Association of Loneliness and Mindfulness in Substance Use Treatment Retention.

BACKGROUND: Elevated mental illness prevalence complicates efforts designed to address the opioid crisis in Appalachia. The recovery community acknowledges that loneliness impacts mood and engagement in care factors; however, the predictive relationship between loneliness and retention in medication-assisted outpatient treatment programs has not been explored. Our objectives were to identify associations between mental health factors and retention in treatment and elucidate treatment retention odds. Data were collected from eighty participants (n = 57 retained, n = 23 not retained) of a mindfulness-based relapse prevention (MBRP) intervention for individuals receiving medication for opioid use disorder (MOUD) in Appalachia. Loneliness, depression, and anxiety did not differ between the retained and not retained, nor did they predict not being retained; however, mindfulness was significantly lower among those not retained in treatment compared to those retained (OR = 0.956, 95% CI (0.912-1.00), and p < 0.05). Preliminary findings provide evidence for mindfulness training integration as part of effective treatment, with aims to further elucidate the effectiveness of mindfulness therapies on symptom reduction in co-occurring mental health disorders, loneliness, and MOUD treatment retention.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Assessing Loneliness among Adults Receiving Outpatient Treatment with Medication for Opioid Use Disorder (MOUD).

Loneliness is a significant risk factor for substance use, however, impacts of treatments on loneliness are relatively unexplored. Living in a rural location is a greater risk factor for loneliness. This study examined data from a quasi-experimental study in rural Appalachia, comparing the effectiveness of Mindfulness-Based Relapse Prevention (MBRP) versus Treatment as Usual (TAU) among adults receiving MOUD in outpatient therapy. Our objective was to determine whether observed reductions in self-reported craving, anxiety, depression, and increased perceived mindfulness would also improve loneliness reports. Eighty participants (n = 35 MBRP; n = 45 TAU) were included in the analysis from a group-based Comprehensive Opioid Addiction Treatment program. Outcomes tracked included craving, anxiety, depression, mindfulness, and loneliness as measured by the Revised UCLA Loneliness Scale (R-UCLA). A linear mixed model ANOVA determined the significance of the treatments on changes in loneliness scores at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. Both groups reported significantly reduced loneliness over the course of the study (F = 16.07, p < 0.01), however there were no significant differences between groups. Loneliness was also significantly positively (p < 0.01) correlated with anxiety (0.66), depression (0.59), and craving (0.38), and significantly (p < 0.01) inversely correlated (-0.52) with mindfulness. Results suggest that participation in MOUD group-based outpatient therapy has the potential to diminish loneliness and associated poor psychological outcomes. Thus, it is possible that a more targeted intervention for loneliness would further diminish loneliness, which is important as loneliness is linked to risk for relapse.

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine.

Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either (i) aluminium hydroxide, (ii) SWE, a squalene-in-water emulsion, (iii) SQ, a squalene-in-water emulsion containing QS21 saponin, (iv) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (v) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (vi) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFNƔ and IL-2-producing CD4+ and CD8+ T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.

Convergence in phosphorus constraints to photosynthesis in forests around the world.

Tropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.

Prevalence of elevated blood lead levels and risk factors among children living in Patna, Bihar, India 2020.

