Target and Nontarget Screening to Support Capacity Scaling for Substance Use Assessment through a Statewide Wastewater Surveillance Network in New York.

Wastewater-based epidemiology (WBE) has been widely implemented around the world as a complementary tool to conventional surveillance techniques to inform and improve public health responses. Currently, wastewater surveillance programs in the U.S. are evaluating integrated approaches to address public health challenges across multiple domains, including substance abuse. In this work, we demonstrated the potential of online solid-phase extraction coupled with liquid chromatography-high-resolution mass spectrometry to support targeted quantification and nontargeted analysis of psychoactive and lifestyle substances as a step toward understanding the operational feasibility of a statewide wastewater surveillance program for substance use assessment in New York. Target screening confirmed 39 substances in influent samples collected from 10 wastewater treatment plants with varying sewershed characteristics and is anticipated to meet the throughput demands as the statewide program scales up to full capacity. Nontarget screening prioritized additional compounds for identification at three confidence levels, including psychoactive substances, such as opioid analgesics, phenethylamines, and cathinone derivatives. Consumption rates of 12 target substances detected in over 80% of wastewater samples were similar to those reported by previous U.S.-based WBE studies despite the uncertainty associated with back-calculations. For selected substances, the relative bias in consumption estimates was sensitive to variations in monitoring frequency, and factors beyond human excretion (e.g., as indicated by the parent-to-metabolite ratios) might also contribute to their prevalence at the sewershed scale. Overall, our study marks the initial phase of refining analytical workflows and data interpretation in preparation for the incorporation of substance use assessment into the statewide wastewater surveillance program in New York.

Wastewater Surveillance for Infectious Disease: A Systematic Review.

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be a valuable source of information regarding SARS-CoV-2 transmission and coronavirus disease 2019 (COVID-19) cases. Although the method has been used for several decades to track other infectious diseases, there has not been a comprehensive review outlining all of the pathogens that have been surveilled through wastewater. Herein we identify the infectious diseases that have been previously studied via wastewater surveillance prior to the COVID-19 pandemic. Infectious diseases and pathogens were identified in 100 studies of wastewater surveillance across 38 countries, as were themes of how wastewater surveillance and other measures of disease transmission were linked. Twenty-five separate pathogen families were identified in the included studies, with the majority of studies examining pathogens from the family Picornaviridae, including polio and nonpolio enteroviruses. Most studies of wastewater surveillance did not link what was found in the wastewater to other measures of disease transmission. Among those studies that did, the value reported varied by study. Wastewater surveillance should be considered as a potential public health tool for many infectious diseases. Wastewater surveillance studies can be improved by incorporating other measures of disease transmission at the population-level including disease incidence and hospitalizations.

Airborne levels of cadmium are correlated with urinary cadmium concentrations among young children living in the New York state city of Syracuse, USA.

Air pollution is a serious public health issue with early childhood exposure being of high concern because of the greater risk that children might experience negative health outcomes. Industrial sources in and near communities are one potential path of exposure that children might face with greater levels of air pollution correlating with higher levels of toxicants detected in children. We compare estimated ambient air concentrations of Cadmium (Cd) to a cohort (n = 281) of 9 to 11-year old children during their early childhood years (0-5 years of age) in a mid-size city in Upstate New York. Levels of Cd air pollution are compared to children's urine-Cd levels. Urine has been shown to be a superior biomarker to blood for Cd exposure particularly for longer-term exposures. We find that participants who reside in households that faced greater Cd air pollution during the child's early years have higher urine-Cd levels. This association is stable and stronger than previously presented associations for blood-Cd. Findings support expanded use of air modelling data for risk screening to reduce the potential health burden that industrial pollution can have.

Establishing a Statewide Wastewater Surveillance System in Response to the COVID-19 Pandemic: A Reliable Model for Continuous and Emerging Public Health Threats.

