Secondhand harms from cannabis use: Findings from Washington State, United States.

OBJECTIVE: There are few studies on harms attributed to others' cannabis use. We assessed individual- and contextual-level correlates of secondhand harms from cannabis use and considered whether cannabis legalization support, along with cannabis user status, predicted such harms. METHOD: Data were from five repeated cross-sectional, state-representative telephone surveys of Washington State residents ages 18 and over, years 2014-2016. For four surveys, outcome variables were past 12-month reports of experiencing any of five harms (family, traffic-related, vandalism, physical or financial), and in 2016 only, three harm types separately: 1) harassment, 2) safety-related (traffic, vandalism, physical), 3) family or financial, attributed to another's cannabis use. All models included a three-category typology comprised of participants' own cannabis use and whether they supported cannabis use legalization (user supporter, non-user non-supporter, non-user supporter). We estimated logistic regression models for the full sample and by gender, adjusting for individual- and Census tract-level covariates. RESULTS: Compared to non-cannabis-users supporting legalization, nonusers who did not support legalization reported significantly greater odds of perceiving secondhand cannabis harms. Cannabis users supporting legalization did not differ from nonuser supporters. Predictors of reported harms also differed by gender. While current drinkers had lower odds of reporting any harm from others' cannabis use overall, heavy drinking women but not men reported greater odds of any cannabis secondhand harm. CONCLUSIONS: Augmenting research on individual harms associated with cannabis use by including secondhand impacts such as social and family problems, along with safety risks, provides a more comprehensive picture of the effects of cannabis use.

Development of a Rapid and Sensitive CANARY Biosensor Assay for the Detection of Shiga Toxin 2 from Escherichia coli.

Shiga-toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). The current Food Safety Inspection Service (FSIS) testing methods for STEC use the Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) protocol, which includes enrichment, cell plating, and genomic sequencing and takes time to complete, thus delaying diagnosis and treatment. We wanted to develop a rapid, sensitive, and potentially portable assay that can identify STEC by detecting Shiga toxin (Stx) using the CANARY (Cellular Analysis and Notification of Antigen Risks and Yields) B-cell based biosensor technology. Five potential biosensor cell lines were evaluated for their ability to detect Stx2. The results using the best biosensor cell line (T5) indicated that this biosensor was stable after reconstitution with assay buffer covered in foil at 4 °C for up to 10 days with an estimated limit of detection (LOD) of ≈0.1-0.2 ng/mL for days up to day 5 and ≈0.4 ng/mL on day 10. The assay detected a broad range of Stx2 subtypes, including Stx2a, Stx2b, Stx2c, Stx2d, and Stx2g but did not cross-react with closely related Stx1, abrin, or ricin. Additionally, this assay was able to detect Stx2 in culture supernatants of STEC grown in media with mitomycin C at 8 and 24 h post-inoculation. These results indicate that the STEC CANARY biosensor developed in this study is sensitive, reproducible, specific, rapid (≈3 min), and may be applicable for surveillance of the environment and food to protect public health.

Development of Thermally Stable Nanobodies for Detection and Neutralization of Staphylococcal Enterotoxin B.

In this study, sixteen unique staphylococcal enterotoxin B (SEB)-reactive nanobodies (nbs), including ten monovalent and six bivalent nbs, were developed. All characterized nbs were highly specific for SEB and did not cross-react with other staphylococcal enterotoxins (SE). Several formats of highly sensitive enzyme-linked immunosorbent assays (ELISAs) were established using SEB nbs and a polyclonal antibody (pAb). The lowest limit of detection (LOD) reached 50 pg/mL in PBS. When applied to an ELISA to detect SEB-spiked milk (a commonly contaminated foodstuff), a LOD as low as 190 pg/mL was obtained. The sensitivity of ELISA was found to increase concurrently with the valency of nbs used in the assay. In addition, a wide range of thermal tolerance was observed among the sixteen nbs, with a subset of nbs, SEB-5, SEB-9, and SEB-62, retaining activity even after exposure to 95 °C for 10 min, whereas the conventional monoclonal and polyclonal antibodies exhibited heat-labile properties. Several nbs demonstrated a long shelf-life, with one nb (SEB-9) retaining 93% of its activity after two weeks of storage at room temperature. In addition to their usage in toxin detection, eleven out of fifteen nbs were capable of neutralizing SEB's super-antigenic activity, demonstrated by their inhibition on IL-2 expression in an ex vivo human PBMC assay. Compared to monoclonal and polyclonal antibodies, the nbs are relatively small, thermally stable, and easy to produce, making them useful in applications for sensitive, specific, and cost-effective detection and management of SEB contamination in food products.

