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Phosphoregulation is ubiquitous in biology. Defining the functional roles of individual phosphorylation sites within a multivalent system remains particularly challenging. We have therefore applied a chemical biology approach to light-control the state of single candidate phosphoserines in the canonical anion channel CFTR while simultaneously measuring channel activity. The data show striking non-equivalency among protein kinase A consensus sites, which vary from 1,000% changes in channel activity upon phosphorylation. Of note, slow phosphorylation of S813 suggests that this site is rate-limiting to the full activation of CFTR. Further, this approach reveals an unexpected coupling between the phosphorylation of S813 and a nearby site, S795. Overall, these data establish an experimental route to understanding roles of specific phosphoserines within complex phosphoregulatory domains. This strategy may be employed in the study of phosphoregulation of other eukaryotic proteins.

Methamphetamine (MA) use is associated with sexual risk behavior as well as systemic and mucosal inflammation, suggesting parallel biological and behavioral mechanisms of HIV transmission among men who have sex with men (MSM) who use MA. Data evaluating the combined biological effects of MA use with concomitant rectal gonococcal and/or chlamydial (GC/CT) infection on inflammation are limited.Secondary analysis of stored rectal and plasma specimens from 100 MSM participating in a NIDA-funded longitudinal cohort in Los Angeles, California.This cross-sectional analysis evaluated systemic and rectal inflammatory markers under two conditions: 1) recent MA use (by urine drug screen) and 2) rectal GC/CT infection. We evaluated 50 participants with recent MA use (25 with and 25 without rectal GC/CT) and 50 MSM without MA use (25 with and 25 without rectal GC/CT). Log-transformed plasma and rectal immune markers were regressed on MA exposure and rectal GC/CT, controlling for HIV status and age.Median age was 32 (range 19-45) and 58% of participants were living with HIV. Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-1ß, and rectal IL-6 were associated with rectal GC/CT and MA use, independent of HIV status. Higher levels of rectal TNF-α, IL-1ß, and IL-17a were associated with rectal GC/CT.Systemic and rectal inflammation was positively associated with rectal GC/CT and MA use. Condomless sex in the setting of GC/CT- and MA-induced immune activation may provide a basis for synergistic bio-behavioral mechanisms that promote HIV/STI transmission among MSM who use MA.

Background International travel facilitates SARS-CoV-2 spread globally. Early detection of variants among arriving international travelers could provide viral information about introduction of variants with differing infectivity, virulence, and vaccine effectiveness, enabling adjustments to treatment and prevention strategies. We initiated a genomic surveillance program at 4 US airports to detect SARS-CoV-2 variants among arriving international travelers. Methods Between November 29, 2021-April 24, 2022, we enrolled arriving air travelers (≥18 years) from flights originating in 16 countries on 5 continents. At four airports, participants self-collected nasal swab samples that were pooled with 5–25 other samples by country of flight. Participants were also given a take-home saliva collection kit; saliva was collected 3-5 days after arrival and mailed back to the laboratory. SARS-CoV-2 reverse transcription–polymerase chain reaction (RT-PCR) was performed on all samples at the laboratory. Positives underwent whole genome sequencing. Demographic, clinical, and travel information was collected. Results We enrolled 28,656 travelers; median age was 42 years (interquartile range 31-55), 48% were female, and 99.4% self-reported COVID-19 vaccination. Overall, 19% (504/2,666) of pooled and 7.5% (285/3804) of individual samples were positive for SARS-CoV-2. Highest pool positivity of 46% occurred during January 3–10, 2022 (Figure 1). Omicron variant accounted for 97% of sequences (Figure 2). We detected the earliest reporting of Omicron sub-lineages BA.2 and BA.3 (7 and 43 days earlier than reported elsewhere) in the United States and North America, respectively. During April 4–18, we detected an increasing trend of pool positivity among travelers on South African flights, detecting one of the first US-reported BA.4 sub-lineages consistent with early surge of cases in South Africa. Weekly pooled positivity for travelers on South African flights aligned with World Health Organization (WHO)-reported 7-day COVID-19 incidence rates over the same period (Figure 3). Conclusion This genomic sequencing surveillance platform is a model for traveler-based SARS-CoV-2 genomic surveillance that can be used as an early warning system to detect future outbreaks and pandemics. Disclosures Renee Wegrzyn, PhD, Ginkgo Bioworks: Stocks/Bonds Robert C. Morfino, MBA, Ginkgo Bioworks Inc: Employee|Ginkgo Bioworks Inc: Stocks/Bonds Scott Milford, n/a, XpresSpa Group, Inc: Stocks/Bonds Scott Milford, n/a, XpresSpa Group, Inc: Stocks/Bonds Ezra T. Ernst, n/a, XpresSpa Group, Inc: Ownership Interest|XpresSpa Group, Inc: Stocks/Bonds William W. Darrow, n/a, XpresSpa Group, Inc: Stocks/Bonds Siyao Lisa Li, n/a, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Thomas Aichele, n/a, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Andrew Rothstein, n/a, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Benjamin Rome, MBA, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Gabrielle Woronoff, PhD, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Keith Robison, PhD, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Dongjuan Dai, PhD, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Allison Hicks, PhD, Ginkgo Bioworks: I am a current employee|Ginkgo Bioworks: Stocks/Bonds Bryan Cosca, n/a, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Alex Plocik, PhD, Ginkgo Bioworks, Inc: Grant/Research Support|Ginkgo Bioworks, Inc: Stocks/Bonds Birgitte Simen, PhD, Ginkgo Bioworks: I am a current employee|Ginkgo Bioworks: Stocks/Bonds.

