Interaction between genetic susceptibility to obesity and food intake on BMI in Finnish school-aged children.

Diet modulates the genetic risk of obesity, but the modulation has been rarely studied using genetic risk scores (GRSs) in children. Our objectives were to identify single nucleotide polymorphisms (SNPs) that drive the interaction of specific foods with obesity and combine these into GRSs. Genetic and food frequency data from Finnish Health in Teens study was utilized. In total, 1142 11-year-old subjects were genotyped on the Metabochip array. BMI-GRS with 30 well-known SNPs was computed and the interaction of individual SNPs with food items and their summary dietary scores were examined in relation to age- and sex-specific BMI z-score (BMIz). The whole BMI-GRS interacted with several foods on BMIz. We identified 7-11 SNPs responsible for each interaction and these were combined into food-specific GRS. The most predominant interaction was witnessed for pizza (p < 0.001): the effect on BMIz was b - 0.130 (95% CI - 0.23; - 0.031) in those with low-risk, and 0.153 (95% CI 0.072; 0.234) in high-risk. Corresponding, but weaker interactions were verified for sweets and chocolate, sugary juice drink, and hamburger and hotdog. In total 5 SNPs close to genes NEGR1, SEC16B, TMEM18, GNPDA2, and FTO were shared between these interactions. Our results suggested that children genetically prone to obesity showed a stronger association of unhealthy foods with BMIz than those with lower genetic susceptibility. Shared SNPs of the interactions suggest common differences in metabolic gene-diet interactions, which warrants further investigation.

Prevalence of Stress and Insomnia among Health Care Workers in India during COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Background: Health care workers (HCWs) are prone to stress and insomnia because of pandemic situations. Assessment of the actual burden of this stress and insomnia is essential to form preventive strategies. The study's objective was to find out the pooled prevalence of stress and insomnia among HCWs in India during the coronavirus disease (COVID-19) pandemic. Material and Methods: We conducted a systematic review and meta-analysis to determine the prevalence of stress and insomnia among HCWs during the COVID-19 pandemic in India. Cross-sectional studies conducted in India regarding stress and insomnia among HCWs were searched from PubMed, Scopus, Embase, and Google Scholar. These studies were published after the declaration of the COVID-19 pandemic till August 31, 2021. Articles were searched independently by both authors. Data were extracted in an Excel sheet and analyzed using the 'Meta' package of the 'R' software version 4.1.0. Result: A total of 23 and 16 studies were included in the final pooled analysis of stress and insomnia, respectively, following preferred reporting items for systematic review and meta-analysis guidelines. A random-effects model was used to determine the pooled prevalence of stress and insomnia. This study is registered in Prospero. The registration number is CRD42021253917. The total numbers of HCWs from India included were 8125 and 4974, respectively, for finding out the pooled prevalence of stress and insomnia. The pooled prevalence of stress and insomnia among HCWs is 43% [95% confidence interval (CI) 30-56%] and 35% (95% CI 28-44%), respectively. Two out of five and one in three Indian HCWs have stress and insomnia, respectively, during the COVID-19 pandemic. Conclusion: Human resource development should be prioritized to decrease the workload among HCWs. The findings from this study will be useful in preparing policy guidelines on mental health screening of HCWs during the pandemic.

Natural Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Review.

PCSK9 (proprotein convertase subtilisin/kexin type 9) is an enzyme that helps to reduce cardiovascular events. This clinical result is attributable primarily to the crucial involvement of PCSK9 in regulating the low-density lipoprotein cholesterol level. Because oral anti-PCSK9 medications have yet to be available, the benefits of this unique treatment approach have been diminished. Identifying naturally occurring PCSK9 inhibitors may lead to considerable progress in this regard. These inhibitors serve as a starting point for producing oral and effective components that could be used with statins to boost the proportion of patients who achieve their LDL-cholesterol goals. In this review, we have briefly summarised the recent information regarding natural components or extracts that have been shown to inhibit PCSK9 activity.

