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Background: The role of social determinants of health (SDH) in patient outcomes, quality of life, and overall well-being has been well documented. However, the inclusion of these variables in randomized control trials (RCTs) remains limited; thus, the extent of generalizability from such trials is brought into question. The purpose of this study is to explore the rates of reporting SDH variables in RCTs focused on shoulder surgery from the past decade. Methods: The PubMed database was searched for RCTs with a focus on shoulder surgery from 2013 to 2023. Duplicates, responses to the editor, biomechanical studies, and nonshoulder studies were excluded. Each article was reviewed and data pertaining to patient demographics and socioeconomic covariates. Journal of publication was recorded, and studies from the 5 most common journals were analyzed. These journals were the Journal of Shoulder and Elbow Surgery, the Journal of Bone and Joint Surgery, the American Journal of Sports Medicine (AJSM), the Bone and Joint Journal, and the Journal of the American Medical Association. Multivariate logistic regression was performed to determine the independent effect of study characteristics on the reporting rates of SDH. Results: A total of 255 articles were reviewed. Of these, 93.3% and 90.2% of articles reviewed reported age and sex, respectively. Employment status was reported in 11.8% of articles. Less than 10% reported race, ethnicity, income, insurance, and housing, with even less performing formal analyses on these variables. Studies that were conducted in the United States, multicenter, had a sample size of 251+, and had a combination of public and private funding which were significantly more likely to report on race and ethnicity. Reporting employment status was significantly associated with being European-based, multicenter, sample size 251+, double-blinded, and published in AJSM. Newer studies were significantly less likely to report education. Only publication in AJSM was significant for reporting income. Study intervention and topic were not significant for any SDH reporting. Discussion: These data reflect how small of a proportion of RCTs report and analyze on SDH variables. These findings reflect a need for future RCTs to accurately report SDH variables that influence outcomes, such as race, ethnicity, education, employment, income, housing status, and insurance. SDH are infrequently reported and analyzed in RCTs pertaining to shoulder surgery. Academic medical journals should incorporate guidelines to encourage studies to include such variables and enable the assessment of outcomes to apply to a broader population.

Background: Academic medicine emphasizes the need to recruit a diverse workforce in graduate medical education. Orthopaedic surgery residency has demonstrated efforts to model program compositions with evolving US demographics. However, it remains unclear whether orthopaedic fellowships, particularly foot and ankle, also reflect these efforts. Methods: Using the publicly available Accreditation Council for Graduate Medical Education (ACGME) Data Resource Book, a census of the gender and racial/ethnic identities of orthopaedic foot and ankle fellows, as well as active orthopaedic surgery residents, were compiled from 2007 to 2022. Linear trend analysis was conducted to evaluate the trends of orthopaedic residents and foot and ankle fellows, with a Pearson correlation for comparison. Results: Prior analysis demonstrated no significant change in sex and ethnic diversity of fellows from 2006 to 2015. The majority of foot and ankle fellows were White (31%-69%) and male (63%-88%). Linear analysis demonstrated growing diversity in female and non-White active orthopaedic surgery residents. Similarly, there was an increasing number of female foot and ankle fellows (0%-38%) reflective of the trend in orthopaedic residency (12%-20%); however, there was no significant change among racial/ethnic identities. Pearson correlation analysis between the trend of orthopaedic residency residents and foot and ankle fellows suggests moderate correlation among female, Asian, and “Unknown” racial/ethnic categories. Conclusion: The proportion of foot and ankle female fellows in ACGME-accredited fellowships has matched or exceeded the percentage of female orthopaedic residents. Despite increased diversity of orthopaedic surgery residents over the past 2 decades, ACGME-accredited foot and ankle fellowships do not yet reflect similar trends among racial/ethnic minorities. Level of Evidence: Level III, retrospective cohort study.