CONTEXT: The COVID-19 pandemic sparked efforts across the globe to implement wastewater surveillance for SARS-CoV-2. PROGRAM: New York State (NYS) established the NYS Wastewater Surveillance Network to estimate the levels of COVID-19 community risk and to provide an early indication of SARS-CoV-2 transmission trends. The network is designed to provide a better understanding of public health burdens and to assist health departments to respond effectively to public health threats. IMPLEMENTATION: Wastewater surveillance across NYS increased from sporadic and geographically spare in 2020 to routine and widespread in 2022, reaching all 62 counties in the state and covering 74% of New Yorkers. The network team focused on engaging local health departments and wastewater treatment plants to provide wastewater samples, which are then analyzed through a network-affiliated laboratory. Both participating local health departments and wastewater treatment plants receive weekly memos on current SARS-CoV-2 trends and levels. The data are also made publicly available at the state dashboard. EVALUATION: Using standard indicators to evaluate infectious disease surveillance systems, the NYS Wastewater Surveillance Network was assessed for accuracy, timeliness, and completeness during the first year of operations. We observed 96.5% sensitivity of wastewater to identify substantial/high COVID-19 transmission and 99% specificity to identify low COVID-19 transmission. In total, 80% of results were reported within 1 day of sample collection and were published on the public dashboard within 2 days of sample collection. Among participating wastewater treatment plants, 32.5% provided weekly samples with zero missing data, 31% missed 1 or 2 weeks, and 36.5% missed 3 or more weeks. DISCUSSION: The NYS Wastewater Surveillance Network continues to be a key component of the state and local health departments' pandemic response. The network fosters prompt public health actions through real-time data, enhancing the preparedness capability for both existing and emerging public health threats.

Utilising fluorescent reporters to probe the mode of action of norbornen-7-one CO releasing molecules.

The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.

Community suicide rates and related factors within a surveillance platform in Western Kenya.

BACKGROUND: Suicide is an important contributor to the burden of mental health disorders, but community-based suicide data are scarce in many low- and middle-income countries (LMIC) including Kenya. Available data on suicide underestimates the true burden due to underreporting related to stigma and legal restrictions, and under-representation of those not utilizing health facilities. METHODS: We estimated the cumulative incidence of suicide via verbal autopsies from the Health and Demographic Surveillance System (HDSS) in Kisumu County, Kenya. We then used content analysis of open history forms among deaths coded as accidents to identify those who likely died by suicide but were not coded as suicide deaths. We finally conducted a case-control study of suicides (both verbal autopsy confirmed and likely suicides) compared to accident-caused deaths to assess factors associated with suicide in this HDSS. RESULTS: A total of 33 out of 4306 verbal autopsies confirmed suicide as the cause of death. Content analysis of a further 228 deaths originally attributed to accidents identified 39 additional likely suicides. The best estimate of suicide-specific mortality rate was 14.7 per 100,000 population per year (credibility window = 11.3 - 18.0). The most common reported method of death was self-poisoning (54%). From the case-control study interpersonal difficulties and stressful life events were associated with increased odds of suicide in both confirmed suicides and confirmed combined with suspected suicides. Other pertinent factors such as age and being male differed depending upon which outcome was used. CONCLUSION: Suicide is common in this area, and interventions are needed to address drivers. The twofold increase in the suicide-specific mortality rate following incorporation of misattributed suicide deaths exemplify underreporting and misclassification of suicide cases at community level. Further, verbal autopsies may underreport suicide specifically among older and female populations.

Linking metal (Pb, Hg, Cd) industrial air pollution risk to blood metal levels and cardiovascular functioning and structure among children in Syracuse, NY.

BACKGROUND: Exposure to air pollution has been linked to individual health effects in occupational environments and communities proximate to air pollution sources. Use of estimated chemical concentrations from the Risk Screening Environmental Indicators (RSEI) model, derived from the Toxics Release Inventory, can help approximate some contributions to individual lifetime exposure to risk from air pollution and holds potential for linkages with specific health outcome data. OBJECTIVES: Our objectives were: (1) use regression modeling to test for associations between observed blood metal concentrations in children and RSEI total air concentrations of the same metals released from proximate manufacturing facilities; (2) determine the relative contribution of RSEI air pollution to blood metal concentrations; and (3) examine associations between chronic metal exposure and cardiovascular functioning and structure in study participants. METHODS: Using data synthesis methods and regression modeling we linked individual blood-based levels of lead, mercury, and cadmium(Pb, Hg, Cd) and cardiovascular functioning and structure to proximate industrial releases of the same metals captured by the Environmental Protection Agency's (EPA) RSEI geographic microdata. RESULTS: We found that RSEI-derived ground-level ambient air concentrations of Hg and Cd were a significant predictor of blood metal levels, when controlling for covariates and other exposure variables. In addition to associations with blood metal findings, RSEI concentrations also predicted cardiovascular dysfunction and risk including changes in left-ventricular mass, blood pressure, and heart rate. DISCUSSION: Right-to-know data, such as EPA's RSEI, can be linked to objective health outcomes, rather than simply serving as a non-specific risk estimate. These data can serve as a proxy for hazard exposure and should be used more widely to understand the dynamics of environmental exposure. Furthermore, since these data are both a product of and contribute to regulatory decision making, they could serve as an important link between disease risk and translation-orientated national environmental health policy.

