Systematic Review.

BACKGROUND: Meniscus root tears (MRTs) are defined as radial tears within 1 cm of the meniscus root insertion or an avulsion of the meniscus root itself. They lead to altered joint loading because of the failure to convert axial (compressive) loads into hoop stresses. Untreated MRTs can result in altered joint biomechanics and accelerated articular cartilage degeneration and the development of osteoarthritis (OA), yet optimal management remains unclear. PURPOSE: To review treatment outcomes after acute MRTs by surgical repair, debridement, meniscectomy, or nonoperative treatment. DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the evidence from human clinical studies was conducted with electronic searches of the PUBMED, Medline, EMBASE, and the Cochrane Library databases. One reviewer extracted the data and 2 reviewers assessed the risk of bias and performed synthesis of the evidence. RESULTS: Eleven studies of low to moderate methodological quality were identified. All treatment options improved functional scores after >12 months. Arthroscopic repair may be associated with better functional outcomes when compared with partial meniscectomy and nonoperative management at 12-month follow-up. Radiographic progression of OA occurred in all treatment groups; there was some evidence that this was delayed after repair when compared with other treatments. Baseline severity of meniscal extrusion, varus malalignment, and pretreatment degeneration were predictors of poor functional outcomes. Age was not found to be an independent predictor of functional outcome. CONCLUSION: The current level 3 and 4 evidence suggests that arthroscopic repair may result in slower progression of radiological deterioration compared with meniscectomy and nonoperative management. The current literature does not support the exclusion of patients from MRT repair on the basis of age. Patients undergoing acute MRT treatments (repair, debridement, or nonoperative) can be expected to experience improvement in functional outcomes after >12 months. The strength of conclusions are limited because of the paucity of high-quality studies on this subject. Further studies, preferably randomized sham controlled trials with function-oriented rehabilitation programs, are needed to compare treatment strategies and stratification of care based on the risk of meniscal extrusion. REGISTRATION: CRD42018085092 (PROSPERO).

Enhancing the inpatient ward learning environment: A practical guide.

Inpatient ward placements are rich with practical learning opportunities for medical students; however, many such opportunities go overlooked and underused. Newly qualified doctors often feel underprepared for work on wards; improving student experience on ward placements can address this. Although this requires an active effort from both students and clinical educators, it is not arduous and has mutual benefit: improving medical education while simultaneously reducing staff workload. Here, we present a guide for both teachers and students highlighting three key areas of ward learning that may be improved: strategies to drive active learning, integration of students into the ward team and underutilised resources to develop a patient-centred approach.

Barriers and Facilitators to Engagement in Rehabilitation Among Stroke Survivors: An Integrative Review.

BACKGROUND: Approximately 795,000 Americans experience a new or recurrent stroke every year, and it remains one of the leading causes of disability worldwide. Patient engagement in rehabilitation and physical activity has been associated with improvements in functional outcomes during inpatient rehabilitation. There is limited knowledge of the barriers and facilitators to patients' engagement in stroke rehabilitation. METHODS: An integrative review with a systematic approach was conducted to explore the current available literature on barriers and facilitators to patient engagement in stroke inpatient rehabilitation. RESULTS: Twenty-five studies were included in the final review. Four major themes described the identified barriers and facilitators: (1) stroke impact, (2) self-efficacy, (3) therapeutic relationship, and (4) motivating factors. Individualized patient-centered goal setting was a commonly studied intervention found to successfully increase engagement. CONCLUSION: Engagement in stroke rehabilitation is associated with improved patient outcomes. Using the identified themes from this review, nurses can develop focused interventions aimed at reducing barriers and increasing stroke patient engagement.

Integrated Review of Psychosocial and Behavioral Health Assessments and Interventions in Pulmonary Hypertension.