Background. There is no mechanism that matches hard-to-place kidneys with the most appropriate candidate. Thus, unwanted kidney offers are typically to recipients with long renal replacement time (vintage) which is a strong risk factor for mortality and graft failure, and in combination with prolonged cold ischemia time (CIT), may promote interactive effects on outcomes. Methods. Consecutive adult isolated kidney transplants between October 2015 and December 2017 were stratified by vintage younger than 1 year and CIT longer than 30 hours. Results. Long (n = 169) relative to short (n = 93) vintage recipients were significantly more likely to be younger (32.2 years vs 56.9 years, P = 0.02), black race (40.8% vs 18.3%, P = 0.02), have higher estimated posttransplant survival (52.6 vs 42.0, P = 0.04), and have a comorbid condition (45.6% vs 30.1%, P = 0.02); they were less likely to receive a donation after circulatory death kidney (27.8% vs 39.8%, P = 0.05). Long vintage was significantly associated with length of stay longer than 4 days (45.5% vs 30.1%, P = 0.02), and 30-day readmission (37.3% vs 22.6%, P = 0.02) but not additional operations (17.8% vs 15.1%, P = 0.58), short-term patient mortality (3.0% vs 2.2%, P = 0.70), or overall graft survival (P = 0.23). On multivariate logistic regression, long vintage remained an independent risk factor for 30-day readmission (adjusted odds ratio, 1.92; 95% confidence interval, 1.06-3.47); however, there was no interaction of vintage and CIT for this outcome (P = 0.84). Conclusions. Readmission is significantly associated with pretransplant dialysis duration; however, CIT is not a modifying factor for this outcome.

Importance: One primary function of occupational therapy state licensure boards (SLBs) is the discipline of ethical misconduct by licensed occupational therapy practitioners. However, SLB sanctioning is poorly understood by practitioners, regulators, and the public., Objective: To identify predictors of occupational therapy practitioner sanctioning outcomes in the United States., Design: Retrospective study; all public final consent orders and database entries provided online by SLBs were analyzed. Supervised gradient boosting machine learning, logistic regression, and contingency tables were used to generate odds ratios for variables associated with each sanctioning outcome. Multinomial testing was used to identify attribute overrepresentation among cases and national practitioner distributions., Participants: A total of 2,400 cases were analyzed across 47 states and Washington, DC., Intervention: None., Outcomes and Measures: Numerous complaint and respondent attribute variables were collected from final consent orders and database entries., Results: Complaint reason, practice setting, and complaint source had the highest influence on predicting sanction outcome; geographic region, number of complaints in a given case, and length of investigation in months were secondarily influential. Being male or a certified occupational therapy assistant was associated with higher odds of severe sanctioning outcomes., Conclusions and Relevance: Disciplinary actions against occupational therapy practitioners were determined by numerous contextual factors; however, the most influential factors were complaint reason, practice setting, and complaint source. These results provide direction for exploring factors that predict sanctioning outcomes in the United States and also provide occupational therapy practitioners and SLBs a basis of applied outcomes that may improve implementation and education regarding clinical practice ethics. Plain-Language Summary: Occupational therapy state licensure boards (SLBs) are responsible for disciplining licensed occupational therapy practitioners for ethical misconduct. SLB sanctioning is poorly understood by practitioners, regulators, and the public. In this study, we identify the factors that predict the sanctioning outcomes of occupational therapy practitioners. The results may help state regulators, educators, and national associations more effectively act in a way that protects the public faith in occupational therapy services by providing contextualized information on practitioner behaviors that result in specific sanctioning outcomes. The study findings also provide occupational therapy practitioners and SLBs a basis of applied outcomes that may improve the implementation of and education regarding clinical practice ethics., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Introduction: Our objective was to investigate the utility of fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) in assessing CT Stage 1A non-small cell lung cancer (NSCLC) in patients under consideration for curative treatment. Performing FDG PET-CT in these patients may lead to unnecessary delays in treatment if it can be shown to provide no added value., Methods: We retrospectively reviewed 735 lesions in 653 patients from the New Zealand Te Whatu Ora Northern region lung cancer database with suspected or pathologically proven Stage 1A NSCLC on CT scan who also underwent FDG PET-CT imaging. We determined how often FDG PET-CT findings upstaged patients and then compared to pathological staging where available., Results: FDG PET-CT provided an overall upstaging rate of 9.7%. Category-specific rates were 0% in Tis, 0.9% in T1mi, 7.4% in T1a, 10% in T1b and 12% in T1c groups. The percentage of lesions upstaged on FDG PET-CT that remained Stage 1A was 100% in T1mi, 100% in T1a, 47.1% in T1b and 40.7% in T1c groups. The P value was statistically significant at 0.004, indicating upstaging beyond Stage 1A was dependent on T category., Conclusion: Our data suggests that FDG PET-CT is indicated for T1b and T1c lesions but is of limited utility in Tis, T1mi and T1a lesions. Adopting a more targeted approach and omitting FDG PET-CT in patients with Tis, T1mi, and T1a lesions may benefit all patients with lung cancer by improving accessibility and treatment timelines., (© 2024 Royal Australian and New Zealand College of Radiologists.)