Comparing prioritization strategies for delivering indoor residual spray (IRS) implementation, using a network approach.

BACKGROUND: Indoor residual spraying (IRS) is an effective method to control malaria-transmitting Anopheles mosquitoes and often complements insecticide-treated mosquito nets, the predominant malaria vector control intervention. With insufficient funds to cover every household, malaria control programs must balance the malaria risk to a particular human community against the financial cost of spraying that community. This study creates a framework for modelling the distance to households for targeting IRS implementation, and applies it to potential risk prioritization strategies in four provinces (Luapula, Muchinga, Eastern, and Northern) in Zambia. METHODS: Optimal network models were used to assess the travel distance of routes between operations bases and human communities identified through remote sensing. Network travel distances were compared to Euclidean distances, to demonstrate the importance of accounting for road routes. The distance to reaching communities for different risk prioritization strategies were then compared assuming sufficient funds to spray 50% of households, using four underlying malarial risk maps: (a) predicted Plasmodium falciparum parasite rate in 2-10 years olds (PfPR), or (b) predicted probability of the presence of each of three main malaria transmitting anopheline vectors (Anopheles arabiensis, Anopheles funestus, Anopheles gambiae). RESULTS: The estimated one-way network route distance to reach communities to deliver IRS ranged from 0.05 to 115.69 km. Euclidean distance over and under-estimated these routes by - 101.21 to 41.79 km per trip, as compared to the network route method. There was little overlap between risk map prioritization strategies, both at a district-by-district scale, and across all four provinces. At both scales, agreement for inclusion or exclusion from IRS across all four prioritization strategies occurred in less than 10% of houses. The distances to reaching prioritized communities were either lower, or not statistically different from non-prioritized communities, at both scales of strategy. CONCLUSION: Variation in distance to targeted communities differed depending on risk prioritization strategy used, and higher risk prioritization did not necessarily translate into greater distances in reaching a human community. These findings from Zambia suggest that areas with higher malaria burden may not necessarily be more remote than areas with lower malaria burden.

The use of spatial and genetic tools to assess Plasmodium falciparum transmission in Lusaka, Zambia between 2011 and 2015.

BACKGROUND: Zambia has set itself the ambitious target of eliminating malaria by 2021. To continue tracking transmission to zero, new interventions, tools and approaches are required. METHODS: Urban reactive case detection (RCD) was performed in Lusaka city from 2011 to 2015 to better understand the location and drivers of malaria transmission. Briefly, index cases were followed to their home and all consenting individuals living in the index house and nine proximal houses were tested with a malaria rapid diagnostic test and treated if positive. A brief survey was performed and for certain responses, a dried blood spot sample collected for genetic analysis. Aggregate health facility data, individual RCD response data and genetic results were analysed spatially and against environmental correlates. RESULTS: Total number of malaria cases remained relatively constant, while the average age of incident cases and the proportion of incident cases reporting recent travel both increased. The estimated R0 in Lusaka was < 1 throughout the study period. RCD responses performed within 250 m of uninhabited/vacant land were associated with a higher probability of identifying additional infections. CONCLUSIONS: Evidence suggests that the majority of malaria infections are imported from outside Lusaka. However there remains some level of local transmission occurring on the periphery of urban settlements, namely in the wet season. Unfortunately, due to the higher-than-expected complexity of infections and the small number of samples tested, genetic analysis was unable to identify any meaningful trends in the data.

Synthetic preparation and immunological evaluation of ß-mannosylceramide and related N-acyl analogues.