Pre-Diagnostic Saliva Microbiota of School-Aged Children Who Developed Type 1 Diabetes or Inflammatory Bowel Diseases.

Altered commensal microbiota composition has been associated with pediatric type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD), but the causal relationship is still unclear. To search for potential pre-diagnostic biomarkers for pediatric T1D or IBD, we compared microbiota in saliva samples in a nested case-control design comprising children developing T1D (nchildren = 52) or IBD (nchildren = 21) and controls with a similar age, sex, and residential area (nchildren = 79). The pre-diagnostic saliva microbiota alpha- and beta-diversity of children who would develop T1D (nsamples = 27) or IBD (nsamples = 14) minimally varied from that of controls. The relative abundances of Abiotrophia were higher, while those of Veillonella, Actinomyces, Megasphaera, Butyrivibrio, and Candidatus ancillula were lower in children who would develop T1D. Within 2 years before diagnosis, the metabolic PWY-5677 pathway (converting succinate into butyrate) was lower in pre-T1D samples than in controls (q = 0.034). No significant pre-IBD differences were found. In conclusion, saliva microbiota diversity or composition were not successful predictors for pediatric T1D nor IBD. Intriguingly, the succinate fermentation pathway was predicted to be lowered before the onset of T1D. Thus, investigating functional pathways might provide a better approach in searching for biomarkers for autoimmune disease in the future.

Analysis of smiling photograph; Operation US-Bangla Air Crash.

Human identification may be difficult when there is no antemortem data available. A photograph of the deceased may be valuable in such cases. Digital advancement and inclusion in the lives of ordinary people makes it easier to retrieve clear, high-resolution photos from social media accounts and other places. This paper describes three cases of forensic dental identification from a US-Bangla plane crash in Nepal in which a charred body was positively identified from a smiling photograph provided by the deceased's family. Each case is unique and their identification rests on the availability of pre- and post-mortem information. Thus, the number of concordant points may vary from single to multiple; there is no defined criteria for minimum number of concordance for a positive dental identification.

Application of the London Atlas of Tooth Development and Eruption in Panoramic Xrays for the Age Estimation.

BACKGROUND: The age estimation of the individual by the forensic experts ascertains the chronological age of an individual. The possibility that the person being examined may be younger or older than a certain age threshold makes this process crucial, as it will establish whether or not the person is an adult under the law. The aim of this study was to test the applicability of the London Atlas of tooth development and eruption in Nepalese subset population. METHODS: The London Atlas for age estimation was tested in 350 digital panoramic radiographs from the patients between four and twenty-four years visiting Tribhuvan University Teaching Hospital, Institute of Medicine, Nepal. RESULTS: The mean values of the estimated age were higher in both the sexes, which was statistically not significant. Both the sexes showed an excellent positive correlation, and was significant with a p value of <0.001. The age estimation upto 10 years group classification was nearly accurate with less than 1 and 2.5 years variation in males and females respectively. The accuracy was good in 16-18 years group with maximum deviation of ±2.5 years. The accuracy was poor in more than 18 years group, as the variability was more than 5 years. CONCLUSIONS: The London Atlas method was best suited for less than 18 years of age and was not very accurate in the age group of 13-14 and 14-15 years where most of the polymorphisms were noted.

Associations of central obesity and habitual food consumption with saliva microbiota and its enzymatic profiles - a pilot study in Finnish children.