Childhood lead exposure remains a key health concern for officials worldwide, contributing some 600,000 new cases of intellectually disabled children annually. Most children affected by high exposure to lead live in low- and middle-income countries. The leaded gasoline phase out in India was completed in 2000. Yet, in 2020, an estimated 275 million children aged 0 to 9 years had blood lead levels (BLLs) ≥ 5 µg/dL known to adversely affect intelligence and behavior. Lead sources reported in India include spices, cookware, paint, traditional medicines and cosmetics, and lead-acid battery recycling and repair. However, their relative contribution has not been characterized. More than 200 lead pollution sites related to battery recycling and repair activities were identified in Bihar and Jharkhand, India. Ninety percent of the recycling sites had soil lead concentrations exceeding the US Environmental Protection Agency's standards. We compared blood and environmental lead levels in two groups of children in Patna, Bihar. Households in proximity to battery recycling operations (Proximal n = 67) versus households distal to these operations (Distal n = 68). The average age of children was 40 months; 46% were female. Overall, the geometric mean (GM) BLL was 11.6 µg/dL. GM BLLs of children in Proximal and Distal households were not significantly different (10.2 µg/dL vs. 13.1 µg/dL respectively; p≤0.07). About 87% children, 56 Proximal and 62 Distal had BLLs ≥5 µg/dl. Lead concentrations in environmental samples were significantly higher in Proximal households (soil mean 9.8 vs. 1.6 µg/ft2; dust mean 52.9 vs. 29.9 µg/ft2 p<0.001; Proximal vs. Distal respectively) whereas concentrations in all spices were higher in Distal households (mean 46.8 vs 134.5 ppm p<0.001; Proximal vs. Distal respectively), and turmeric (mean 59.4 vs. 216.9 ppm Proximal vs. Distal respectively). In multivariate analyses for all children lead in spices and turmeric and number of rooms in the house were significant while for the Proximal group only lead in spices remained in the model. The predictive value of these models was poor. For the Distal group, a model with lead concentration in spices, turmeric and soil and number of rooms in the house was a much better fit. Of the 34 water samples collected, 7 were above the Indian standard of 10 ppb for lead in drinking water (2 in the Proximal area, 5 in the Distal area). Children in Patna, Bihar, India are exposed to multiple sources of lead, with lead levels in house dust and loose, locally sourced spices the most likely to increase blood lead levels. A holistic approach to blood lead testing and source identification and remediation are necessary to prevent lead exposure.

The ethics of family integrated care in the NICU: Improving care for families without causing harm.

The philosophy of care in Neonatal Intensive care Units (NICU) has changed with increasing integration of families. We examined parents' and clinicians' perspective about Family Integrated Care (FiCare) in our quaternary NICU. We found that parents and clinicians reported many benefits for families. They were all enthusiastic about FiCare for non-medical items such as changing diapers and skin-to-skin care; for more medical items, such as presenting at rounds, being present during resuscitation or procedures, most physicians wished for more parental involvement, more than other professionals, even parents. All parents described how FiCare benefited them, had empowered them, helped them feel like parents and become a family; but several parents, who could not participate as much or did not want to assume clinical roles, reported feeling guilty. Having a flexible, yet transparent FiCare philosophy is key, as opposed to having homogeneous goals. For example, an aim to have all parents present at rounds in a quality improvement initiative can cause harm to some families. We suggest how to ethically improve FiCare in the best interest of families while minimizing harms. It is important for FiCare not to be "Family Imposed Care." Optimizing FiCare can only be done when parents' priorities guide our actions, while also keeping in mind clinicians' perspectives and respecting the reality of each NICU.

Testing Mindfulness-Based Relapse Prevention with Medications for Opioid Use Disorder Among Adults in Outpatient Therapy: a Quasi-experimental Study.

OBJECTIVES: This study aimed to explore the effectiveness of mindfulness-based relapse prevention (MBRP) with individuals receiving medication for opioid use disorder (MOUD) in a naturalistic, open-ended outpatient group treatment setting. METHODS: Eighty participants (mean age 36.3) who had at least 90 consecutive days substance free self-selected into treatment (MBRP, n = 35) or comparison groups (treatment as usual, TAU, n = 45). Outcomes tracked included treatment retention and relapse, and self-reported craving, anxiety, depression, and mindfulness at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. MBRP group participants attended biweekly 60-min sessions for 24 weeks. A linear mixed model analysis of variance determined the significance of the MBRP intervention on changes in craving, anxiety, depression, and mindfulness. RESULTS: No significant differences in sex, education level, insurance status, relationship status, or employment status were detected at baseline between groups. The 36-week retention (74%, MBRP/MOUD; 71%, TAU/MOUD) and relapse rates (43%, MBRP/MOUD; 47%, TAU/MOUD) were similar for the groups. There were only four relapses on opioids. Significant reductions (p < .05) were observed in the MBRP/MOUD group for craving, anxiety, and depression in addition to significant increases in mindfulness compared to those in TAU/MOUD. CONCLUSIONS: Although state and federal resources are available to expand MOUD, no standard of behavioral therapy has been established as most complimentary to MOUD. The current study results suggest MBRP can be implemented as an outpatient therapy for individuals in MOUD.