BACKGROUND: The medical management of patients with pulmonary hypertension (PH) has advanced, with few evidence-based recommendations about psychosocial and behavioral health interventions. There is also a lack of comprehensive understanding of PH psychosocial and behavioral health needs. Some psychosocial and behavioral health interventions have been tested; however, there is a gap in the systematic evaluation of nonpharmacological complementary approaches to augment PH management when addressing psychosocial and behavioral health needs. OBJECTIVES: The objectives are to explore psychosocial and behavioral health needs and describe psychosocial and behavioral health interventions for patients with PH. METHODS: We conducted an integrative systematic review of publications between January 1, 2010, and January 31, 2020, obtained from electronic databases: EMBASE, PubMed, Cumulative Index of Nursing and Allied Health Literature, Cochrane, PsycINFO, and Web of Science. The literature searches focused on empirical literature reporting psychosocial needs and psychosocial and behavioral health interventions for adult PH patients. We included peer-reviewed studies published in English. Search terms used in the study were: "hypertension," "pulmonary hypertension," "psychosocial," "depression," "anxiety," "quality of life," "behavioral health," "self-management," "psychosocial intervention," and "psychological distress." Excluded were opinion and discussion publications, reviews, non-PH populations, and pediatric articles. We used the constant comparison method to guide the synthesis of reports applying the Joanna Briggs quality assessment guidelines. RESULTS: A total of 44 articles meeting the criteria were included for final consideration. We conducted an integrative systematic review of 27 quantitative studies, narrative synthesis of 10 qualitative studies, and 7 psychosocial and behavioral health intervention studies. PH patients reported psychosocial needs, such as financial, social connections, sexual health, and palliative care needs, as well as levels of psychological distress symptoms. The results from both quantitative and qualitative studies revealed similar overarching psychosocial and behavioral health conceptual categories. Patients described their ongoing needs in PH management by relying on their psychosocial and behavioral health capabilities to adjust to changes at each stage of disease progression. Patients had high levels of psychosocial and behavioral health needs requiring interventions beyond medical treatment. DISCUSSION: Pilot studies testing psychosocial and behavioral health interventions reported improvement in levels of anxiety and depression and health-related quality of life. Larger scale studies are needed to advance this knowledge. Psychosocial and behavioral health interventions with cognitive-guided foci have the potential of meeting these unmet needs.

Creating a Film to Teach Health Professions Students the Importance of Interprofessional Collaboration.

Objective. To produce, implement, and evaluate the effectiveness of a film to develop the foundational knowledge and skills of health professions students and teach them the importance of interprofessional collaboration. Methods. An existing interprofessional case study about a Hispanic man suffering from multiple chronic health conditions and the impact his health had on his family served as the basis for the film. To ensure a high-quality production, faculty members partnered with a local theatre company to produce the film. Upon completion, the film was integrated into an annual interprofessional forum and evaluated by both students and faculty members in 2016, 2017, and 2018. Results. The 22-minute film, entitled Meet Fred Santiago: Improving Care Through Interprofessional Collaboration, was shown to 1921 students and 250 faculty members who participated in the interprofessional forum over the three years. Of these, 1858 students and 174 faculty members completed a program evaluation following the forum. The majority (>86%) of student and faculty respondents agreed or strongly agreed that the film presented a realistic view of the challenges faced by people with multiple chronic health problems. The majority of students (>85%) agreed or strongly agreed that the film helped them appreciate the breadth of issues confronting individuals with multiple chronic health problems. Conclusion. The film, Meet Fred Santiago, is an effective tool for introducing health professions students to the complex interrelationship of medical, psychological, and social issues experienced by individuals with chronic health conditions.

Protection of swine by potent neutralizing anti-Japanese encephalitis virus monoclonal antibodies derived from vaccination.

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus endemic in the Asia Pacific region. Despite use of several highly effective vaccines, it is estimated that up to 44,000 new cases of Japanese encephalitis (JE) occur every year including 14,000 deaths and 24,000 survivors with permanent sequelae. Humoral immunity induced by vaccination is critical for effective protection. Potently neutralizing antibodies reactive with the JEV envelope (E) protein are important since protective immune responses induced by both live-attenuated and inactivated JE vaccines target the E protein. Our understanding of how vaccine-induced humoral immunity protects vaccinees from morbidity and mortality is, however, limited and largely obtained from in vitro studies. With the exception of neurovirulence mouse models, very few platforms are available for evaluating the protective efficacy of neutralizing antibodies against JEV in vivo. Swine are a major amplifying host in the natural JEV transmission cycle and develop multiple pathological outcomes similar to humans infected with JEV. In this study, prophylactic passive immunization was performed in a miniature swine model, using two vaccination-induced monoclonal antibodies (mAb), JEV-31 and JEV-169. These were selected as representatives for antibodies reactive with the major antigenic structures in the E protein of JEV and related flaviviruses. JEV-31 recognizes the lateral ridge of E protein domain III (EDIII) whilst JEV-169 has a broad footprint of binding involving residues throughout domains I (EDI) and II (EDII) of the E protein. Detection of neutralizing antibodies in the serum of immunized animals mimics the presence of neutralizing antibodies in vaccinated individuals. Passive immunization with both mAbs significantly reduced the severity of diseases that resemble the symptoms of human JE including fever, viremia, viral shedding, systemic infection, and neuroinvasion. In contrast to the uniformed decrease of viral loads in lymphoid and central nervous systems, distinct kinetics in the onset of fever and viremia between animals receiving JEV-31 and JEV-169 suggest potential differences in immune protection mechanisms between anti-EDI and anti-EDIII neutralizing antibodies elicited by vaccination. Our data demonstrate the feasibility of using swine models in characterizing the protective humoral immunity against JEV and increase our understanding of how clonal populations of anti-E mAbs derived from JE vaccination protect against infection in vivo.