Background: Variation in diversity and composition of saliva microbiota has been linked to weight status, but findings have been inconsistent. Focusing on clinically relevant conditions such as central obesity and using advanced sequencing techniques might fill in the gaps of knowledge. Aims: We investigated saliva microbiota with shallow metagenome sequencing in children with (n = 14) and without (n = 36) central obesity. Additionally, we examined the role of habitual food consumption on microbial enzymatic repertoire. Methods: Data comprised 50 children (50% male) with a mean age of 14.2 (SD 0.3) years, selected from the Finnish Health in Teens (Fin-HIT) cohort. Dietary scores for consumption frequency of sweet treats (STI), dairy products (DCI) and plants (PCI) were derived based on a self-administered food frequency questionnaire. Central obesity was defined based on waist-height ratio using the cut-off 0.5. Saliva samples were subjected to whole-metagenome shotgun sequencing, and taxonomic and functional profiling was achieved with METAnnotatorX2 bioinformatics platform. Results: Groups had an average 20 (95% CI 14-27) cm difference in waist circumference. We identified the lack of Pseudomonas guguagenesis and Prevotella scopos, oulorum and oris as putative biomarkers associated with central obesity and observed a total of 16 enzymatic reactions differing between the groups. DCI was associated with the highest number of enzyme profiles (122), followed by STI (60) and DCI (25) (Pearson correlation p < 0.05). Intriguingly, STI showed a high positive/negative correlation ratio (5.09), while DCI and PCI showed low ratios (0.54 and 0.33, respectively). Thus, the main driver of enzymatic reactions was STI, and the related pathways involved nitrate metabolism induced by Haemophilus parainfluenzae and Veilonella dispar among others. Conclusion: Clinically relevant differences in central obesity were only modestly reflected in the composition of saliva microbiota. Habitual consumption of sweet treats was a strong determinant of enzymatic reactions of saliva microbiota in children with and without central obesity. The clinical relevance of these findings warrants further studies.

The Composition and Functional Capacities of Saliva Microbiota Differ Between Children With Low and High Sweet Treat Consumption.

Excess sugar consumption-common in youth-is associated with poor health. Evidence on the relationship between sugar consumption and the oral microbiome, however, remains scarce and inconclusive. We explored whether the diversity, composition, and functional capacities of saliva microbiota differ based on the consumption of select sugary foods and drinks ("sweet treats"). Using 16S rRNA gene sequencing, we characterized saliva microbiota from 11 to 13-year-old children who participated in the Finnish Health in Teens (Fin-HIT) cohort study. The sample comprised children in the lowest (n = 227) and highest (n = 226) tertiles of sweet treat consumption. We compared differences in the alpha diversity (Shannon, inverse Simpson, and Chao1 indices), beta diversity (principal coordinates analysis based on Bray-Curtis dissimilarity), and abundance (differentially abundant operational taxonomic units (OTUs) at the genus level) between these low and high consumption groups. We performed PICRUSt2 to predict the metabolic pathways of microbial communities. No differences emerged in the alpha diversity between low and high sweet treat consumption, whereas the beta diversity differed between groups (p = 0.001). The abundance of several genera such as Streptococcus, Prevotella, Veillonella, and Selenomonas was higher in the high consumption group compared with the low consumption group following false discovery rate correction (p < 0.05). Children with high sweet treat consumption exhibited higher proportions of nitrate reduction IV and gondoate biosynthesis pathways compared with the low consumption group (p < 0.05). To conclude, sweet treat consumption shapes saliva microbiota. Children who consume a high level of sweet treats exhibited different compositions and metabolic pathways compared with children who consume low levels of sweet treats. Our findings reveal novel insights into the relationship between sugary diets and oral microbiota.

A Microfluidic Platform to Monitor Real-Time Effects of Extracellular Vesicle Exchange between Co-Cultured Cells across Selectively Permeable Barriers.