Risky drinking and other drug use in adults with chronic conditions in the United States: differential associations by race/ethnicity.

Co-use of multiple drugs may prolong or increase heavy drinking, even for individuals with health conditions adversely affected by it. Patterns of alcohol and drug use may vary across racial/ethnic groups, with differential implications for health. This study examines racial/ethnic differences in the associations between risky drinking and other drug use in adults with diabetes, hypertension, heart disease, or cancer. Multiple logistic regression modeling, stratified by condition, was performed using a nationally representative sample of adults drawn from the 2015 to 2019 National Survey on Drug and Health. The outcome was risky drinking (consuming more than 7/14 drinks weekly). Other drugs considered were tobacco, marijuana, illicit drugs, and non-medical prescription drugs. Covariates included age, sex, education, income, marital/cohabitation status, health insurance coverage, and self-rated health status. Each drug category was positively associated with risky drinking across all four conditions. Racial/ethnic minority adults were less likely than White adults to engage in risky drinking, with this pattern most consistent for those with hypertension. Other drug use in minority adults (i.e. tobacco and illicit drug use in Black and Hispanic adults, and marijuana and prescription drug use in Asian adults) was associated with disproportionately greater odds of risky drinking compared with White adults. This pattern was more prominent for those with a heart condition, and not found for those with cancer. Future interventions might address co-use of alcohol and other drugs in adults with chronic conditions, with special attention to racial/ethnic minority adults.

A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT/G Toxin in Mice.

Equine-derived antitoxin (BAT®) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT® is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with KD values ranging from 3.86 nM to 103 nM (median KD 20.9 nM). Five mAb-binding non-overlapping epitopes were humanized and affinity matured to create antibodies hu6G6.2, hu6G7.2, hu6G9.1, hu6G10, and hu6G11.2, with IgG KD values ranging from 51 pM to 8 pM. Three IgG combinations completely protected mice challenged with 10,000 LD50s of BoNT/G at a total mAb dose of 6.25 µg per mouse. The mAb combinations have the potential for use in the diagnosis and treatment of botulism due to serotype G and, along with antibody combinations to BoNT/A, B, C, D, E, and F, provide the basis for a fully recombinant heptavalent botulinum antitoxin to replace the legacy equine product.

At-Risk Drinking in US Adults with Health Conditions: Differences by Gender, Race, and Ethnicity in the National Survey of Drug Use and Health, 2015-2019.

Few studies in the US address alcohol consumption patterns in adults with chronic health conditions, and little is known about race and ethnicity differences. This study examined at-risk drinking prevalence rates among US adults with hypertension, diabetes, heart condition or cancer and assessed differences by gender and, among adults aged 50 and older, by race and ethnicity. We used data from the 2015-2019 National Survey on Drug Use and Health (N = 209,183) to estimate (1) prevalence rates and (2) multivariable logistic regression models predicting odds of at-risk drinking among adults with hypertension, diabetes, heart condition, or cancer, compared to adults with none of these conditions. To examine subgroup differences, analyses were stratified by gender (ages 18-49 and ages 50 +) and by gender and race and ethnicity for adults ages 50 + . Results showed that all adults with diabetes and women ages 50 + with heart conditions in the full sample had lower odds of at-risk drinking relative to their counterparts without any of the four conditions. Men ages 50 + with hypertension had greater odds. In race and ethnicity assessments among adults ages 50 + , only non-Hispanic White (NHW) men and women with diabetes and heart conditions had lower odds, and NHW men and women and Hispanic men with hypertension had greater odds of at-risk drinking. There were differential associations of at-risk drinking with demographic and lifestyle indicators across race and ethnicity groups. These findings underscore tailored efforts in community and clinical settings to reduce at-risk drinking in subgroups with health condition diagnoses.