Implemented in 2007, the Pantawid Pamilyang Pilipino Program (4Ps) otherwise known as the Conditional Cash Transfer Program (CCT) is a flagship economic and social reform of the Philippine government in order to reduce poverty particularly in the areas of education, healthcare, and the economy as a whole. The emergence of the pandemic interested the researchers in examining the implementation of such a program among its beneficiaries using trend analysis (2015-2021). From 17 regions in the Philippines, the researchers used cluster sampling and took the National Capital Regional (NCR) as an area of interest. The aggregated data from the National Capital Region (NCR) was chosen and used in this study. Results of the study show an erratic trend on the number of 4Ps beneficiaries in the National Capital Region and when disaggregated by years, sex, provinces, and age group. The NCR 2nd and 3rd Districts have the highest number of 4Ps beneficiaries representing NCR, with 30%-31%, while the lowest provinces which are 1st and 4th districts range from 19%-20%. In terms of sex, 93% are female beneficiaries while 7% are male ones from 2015-2018 only because starting 2019 to 2021, the proportion of both sexes became stable and stays with 90% for female grantees and 10% for male grantees. The age group with the least grantee is 18 years old and below, which equates to around 1-2% per year. Further, a "high level" of health compliance among the child monitored 4Ps beneficiaries was observed in 2015 (90%), 2018 (91%), 2019 (93%), and 2020 (97%). It was then concluded that the COVID-19 pandemic had not affected the number of child and adult 4Ps beneficiaries. Interestingly, under 5 mortality rates have significantly reduced from 2015 to the 1st quarter of 2021.

Spray drying is a rapid, continuous, cost-effective, reproducible, and scalable process for reducing the moisture content of a fluid material into a solid powder. To improve this process in juice powder production, automation can be applied to increase efficiency and productivity. Hence, fuzzy logic is used in this study as a control system in the spray-drying process of concentrated liquid bignay juice into juice powder, where the inlet temperature and carrier agent concentrations affecting the properties of the juice powder, such as moisture content and product yield, are considered. The proposed fuzzy system can provide feedback to the control variables, inlet temperature, and carrier agent concentration based on the moisture content and product yield of the juice powder.

Introduction Despite prioritization, routine antenatal influenza vaccine coverage is Methods From 2015 through 2018, 40,230 additional doses of influenza vaccine were added to the available stock and administered as part of routine antenatal care. Educational talks were given daily and data were collected on women attending ANCs. We compared characteristics of vaccinated and unvaccinated women using multivariable logistic regression. Results We screened 62,979 pregnant women during the period when Southern Hemisphere influenza vaccines were available (27,068 in Gauteng and 35,911 in WC). Vaccine coverage at the targeted clinics was 78.7% (49,355/62682), although pregnant women in WC were more likely to be vaccinated compared to those in the Gauteng (Odds ratio (OR) =3.7 p 35 years were less likely to be vaccinated than women aged 18—24 years (OR = 0.9 p = 0.053; OR = 0.9 p < 0.001). HIV positive status was not associated with vaccination (OR = 1.0 p = 0.266). Reasons for not vaccinating included: vaccine stock-outs where ANCs depleted available stock of vaccines and/or were awaiting delivery of vaccines (54.6%, 6949/12723), refusal/indecision (25.8%, 3285), and current illness that contraindicated vaccination (19.6%, 2489). Conclusion Antenatal vaccination uptake was likely improved by the increased vaccine supply and vaccine education offered during our campaign.