Exosomes and other extracellular vesicles (EVs) play a significant yet poorly understood role in cell-cell communication during homeostasis and various pathological conditions. Conventional in vitro and in vivo approaches for studying exosome/EV function depend on time-consuming and expensive vesicle purification methods to obtain sufficient vesicle populations. Moreover, the existence of various EV subtypes with distinct functional characteristics and submicron size makes their analysis challenging. To help address these challenges, we present here a unique chip-based approach for real-time monitoring of cellular EV exchange between physically separated cell populations. The extracellular matrix (ECM)-mimicking Matrigel is used to physically separate cell populations confined within microchannels, and mimics tissue environments to enable direct study of exosome/EV function. The submicron effective pore size of the Matrigel allows for the selective diffusion of only exosomes and other smaller EVs, in addition to soluble factors, between co-cultured cell populations. Furthermore, the use of PEGDA hydrogel with a very small pore size of 1.2 nm in lieu of Matrigel allows us to block EV migration and, therefore, differentiate EV effects from effects that may be mediated by soluble factors. This versatile platform bridges purely in vitro and in vivo assays by enabling studies of EV-mediated cellular crosstalk under physiologically relevant conditions, enabling future exosome/EV investigations across multiple disciplines through real-time monitoring of vesicle exchange.

Versatile Encapsulation and Synthesis of Potent Liposomes by Thermal Equilibration.

The wide-scale use of liposomal delivery systems is challenged by difficulties in obtaining potent liposomal suspensions. Passive and active loading strategies have been proposed to formulate drug encapsulated liposomes but are limited by low efficiencies (passive) or high drug specificities (active). Here, we present an efficient and universal loading strategy for synthesizing therapeutic liposomes. Integrating a thermal equilibration technique with our unique liposome synthesis approach, co-loaded targeting nanovesicles can be engineered in a scalable manner with potencies 200-fold higher than typical passive encapsulation techniques. We demonstrate this capability through simultaneous co-loading of hydrophilic and hydrophobic small molecules and targeted delivery of liposomal Doxorubicin to metastatic breast cancer cell line MDA-MB-231. Molecular dynamic simulations are used to explain interactions between Doxorubicin and liposome membrane during thermal equilibration. By addressing the existing challenges, we have developed an unparalleled approach that will facilitate the formulation of novel theranostic and pharmaceutical strategies.

Operation makalu air crash: influence of cognitive and human factors on decision-making.

Two onboard crew members lost their lives in the fatal Makalu Air Cessna Grand Caravan 208B domestic cargo flight crash on May 16, 2018. The Disaster Victim Identification (DVI) procedure comprises external examination, photography, DNA collection, fingerprint collection, postmortem examination, antemortem information collection from the family members, and reconciliation. The major challenge of this operation was dealing with cognitive bias. The antemortem dental information of one of the deceased was revealed to the forensic experts just before the postmortem examination. This influenced the testing strategies. There was a tendency to neglect the complete dental examination presuming the identification was established. Later, during a thorough examination, the forensic odontologist realised that the initial decision was erroneous. Furthermore, there are few experience-based resources available to resolve cognitive bias issues. The authors begin by summarising complicated operations in which they have been involved, followed by a discussion of the key sources of cognitive bias along with the solution to resolve these issues in DVI preparedness planning.

Adherence to and acceptability of three alcohol-free, antiseptic oral rinses: A community-based pilot randomized controlled trial among pregnant women in rural Nepal.