Associations between early childhood adversity and behavioral, substance use, and academic outcomes in childhood through adolescence in a U.S. longitudinal cohort.

BACKGROUND: Childhood adversity is strongly associated with adolescent substance use, but few epidemiologic studies have investigated early childhood adversity (ECA) before age 5. This study investigated pathways by which ECA is associated with adolescent alcohol and cannabis use and high school completion through childhood behavioral and academic mediators and their reciprocal effects. METHODS: Data were from the National Longitudinal Survey of Youth 1979-Child/Young Adult Cohort which surveyed children born 1984-1999 and followed through 2016 (n = 5521). Outcomes included alcohol and cannabis use frequency at ages 15-18, and high school completion by age 19. ECA at ages 0-4 was a cumulative score of maternal heavy drinking/drug use, low emotional support, low cognitive stimulation, and household poverty. Multilevel path models were conducted with ECA, childhood mediators (behavioral (externalizing and internalizing problems) and academics (reading and math scores), accounting for demographics and confounders. RESULTS: ECA was indirectly associated with adolescent cannabis frequency through mediators of externalizing/internalizing problems, low academics, and early cannabis onset before age 14. ECA was also indirectly associated with alcohol frequency via the same mediators, but not early alcohol onset. Greater behavioral problems elevated substance use risk; whereas, low academics reduced risk. Reciprocal effects were evident between childhood behavioral problems and cannabis frequency to high school completion. CONCLUSION: Adversity from birth to age 4 is associated with childhood behavioral problems and lower academics, which increased adolescent alcohol and cannabis use and lowered high school completion. Early childhood interventions with parents and preschools/daycare may reduce early onset and adolescent substance use.

Synthesis and in vitro antiprotozoal evaluation of novel metronidazole-Schiff base hybrids.

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T. vaginalis, exhibiting IC50 values < 5 µM. Compound 20, the most active compound against T. vaginalis, exhibited an IC50 value of 3.4 µM. A few compounds also exhibited activity against Plasmodium falciparum and Trypanosomal brucei brucei, with compound 6 exhibiting an IC50 value of 0.7 µM against P. falciparum and compound 22 exhibiting an IC50 value of 1.4 µM against T.b. brucei. Compound 22 is a broad-spectrum antiprotozoal agent, showing activities against all three pathogenic protozoans under investigation.

Ethnic enclaves and ethnoburbs: Are there differences in associations with juvenile offense type among Asian Americans?

Little is known about the neighborhood context of offending for Asian American youth. The current study differentiates between coethnic neighborhood types and considers if residence in ethnoburbs-a more recently conceptualized coethnic neighborhood-is associated with more serious arrests (for substance, property, weapon, or violent offenses). Asian youth in ethnic enclaves had lower odds of a violence arrest relative to youth in non-coethnic neighborhoods. Youth in ethnoburbs had greater odds of a weapons arrest, but this association is attenuated after adjusting for individual-level covariates. Implications for future research include exploring mechanisms for place-based targeted intervention strategies.

Valorizing Tree-Nutshell Particles as Delivery Vehicles for a Natural Herbicide.

The United States is a principal producer of tree nuts (almonds, pistachios, and walnuts), resulting in the generation of excess of tree-nutshell by-products each year, with few market outlets. A nutshell is an essential, lignocellulosic layer that protects a kernel (seed) from the environment during cultivation. The objective of this study was to develop nutshell by-products as herbicide delivery systems, which would not only enable sustainable weed control in fields but also increases nutshell value and reduce the cost of waste disposal. We recently identified a natural salicylaldehyde (SA) that emits volatiles with both herbicidal and antifungal properties. In this study, walnut shell particles saturated with 0.8 to 1.6 M SA were developed as delivery vehicles for SA to soil, which allowed for the controlled release of an SA fumigant for weed control. The pre- and post-emergent herbicidal efficacy of SA was investigated using model monocot (Lolium arundinaceum (Schreb.) Darbysh; turfgrass) and dicot (Brassica rapa var. pekinensis; Chinese cabbage) plants. We compared (1) the effects of different types of solvents for dissolving SA (dimethyl sulfoxide (DMSO) and ethanol (60%, v/v)), and (2) the effect of covering soil with plastic layers (i.e., soil pasteurization) or not covering soil during SA fumigation using nutshells. Results: In the pre-emergent herbicidal testing with the soil covered, the dicot plants exhibited levels of higher susceptibility to SA in DMSO emitted from nutshells when compared to the monocot plants. The seed germination frequencies in the dicots were 15% and 1% with 0.8 and 1.6 M SA, respectively, while those in the monocots were 32% and 18%, respectively, under the same test conditions. In the post-emergent herbicidal testing with the soil covered, the growth of both the monocot and dicot plants was completely prevented after 5 to 7 days of SA fumigation, resulting in the deaths of entire plants. It was noteworthy that in the post-emergent herbicidal testing, SA dissolved in ethanol (60%, v/v) completely disrupted the growth of the monocot and dicot plants as early as 3 days after SA emission from the nutshells, even without the soil being covered. Tree-nutshell particles could serve as effective SA delivery vehicles with controlled release capabilities for SA. The SA exhibited pre- and post-emergent herbicidal activities against the monocot and dicot plants at most growth stages. SA (0.8 and 1.6 M) dissolved in ethanol (60%, v/v) might exert a synergism for higher herbicidal activity after emission from nutshells. Since tree nuts capture/store a substantial amount of carbon over their life-cycles, the new and sustainable utility of using nutshells not only reduces carbon emissions but also valorizes tree-nut by-products, thus benefitting the tree-nut industry.

Age of onset and alcohol and cannabis use disorders among Mexican American young adults: Robust substance-specific effects of early use as a risk factor.

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD.

Associations of clustered health risk behaviors with diabetes and hypertension in White, Black, Hispanic, and Asian American adults.

BACKGROUND: The clustering of Big Four contributors to morbidity and mortality-alcohol misuse, smoking, poor diet, and physical inactivity-may further elevate chronic health risk, but there is limited information about their specific combinations and associated health risks for racial/ethnic minority groups. We aimed to examine patterns of clustering in risk behaviors for White, Black, Hispanic, and Asian American adults and their associations with diabetes and hypertension. As these behaviors may be socioeconomically-patterned, we also examined associations between clustering and socioeconomic status (SES). METHODS: Latent class analyses and multinomial and logistic regressions were conducted using a nationally-representative sample of United States (US) adults ages 40-70 (N = 35,322) from Waves 2 (2004-2005) and 3 (2012-2013) of the National Epidemiologic Survey on Alcohol and Related Conditions. Obesity was used as a proxy for unhealthy diet. The outcomes were diabetes and hypertension. RESULTS: A relatively-healthy-lifestyle class was found only among White adults. Common patterns of unhealthy clustering were found across groups with some variations: the obese-inactive class among White, Black, and Hispanic adults (and the inactive class among Asian adults); the obese-inactive-smoking class among White, Black, and Hispanic adults; the smoking-risky-drinking class among White and Hispanic adults; and the smoking-risky-drinking-inactive class among Black and Asian adults. Positive associations of unhealthier clustering (having a greater number of risk behaviors) with lower SES (i.e., family income and education) and with health conditions were more consistent for Whites than for other groups. For racial minority groups, lower education than income was more consistently associated with unhealthy clusters. The associations between unhealthier clustering and diabetes and hypertension were less clear for Blacks and Asians than for Whites, with no significant association observed for Hispanics. CONCLUSION: Concerted efforts to address clustered risk behaviors in most US adults, particularly in racial/ethnic minority groups given the high prevalence of unhealthy clustering, are warranted.

Antimicrobial properties of tomato leaves, stems, and fruit and their relationship to chemical composition.

BACKGROUND: We previously reported that the tomato glycoalkaloid tomatine inhibited the growth of Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus-like strain C1 that cause disease in humans and farm and domesticated animals. The increasing prevalence of antibiotic resistance requires development of new tools to enhance or replace medicinal antibiotics. METHODS: Wild tomato plants were harvested and divided into leaves, stems, and fruit of different colors: green, yellow, and red. Samples were freeze dried and ground with a handheld mill. The resulting powders were evaluated for their potential anti-microbial effects on protozoan parasites, bacteria, and fungi. A concentration of 0.02% (w/v) was used for the inhibition of protozoan parasites. A high concentration of 10% (w/v) solution was tested for bacteria and fungi as an initial screen to evaluate potential anti-microbial activity and results using this high concentration limits its clinical relevance. RESULTS: Natural powders derived from various parts of tomato plants were all effective in inhibiting the growth of the three trichomonads to varying degrees. Test samples from leaves, stems, and immature 'green' tomato peels and fruit, all containing tomatine, were more effective as an inhibitor of the D1 strain than those prepared from yellow and red tomato peels which lack tomatine. Chlorogenic acid and quercetin glycosides were present in all parts of the plant and fruit, while caffeic acid was only found in the fruit peels. Any correlation between plant components and inhibition of the G3 and C1 strains was not apparent, although all the powders were variably effective. Tomato leaf was the most effective powder in all strains, and was also the highest in tomatine. S. enterica showed a minor susceptibility while B. cereus and C. albicans fungi both showed a significant growth inhibition with some of the test powders. The powders inhibited growth of the pathogens without affecting beneficial lactobacilli found in the normal flora of the vagina. CONCLUSIONS: The results suggest that powders prepared from tomato leaves, stems, and green tomato peels and to a lesser extent from peels from yellow and red tomatoes offer potential multiple health benefits against infections caused by pathogenic protozoa, bacteria, and fungi, without affecting beneficial lactobacilli that also reside in the normal flora of the vagina.

Antifungal Efficacy of Redox-Active Natamycin against Some Foodborne Fungi-Comparison with Aspergillus fumigatus.

The fungal antioxidant system is one of the targets of the redox-active polyene antifungal drugs, including amphotericin B (AMB), nystatin (NYS), and natamycin (NAT). Besides medical applications, NAT has been used in industry for preserving foods and crops. In this study, we investigated two parameters (pH and food ingredients) affecting NAT efficacy. In the human pathogen, Aspergillus fumigatus, NAT (2 to 16 µg mL-1) exerted higher activity at pH 5.6 than at pH 3.5 on a defined medium. In contrast, NAT exhibited higher activity at pH 3.5 than at pH 5.6 against foodborne fungal contaminants, Aspergillus flavus, Aspergillus parasiticus, and Penicillium expansum, with P. expansum being the most sensitive. In commercial food matrices (10 organic fruit juices), food ingredients differentially affected NAT antifungal efficacy. Noteworthily, NAT overcame tolerance of the A. fumigatus signaling mutants to the fungicide fludioxonil and exerted antifungal synergism with the secondary metabolite, kojic acid (KA). Altogether, NAT exhibited better antifungal activity at acidic pH against foodborne fungi; however, the ingredients from commercial food matrices presented greater impact on NAT efficacy compared to pH values. Comprehensive determination of parameters affecting NAT efficacy and improved food formulation will promote sustainable food/crop production, food safety, and public health.

Quercetin Ameliorates Insulin Resistance and Restores Gut Microbiome in Mice on High-Fat Diets.

Quercetin is a flavonoid that has been shown to have health-promoting capacities due to its potent antioxidant activity. However, the effect of chronic intake of quercetin on the gut microbiome and diabetes-related biomarkers remains unclear. Male C57BL/6J mice were fed HF or HF supplemented with 0.05% quercetin (HFQ) for 6 weeks. Diabetes-related biomarkers in blood were determined in mice fed high-fat (HF) diets supplemented with quercetin. Mice fed the HFQ diet gained less body, liver, and adipose weight, while liver lipid and blood glucose levels were also lowered. Diabetes-related plasma biomarkers insulin, leptin, resistin, and glucagon were significantly reduced by quercetin supplementation. In feces, quercetin supplementation significantly increased the relative abundance of Akkermansia and decreased the Firmicutes/Bacteroidetes ratio. The expression of genes Srebf1, Ppara, Cyp51, Scd1, and Fasn was downregulated by quercetin supplementation. These results indicated that diabetes biomarkers are associated with early metabolic changes accompanying obesity, and quercetin may ameliorate insulin resistance.

Evaluation of Cellular Absorption and Metabolism of ß-Carotene Loaded in Nanocarriers after In Vitro Digestion.

Three protein emulsifiers encapsulating ß-carotene (BC) with accompanying lipids into nanoemulsions (NEs) or without lipids into nanoparticles (NPs) were fabricated to study the effect of the type of interfacial protein on carrier design and the structure remodeling during digestion on the overall uptake and metabolism of BC in Caco-2 cells. BC-loaded micelles and micellar-like aggregates were collected after in vitro digestion and applied to Caco-2 cell monolayers. The digestion process significantly enhanced the cellular uptake of BC by 1.2-2.2 times and 4.1-8.2 times loaded in NEs and NPs, respectively. Whey protein isolate-based carriers improved the absorption but decreased the metabolism of BC to retinyl palmitate. The presence of lipids was found to improve metabolism and aid the transport of retinoids to the basolateral side of Caco-2 monolayers. Understanding the transportation behavior of the protein-based nanocarries after digestion may contribute to the design of biosafe carriers with higher bioavailability to deliver lipophilic nutrients.

Cooked Black Turtle Beans Ameliorate Insulin Resistance and Restore Gut Microbiota in C57BL/6J Mice on High-Fat Diets.

Colored common beans are associated with health promoting and chronic disease prevention effects. Male C57BL/6J mice were fed high-fat (HF) diets supplemented with cooked black turtle beans (HFB) to prevent obesity related insulin resistance. Mice on both HF and HFB were obese compared to mice fed a low-fat (LF) diet. Plasma low density lipoprotein (LDL) and triglyceride concentrations of mice fed HFB diet were 28% and 36.6% lower than those on HF diet. Homeostatic model assessment of insulin resistance (HOMA-IR) index of mice fed HFB diet was 87% lower than that of mice fed HF diet. Diabetes related biomarkers, gastric inhibitory polypeptide (GIP), leptin, glucagon, and inflammatory cytokines interleukin 4 (IL-4) and IL-5, 10 and 12, IFN-g and TNF-α were significantly affected by HFB diet. Pparα, Cyp7a1 and Fasn were down-regulated by HFB diet while LDL-R, Srebp-2, Adipoq and Slc2a4 were up-regulated by HFB diet. The ratio of Firmicutes/Bacteroidetes (F/B) was also decreased 64.1% by HFB diet compared to HF diet. The results indicated that cooked black turtle bean consumption could ameliorate insulin resistance and lower plasma LDL in mice fed HF diet through glucose signaling pathway and JNK/c-Jun pathway. Meanwhile, cooked black turtle bean consumption restored the gut microbiome.

Bioactive half-sandwich Rh and Ir bipyridyl complexes containing artemisinin.

Reaction of dihydroartemisinin (DHA) with 4-methyl-4'-carboxy-2,2'-bipyridine yielded the new ester derivative L1. Six novel organometallic half-sandwich chlorido Rh(III) and Ir(III) complexes (1-6) containing pentamethylcyclopentadienyl, (Cp*), tetramethylphenylcyclopentadienyl (Cpxph), or tetramethylbiphenylcyclopentadienyl (Cpxbiph), and N,N-chelated bipyridyl group of L1, have been synthesized and characterized. The complexes were screened for inhibitory activity against the Plasmodium falciparum 3D7 (sensitive), Dd2 (multi-drug resistant) and NF54 late stage gametocytes (LSGNF54), the parasite strain Trichomonas vaginalis G3, as well as A2780 (human ovarian carcinoma), A549 (human alveolar adenocarcinoma), HCT116 (human colorectal carcinoma), MCF7 (human breast cancer) and PC3 (human prostate cancer) cancer cell lines. They show nanomolar antiplasmodial activity, outperforming chloroquine and artemisinin. Their activities were also comparable to dihydroartemisinin. As anticancer agents, several of the complexes showed high inhibitory effects, with Ir(III) complex 3, containing the tetramethylbiphenylcyclopentadienyl ligand, having similar IC50 values (concentration for 50% of maximum inhibition of cell growth) as the clinical drug cisplatin (1.06-9.23 µM versus 0.24-7.2 µM, respectively). Overall, the iridium complexes (1-3) are more potent compared to the rhodium derivatives (4-6), and complex 3 emerges as the most promising candidate for future studies.

Drinking and Neighborhood Contexts of Alcohol's Harms from Others.

AIMS: Negative consequences of alcohol (or secondhand effects) extend beyond drinkers to affect other people, including both known others (friends, family members, spouses/partners) and strangers. Secondhand effects of alcohol manifest across various social environments, including the places where people drink and the neighborhoods where they live. These neighborhoods are characterized by different levels of alcohol availability and degrees of residential social cohesion. Hence, social environments may confer risk or protect from harms from others' drinking. The current study explores: (a) how drinking venues and neighborhood contexts relate to harms from other people's drinking (both known others and strangers), and (b) whether these associations vary by gender. METHODS: Using pooled data from the National Alcohol Survey and National Alcohol's Harms to Others Survey (N = 5425), we regressed harms from various drinking others on social environment characteristics (drinking venues, alcohol availability and social cohesion) for the full sample and separately by gender. We used the false discovery rate method to adjust for multiple testing. RESULTS: Overall, greater neighborhood social cohesion was associated with lower odds of harm from drinking others and, specifically, harm from drinking strangers. The effect of social cohesion was most pronounced for men. CONCLUSIONS: Social cohesion was the most salient neighborhood factor associated with reduced alcohol-related harms from strangers. Directions for future research and policies to mitigate these harms are discussed.

Anti-Parasitic Activity of Cherry Tomato Peel Powders.

Trichomoniasis in humans, caused by the protozoal parasite Trichomonas vaginalis, is the most common non-viral sexually transmitted disease, while Tritrichomonas foetus causes trichomonosis, an infection of the gastrointestinal tract and diarrhea in farm animals and domesticated cats. As part of an effort to determine the inhibitory effects of plant-based extracts and pure compounds, seven commercially available cherry tomato varieties were hand-peeled, freeze-dried, and pounded into powders. The anti-trichomonad inhibitory activities of these peel powders at 0.02% concentration determined using an in vitro cell assay varied widely from 0.0% to 66.7% against T. vaginalis G3 (human); from 0.9% to 66.8% for T. foetus C1 (feline); and from 0.0% to 81.3% for T. foetus D1 (bovine). The organic Solanum lycopersicum var. cerasiforme (D) peels were the most active against all three trichomonads, inhibiting 52.2% (G3), 66.8% (C1), and 81.3% (D1). Additional assays showed that none of the powders inhibited the growth of foodborne pathogenic bacteria, pathogenic fungi, or non-pathogenic lactobacilli. Tomato peel and pomace powders with high content of described biologically active compounds could serve as functional food and feed additives that might help overcome adverse effects of wide-ranging diseases and complement the treatment of parasites with the anti-trichomonad drug metronidazole.