Infection and transmission of Cache Valley virus by Aedes albopictus and Aedes aegypti mosquitoes.

BACKGROUND: Cache Valley virus (CVV; Bunyavirales, Peribunyaviridae) is a mosquito-borne arbovirus endemic in North America. Although severe diseases are mainly observed in pregnant ruminants, CVV has also been recognized as a zoonotic pathogen that can cause fatal encephalitis in humans. Human exposures to CVV and its related subtypes occur frequently under different ecological conditions in the New World; however, neurotropic disease is rarely reported. High prevalence rates of neutralizing antibodies have been detected among residents in several Latin American cities. However, zoophilic mosquito species involved in the enzootic transmission are unlikely to be responsible for the transmission leading to human exposures to CVV. Mechanisms that lead to frequent human exposures to CVV remain largely unknown. In this study, competence of two anthropophilic mosquitoes, Aedes albopictus and Ae. aegypti, for CVV was determined using per os infection to determine if these species could play a role in the transmission of CVV in the domestic and peridomestic settings of urban and suburban areas. RESULTS: Aedes albopictus were highly susceptible to CVV whereas infection of Ae. aegypti occurred at a significantly lower frequency. Whilst the dissemination rates of CVV were comparable in the two species, the relatively long period to attain maximal infectious titer in Ae. aegypti demonstrated a significant difference in the replication kinetics of CVV in these species. Detection of viral RNA in saliva suggests that both Ae. albopictus and Ae. aegypti are competent vectors for CVV under laboratory conditions. CONCLUSIONS: Differential susceptibility to CVV was observed in Ae. albopictus and Ae. aegypti, reflecting their relatively different capacities for vectoring CVV in nature. The high susceptibility of Ae. albopictus to CVV observed in this study suggests its potential role as an efficient vector for CVV. Complemented by the reports of multiple CVV isolates derived from Ae. albopictus, our finding provides the basis for how the dispersal of Ae. albopictus across the New World may have a significant impact on the transmission and ecology of CVV.

Culex tarsalis is a competent vector species for Cache Valley virus.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne orthobunyavirus endemic in North America. The virus is an important agricultural pathogen leading to abortion and embryonic lethality in ruminant species, especially sheep. The importance of CVV in human public health has recently increased because of the report of severe neurotropic diseases. However, mosquito species responsible for transmission of the virus to humans remain to be determined. In this study, vector competence of three Culex species mosquitoes of public health importance, Culex pipiens, Cx. tarsalis and Cx. quinquefasciatus, was determined in order to identify potential bridge vector species responsible for the transmission of CVV from viremic vertebrate hosts to humans. RESULTS: Variation of susceptibility to CVV was observed among selected Culex species mosquitoes tested in this study. Per os infection resulted in the establishment of infection and dissemination in Culex tarsalis, whereas Cx. pipiens and Cx. quinquefasciatus were highly refractory to CVV. Detection of viral RNA in saliva collected from infected Cx. tarsalis provided evidence supporting its role as a competent vector. CONCLUSIONS: Our study provided further understanding of the transmission cycles of CVV and identifies Cx. tarsalis as a competent vector.

North American Culex pipiens and Culex quinquefasciatus are competent vectors for Usutu virus.

BACKGROUND: Usutu virus (USUV) is a member of the Japanese encephalitis virus (JEV) serocomplex in the Flaviviridae family. Emergence of USUV in Europe has led to disease burdens in birds and created increasing concern for the potential zoonotic transmission to humans. Whilst USUV has not been detected in the New World, the identification of competent vector species in North America is critical in the assessment of the likelihood of its dispersal and establishment of enzootic transmission cycles. The objective of this study was to determine vector competence of potential mosquito vectors in North America for USUV. Three medically important mosquito species were selected for testing because of their involvement in the transmission of West Nile virus and St. Louis encephalitis virus, two related JEV serocomplex flaviviruses in the New World. METHODOLOGY/PRINCIPAL FINDINGS: Oral challenge of Culex pipiens, Culex quinquefasciatus, and Aedes albopictus was performed to determine the susceptibility and vector competence of North American mosquitoes for USUV. Infection status was monitored by the isolation of virus from homogenized mosquito tissues. The disseminated form of infection was demonstrated by the detection of infectious virus in the head, wings, and legs of infected mosquitoes. The presence of viral RNA in saliva of infected Cx. pipiens and Cx. quinquefasciatus indicated that both species are competent for transmission of USUV. CONCLUSIONS/SIGNIFICANCE: Results indicate that members of the Cx. pipiens complex are susceptible to USUV and competent for its transmission potential in North America in the event of its introduction. In contrast, Ae. albopictus were highly refractory to USUV infection, suggesting that this species is unlikely to contribute to USUV transmission in North America.