Understanding the structure of biomolecules is vital for deciphering their roles in biological systems. Single-molecule techniques have emerged as alternatives to conventional ensemble structure analysis methods for uncovering new biology in molecular dynamics and interaction studies, yet only limited structural information could be obtained experimentally. Here, we address this challenge by introducing iMAX FRET, a one-pot method that allows ab initio 3D profiling of individual molecules using two-color FRET measurements. Through the stochastic exchange of fluorescent weak binders, iMAX FRET simultaneously assesses multiple distances on a biomolecule within a few minutes, which can then be used to reconstruct the coordinates of up to four points in each molecule, allowing structure-based inference. We demonstrate the 3D reconstruction of DNA nanostructures, protein quaternary structures, and conformational changes in proteins. With iMAX FRET, we provide a powerful approach to advance the understanding of biomolecular structure by expanding conventional FRET analysis to three dimensions.

Here, we present a protocol using genetic engineering techniques to prepare small extracellular vesicles (sEVs) enriched in the chaperone protein DNAJB6. We describe steps to prepare cell lines overexpressing DNAJB6, followed by the isolation and characterization of sEVs from cell conditioned media. Further, we describe assays to examine effects of DNAJB6-loaded sEVs on protein aggregation in Huntington's disease cellular models. The protocol can be readily repurposed to study protein aggregation in other neurodegenerative disorders or extended to other therapeutic proteins. For complete details on the use and execution of this protocol, please refer to Joshi et al. (2021). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cell-derived extracellular vesicles (EVs) are effectors of cell-to-cell communication that are in the spotlight as promising candidates for in vivo drug delivery because of their ability to enter cells and deliver cargo. For example, proteins of interest can be loaded into EVs to mediate protein transfer into target cells. To determine causality between EV content and function, which is also important to assess the clinical safety of EVs, it is crucial to comprehensively characterize their complete molecular composition. Here, we investigated EVs loaded with the chaperone protein DNAJB6. Chaperone proteins assist in protein folding and have been suggested to alleviate protein aggregation diseases, such as Alzheimer's disease and Huntington's disease. We analyzed and compared the proteome of EVs isolated from wildtype HEK293T cells with that of EVs from HEK 293T cells overexpressing DNAJB6-WT or loss-of-function mutant DNAJB6-M3. Comprehensive analysis of proteomics data showed enhanced levels of DNAJB6 as well as protein-folding-related proteins in EVs derived from DNAJB6-overexpression cells. Interestingly, upregulation of a chaperone and its protein-folding-related proteins resulted in downregulation of another chaperone plus its related proteins, and vice versa. This implies the presence of compensatory mechanisms in the cellular expression of chaperones. Collectively, we provide the proteomic EV signatures underlying EV mediated DNAJB6 transmission by HEK293T cells, with the aim of establishing a causal relationship between EV protein content and EV function.

Huntington disease (HD) is a devastating neurodegenerative disorder characterized by aggregation of huntingtin (HTT) protein containing expanded polyglutamine (polyQ) tracts. DNAJB6, a member of the DNAJ chaperone family, was reported to efficiently inhibit polyQ aggregation in vitro , in cell models, and in vivo in flies, xenopus, and mice. For the delivery of exogenous DNAJB6 to the brain, the DNAJB6 needs to be protected against (enzymatic) degradation and show good penetration into brain tissue. Here, we tested the potential of small extracellular vesicles (sEVs) derived from neural stem cells (NSCs) for delivery of DNAJB6 as anti-amyloidogenic cargo. Administration of sEVs isolated from DNAJB6-overexpressing cells to cells expressing expanded polyQ tracts suppressed HTT aggregation. Furthermore, intrathecal injection of DNAJB6-enriched sEVs into R6/2 transgenic HD mice significantly reduced mutant HTT aggregation in the brain. Taken together, our data suggest that sEV-mediated molecular chaperone delivery may hold potential to delay disease onset in HD., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Drug delivery to the brain is greatly hampered by the presence of the blood-brain barrier (BBB) which tightly regulates the passage of molecules from blood to brain and vice versa. Nanocarriers, in which drugs can be encapsulated, can move across the blood-brain barrier (BBB) via the process of transcytosis, thus showing promise to improve drug delivery to the brain. Here, we demonstrate the use of natural nanovesicles, that is, exosomes, derived from C17.2 neural stem cells (NSCs) to efficiently carry a protein cargo across an in vitro BBB model consisting of human brain microvascular endothelial cells. We show that the exosomes are primarily taken up in brain endothelial cells via endocytosis, while heparan sulfate proteoglycans (HSPGs) act as receptors. Taken together, our data support the view that NSC exosomes may act as biological nanocarriers for efficient passage across the BBB. Nanomedicines that target HSPGs may improve their binding to brain endothelial cells and, possibly, show subsequent transcytosis across the BBB., (© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Extracellular vesicles (EVs), such as exosomes, can mediate long-distance communication between cells by delivering biomolecular cargo. It is speculated that EVs undergo back-fusion at multivesicular bodies (MVBs) in recipient cells to release their functional cargo. However, direct evidence is lacking. Tracing the cellular uptake of EVs with high resolution as well as acquiring direct evidence for the release of EV cargo is challenging mainly because of technical limitations. Here, we developed an analytical methodology, combining state-of-the-art molecular tools and correlative light and electron microscopy, to identify the intracellular site for EV cargo release. GFP was loaded inside EVs through the expression of GFP-CD63, a fusion of GFP to the cytosolic tail of CD63, in EV producer cells. In addition, we genetically engineered a cell line which expresses anti-GFP fluobody that specifically recognizes the EV cargo (GFP). Incubation of anti-GFP fluobody-expressing cells with GFP-CD63 EVs resulted in the formation of fluobody punctae, designating cytosolic exposure of GFP. Endosomal damage was not observed in EV acceptor cells. Ultrastructural analysis of the underlying structures at GFP/fluobody double-positive punctae demonstrated that EV cargo release occurs from endosomes/lysosomes. Finally, we show that neutralization of endosomal pH and cholesterol accumulation in endosomes leads to blockage of EV cargo exposure. In conclusion, we report that a fraction of internalized EVs fuse with the limiting membrane of endosomes/lysosomes in an acidification-dependent manner, which results in EV cargo exposure to the cell cytosol.

The present study deals with swelling and infusion kinetics of tea granules in tea bags. The swelling and infusion kinetics of tea bags differing in tea loading and tea bag shapes were compared with loose tea. Increment in temperature and dipping frequency of tea bag in hot water increased the infusion kinetics of tea bags. Reduction in particle size enhanced the swelling and infusion kinetics of tea in a tea bag. The effects of tea particle size, tea bag dipping rate, loading of tea granules in tea bag and tea bag shapes on infusion kinetics were investigated. Increase in tea loading in tea bags resulted in reduced infusion kinetics. Double chambered tea bag showed the highest swelling (30%) and infusion kinetics (8.30% Gallic acid equivalence) while single chambered tea bags showed the lowest kinetics, amongst the various bags studied. The swelling and infusion kinetics of loose tea was always faster and higher than that of tea bags. It was found that overall effect of percentage filling of tea granules and height of tea bed in a tea bag affects tea infusion kinetics the most. Weibull model was found to be in good agreement with the swelling data.

In this study, the swelling kinetics of individual tea particles as well as bed of tea granules were investigated for different types of teas. The swelling experiments involved image analysis and volume measurements of tea particles. Each individual particle shows different swelling characteristics. Separating funnels and cylindrical columns of varying sizes were used to study the changes in volume of tea bed. Swelling in separating funnel was observed to be more than that in column. The effect of temperature, particle size, bed height and vessel diameter were investigated. The extent as well as the rate of swelling is found to increase with rise in temperature (60 to 80 °C) and reduction in particle size. A decrease in swelling is observed with increase in bed height as well as decrease in vessel diameter and vice a versa. About 70 to 75 % swelling occurs in the first 40 to 45 s. Two empirical models viz. Weibull and Peleg were used to fit the experimental data. The rate parameters obtained for a sample T5 at different temperatures were in the range of 0.012 to 0.016. The volume changes of all the teas were compared with their elution behavior, by measuring the absorbance of a diluted sample of brew at 272 nm. The activation energies for the process of tea swelling calculated for T1 (1.2 mm), T5 (2.2 mm) and T5 (0.72 mm) were 14.156, 8.37 and 13.42 kJ/mol respectively.

A new steroidal saponin, chloragin (1), was isolated and characterised from the aerial part of Chlorophytum nimonii. The structure of chloragin (1) was established as tigogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-xyloopyranoside on the basis of detailed chemical and spectral evidence. The saponin showed potent antihyperglycaemic and antidyslipidaemic activities in albino rats.

S,S'-[disulfanediylbis(dialkylaminopropane-2,1-diyl)]bis- (dialkylaminothiocarbamate) (14-31) were prepared and evaluated for the spermicidal activity and antifungal activity. Dialkyldithiocarbamates (1-5) were reacted with epichlorohydrin to give 1-dialkylaminocarbothioic acid S-[(2,3-epithio)propyl]ester (7-11), these on further reaction with a secondary amine gave S,S'-[disulfanediylbis(dialkylaminopropane-2,1-diyl)]bis- (dialkylaminothiocarbamate) (14-31). Some of these compounds (16, 19-21, 23, 30, 31) were found to be very potent spermicidal agents with marginal antifungal activity. Two compounds (20, 21) were 25 times more active than nonoxynol-9 (N-9), the spermicide currently in the market.

Synthesis and characterization of several 26pi core-modified hexaphyrins are reported. The synthetic methodology involved a well-known acid-catalyzed MacDonald-type condensation reaction of the required tripyrrane with electron deficient pentafluorobenzaldehyde. The nature of the product and yield depends on the nature of the acid catalyst and its concentration. Dioxahexaphyrin 9 was isolated only when 0.5 equiv of TFA was used as a catalyst, while dithiahexaphyrin 10 and diselenahexaphyrin 11 were formed with TFA, PTSA, and even in the absence of catalyst. The detailed 1H and 2-D COSY as well as HSQC experiments reveal the solution structure as well as the conformational mobility of hexaphyrins. In the tetracationic state, 10 and 11 exhibit a four heterocyclic ring inverted structure, while only two completely inverted heterocyclic rings were observed for 9. The other four heterocyclic rings are only partially inverted in 9. All the hexaphyrins reported here show aromatic character inferred from large Deltadelta values (difference in chemical shift between the most shielded and the most deshielded protons). Electronic absorption spectral studies also support the conformational changes observed upon protonation.

[structure: see text] Core-modified aromatic decaphyrins with 42pi conjugated electrons exhibit the highest two-photon absorption cross-section value (sigma(2) = 108,000 GM) known for any organic molecule, suggesting possible device applications in the field of nonlinear optics.

[reaction: see text] First examples of aromatic core-modified twisted heptapyrrolic systems with six meso links have been obtained via a general [3 + 4] acid-catalyzed condensation method. Despite the twisted conformation, these heptaphyrins exhibit aromaticity in solution, unlike most of the all-aza analogues.

The synthesis and structural characterization of the first examples of aromatic core-modified figure-eight octaphyrins with six meso links and their formation with and without acid catalysts are highlighted.

[reaction: see text] Synthesis and structural characterization of aromatic core-modified 26 pi hexaphyrin analogues are reported.

The syntheses of new aromatic 30pi heptaphyrins either through a [5 + 2] or a [4 + 3] acid-catalyzed condensation and oxidative coupling reactions of easily available and air-stable precursors are reported. The methodology followed is not only simple and efficient but also allows synthesis of a range of heptaphyrins with different heteroatoms in the core. The oxidative coupling reactions of modified tripyrranes 11 and tetrapyrranes 12 were found to be dependent on the acid concentration used and as well as the substituents present on the meso position. The change of meso aryl substituents in 11 and 12 to meso mesityl substituents gave a new heptaphyrin 18. The structural characterization has been done with extensive 1H and 2D NMR studies. The heptaphyrins reported here show rich structural diversity when the connections of the heterocyclic rings are altered, and accordingly, one ring and two ring inversions have been observed. By a judicious choice of the precursors it has been possible to control the site of ring inversion either in the bithiophene unit or in the tripyrrane unit. Theoretical calculations performed on three different heptaphyrins, 4, 5, and 17, also reveal that the inverted structures are approximately 35-40 kJ lower in energy relative to the corresponding noninverted structures. Furthermore, one of the heptaphyrins 10c shows the presence of two conformers in solution in the ratio 1:2 and no interconversion between the conformers have been observed in the temperature range of 343-228 K. On protonation, the aromaticity and the ring inversions are retained and the deltadelta values vary in the range 10.07-20.59 ppm. The energies of the Soret maxima and the HOMO-LUMO gap vary linearly with the increase in pi electrons further justifying the aromatic nature of the heptaphyrins.

The Baylis-Hillman (BH) reaction of substituted 5-isoxazolecarboxaldehydes with cyclohexenone in the presence of TiCl(4) invariably lead to the formation of hemiacetals beside the BH adducts. A similar reaction in the presence of DABCO, DBU, or 3-HQN yielded minor quantities of phenols in addition to the usual BH adducts. Similar to 5-isoxazolecarboxaldehydes, the TiCl(4)-mediated BH reaction of cyclohexenone with various benzaldehydes also furnishes hemiacetals in considerable yields. The reaction mechanism involving the formation of alpha-chloromethyl enone as an intermediate has been proposed. The synthesis of hemiacetals 5 and 14 from compound 4 in the presence of cyclohexenone and cyclopentenone, respectively, under acidic conditions indicates that enolization and aromatization of the cyclohexene ring are the key steps in the reaction mechanism.

A new series of compounds belonging to N,N'- [bis (1-aryl-6-hydroxy-hex-2-ene-1-one-3-yl)-1,n-alkanediamines (2-5a-f) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds namely 2c, 2e, 4c, 5b, 5c, 5e and 5f exhibit potent antioxidant activity. These compounds have also been evaluated for hypolipidemic activity.

Among alternative therapeutic approaches that have shown global popularity during the past decades, herbal medicine stands out as a major concern in the countries where allopathic medicine prevails. The sales of herbal products as health care adjuvants in these countries have increased exponentially. Lack of quality control, commercial profiteering and exploitation leading to adulterations, lack of proper knowledge about the herbs and their contents that may exhibit drug-drug interactions and other adverse side-effects, and inappropriate usage of the herbal products have become a cause for concern in the health care professions, particularly in the United States. This review provides an incisive description of the known chemical, pharmacological, clinical and toxicological profiles of four of the most widely used herbal products.

The availability of herbal products as "over-the-counter" drugs and their increasing usage in the US and Canada have caused concern at the US FDA, since these products are not currently monitored for their safety, efficacy and quality. Reliable information on these aspects of the products is not available. Most of the clinical trials carried out to date have been lacking in scientific design, data collection and interpretation, and systematic toxicological evaluation. A critical review of the existing data on three of the widely used herbs and their products is presented. Of the three herbs, garlic and ginger, through both experimental and clinical data, as well as their liberal consumption by man over millennia, appear to be very safe for therapeutic use. However, further and large-scale, well-designed clinical investigations are needed to establish their efficacy before they can enter the mainstream drug market of North America. It is hoped that this review will equip the physicians and interested biomedical scientists with a comprehensive summary of the total information available to date on the herbs described.

[reaction: see text] Synthesis of new meso aryl 30pi heptaphyrins 2, 3, and 4 is achieved. Spectroscopic studies reveal that 2, 3, and 4 are aromatic and possess an inverted structure.

The needles of Taxus wallichiana gave a new brevifoliol derivative whose structure was established by spectral data.

Demethylation of some aconitine-type norditerpenoid alkaloids was carried out with trimethylsilyl iodide and with HBr in glacial AcOH. Aconitine (10), cammaconine (23), delphinine (3), falconerine (18), lappaconitine (22), and talatizamine (24) afforded partially demethylated products. When methoxyl groups are present at the C-16 and C-18 positions, these are demethylated, and the methoxyl group at the C-1 position underwent demethylation in none the alkaloids studied except falconerine (18). With HBr-AcOH, in the case of alkaloids possessing a C-3 hydroxyl group, the methoxymethyl at C-18 formed a tetrahydrofuran, cyclizing at the C-6 position. Detailed NMR spectral studies (1H, 13C, 1H homonuclear COSY, HETCOR, and selective INEPT) carried out on the demethylation products have enabled accurate chemical shift assignments to be made for the demethylated alkaloids.

From the aerial parts of Consolida oliveriana (DC) Schröd. a new norditerpenoid alkaloid consolidine (2) has been isolated, in addition to the known alkaloids pubescenine (1), gigactonine, and delsoline and the diterpenoid alkaloid ajaconine (4). The structure of alkaloid 2 was established on the basis of its physical and spectroscopic data including detailed NMR studies. A detailed NMR study on ajaconine (4) resulted in the revision of 11 13C chemical shift assignments.

Three new hetisane-type diterpenoid alkaloids, davisinol (6), 18-benzoyldavisinol (7), and Davisin (9) have been isolated from Delphinium davisii Munz. and their structures established by detailed spectroscopic studies. Accurate 1H- and 13C-NMR assignments have been made for kobusine (8), a related hetisane-type alkaloid, and karakoline (5), a norditerpenoid alkaloid. The known norditerpenoid alkaloids 14-acetylperegrine (4), 6-deacetylperegrine (3), and karakoline (5) and the diterpenoid alkaloids hetisine and hetisinone were also isolated.

Vakhmatine [1] and the new diterpenoid alkaloid 13-O-acetylvakhmatine [3] have been isolated from the polar alkaloidal fractions of the seeds of Consolida ambigua, together with ajacine, delcosine, gigactonine, and takaosomine. Structure 3 has been established on the basis of spectroscopic data and chemical correlation with 1.

C22H16O6, Mr = 376.37, monoclinic, P21/c, a = 9.555 (3), b = 15.664 (2), c = 12.300 (4) A, beta = 100.08 (2) degrees, V = 1812.5 (5) A3, Z = 4, Dx = 1.379 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 8.0 cm-1, F(000) = 784, room temperature, R = 0.047, wR = 0.064 for 3203 observed reflections [I greater than 3 sigma (I)]. The molecule exists as the syn-trans isomer in the crystal. The crystal structure exhibits a number of C--H...O intermolecular contacts.

C32H46N2O8, Mr = 586.73, m.p. 458-460 K, monoclinic, P2(1), a = 9.187 (2), b = 14.979 (3), c = 11.474 (2) A, beta = 104.09 (2) degrees, V = 1531.5 (9) A3, Z = 2, D chi = 1.27 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 7.1 cm-1, F(000) = 632, room temperature, R = 0.039, wR = 0.053 for 3077 observed reflections [I greater than 3 sigma(I)]. The aminoethyl C(21) atom is disordered. There is an intramolecular hydrogen bond between O(1)--H(O1) and N(1) atoms, and between O(3)--H(O3) and O(4), stabilizing the boat conformations adopted by the rings A and D.