Background The data is sparse on the uptake of preventative vaccinations during the COVID-19 pandemic in the pregnant population. Our goal was to determine if the COVID-19 pandemic affected the rate of influenza and tetanus, diphtheria, and acellular pertussis (TDAP) vaccination in a predominantly African American pregnant population. Methods This retrospective descriptive cross-sectional study compared the influenza vaccination rates of pregnant women 18 years and older between the pre-COVID influenza season (September 1, 2019 to March 1, 2020) and the COVID influenza season (September 1, 2020 to March 1, 2021). Results The influenza vaccination rate was statistically significant with a rise from 51.9% pre-pandemic to 72.4% post-pandemic (unadjusted odds ratio (OR) 2.437; 95% confidence interval (CI), 1.64- 3.62; p=0.001). The TDAP vaccination rates remained consistent from the pre-pandemic rate of 65.6% to the pandemic rate of 68.6% (p=0.435). Conclusion We concluded that the pandemic had a positive impact on influenza vaccination rates in the pregnant population.

INTRODUCTION Due to the high cost of operating room time, hospitals have been under increasing pressure to optimize operating room (OR) efficiency. One parameter that has been used to predict OR efficiency is First Case On-Time Start (FCOTS). In this brief report, the authors describe results from a quality improvement project designed to identify the rates and primary causes of first case delay for elective procedures within the orthopedic department at their suburban community hospital. METHODS This was a retrospective, quality improvement project. The authors reviewed information from their anesthesia group to identify the rate and causes for delayed FCOTS, as well as observations and employee interviews to map contributing factors of delay. RESULTS Surgery data on 159 days reviewed indicated that 107 (67.3%) days had first case delays. Of the 398 total first cases during this period, 156 (39.2%) were found to be delayed. The authors identified surgeon practices, with 74 (56.5%) as the main contributor to delay, followed by pre-operative processes, with 24 (18.3%), and room-related causes, 17 (13.0%). The anesthesia department and the patient were minor causes of delay, with 9 (6.9%) and 7 (5.3%) of case delays respectively. DISCUSSION Results were similar to other studies, indicating surgeons and pre-operative as main cause for delay. A fishbone diagram revealed patient factors, inefficiency in the pre-operative process, and staff tardiness as some of the causes. CONCLUSIONS During this project, surgeon practices and preoperative processes were the main factors contributing to OR inefficiency within the community-based hospital. Future strategies to improve daily OR flow within similar institutions should target surgeon on-time arrival and streamlining of the pre-operative process to effectively reduce FCOTS delays.

Background Aberrant lipogenicity and deregulated autophagy are common in most advanced human cancer and therapeutic strategies to exploit these pathways are currently under consideration. Group III Phospholipase A2 (sPLA2-III/PLA2G3), an atypical secretory PLA2, is recognized as a regulator of lipid metabolism associated with oncogenesis. Though recent studies reveal that high PLA2G3 expression significantly correlates with poor prognosis in several cancers, however, role of PLA2G3 in ovarian cancer (OC) pathogenesis is still undetermined. Methods CRISPR-Cas9 and shRNA mediated knockout and knockdown of PLA2G3 in OC cells were used to evaluate lipid droplet (LD) biogenesis by confocal and Transmission electron microscopy analysis, and the cell viability and sensitization of the cells to platinum-mediated cytotoxicity by MTT assay. Regulation of primary ciliation by PLA2G3 downregulation both genetically and by metabolic inhibitor PFK-158 induced autophagy was assessed by immunofluorescence-based confocal analysis and immunoblot. Transient transfection with GFP-RFP-LC3B and confocal analysis was used to assess the autophagic flux in OC cells. PLA2G3 knockout OVCAR5 xenograft in combination with carboplatin on tumor growth and metastasis was assessed in vivo. Efficacy of PFK158 alone and with platinum drugs was determined in patient-derived primary ascites cultures expressing PLA2G3 by MTT assay and immunoblot analysis. Results Downregulation of PLA2G3 in OVCAR8 and 5 cells inhibited LD biogenesis, decreased growth and sensitized cells to platinum drug mediated cytotoxicity in vitro and in in vivo OVCAR5 xenograft. PLA2G3 knockdown in HeyA8MDR-resistant cells showed sensitivity to carboplatin treatment. We found that both PFK158 inhibitor-mediated and genetic downregulation of PLA2G3 resulted in increased number of percent ciliated cells and inhibited cancer progression. Mechanistically, we found that PFK158-induced autophagy targeted PLA2G3 to restore primary cilia in OC cells. Of clinical relevance, PFK158 also induces percent ciliated cells in human-derived primary ascites cells and reduces cell viability with sensitization to chemotherapy. Conclusions Taken together, our study for the first time emphasizes the role of PLA2G3 in regulating the OC metastasis. This study further suggests the therapeutic potential of targeting phospholipases and/or restoration of PC for future OC treatment and the critical role of PLA2G3 in regulating ciliary function by coordinating interface between lipogenesis and metastasis.