OBJECTIVES: Antiseptic oral rinses have been evaluated as interventions to reduce the risk of adverse pregnancy outcomes associated with periodontal disease in pregnant women. Oral rinse use is not common in Nepal or other countries in South Asia, where the prevalence of adverse pregnancy outcomes is high. Understanding whether pregnant women in rural communities in this region would incorporate rinse use into their daily teeth cleaning routine is an important prerequisite to future research on this topic in South Asia. METHODS: We conducted a community-based pilot randomized controlled trial of three alcohol-free, antiseptic oral rinses among pregnant women <22 weeks pregnant in rural Nepal with the aim of assessing rinse acceptability, adherence, and effect on clinical periodontal measures. At baseline, participants underwent a clinical periodontal examination, and then were classified as healthy or having at least mild gingivitis (≥1 site with probing depth (PD) 3 mm and bleeding on probing (BOP) or ≥4 mm (PD)). Participants were stratified by periodontal status and randomized within each exposure category to chlorhexidine (CHX) (0.12%), cetylpyridinium chloride (CPC) (0.05%), salt and water (NaCl), or control (no rinse). Rinse participants were followed weekly for 12 weeks, and all participants underwent a second periodontal examination and answered a questionnaire. RESULTS: Pregnant women in the rural Terai region of Nepal showed high adherence to (mean weekly rinse use: 185 mL (standard deviation: 66 mL)) a recommended 210 mL and acceptability of all three rinses. Participants reported greater frequency of tooth brushing with toothpaste and improvements in other recommended oral hygiene behaviours. CHX significantly reduced rates of gingivitis (defined as a participant with BOP ≥ 10% of sites) and the extent of BOP (gingivitis at the end of follow-up for CHX vs control: RR 0.37, 95% CI: 0.16, 0.84). CPC and NaCl rinse groups had rates of gingivitis and extent of BOP similar to the control group (gingivitis at the end of follow-up for CPC: RR 0.81, 95% CI: 0.47, 1.38; NaCl: RR 0.92, 95% CI: 0.55, 1.56). CONCLUSIONS: Adherence to and acceptability of three alcohol-free, antiseptic oral rinses were high among pregnant women in rural Nepal. Among participants with mild gingivitis at baseline, CHX rinse was most effective at reducing signs of disease compared to the control group. Oral rinse should be considered as a supplement to current oral self-care routines for pregnant women in settings where rinse use is uncommon and access to oral health services is limited.

Determinants of Home Delivery among Mothers in Urban and Rural Vadodara District, Gujarat, India.

BACKGROUND: Maternal health is severely affected by home deliveries because it contributes to maternal mortality, especially if home births are not made safer. OBJECTIVES: The present study aimed to assess the determinants of home delivery among mothers in urban and rural Vadodara district, Gujarat. MATERIALS AND METHODS: This community-based, cross-sectional study was carried out during April 2017-July 2017. The mothers who delivered at home and hospital in urban and rural Vadodara district between April 15 and March 16 were included in the study. A semi-structured questionnaire was used for interviewing all the mothers. Information regarding sociodemographic and obstetrics characteristics of mothers was recorded. The study finding was presented in the form of frequencies and percentages, and the association was found with Chi-square test.P ≤0.05 was considered statistically significant. RESULTS: The present study was carried out among 138 mothers, of them, 71.7% were in the age group of 20-25 years. The mean age of mothers was 24.5 ± 4.4 years. The analysis of sociodemographic and obstetric factors revealed that mothers age more than 25 years, mothers from nuclear family, illiterate mothers, late antenatal care registration by mothers, mothers not registered in Janani Suraksha Yojna/Chiranjeevi Yojana scheme, and prior experience of home delivery by mothers were significantly associated with home delivery (P < 0.05 each). CONCLUSIONS: This study highlighted that several sociodemographic and obstetrics determinants related to mother were associated with home delivery in the study setting. Taking these findings into consideration, it is recommended that appropriate maternity services should be designed with a special focus on poor, uneducated, and multiparous women as well as it should ensure early registration of pregnancy for every pregnant woman. Institutional delivery should be encouraged and advocated among mothers having all previous deliveries at home.

Risk of preterm birth associated with maternal gingival inflammation and oral hygiene behaviours in rural Nepal: a community-based, prospective cohort study.