Population structure and genome-wide association studies in bread wheat for phosphorus efficiency traits using 35 K Wheat Breeder's Affymetrix array.

Soil bioavailability of phosphorus (P) is a major concern for crop productivity worldwide. As phosphatic fertilizers are a non-renewable resource associated with economic and environmental issues so, the sustainable option is to develop P use efficient crop varieties. We phenotyped 82 diverse wheat (Triticum aestivum L.) accessions in soil and hydroponics at low and sufficient P. To identify the genic regions for P efficiency traits, the accessions were genotyped using the 35 K-SNP array and genome-wide association study (GWAS) was performed. The high-quality SNPs across the genomes were evenly distributed with polymorphic information content values varying between 0.090 and 0.375. Structure analysis revealed three subpopulations (C1, C2, C3) and the phenotypic responses of these subpopulations were assessed for P efficiency traits. The C2 subpopulation showed the highest genetic variance and heritability values for numerous agronomically important traits as well as strong correlation under both P levels in soil and hydroponics. GWAS revealed 78 marker-trait associations (MTAs) but only 35 MTAs passed Bonferroni Correction. A total of 297 candidate genes were identified for these MTAs and their annotation suggested their involvement in several biological process. Out of 35, nine (9) MTAs were controlling polygenic trait (two controlling four traits, one controlling three traits and six controlling two traits). These multi-trait MTAs (each controlling two or more than two correlated traits) could be utilized for improving bread wheat to tolerate low P stress through marker-assisted selection (MAS).

Adapting technology-based HIV prevention and care interventions for youth: lessons learned across five U.S. Adolescent Trials Network studies.

BACKGROUND: U.S. sexual and gender minority youth experience individual, interpersonal, and structural-level barriers to HIV prevention and care. Innovative, youth-driven approaches to mobile and electronic interventions that support use of new biomedical prevention, testing, and treatment options may address these barriers. Adapting evidence-based interventions for youth must balance core intervention components with responsiveness to the distinct needs of end-users. METHODS: The UNC/Emory Center for Innovative Technology (iTech) adapts and evaluates technology-based interventions for youth living with or at risk for HIV. We analyzed formative research (focus groups and individual usability sessions) across five iTech studies: two apps promoting HIV testing and pre-exposure prophylaxis (PrEP), one app promoting behavioral risk reduction and PrEP, one PrEP adherence app, and one mobile-optimized website for increasing viral suppression, with the aim of informing best practices for technology-based intervention development. Each study presented prototypes of adapted mHealth interventions to samples of their target end-user population for use and/or evaluation. RESULTS: One hundred and thirty-eight youth across seven geographically diverse sites provided feedback during the intervention adaptation process. We found high interest in and acceptability of all five intervention prototypes. Cross-study themes included: (I) Desire for multiple privacy protections (e.g., password, fingerprint) to keep HIV status, sexual identity, and sexual behavior confidential. (II) Strong but varied preferences for the look and feel of platforms. Imagery should be discrete but representative. Participants valued customizable platforms and positive themes, motivational language, and humor. Youth wanted information presented using multiple modalities (e.g., text, video, image) to increase engagement. (III) Youth preferred engagement features and functions consistent with familiar platforms (e.g., Snapchat, Instagram). Gamification features that resulted in tangible versus virtual rewards were predicted to increase engagement. Intervention messaging functions were perceived as useful; customization was desired as a way to control frequency, mode (e.g., SMS, in-app message, push notification), and content. (IV) Youth voiced varied preferences for platform content including: featuring young role models from the lesbian, gay, bisexual, transgender, queer and/or questioning (LGBTQ) community, incorporating mental health resources, and maintaining a holistic health-focus (not HIV-centric). CONCLUSIONS: We found high acceptability and consistent feedback in youths' evaluations of these mHealth interventions; divergence was most commonly found in preferred content versus features and functions. Identifying broadly accepted aspects of mHealth interventions for youth supports the feasibility of adaptation (versus de novo creation) and should guide the focus of future formative research phases. Continued research is needed to better understand how to balance usability preferences with finite resources for customization.