The synthesis of the invariant natural killer (iNK) T cell agonist ß-mannosylceramide along with a series of fatty amide analogues is reported. Of the six ß-glycosylation protocols investigated, the sulfoxide methodology developed by Crich and co-workers proved to be the most effective where the reaction of a mannosyl sulfoxide and phytosphingosine derivative gave a key glycolipid intermediate as a 95 : 5 mixture of ß- to α-anomers in high yield. A series of mannosyl ceramides were evaluated for their ability to activate D32.D3 NKT cells and induce antitumour activity.

Variability in the spatial density of vacant properties contributes to background lead (Pb) exposure in children.

BACKGROUND: Heightened blood lead levels (BLL) are associated with cognitive deficiencies and adverse behavioral outcomes. Lead-contaminated house dust is the primary source of exposure in U.S. children, and evidence suggests that even background (low-level) exposure has negative consequences. Identifying sources of background exposure is of great public health significance because of the larger number of children that can be affected. METHODS: Blood lead was assessed in a bi-racial sample of children from Syracuse, NY, aged 9-11, using established biomonitoring methods. The spatial density of vacant properties was modelled from publicly available georeferenced datasets. Further, regression models were used to measure the impact of this spatial density variable on children's BLL. RESULTS: In a sample of 221 children, with a mean BLL of 1.06 µg/dL (SD = 0.68), results showed increases in spatial density of vacant properties predict increases in median blood-PB levels, b = 0.14 (0.06-0.21), p < .001. This association held true even after accounting for demographic covariates, and age of individual housing. Further analysis showed spatial autocorrelation of the residuals changed from a clustered pattern to a random pattern once the spatial density variable was introduced to the model. DISCUSSION: This study is the first to identify a background-lead exposure source using spatial density modelling. As vacant properties deteriorate, lead-contaminated dust likely disperses into the surrounding environment. High-density areas have an accumulation of lead hazards in environmental media, namely soil and dust, putting more children at risk of exposure.

A disruptive cue improves handwashing in school children in Zambia.

Behavioral economics hold great promise in changing patterns of behavior that influence human health. Handwashing with soap is one such behavior that is important in reducing exposure to pathogens, and in school-age children, handwashing helps reduce absenteeism through the prevention of respiratory and diarrheal diseases. However, the gap between knowledge on the importance of handwashing and actual handwashing practice, especially with soap, persists. Many traditional behavior change communication approaches have failed in achieving and sustaining improved handwashing practices. Cognitive psychology research on habits as well as nudge theory, a component of behavioral economics predicated on the idea of making a behavior as easy as possible to do, suggests that introducing a disruptive cue into the environment may be able to interrupt current habitual neurological patterns to effect and then sustain behavior change. We used a participatory process to identify and introduce a locally appropriate disruptive cue to improve handwashing behavior in schools in Zambia. We then utilized a school-randomized controlled trial to test the soap-on-a-rope in 50 government schools in Namwala District of Southern Province. Two outcomes were considered among school children; washing hands with water and using soap while washing hands. Following the intervention, soap use was more likely in intervention schools than control schools [Odds ratio = 7.23, 95% confidence interval = (1.76-29.71)], though both intervention and control schools saw an increase in handwashing without soap. This low-cost intervention could be scaled throughout Zambia and may work well in other countries of similar circumstances.

Accuracy and impact of spatial aids based upon satellite enumeration to improve indoor residual spraying spatial coverage.

BACKGROUND: Indoor residual spraying (IRS) is a key tool in the fight to control, eliminate and ultimately eradicate malaria. IRS protection is based on a communal effect such that an individual's protection primarily relies on the community-level coverage of IRS with limited protection being provided by household-level coverage. To ensure a communal effect is achieved through IRS, achieving high and uniform community-level coverage should be the ultimate priority of an IRS campaign. Ensuring high community-level coverage of IRS in malaria-endemic areas is challenging given the lack of information available about both the location and number of households needing IRS in any given area. A process termed 'mSpray' has been developed and implemented and involves use of satellite imagery for enumeration for planning IRS and a mobile application to guide IRS implementation. This study assessed (1) the accuracy of the satellite enumeration and (2) how various degrees of spatial aid provided through the mSpray process affected community-level IRS coverage during the 2015 spray campaign in Zambia. METHODS: A 2-stage sampling process was applied to assess accuracy of satellite enumeration to determine number and location of sprayable structures. Results indicated an overall sensitivity of 94% for satellite enumeration compared to finding structures on the ground. RESULTS: After adjusting for structure size, roof, and wall type, households in Nchelenge District where all types of satellite-based spatial aids (paper-based maps plus use of the mobile mSpray application) were used were more likely to have received IRS than Kasama district where maps used were not based on satellite enumeration. The probability of a household being sprayed in Nchelenge district where tablet-based maps were used, did not differ statistically from that of a household in Samfya District, where detailed paper-based spatial aids based on satellite enumeration were provided. CONCLUSION: IRS coverage from the 2015 spray season benefited from the use of spatial aids based upon satellite enumeration. These spatial aids can guide costly IRS planning and implementation leading to attainment of higher spatial coverage, and likely improve disease impact.