OBJECTIVES: Observational studies have identified associations between periodontitis and adverse pregnancy outcomes, but randomised controlled trials evaluating the efficacy of periodontal therapy have yielded inconsistent results. Few studies have explored relationships between gingival inflammation and these outcomes or been conducted in rural, low-income communities, where confounding risk factors differ from other settings. METHODS: We conducted a community-based, prospective cohort study with the aim of estimating associations between the extent of gingival inflammation in pregnant women and incidence of preterm birth in rural Nepal. Our primary exposure was gingival inflammation, defined as bleeding on probing (BOP) ≥10%, stratified by BOP <30% and BOP ≥30%. A secondary exposure, mild periodontitis, was defined as ≥2 interproximal sites with probing depth (PD) ≥4 mm (different teeth) or one site with PD ≥5 mm. Our primary outcome was preterm birth (<37 weeks gestation). We used Poisson regression to model this relationship, adjusting for potential confounders. RESULTS: Of 1394 participants, 554 (39.7%) had gingival inflammation, 54 (3.9%) mild periodontitis and 197 (14.1%) delivered preterm. In the adjusted regression model, increasing extent of gingival inflammation was associated with a non-significant increase in risk of preterm birth (BOP ≥30% vs no BOP: adjusted relative risk (aRR) 1.37, 95% CI: 0.81 to 2.32). A secondary analysis, stratifying participants by when in pregnancy their oral health status was assessed, showed an association between gingival inflammation and preterm birth among women examined in their first trimester (BOP ≥30% vs no BOP: aRR 2.57, 95% CI: 1.11 to 5.95), but not later in pregnancy (BOP ≥30% vs no BOP: aRR 1.05, 95% CI: 0.52 to 2.11). CONCLUSIONS: Gingival inflammation in women examined early in pregnancy and poor oral hygiene behaviours were risk factors for preterm birth. Future studies should evaluate community-based oral health interventions that specifically target gingival inflammation, delivered early in or before pregnancy, on preterm birth. TRIAL REGISTRATION NUMBER: Nepal Oil Massage Study, NCT01177111.

Feasibility of training community health workers to conduct periodontal examinations: a validation study in rural Nepal.

BACKGROUND: In many low- and middle-income countries, insufficient human resources limit access to oral health services. Shifting clinical tasks to less specialized health professionals, such as community health workers, has been used as a strategy to expand the health workforce, especially in remote or underserved locations. The objective of this study was to evaluate the validity of periodontal examinations conducted by auxiliary nurse midwives in a rural home setting in Nepal. METHODS: Twenty-one pregnant women < 26 weeks gestation from Sarlahi District, Nepal, underwent full mouth periodontal examinations measuring probing depth (PD) and bleeding on probing (BOP) on 6 sites per tooth by one of five auxiliary nurse midwives, who were trained for this study but had no previous training in dentistry. After a 15-min break, each participant was examined again by an experienced dentist. Measures of validity for PD and BOP were calculated comparing the pooled and individual auxiliary nurse midwives to the dentist. A multivariable GEE model estimated the effect of periodontal characteristics on agreement between the auxiliary nurse midwives and the dentist. RESULTS: Participant mean age was 22 years (SD: ±3 years), mean PD was 1.4 mm (SD: 03 mm), and 86% of women had BOP (according to the dentist). Percent agreement, weighted kappa scores, and intraclass correlation coefficients for PD, with an allowance of ±1 mm, exceeded 99%, 0.7, and 0.9, respectively, indicating an acceptable level of agreement. Auxiliary nurse midwives tended to report higher PD scores relative to the dentist, although this over-estimation was small and unlikely to impact population-based estimates of important indicators of oral health status. GEE regression modeling indicated similar agreement for mandible vs. maxilla, left vs. right side, and PD (≤2 mm, > 2 mm), and lower agreement for posterior teeth and lingual and proximal sites. CONCLUSION: Auxiliary nurse midwives were able to accurately conduct periodontal examinations in a rural home setting, suggesting the potential to shift tasks away from highly trained dentists and periodontal examiners in low-resource communities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01177111 (Nepal Oil Massage Study); registered on August 6th, 2010.

Achalasia Revealed by Respiratory Failure and Hemodynamic Instability.

Achalasia is a rare condition that most often presents with progressive dysphagia to solids and liquids. We report a case of achalasia presenting with acute respiratory failure and hemodynamic instability requiring both ventilator and vasopressor support because of extrinsic compression of the airway and left atrium by a dilated and fluid-filled esophagus. This is the first case reported of achalasia, causing both left atrial compression and airway compression.

Incidence of Natal Teeth in Sarlahi District of Nepal.