North American domestic pigs are susceptible to experimental infection with Japanese encephalitis virus.

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is capable of causing encephalitic diseases in children. While humans can succumb to severe disease, the transmission cycle is maintained by viremic birds and pigs in endemic regions. Although JEV is regarded as a significant threat to the United States (U.S.), the susceptibility of domestic swine to JEV infection has not been evaluated. In this study, domestic pigs from North America were intravenously challenged with JEV to characterize the pathological outcomes. Systemic infection followed by the development of neutralizing antibodies were observed in all challenged animals. While most clinical signs were limited to nonspecific symptoms, virus dissemination and neuroinvasion was observed at the acute phase of infection. Detection of infectious viruses in nasal secretions suggest infected animals are likely to promote the vector-free transmission of JEV. Viral RNA present in tonsils at 28 days post infection demonstrates the likelihood of persistent infection. In summary, our findings indicate that domestic pigs can potentially become amplification hosts in the event of an introduction of JEV into the U.S. Vector-free transmission to immunologically naïve vertebrate hosts is also likely through nasal shedding of infectious viruses.

Shedding of Japanese Encephalitis Virus in Oral Fluid of Infected Swine.

Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne flavivirus endemic in the Asia-Pacific region. Maintenance of JEV in nature involves enzootic transmission by competent Culex mosquitoes among susceptible avian and swine species. Historically, JEV has been regarded as one of the most important arthropod-borne viruses in Southeast Asia. Oronasal shedding of JEV from infected amplification hosts was not recognized until the recent discovery of vector-free transmission of JEV among domestic pigs. In this study, oral shedding of JEV was characterized in domestic pigs and miniature swine representing the feral phenotype. A rope-based sampling method followed by the detection of viral RNA using RT-qPCR allowed the collection and detection of JEV in oral fluid samples collected from intradermally challenged animals. The results suggest that the shedding of JEV in oral fluid can be readily detected by molecular diagnostic assays at the acute phase of infection. It also demonstrates the feasibility of this technique for the diagnosis and surveillance of JEV in swine species.

Teaching evidence-based practice principles to prepare health professions students for an interprofessional learning experience.

OBJECTIVE: The research assessed online learning modules designed to teach health professions students evidence-based practice (EBP) principles in an interprofessional context across two institutions. METHODS: Students from nine health professions at two institutions were recruited to participate in this pilot project consisting of two online learning modules designed to prepare students for an in-person case-based interprofessional activity. Librarians and an instructional designer created two EBP modules. Students' competence in EBP was assessed before and after the modules as well as after the in-person activity. Students evaluated the online learning modules and their impact on the students' learning after the in-person session. RESULTS: A total of 39 students from 8 health professions programs participated in the project. Average quiz scores for online EBP module 1 and module 2 were 83% and 76%, respectively. Following completion of the learning modules, adapted Fresno test of competence in EBP scores increased (p=0.001), indicating that the modules improved EBP skill competence. Student evaluations of the learning modules were positive. Students indicated that they acquired new information skills that contributed to their ability to develop a patient care plan and that they would use these information skills in their future clinical practice. CONCLUSIONS: Online EBP learning modules were effective in developing EBP knowledge and skills for health professions students. Using the same modules ensured that students from different health professions at different stages of their professional programs had consistent knowledge and enabled each student to fully engage in an interprofessional evidence-based activity. Student feedback indicated the modules were valued and beneficial.

Differential outcomes of Zika virus infection in Aedes aegypti orally challenged with infectious blood meals and infectious protein meals.