Self-Assembly of Cyclohelicate [M3 L3 ] Triangles Over [M4 L4 ] Squares, Despite Near-Linear Bis-terdentate L and Octahedral M.

Self-assembly of 1:1:2 MII (BF4 )2 (M=Zn or Fe), pyrazine-2,5-dicarbaldehyde (1) and 2-(2-aminoethyl)pyridine gave trimetallic triangle architectures rather than the anticipated tetrametallic [2×2] squares. Options for the nontrivial synthesis of 1 are considered, and synthetic details provided for both preferred routes. Rare cyclohelicate triangle architectures are observed for the pair of structurally characterized yellow-brown [Zn3 L3 ](BF4 )6 and dark green [Fe3 L3 ](BF4 )6 complexes of the neutral bis-terdentate Schiff base L. In order to form these pyrazine-edged triangles, the octahedral metal ions-with all 6 N-donors provided by the terdentate binding pockets of two L-are located 0.4-0.5 Šout of the plane of the bridging pyrazines, towards the center of the triangle. Density functional theory calculations confirm that simple particle counting entropic arguments, which predict triangles over squares, are correct here, with the triangles shown to be energetically favored over the corresponding squares. However, importantly, DFT analysis of these and related triangle versus square systems also show that vibrational contributions to entropy dominate and may significantly influence the preferred architecture, such that simple particle counting cannot in general be reliably employed to predict the observed architecture.

Reported community-level indoor residual spray coverage from two-stage cluster surveys in sub-Saharan Africa.

BACKGROUND: Malaria is an important cause of morbidity and mortality in malaria-endemic areas. Indoor residual spray is an effective intervention to control malaria, but high community-level coverage is needed to maximize its impact. METHODS AND RESULTS: Using thirty-four two-stage cluster surveys (e.g., demographic and health surveys) and lot quality assurance sampling, indoor residual spray was estimated at the community level (i.e. enumeration-area) across sub-Saharan Africa since 2010. For communities receiving indoor residual spray a logistic regression predicted whether community-level coverage exceeded 50% or not. Household-level coverage was equitable both in terms of wealth and urban/rural, with poorer and rural houses more likely to be sprayed than richer and urban houses. Coverage of indoor residual spray at the community level is poor across the continent, with 54% of communities receiving the intervention not reaching 50% coverage. Having >50% coverage at the community-level was not associated with increasing the number of houses sprayed in the country. CONCLUSIONS: Implementation and monitoring of indoor residual coverage at small geographical scales need to improve greatly to receive maximum benefit of the intervention.

Shifting the burden or expanding access to care? Assessing malaria trends following scale-up of community health worker malaria case management and reactive case detection.

BACKGROUND: Malaria is a significant burden to health systems and is responsible for a large proportion of outpatient cases at health facilities in endemic regions. The scale-up of community management of malaria and reactive case detection likely affect both malaria cases and outpatient attendance at health facilities. Using health management information data from 2012 to 2013 this article examines health trends before and after the training of volunteer community health workers to test and treat malaria cases in Southern Province, Zambia. RESULTS: An estimated 50% increase in monthly reported malaria infections was found when community health workers were involved with malaria testing and treating in the community (incidence rate ratio 1.52, p < 0.001). Furthermore, an estimated 6% decrease in outpatient attendance at the health facility was found when community health workers were involved with malaria testing and treating in the community. CONCLUSIONS: These results suggest a large public health benefit to both community case management of malaria and reactive case detection. First, the capacity of the malaria surveillance system to identify malaria infections was increased by nearly one-third. Second, the outpatient attendance at health facilities was modestly decreased. Expanding the capacity of the malaria surveillance programme through systems such as community case management and reactive case detection is an important step toward malaria elimination.