BACKGROUND: The presence of natal or neonatal teeth, which have been associated with environmental factors and hereditary syndromes, can have an impact on the psychosocial growth of children. METHODS: We aimed to estimate the incidence of natal tooth in Sarlahi district of Nepal.Live births from Sarlahi district in Nepal were assessed for natal teeth and other related factors. RESULTS: Among 28,695 live births between 2010 and 2017, we observed 7 cases of natal teeth accounting for an incidence rate of 2.44 per 10,000 (95% CI: 0.98 - 5.03). Out of 7 neonates with natal tooth, 4 were female and 3 were low birth weight (<2500 grams). None were preterm or had any associated cleft lip or palate. CONCLUSIONS: Incidence of natal tooth in Nepal is rare.It is important for health care providers to know about the possibility of occurrence of natal tooth and its management.

Molecular features of steroid-binding antidins and their use for assaying serum progesterone.

Chicken avidin (Avd) and streptavidin from Streptomyces avidinii are extensively used in bionanotechnology due to their extremely tight binding to biotin (Kd ~ 10-15 M for chicken Avd). We previously reported engineered Avds known as antidins, which have micro- to nanomolar affinities for steroids, non-natural ligands of Avd. Here, we report the 2.8 Å X-ray structure of the sbAvd-2 (I117Y) antidin co-crystallized with progesterone. We describe the creation of new synthetic phage display libraries and report the experimental as well as computational binding analysis of progesterone-binding antidins. We introduce a next-generation antidin with 5 nM binding affinity for progesterone, and demonstrate the use of antidins for measuring progesterone in serum samples. Our data give insights on how to engineer and alter the binding preferences of Avds and to develop better molecular tools for modern bionanotechnological applications.

Designing Magnetically Responsive Biohybrids Composed of Cord Blood-Derived Natural Killer Cells and Iron Oxide Nanoparticles.

We report the generation of magnetically responsive, cord blood-derived natural killer (NK) cells using iron oxide nanoparticles (IONPs). NK cells are a promising immune cell population for cancer cell therapy as they can target and lyse target tumor cells without prior education. However, NK cells cannot home to disease sites based on antigen recognition, instead relying primarily on external stimuli and chemotactic gradients for transport. Hence, we hypothesized that conjugating IONPs onto the surface of NK cells provides an added feature of magnetic homing to the NK cells, improving their therapeutic function. We describe a robust design for conjugating the IONPs onto the surface of NK cells, which maintains their intrinsic phenotype and function. The conferred magnetic-responsiveness is utilized to improve the cytolytic function of the NK cells for target cells in 2D and 3D models. These findings demonstrate the feasibility of improving NK cell homing and therapeutic efficacy with our NK:IONP "biohybrid".

Mitochondrial-Directed Antioxidant Reduces Microglial-Induced Inflammation in Murine In Vitro Model of TC-83 Infection.

Venezuelan equine encephalitis virus (VEEV) is an arbovirus that is associated with robust inflammation that contributes to neurodegenerative phenotypes. In addition to triggering central nervous system (CNS) inflammation, VEEV will also induce mitochondrial dysfunction, resulting in increased cellular apoptosis. In this study, we utilize the TC-83 strain of VEEV to determine the role of mitochondrial oxidative stress in mediating inflammation elicited by murine brain microglial cells. Using an in vitro model, we show that murine microglia are susceptible to TC-83 infection, and that these cells undergo mitochondrial stress as the result of infection. We also indicate that bystander microglia contribute more significantly to the overall inflammatory load than directly infected microglia. Use of a mitochondrial targeted antioxidant, mitoquinone mesylate, greatly reduced the pro-inflammatory cytokines released by both direct infected and bystander microglia. Our data suggest that release of interleukin-1ß, a key instigator of neuroinflammation during VEEV infection, may be the direct result of accumulating mitochondrial stress. This data improves our understanding inflammation elicited by murine microglia and will aid in the development of more accurate in vitro and in vivo murine model of VEEV-induced neuroinflammation.