BACKGROUND: Infection of mosquitoes is an essential step for the transmission of mosquito-borne arboviruses in nature. Engorgement of infectious blood meals from viremic infected vertebrate hosts allows the entry of viruses and initiates infection of midgut epithelial cells. Historically, the infection process of arboviruses in mosquitoes has been studied through the engorgement of mosquitoes from viremic laboratory animals or from artificial feeders containing blood mixed with viruses harvested from cell cultures. The latter approach using so-called artificial blood meals is more frequently used since it is readily optimized to maximize viral titer, negates the use of animals and can be used with viruses for which there are no small animal models. Use of artificial blood meals has enabled numerous studies on mosquito infections with a wide variety of viruses; however, as described here, with suitable modification it can also be used to study the interplay between infection, specific blood components, and physiological consequences associated with blood engorgement. For hematophagous female mosquitoes, blood is the primary nutritional source supporting all physiological process including egg development, and also influences neurological processes and behaviors such as host-seeking. Interactions between these blood-driven vector biological processes and arbovirus infection that is mediated via blood engorgement have not yet been specifically studied. This is in part because presentation of virus in whole blood inevitably induces enzymatic digestion processes, hormone driven oogenesis, and other biological changes. In this study, the infection process of Zika virus (ZIKV) in Aedes aegypti was characterized by oral exposure via viral suspension meals within minimally bovine serum albumin complemented medium or within whole blood. The use of bovine serum albumin in infectious meals provides an opportunity to evaluate the role of serum albumin during the process of flavivirus infection in mosquitoes. METHODS: Infectious whole blood meals and infectious bovine serum albumin meals containing ZIKV were orally presented to two different groups of Ae. aegypti through membrane feeding. At 7 and 14 days post infection, infectious viruses were detected and viral dissemination from gut to other mosquito tissues was analyzed in orally challenged mosquitoes with 50% tissue culture infectious dose method on Vero76 cells. RESULTS/CONCLUSIONS: Zika virus infection was significantly impaired among mosquitoes orally challenged with infectious protein meals as compared to infectious whole blood meals. These results indicate the importance of the blood meal in the infection process of arboviruses in mosquitoes. It provides the basis for future studies to identify critical components in the blood of vertebrate hosts that facilitate arbovirus infection in mosquitoes.

Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells.

Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an insulin-like growth factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells and whether this contributes to therapy resistance. Here we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines. In MCF-7 and ZR75.1 breast cancer cells, IGF-1 induces peroxisome proliferator-activated receptor γ coactivator 1ß (PGC-1ß) and PGC-1α-related coactivator (PRC). Suppression of PGC-1ß and PRC with siRNA reverses the effects of IGF-1 and disrupts mitochondrial morphology and membrane potential. IGF-1 also induced expression of the redox regulator nuclear factor-erythroid-derived 2-like 2 (NFE2L2 alias NRF-2). Of note, MCF-7 cells with acquired resistance to an IGF-1 receptor (IGF-1R) tyrosine kinase inhibitor exhibited reduced expression of PGC-1ß, PRC, and mitochondrial biogenesis. Interestingly, these cells exhibited mitochondrial dysfunction, indicated by reactive oxygen species expression, reduced expression of the mitophagy mediators BNIP3 and BNIP3L, and impaired mitophagy. In agreement with this, IGF-1 robustly induced BNIP3 accumulation in mitochondria. Other active receptor tyrosine kinases could not compensate for reduced IGF-1R activity in mitochondrial protection, and MCF-7 cells with suppressed IGF-1R activity became highly dependent on glycolysis for survival. We conclude that IGF-1 signaling is essential for sustaining cancer cell viability by stimulating both mitochondrial biogenesis and turnover through BNIP3 induction. This core mitochondrial protective signal is likely to strongly influence responses to therapy and the phenotypic evolution of cancer.

Culex Species Mosquitoes and Zika Virus.

Recent reports of Zika virus (ZIKV) isolates from Culex species mosquitoes have resulted in concern regarding a lack of knowledge on the number of competent vector species for ZIKV transmission in the new world. Although observations in the field have demonstrated that ZIKV isolation can be made from Culex species mosquitoes, the detection of ZIKV in these mosquitoes is not proof of their involvement in a ZIKV transmission cycle. Detection may be due to recent feeding on a viremic vertebrate, and is not indicative of replication in the mosquito. In this study, susceptibility of recently colonized Culex species mosquitoes was investigated. The results showed a high degree of refractoriness among members of Culex pipiens complex to ZIKV even when exposed to high-titer bloodmeals. Our finding suggests that the likelihood of Culex species mosquitoes serving as secondary vectors for ZIKV is very low, therefore vector control strategies for ZIKV should remain focused on Aedes species mosquitoes. Our demonstration that Culex quinquefasciatus from Vero Beach, FL, is refractory to infection with ZIKV is especially important and timely. Based on our data, we would conclude that the autochthonous cases of Zika in Florida are not due to transmission by C. quinquefasciatus, and so control efforts should focus on other species, logically Aedes aegypti and Aedes albopictus.