Cognitive and motivational factors driving sharing of internet memes.

As naturally occurring examples of folk culture and creativity, internet memes provide a rich testbed to examine the interrelationships among cognitive and motivational factors that influence their impact. In two studies with participants recruited over the internet, we measured a variety of appraisals of both apolitical and political memes with a focus on the role of metaphorical aptness and personal relatability as predictors of comprehensibility and humor. Structural equation modeling was used to analyze interconnections among appraisals. A major network path connects relatability to aptness, which in turn is linked to appraisals of comprehensibility, humor, and propensity to share. For political memes, the congruity of the meme with the person's political position (liberal or conservative) has a powerful but indirect impact on the propensity to share it. These findings indicate that appraisals of memes are based on cognitive and motivational processes that also underlie metaphor comprehension and appreciation of humor.

Dipyrrinato-Iridium(III) Complexes for Application in Photodynamic Therapy and Antimicrobial Photodynamic Inactivation.

The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η5 -cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [IrIII (dipy)(ppy)2 ] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [IrIII (Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment.

IMPORTANCE: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear. OBJECTIVE: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded. EXPOSURES: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise. RESULTS: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73). CONCLUSIONS AND RELEVANCE: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

The Tail of Kinesin-14a in Giardia Is a Dual Regulator of Motility.

Kinesin-14s are microtubule-based motor proteins that play important roles in mitotic spindle assembly [1]. Ncd-type kinesin-14s are a subset of kinesin-14 motors that exist as homodimers with an N-terminal microtubule-binding tail, a coiled-coil central stalk (central stalk), a neck, and two identical C-terminal motor domains. To date, no Ncd-type kinesin-14 has been found to naturally exhibit long-distance minus-end-directed processive motility on single microtubules as individual homodimers. Here, we show that GiKIN14a from Giardia intestinalis [2] is an unconventional Ncd-type kinesin-14 that uses its N-terminal microtubule-binding tail to achieve minus-end-directed processivity on single microtubules over micrometer distances as a homodimer. We further find that although truncation of the N-terminal tail greatly reduces GiKIN14a processivity, the resulting tailless construct GiKIN14a-Δtail is still a minimally processive motor and moves its center of mass via discrete 8-nm steps on the microtubule. In addition, full-length GiKIN14a has significantly higher stepping and ATP hydrolysis rates than does GiKIN14a-Δtail. Inserting a flexible polypeptide linker into the central stalk of full-length GiKIN14a nearly reduces its ATP hydrolysis rate to that of GiKIN14a-Δtail. Collectively, our results reveal that the N-terminal tail of GiKIN14a is a de facto dual regulator of motility and reinforce the notion of the central stalk as a key mechanical determinant of kinesin-14 motility [3].

Exploring the relationship between structure and activity in BODIPYs designed for antimicrobial phototherapy.

A synthetic strategy to BODIPY dyes is presented giving access to a range of new compounds relevant in the context of antimicrobial photodynamic therapy (aPDT). BODIPYs with the 8-(4-fluoro-3-nitrophenyl) and the 8-pentafluorophenyl substituents were used for the synthesis of new mono- and dibrominated BODIPYs. The para-fluorine atoms in these electron-withdrawing groups facilitate functional modification via nucleophilic aromatic substitution (SNAr) with a number of amines and thio-carbohydrates. Subsequently, the antibacterial phototoxic activity of these BODIPYs has been assessed in bacterial assays against the Gram-positive germ S. aureus and also against the Gram-negative germ P. aeruginosa. The bacterial assays allowed to identify substitution patterns which ensured antibacterial activity not only in phosphate-buffered saline (PBS) but also in the presence of serum, hereby more realistically modelling the complex biological environment that is present in clinical applications.

A theory of plant function helps to explain leaf-trait and productivity responses to elevation.