Location, location, location: environmental factors better predict malaria-positive individuals during reactive case detection than index case demographics in Southern Province, Zambia.

BACKGROUND: Decreasing malaria transmission leads to increasing heterogeneity with increased risk in both hot spots (locations) and hot pops (certain demographics). In Southern Province, Zambia, reactive case detection has formed a part of malaria surveillance and elimination efforts since 2011. Various factors may be associated with finding malaria infections during case investigations, including the demographics of the incident case and environmental characteristics of the location of the incident case. METHODS: Community health worker registries were used to determine what factors were associated with finding a malaria infection during reactive case detection. RESULTS: Location was a more powerful predictor of finding malaria infections during case investigations than the demographics of the incident case. After accounting for environmental characteristics, no demographics around the incident case were associated with finding malaria infections during case investigations. Various time-invariant measures of the environment, such as median enhanced vegetation index, the topographic position index, the convergence index, and the topographical wetness index, were all associated as expected with increased probability of finding a malaria infection during case investigations. CONCLUSIONS: These results suggest that targeting the locations highly at risk of malaria transmission is of importance in elimination settings.

Quantifying seasonal and diel variation in Anopheline and Culex human biting rates in Southern Ecuador.

BACKGROUND: Quantifying mosquito biting rates for specific locations enables estimation of mosquito-borne disease risk, and can inform intervention efforts. Measuring biting itself is fraught with ethical concerns, so the landing rate of mosquitoes on humans is often used as a proxy measure. Southern coastal Ecuador was historically endemic for malaria (Plasmodium falciparum and Plasmodium vivax), although successful control efforts in the 2000s eliminated autochthonous transmission (since 2011). This study presents an analysis of data collected during the elimination period. METHODS: Human landing catch (HLC) data for three mosquito taxa: two malaria vectors, Anopheles albimanus and Anopheles punctimacula, and grouped Culex spp. were examined for this study. These data were collected by the National Vector Control Service of the Ministry of Health over a 5-year time span (2007-2012) in five cities in southern coastal Ecuador, at multiple households, in all months of the year, during dusk-dawn (18:00-6:00) hours, often at both indoor and outdoor locations. Hurdle models were used to determine if biting activity was fundamentally different for the three taxa, and to identify spatial and temporal factors influencing bite rate. Due to the many different approaches to studying and quantifying bite rates in the literature, a glossary of terms was created, to facilitate comparative studies in the future. RESULTS: Biting trends varied significantly with species and time. All taxa exhibited exophagic feeding behavior, and outdoor locations increased both the odds and incidence of bites across taxa. Anopheles albimanus was most frequently observed biting, with an average of 4.7 bites/h. The highest and lowest respective months for significant biting activity were March and July for An. albimanus, July and August for An. punctimacula, and February and July for Culex spp. CONCLUSIONS: Fine-scale differences in endophagy and exophagy, and temporal differences among months and hours exist in biting patterns among mosquito taxa in southern coastal Ecuador. This analysis provides detailed information for targeting vector control activities, and household level vector prevention strategies. These data were collected as part of routine vector surveillance conducted by the Ministry of Health, and such data have not been collected since. Reinstating such surveillance measures would provide important information to aid in preventing malaria re-emergence.

Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification.

The current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis. The library was designed to yield derivatives with ranging polarities and the ability to engage in both covalent and noncovalent interactions, while still remaining within the drimane sesquiterpene scaffold. The prepared compounds were screened against 14 relevant marine micro- and macrofouling species. Several of the polygodial analogues displayed inhibitory activities at sub-microgram/mL concentrations. These antifouling effects were most pronounced against the macrofouling ascidian Ciona savignyi and the barnacle Balanus improvisus, with inhibitory activities observed for selected compounds comparable or superior to several commercial antifouling products. The inhibitory activity against the microfouling bacteria and microalgae was reversible and significantly less pronounced than for the macrofoulers. This study illustrates that the macro- and microfoulers are targeted by the compounds via different mechanisms.

Phylogenetically driven sequencing of extremely halophilic archaea reveals strategies for static and dynamic osmo-response.

Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (≥5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes.