A Randomized, Parallel Design Study to Compare the Effects of Two Different Interdental Cleaning Modalities on Gingivitis and Plaque After a 4-Week Period of Home Use.

The study objective was to evaluate the effect of two different interdental oral cleaning modalities on gingivitis and plaque following a 4-week period of home use. This was a randomized, parallel, single-blinded study. Subjects were routine manual toothbrush (MTB) users with moderate to severe gingivitis, aged 18 to 65 years. Subjects were required at baseline to have a gingival bleeding score of ≥1 on at least 50 gingival sites per the Gingival Bleeding Index (GBI) and to have an overall plaque score of ≥0.6 per the Rustogi Modified Navy Plaque Index (RMNPI) following a 3- to 6-hour plaque accumulation period. Subjects were randomly assigned to one of three groups based on the oral care cleaning modalities: (1) NON group: MTB alone, (2) IDB group: MTB plus an interdental brush, or (3) MPF group: MTB plus a Philips® Sonicare® Power Flosser with the Quad Stream nozzle. All subjects used the MTB with fluoride toothpaste. Efficacy measures (Modified Gingival Index [MGI], GBI, and RMNPI) and safety were assessed at baseline, 2 weeks, and 4 weeks. The primary efficacy endpoint was the reduction in gingival inflammation from baseline to week 4 as measured by the MGI. A total of 189 subjects were randomized and 186 completed the study. The adjusted mean percent reduction in gingival inflammation from baseline to week 4 was 2.80% for the NON group, 11.32% for the IDB group, and 20.87% for the MPF group. The differences between the MPF group and the NON and IDB groups were statistically significant (.0001). In conclusion, use of the MTB with the Philips Sonicare Power Flosser showed statistically significant benefits compared to an MTB alone and an MTB used with an interdental brush in reducing gingival inflammation following 4 weeks of home use.

A Randomized, Parallel Design Study to Compare the Effects of Different Interdental Cleaning Modalities on Gingivitis and Plaque After a 6-Week Period of Home Use.

The objective of this study was to evaluate the effect of different interdental oral cleaning modalities on gingivitis and plaque following a 6-week period of home use. This was a randomized, four-arm, parallel design clinical trial. Study subjects were manual toothbrush (MTB) users with moderate to severe gingivitis, aged 18 to 65 years. Subjects were required at baseline to have a gingival bleeding score of ≥1 on at least 50 gingival sites per the Gingival Bleeding Index (GBI) and to have an overall plaque score of ≥0.6 per the Rustogi Modified Navy Plaque Index (RMNPI) following a 3- to 6-hour plaque accumulation period. Subjects were randomly assigned to use one of four oral care cleaning modalities: (1) NON group: MTB alone, (2) FLS group: MTB plus string floss, (3) IDB group: MTB plus an interdental brush, or (4) CPF group: MTB plus the Philips® Sonicare® Cordless Power Flosser with the Quad Stream nozzle. Efficacy measures (Modified Gingival Index [MGI], GBI, and RMNPI) and safety were assessed at baseline, 2 weeks, and 6 weeks. The primary efficacy endpoint was the reduction in gingival inflammation from baseline to week 6 as measured by the MGI. Of the 372 subjects randomized in the study, 364 completed a post-baseline MGI evaluation and were included in the analyses. The adjusted mean percent reduction in gingival inflammation from baseline to week 6 was -2.10% for the NON group, 2.82% for the FLS group, 2.60% for the IDB group, and 29.10% for the CPF group. Pairwise comparisons indicated that the CPF group was statistically significantly different from the NON, FLS, and IDB groups (.0001). In conclusion, adjunctive use of the Philips Sonicare Cordless Power Flosser with the Quad Stream nozzle and an MTB showed statistically better results in term of reducing gingival inflammation following 6 weeks of home use when compared to an MTB alone, an MTB used with string floss, and an MTB used with an interdental brush.

The effects of scaling and root planing plus home oral hygiene maintenance in Stage I/II periodontitis population: A 24-week randomized clinical trial.

OBJECTIVES: To compare the effects of powered and manual toothbrushing following scaling and root planing on bleeding on probing and other clinical indicators of periodontitis. MATERIALS AND METHODS: This was a randomized, examiner-blind, parallel-design, 24-week clinical study. Eligible subjects were 18-75 years of age with Stage I or II periodontitis. All subjects received scaling and root planing (SRP) within 28 days of enrollment. Thereafter, subjects were randomized to twice daily at-home use of either a powered toothbrush (PTB) or a manual toothbrush (MTB). Randomization was balanced for gender and periodontitis stage. No other oral hygiene aids were permitted. Subjects were evaluated every 4 weeks for the following measures: bleeding on probing (BOP), surface plaque (MPI), probing pocket depth (PPD) and clinical attachment level until Week 24. RESULTS: Of 328 randomized subjects, 299 subjects completed the study. For BOP at Week 24, the Least Squares (LS) Mean, standard error (SE) reduction from baseline was 0.24 (0.01) for the PTB group and 0.02 (0.01) for the MTB group, resulting in a statistically significant treatment difference of 0.22 (0.01), p-value < 0.0001. There were also concomitant reductions in MPI and PPD at Week 24, resulting in statistically significant (p-value < 0.0001) LS Mean (SE) treatment differences of 0.86 (0.04) and 0.24 (0.01), for MPI and PPD, respectively. CONCLUSION: When combined with SRP, daily home oral hygiene maintenance including a powered toothbrush significantly reduced clinical symptoms of periodontitis and surface plaque levels compared to a manual toothbrush in a Stage I/II periodontitis population. (ClinicalTrials.gov Identifier: NCT04254770).

Th2 cytokine signaling through IL-4Rα increases eotaxin-3 secretion and tension in human esophageal smooth muscle.

In esophageal epithelial cells in eosinophilic esophagitis (EoE), Th2 cytokines (IL-4, IL-13) signal through IL-4Rα, activating JAK to increase eotaxin-3 secretion, which draws eosinophils into the mucosa. We explored whether Th2 cytokines also might stimulate eotaxin-3 secretion and increase tension in esophageal smooth muscle (ESM), which might impair esophageal distensibility, and whether those events could be blocked by proton pump inhibitors (PPIs) or agents that disrupt IL-4Rα signaling. We established human ESM cell cultures from organ donors, characterizing Th2 cytokine receptor and P-type ATPase expression by qPCR. We measured Th2 cytokine-stimulated eotaxin-3 secretion by enzyme-linked immunosorbent assay (ELISA) and ESM cell tension by gel contraction assay, before and after treatment with omeprazole, ruxolitinib (JAK inhibitor), or IL-4Rα blocking antibody. CPI-17 (inhibitor of a muscle-relaxing enzyme) effects were studied with CPI-17 knockdown by siRNA or CPI-17 phospho(T38A)-mutant overexpression. ESM cells expressed IL-4Rα and IL-13Rα1 but only minimal H+-K+-ATPase mRNA. Th2 cytokines increased ESM eotaxin-3 secretion and tension, effects blocked by ruxolitinib and IL-4Rα blocking antibody but not consistently blocked by omeprazole. IL-13 increased ESM tension by increasing CPI-17 expression and phosphorylation, effects blocked by CPI-17 knockdown. Blocking IL-4Rα decreased IL-13-stimulated eotaxin-3 secretion, CPI-17 expression, and tension in ESM. Th2 cytokines increase ESM eotaxin-3 secretion and tension via IL-4Rα signaling that activates CPI-17. Omeprazole does not reliably inhibit this process, but IL-4Rα blocking antibody does. This suggests that ESM eosinophilia and impaired esophageal distensibility might persist despite elimination of mucosal eosinophils by PPIs, and IL-4Rα blocking agents might be especially useful in this circumstance.NEW & NOTEWORTHY We have found that Th2 cytokines increase eotaxin-3 secretion and tension in esophageal smooth muscle (ESM) cells via IL-4Rα signaling. Unlike esophageal epithelial cells, ESM cells do not express H+-K+-ATPase, and omeprazole does not inhibit their cytokine-stimulated eotaxin-3 secretion or tension. An IL-4Rα blocking antibody reduces both eotaxin-3 secretion and tension induced by Th2 cytokines in ESM cells, suggesting that an agent such as dupilumab might be preferred for patients with EoE with esophageal muscle involvement.

#DebunkingDesire: Sexual Science, Social Media, and Strategy in the Pursuit of Knowledge Dissemination.

Approximately 1 in 3 women experience low sexual desire. Despite this being a common concern, many women never seek professional help for their difficulties and will instead turn to online resources for information. We sought to address this need for digitally-accessible, evidence-based information on low sexual desire by creating a social media Knowledge Translation (KT) campaign called #DebunkingDesire. Our team led a 10 month social media campaign where our primary outcomes for the campaign were impressions, reach, and engagement. We generated over 300,000 social media impressions; appeared on 11 different podcasts that were listened to/downloaded 154,700 times; hosted and participated in eight online events; and attracted website users from 110 different countries. Over the course of the campaign we compiled lessons learned on what worked for disseminating our key messages and the importance of creating community for this population. These findings point to the utility of using social media as part of KT campaigns in sexual health, and to the importance of collaborating with patient partners and considering social media ads and podcasts to meet reach goals.

Bridging Health Disparities and Improving Reproductive Outcomes With Health Center-Affiliated Doula Programs.

Doulas are community perinatal professionals trained in pregnancy health, childbirth preparation, labor support, lactation counseling, and postnatal care. Doulas serve as patient advocates and provide laboring patients with continuous one-to-one support including informational, physical, and emotional support. Research shows that access to continuous labor support contributes to positive health outcomes such as increasing rates of spontaneous vaginal delivery, shorter labor, less need for analgesics, and increased satisfaction with the birthing process. However, despite their benefits, socioeconomic, structural, and systemic factors limit doula accessibility and manifest in low utilization among patients who could benefit from doulas the most. Given the positive health implications of doula support and the need for these services in underserved populations, there is an urgency to increase the accessibility of doulas. Several health centers in the United States have created successful doula programs to meet the needs of their patient populations. To better understand these programs, we interviewed and collaborated on this paper with program representatives from Boston Medical Center's Birth Sisters and DREAM: Delivery Resources, Education, and Advocacy for Moms; UNC Health's Birth Partners; and Michigan Medicine's Dial-A-Doula. Because many health centers serve as large public safety-net hospitals, having more health center-affiliated doula programs nationwide could be a positive step in bridging disparities and improving maternal and child health.

Placing diverse knowledge systems at the core of transformative climate research.

We argue that solutions-based research must avoid treating climate change as a merely technical problem, recognizing instead that it is symptomatic of the history of European and North American colonialism. It must therefore be addressed by decolonizing the research process and transforming relations between scientific expertise and the knowledge systems of Indigenous Peoples and of local communities. Partnership across diverse knowledge systems can be a path to transformative change only if those systems are respected in their entirety, as indivisible cultural wholes of knowledge, practices, values, and worldviews. This argument grounds our specific recommendations for governance at the local, national, and international scales. As concrete mechanisms to guide collaboration across knowledge systems, we propose a set of instruments based on the principles of consent, intellectual and cultural autonomy, and justice. We recommend these instruments as tools to ensure that collaborations across knowledge systems embody just partnerships in support of a decolonial transformation of relations between human communities and between humanity and the more-than-human world.

Percutaneous thoraco-lumbar-sacral pedicle screw placement accuracy results from a multi-center, prospective clinical study using a skin marker-based optical navigation system.

STUDY DESIGN: Prospective multi-center study. OBJECTIVE: The study aimed to evaluate the accuracy of pedicle screw placement using a skin marker-based optical surgical navigation system for minimal invasive thoraco-lumbar-sacral pedicle screw placement. METHODS: The study was performed in a hybrid Operating Room with a video camera-based navigation system integrated in the imaging hardware. The patient was tracked with non-invasive skin markers while the instrument tracking was via an on-shaft optical marker pattern. The screw placement accuracy assessment was performed by three independent reviewers, using the Gertzbein grading. The screw placement time as well as the staff and patient radiation doses was also measured. RESULTS: In total, 211 screws in 39 patients were analyzed for screw placement accuracy. Of these 32.7% were in the thoracic region, 59.7% were in the lumbar region, and 7.6% were in the sacral region. An overall accuracy of 98.1% was achieved. No screws were deemed severely misplaced (Gertzbein grading 3). The average time for screw placement was 6 min and 25 secs (± 3 min 33 secs). The average operator radiation dose per subject was 40.3 µSv. The mean patient effective dose (ED) was 11.94 mSv. CONCLUSION: Skin marker-based ON can be used to achieve very accurate thoracolumbarsacral pedicle screw placements.

Comparative cost of diets for low-income families in the Caribbean.

Objective: To assess the ability of low-income families to obtain a standard basket of healthy foods before and during the COVID-19 pandemic. Methods: The costs of 191 food items were averaged from supermarkets, municipal markets, wholesalers, and community food outlets in high- and low-income areas in three Caribbean countries. The analysis compared foods not only by selecting high- and low-ranked commodities but by the proportions of those foods, by food group, that will be required to meet a low-cost, nutritionally balanced diet of 2 400 kcal. Results: The main finding was that low-income households will need between 22% and 47% of their earnings to obtain a healthy diet. Despite higher food prices in Saint Kitts and Nevis, low-income households there will need a smaller proportion of their income to obtain a similar basket of foods than in Jamaica or Saint Vincent and the Grenadines. Conclusions: While the COVID-19 pandemic has added economic stressors to low-income households the basic vulnerability of the poor to obtain a healthy diet remains. Despite country variations, the findings point to the need for an increase in the minimum wage, particularly in Jamaica. It is essential to embed policies that ensure reduced economic and social vulnerability at the household level.

Experiences of a Regional Quality Improvement Collaborative to Reduce Unplanned Extubations in the Neonatal Intensive Care Unit.

BACKGROUND: Unplanned extubations (UEs) occur frequently in the neonatal intensive care unit (NICU). These events can be associated with serious short-term and long-term morbidities and increased healthcare costs. Most quality improvement (QI) initiatives focused on UE prevention have concentrated efforts within individual NICUs. METHODS: We formed a regional QI collaborative involving the four regional perinatal center (RPC) NICUs in upstate New York to reduce UEs. The collaborative promoted shared learning and targeted interventions specific to UE classification at each center. RESULTS: There were 1167 UEs overall during the four-year project. Following implementation of one or more PDSA cycles, the combined UE rate decreased by 32% from 3.7 to 2.5 per 100 ventilator days across the collaborative. A special cause variation was observed for the subtype of UEs involving removed endotracheal tubes (rETTs), but not for dislodged endotracheal tubes (dETTs). The center-specific UE rates varied; only two centers observed significant improvement. CONCLUSIONS: A collaborative approach promoted knowledge sharing and fostered an overall improvement, although the individual centers' successes varied. Frequent communication and shared learning experiences benefited all the participants, but local care practices and varying degrees of QI experience affected each center's ability to successfully implement potentially better practices to prevent UEs.

Is Myofascial Decompression Effective at Increasing Hamstring Flexibility in the Athletic Population? A Critically Appraised Topic.

CLINICAL SCENARIO: There are a variety of therapeutic modalities used to treat flexibility issues in athletes, which can be the main cause of hamstring injuries. Myofascial decompression is one modality used to treat these patients. FOCUSED CLINICAL QUESTION: Is myofascial decompression effective at increasing hamstring flexibility in the athletic population? Summary of Search, "Best Evidence" Appraised, and Key Findings: The literature was searched for studies of level 2 evidence or higher that investigated the use of myofascial decompression to increase hamstring flexibility, that were published in the last 5 years. Two high-quality randomized controlled trials were included and one cohort study. CLINICAL BOTTOM LINE: There is not enough consistent, clinically significant, high-level evidence to support the use of myofascial decompression to increase hamstring flexibility. STRENGTH OF RECOMMENDATION: There is level B evidence to support that myofascial decompression is effective at increasing hamstring flexibility.

Comparative cost of diets for low-income families in the Caribbean

[ABSTRACT]. Objective. To assess the ability of low-income families to obtain a standard basket of healthy foods before and during the COVID-19 pandemic. Methods. The costs of 191 food items were averaged from supermarkets, municipal markets, wholesalers, and community food outlets in high- and low-income areas in three Caribbean countries. The analysis compared foods not only by selecting high- and low-ranked commodities but by the proportions of those foods, by food group, that will be required to meet a low-cost, nutritionally balanced diet of 2 400 kcal. Results. The main finding was that low-income households will need between 22% and 47% of their earnings to obtain a healthy diet. Despite higher food prices in Saint Kitts and Nevis, low-income households there will need a smaller proportion of their income to obtain a similar basket of foods than in Jamaica or Saint Vincent and the Grenadines. Conclusions. While the COVID-19 pandemic has added economic stressors to low-income households the basic vulnerability of the poor to obtain a healthy diet remains. Despite country variations, the findings point to the need for an increase in the minimum wage, particularly in Jamaica. It is essential to embed policies that ensure reduced economic and social vulnerability at the household level.

[RESUMEN]. Objetivo. Evaluar la capacidad de las familias de bajos ingresos para obtener una cesta estándar de alimentos saludables antes y durante la pandemia de COVID-19. Métodos. Se promediaron los costos de 191 alimentos en supermercados, mercados municipales, mayoristas y puestos de venta de alimentos en la comunidad en zonas de altos y bajos ingresos de tres países del Caribe. En el análisis se compararon los comestibles por grupo de alimentos mediante una selección de productos de alto y bajo rango, así como por las proporciones necesarias para tener un régimen alimentario nutricionalmente equilibrado de 2 400 kcal y de bajo costo. Resultados. La conclusión principal fue que los hogares de bajos ingresos necesitan entre 22% y 47% de sus ingresos para tener un régimen alimentario saludable. A pesar de los elevados precios de los alimentos en Saint Kitts y Nevis, los hogares de bajos ingresos necesitarán una proporción menor de sus ingresos para obtener una cesta de alimentos similar en Jamaica o San Vicente y las Granadinas. Conclusiones. La vulnerabilidad básica de las personas pobres para tener un régimen alimentario saludable persiste, a lo que se suma que la pandemia de COVID-19 ha agregado factores económicos estresantes a los hogares de bajos ingresos. A pesar de las variaciones entre países, los resultados apuntan a la necesidad de incrementar el salario mínimo, particularmente en Jamaica. Es esencial incorporar políticas que garanticen una reducción de la vulnerabilidad económica y social a nivel de los hogares.

[RESUMO]. Objetivo. Avaliar a capacidade das famílias de baixa renda de adquirir uma cesta básica de alimentos saudáveis antes e durante a pandemia de COVID-19. Métodos. Calculou-se a média do custo de 191 produtos alimentícios em supermercados, mercados municipais, atacadistas e estabelecimentos comunitários em áreas de alta e baixa renda em três países do Caribe. A análise comparou os alimentos não apenas pela escolha de produtos classificados em posição alta e baixa, mas também pelas proporções desses alimentos, por grupo alimentar, necessárias para ter uma alimentação de baixo custo e nutricionalmente equilibrada, com 2 400 kcal. Resultados. A principal constatação foi que as famílias de baixa renda precisarão gastar entre 22% e 47% de sua renda para ter uma alimentação saudável. Apesar do maior preço dos alimentos em Saint Kitts e Nevis, as famílias de baixa renda nesse país precisarão usar uma menor proporção da renda para comprar uma cesta de alimentos semelhante à adquirida na Jamaica ou em São Vicente e Granadinas. Conclusões. Embora a pandemia de COVID-19 tenha agregado fatores de estresse econômico às famílias de baixa renda, persiste a vulnerabilidade subjacente das pessoas pobres em relação à obtenção de uma alimentação saudável. Apesar das variações entre os países, as constatações indicam a necessidade de um aumento do salário mínimo, sobretudo na Jamaica. É essencial a incorporação de políticas que reduzam a vulnerabilidade econômica e social no âmbito familiar.

Comparative cost of diets for low-income families in the Caribbean / Costo comparativo del régimen alimentario de las familias de bajos ingresos en el Caribe / Custo comparativo da alimentação para famílias de baixa renda no Caribe

ABSTRACT Objective. To assess the ability of low-income families to obtain a standard basket of healthy foods before and during the COVID-19 pandemic. Methods. The costs of 191 food items were averaged from supermarkets, municipal markets, wholesalers, and community food outlets in high- and low-income areas in three Caribbean countries. The analysis compared foods not only by selecting high- and low-ranked commodities but by the proportions of those foods, by food group, that will be required to meet a low-cost, nutritionally balanced diet of 2 400 kcal. Results. The main finding was that low-income households will need between 22% and 47% of their earnings to obtain a healthy diet. Despite higher food prices in Saint Kitts and Nevis, low-income households there will need a smaller proportion of their income to obtain a similar basket of foods than in Jamaica or Saint Vincent and the Grenadines. Conclusions. While the COVID-19 pandemic has added economic stressors to low-income households the basic vulnerability of the poor to obtain a healthy diet remains. Despite country variations, the findings point to the need for an increase in the minimum wage, particularly in Jamaica. It is essential to embed policies that ensure reduced economic and social vulnerability at the household level.

RESUMEN Objetivo. Evaluar la capacidad de las familias de bajos ingresos para obtener una cesta estándar de alimentos saludables antes y durante la pandemia de COVID-19. Métodos. Se promediaron los costos de 191 alimentos en supermercados, mercados municipales, mayoristas y puestos de venta de alimentos en la comunidad en zonas de altos y bajos ingresos de tres países del Caribe. En el análisis se compararon los comestibles por grupo de alimentos mediante una selección de productos de alto y bajo rango, así como por las proporciones necesarias para tener un régimen alimentario nutricionalmente equilibrado de 2 400 kcal y de bajo costo. Resultados. La conclusión principal fue que los hogares de bajos ingresos necesitan entre 22% y 47% de sus ingresos para tener un régimen alimentario saludable. A pesar de los elevados precios de los alimentos en Saint Kitts y Nevis, los hogares de bajos ingresos necesitarán una proporción menor de sus ingresos para obtener una cesta de alimentos similar en Jamaica o San Vicente y las Granadinas. Conclusiones. La vulnerabilidad básica de las personas pobres para tener un régimen alimentario saludable persiste, a lo que se suma que la pandemia de COVID-19 ha agregado factores económicos estresantes a los hogares de bajos ingresos. A pesar de las variaciones entre países, los resultados apuntan a la necesidad de incrementar el salario mínimo, particularmente en Jamaica. Es esencial incorporar políticas que garanticen una reducción de la vulnerabilidad económica y social a nivel de los hogares.

RESUMO Objetivo. Avaliar a capacidade das famílias de baixa renda de adquirir uma cesta básica de alimentos saudáveis antes e durante a pandemia de COVID-19. Métodos. Calculou-se a média do custo de 191 produtos alimentícios em supermercados, mercados municipais, atacadistas e estabelecimentos comunitários em áreas de alta e baixa renda em três países do Caribe. A análise comparou os alimentos não apenas pela escolha de produtos classificados em posição alta e baixa, mas também pelas proporções desses alimentos, por grupo alimentar, necessárias para ter uma alimentação de baixo custo e nutricionalmente equilibrada, com 2 400 kcal. Resultados. A principal constatação foi que as famílias de baixa renda precisarão gastar entre 22% e 47% de sua renda para ter uma alimentação saudável. Apesar do maior preço dos alimentos em Saint Kitts e Nevis, as famílias de baixa renda nesse país precisarão usar uma menor proporção da renda para comprar uma cesta de alimentos semelhante à adquirida na Jamaica ou em São Vicente e Granadinas. Conclusões. Embora a pandemia de COVID-19 tenha agregado fatores de estresse econômico às famílias de baixa renda, persiste a vulnerabilidade subjacente das pessoas pobres em relação à obtenção de uma alimentação saudável. Apesar das variações entre os países, as constatações indicam a necessidade de um aumento do salário mínimo, sobretudo na Jamaica. É essencial a incorporação de políticas que reduzam a vulnerabilidade econômica e social no âmbito familiar.

A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects.

Mitragynine and 7-hydroxymitragynine (7OH) are the major alkaloids mediating the biological actions of the psychoactive plant kratom. To investigate the structure-activity relationships of mitragynine/7OH templates, we diversified the aromatic ring of the indole at the C9, C10, and C12 positions and investigated their G-protein and arrestin signaling mediated by mu opioid receptors (MOR). Three synthesized lead C9 analogs replacing the 9-OCH3 group with phenyl (4), methyl (5), or 3'-furanyl [6 (SC13)] substituents demonstrated partial agonism with a lower efficacy than DAMGO or morphine in heterologous G-protein assays and synaptic physiology. In assays limiting MOR reserve, the G-protein efficacy of all three was comparable to buprenorphine. 6 (SC13) showed MOR-dependent analgesia with potency similar to morphine without respiratory depression, hyperlocomotion, constipation, or place conditioning in mice. These results suggest the possibility of activating MOR minimally (G-protein Emax ≈ 10%) in cell lines while yet attaining maximal antinociception in vivo with reduced opioid liabilities.

Disturbance-Induced Trophic Niche Shifts In Ground Beetles (Coleoptera: Carabidae) In Restored Grasslands.

Ecosystem restoration is a critical component of land management, countering the loss of native biodiversity. Restoration efforts are enhanced by reintroducing naturally occurring ecosystem processes, including disturbances that may impact species characteristics such as niche position or niche size. In grasslands, grazing and fire affect plant diversity and habitat complexity, which potentially influence insect dietary behaviors and thus their contributions to functions like seed and arthropod predation. Using carbon and nitrogen stable isotopes, we characterized variation in the dietary niche of six ground beetle species (Coleoptera: Carabidae) in response to grazing by reintroduced bison and prescribed fire disturbances in twenty tallgrass prairies. Management disturbances did not affect activity density for most beetle species and mean trophic position was mostly unaffected. However, five of six species exhibited increased trophic niche area and breadth with disturbances, indicating a switch to a more generalist diet that incorporated a wider range of food items. The combination of bison and fire impacts may increase vegetation patchiness and heterogeneity, driving these diet changes. Morphological traits and microhabitat preferences might mediate response to disturbances and the resulting heterogeneity. Combining prescribed fire and grazing, which increases plant diversity and vegetation structural diversity, may help beetle communities establish over time and support the ecological functions to which these insects contribute.

Site selective C-H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy.

Mitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material "kratom", which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.

Randomized Placebo-Controlled Trial of Topical Mupirocin to Reduce Staphylococcus aureus Colonization in Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: To evaluate the efficacy of topical mupirocin in reducing Staphylococcus aureus colonization in infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A prospective double-blind randomized controlled trial of mupirocin vs placebo in S aureus-colonized infants was conducted in a tertiary care NICU between October 2016 and December 2019. Weekly universal active surveillance with polymerase chain reaction screening identified colonized infants. Colonized infants received a 5-day course of mupirocin (mupirocin group) or petroleum jelly (control group). Repeat courses were given for additional positive screens. RESULTS: A total of 216 infants were enrolled; 205 were included in data analyses. Primary decolonization was more successful for mupirocin-treated infants (86 of 104 [83%]) than for controls (20 of 101; 20%) (P < .001). Although recurrent S aureus colonization occurred frequently (59 of 81 [73%] mupirocin-treated and 26 of 33 [79%] controls), subsequent decolonization remained more successful for mupirocin-treated infants than for controls (38 of 49 [78%] vs 2 of 21 [10%]; P < .001). Subgroup analyses of infants of ≤30 weeks' gestational age yielded similar results; decolonization occurred more often in mupirocin-treated infants compared with control infants (63 of 76 [83%] vs 13 of 74 [18%]; P < .001). Bacterial sterile site infections tended to be less frequent in mupirocin-treated infants compared with controls (2 of 104 [2%] vs 8 of 101 [8%]; P = .057). No invasive S aureus infections occurred in mupirocin-treated infants, but 50% of infections in controls were from S aureus, and 1 resulted in death. CONCLUSIONS: Universal active surveillance and targeted treatment with topical mupirocin is a successful decolonization strategy for NICU infants and may prevent S aureus infection. However, S aureus colonization frequently recurs, necessitating repeat treatment. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02967432.