Several publications have examined leaf-trait and carbon-cycling shifts along an Amazon-Andes transect spanning 3.5 km in elevation and 16°C in mean annual temperature. Photosynthetic capacity was previously shown to increase as temperature declines with increasing elevation, counteracting enzyme-kinetic effects. Primary production declines, nonetheless, due to decreasing light availability. We aimed to predict leaf-trait and production gradients from first principles, using published data to test an emerging theory whereby photosynthetic traits and primary production depend on optimal acclimation and/or adaptation to environment. We re-analysed published data for 210 species at 25 sites, fitting linear relationships to elevation for both predicted and observed photosynthetic traits and primary production. Declining leaf-internal/ambient CO2 ratio (χ) and increasing carboxylation (Vcmax ) and electron-transport (Jmax ) capacities with increasing elevation were predicted. Increases in leaf nitrogen content with elevation were explained by increasing Vcmax and leaf mass-per-area. Leaf and soil phosphorus covaried, but after controlling for elevation, no nutrient metric accounted for any additional variance in photosynthetic traits. Primary production was predicted to decline with elevation. This analysis unifies leaf and ecosystem observations in a common theoretical framework. The insensitivity of primary production to temperature is shown to emerge as a consequence of the optimisation of photosynthetic traits.

Investigating the Impact of Conformational Molecular Engineering on the Crystal Packing of Cavity Forming Porphyrins.

Herein we report the synthesis of 5,10,15,20-tetraaryl-(X)-substituted-2,3,7,8,12,13,17,18-octaethylporphyrins (OETArXPs) and a structural investigation of their solid-state properties via small molecule X-ray diffraction. A series of halogen (fluorine to iodine), nitrogenous (azido, cyano), alkyl (TMS-acetylene and acetylene), and chained (benzyloxy) porphyrins were chosen as the initial target molecules. Following this, a selection of tetravalent metal complexes [Cu(II), Ni(II), and Pd(II)] based on these porphyrins were synthesized to allow for an investigation of the effects of metal complexes on the structural properties of these highly substituted porphyrins. The size of the halogen atom affects the potential of intermolecular interactions and the resulting crystal packing in these 4-halo-OETArXP complexes. The fluorine series have an equal preference for alkyl or aryl groups (ortho-hydrogen), the chlorine series favor interactions between the alkyl groups, and the bromine appears to favor the aryl (ortho- and meta-hydrogens). This results in an extensive cupping pattern in the unit cell. For the 2,6-halo-OETArXP it was established that the change in position alters the types of the intermolecular contacts toward face-to-edge or face-to-face interactions and alters the packing patterns observed. Within the 4-benzyloxy-OETArXP series the meso-substituent favors interacting with the core of the porphyrin macrocycle. The 4-cyano-OETArXP is a suitable hydrogen-bond acceptor and results in an interesting Z-shape network. Additionally, it was highlighted that solvent effects play a much larger role in crystal packing than intermolecular/intramolecular interaction or metal(II) center substitution. This is accompanied by a study using both the azide- and acetylene-OETArXPs as a base molecule to allow for a quick one-step reaction for the generation of a variety of functionalized compounds. Using a copper(I)-catalyzed azide-alkyne cycloaddition reaction, we were able to append hydrogen bonding functionalities to the OETArXPs framework in high yields. The crystal packing images included in this work shows the potential to create selective and functional receptor sites based on free base porphyrins. However, insofar as analytical measurements indicate, the design of such a free base porphyrin through crystal engineering has not yet been realized. The variety of porphyrin packing arrangements herein indicates the need for further studies.

In Vivo Evaluation of Taste-Masked Fast-Disintegrating Sublingual Tablets of Epinephrine Microcrystals.

In community settings, IM injection of 0.3 mg epinephrine (Epi) using an auto-injector is the drug of choice for treatment of anaphylaxis. Previously, a taste-masking (TM) formulation of fast-disintegrating sublingual tablets (FDSTs) was developed in our lab. Also, Epi was micronized (Epi-MC) successfully and reduced the previously achieved bioequivalent sublingual Epi dose to 0.3 mg IM injection by half using non-taste-masked fast-disintegrating sublingual tablets (TM-FDSTs). Our objective for this study was to evaluate the sublingual absorption of Epi-MC using TM-FDST. These sublingual Epi tablets have potential for out-of-hospital treatment of anaphylaxis and are suitable for human studies. TM-FDSTs containing Epi-MC were manufactured by direct compression. The rate and extent of Epi absorption from our developed 20 mg Epi-MC-TM-FDSTs (n = 5) were evaluated in rabbits and compared to the previous result from 20 mg Epi-MC in non-TM-FDSTs and EpiPen® auto-injector. Blood samples were collected over 1 h, and Epi concentrations were measured using HPLC with electrochemical detection. Mean ± SEM AUC0-1 h and Cmax from 20 mg Epi-MC-TM-FDSTs (733 ± 78 ng/ml/min and 30 ± 8 ng/ml) and 20 mg Epi-MC-non-TM-FDSTs (942 ± 109 ng/ml/min and 38 ± 4 ng/ml) were not significantly different (p > 0.05) from each other or from EpiPen® (592 ± 50 ng/ml/min and 28 ± 3 ng/ml) but were significantly higher (p < 0.05) than endogenous Epi after placebo FDSTs (220 ± 32 ng/ml/min and 8 ± 1 ng/ml). Mean ± SD Tmax was not significantly different (p > 0.05) among all formulations. Epi-MC-TM-FDSTs formulation improved Epi absorption twofold and reduced the required bioequivalent dose by 50%, similar to results obtained using non-TM-FDSTs. The incorporation of TM excipients did not interfere with the absorption of Epi-MC.

Application of Porous Materials to Carbohydrate Chemistry and Glycoscience.

There is a growing interest in using a range of porous materials to meet research needs in carbohydrate chemistry and glycoscience in general. Among the applications of porous materials reviewed in this chapter, enrichment of glycans from biological samples prior to separation and analysis by mass spectrometry is a major emphasis. Porous materials offer high surface area, adjustable pore sizes, and tunable surface chemistry for interacting with glycans, by boronate affinity, hydrophilic interactions, molecular imprinting, and polar interactions. Among the materials covered in this review are mesoporous silica and related materials, porous graphitic carbon, mesoporous carbon, porous polymers, and nanoporous gold. In some applications, glycans are enzymatically or chemically released from glycoproteins or glycopeptides, and the porous materials have the advantage of size selectivity admitting only the glycans into the pores and excluding proteins. Immobilization of lectins onto porous materials of suitable pore size allows for the use of lectin-carbohydrate interactions in capture or separation of glycoproteins. Porous material surfaces modified with carbohydrates can be used for the selective capture of lectins. Controlled release of therapeutics from porous materials mediated by glycans has been reported, and so has therapeutic targeting using carbohydrate-modified porous particles. Additional applications of porous materials in glycoscience include their use in the supported synthesis of oligosaccharides and in the development of biosensors for glycans.

Nitrogen and phosphorus availabilities interact to modulate leaf trait scaling relationships across six plant functional types in a controlled-environment study.

Nitrogen (N) and phosphorus (P) have key roles in leaf metabolism, resulting in a strong coupling of chemical composition traits to metabolic rates in field-based studies. However, in such studies, it is difficult to disentangle the effects of nutrient supply per se on trait-trait relationships. Our study assessed how high and low N (5 mM and 0.4 mM, respectively) and P (1 mM and 2 µM, respectively) supply in 37 species from six plant functional types (PTFs) affected photosynthesis (A) and respiration (R) (in darkness and light) in a controlled environment. Low P supply increased scaling exponents (slopes) of area-based log-log A-N or R-N relationships when N supply was not limiting, whereas there was no P effect under low N supply. By contrast, scaling exponents of A-P and R-P relationships were altered by P and N supply. Neither R : A nor light inhibition of leaf R was affected by nutrient supply. Light inhibition was 26% across nutrient treatments; herbaceous species exhibited a lower degree of light inhibition than woody species. Because N and P supply modulates leaf trait-trait relationships, the next generation of terrestrial biosphere models may need to consider how limitations in N and P availability affect trait-trait relationships when predicting carbon exchange.