Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes.

Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme. Methods: In this study, four cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) were evaluated for their inhibitory effects against recombinant human DPP-IV and their potential inhibition mechanism was explored using both in vitro and in silico approaches. Results: All four cannabinoids resulted in a dose-dependent response with IC50 values of between 4.0 and 6.9 µg/mL. Kinetic analysis revealed a mixed mode of inhibition. CD spectra indicated that binding of cannabinoids results in structural and conformational changes in the secondary structure of the enzyme. These findings were supported by molecular docking studies which revealed best docking scores at both active and allosteric sites for all tested inhibitors. Furthermore, molecular dynamics simulations showed that cannabinoids formed a stable complex with DPP-IV protein via hydrogen bonds at an allosteric site, suggesting that cannabinoids act by either inducing conformational changes or blocking the active site of the enzyme. Conclusion: These results demonstrated that cannabinoids may modulate DPP-IV activity and thereby potentially assist in improving glycaemic regulation in type 2 diabetes.

Phytochemicals from Pterocarpus angolensis DC and Their Cytotoxic Activities against Breast Cancer Cells.

Pterocarpus anglonesis DC is an indigenous medicinal plant belonging to the Pterocarpus genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater fever, gonorrhea, ringworm, diarrhea, heavy menstruation, and breast milk stimulation. Column chromatography of the stem bark extracts resulted in the isolation of eight compounds, which included friedelan-3-one (1), 3α-hydroxyfriedel-2-one (2), 3-hydroxyfriedel-3-en-2-one (3), lup-20(29)-en-3-ol (4), Stigmasta-5-22-dien-3-ol (5), 4-O-methylangolensis (6), (3ß)-3-acetoxyolean-12-en-28-oic acid (7), and tetradecyl (E)-ferulate (8). The structures were established based on NMR, IR, and MS spectroscopic analyses. Triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-cancerous mammary epithelial cell lines (MCF-12A) were used to test the compounds' cytotoxicity. Overall, the compounds showed either no toxicity or very low toxicity to all three cell lines tested, except for the moderate toxicity displayed by lupeol (4) towards the non-cancerous MCF-12A cells, with an IC50 value of 36.60 µM. Compound (3ß)-3-acetoxyolean-12-en-28-oic acid (7) was more toxic towards hormone-responsive (MCF-7) breast cancer cells than either triple-negative breast cancer (HCC70) or non-cancerous breast epithelial (MCF-12A) cells (IC50 values of 83.06 vs. 146.80 and 143.00 µM, respectively).

Making Topologically Trivial Non-Hermitian Systems Nontrivial via Gauge Fields.

Non-Hermiticity significantly enriches the concepts of symmetry and topology in physics. Particularly, non-Hermiticity gives rise to the ramified symmetries, where the non-Hermitian Hamiltonian H is transformed to H^{†}. For time-reversal (T) and sublattice symmetries, there are six ramified symmetry classes leading to novel topological classifications with various non-Hermitian skin effects. As artificial crystals are the main experimental platforms for non-Hermitian physics, there exists the symmetry barrier for realizing topological physics in the six ramified symmetry classes: while artificial crystals are in spinless classes with T^{2}=1, nontrivial classifications dominantly appear in spinful classes with T^{2}=-1. Here, we present a general mechanism to cross the symmetry barrier. With an internal parity symmetry P, the square of the combination T[over ˜]=PT can be modified by appropriate gauge fluxes. Using the general mechanism, we systematically construct spinless models for all non-Hermitian spinful topological phases in one and two dimensions, which are experimentally realizable. Our Letter suggests that gauge structures may significantly enrich non-Hermitian physics at the fundamental level.

Adhesions in the setting of hip arthroscopy.

With the growing number of primary arthroscopies performed, patients requiring revision hip arthroscopies for various issues is high including postoperative adhesion formation, a source of pain, mechanical symptoms, range of motion limitation, stiffness, and microinstability. Adhesions are a consequence of biological pathways that have been stimulated by injury or surgical interventions leading to an increased healing response. Preventative efforts have included surgical adjuncts during/after primary hip arthroscopy, biologic augmentation, and postoperative rehabilitation. Treatment options for adhesion formation includes surgical lysis of adhesions with or without placement of biologic membranes aimed at inhibiting adhesion reformation as well as systemic medications to further reduce the risk. Postoperative rehabilitation exercises have also been demonstrated to prevent adhesions as a result of hip arthroscopy. Ongoing clinical trials are further investigating pathways and prevention of adhesion formation.

Mechanochemically-Assisted Passerini Reactions: A Practical and Convenient Method for the Synthesis of Novel α-Acyloxycarboxamide Derivatives.

A carboxylic acid, an aldehyde, and an isonitrile were combined in a single step (Passerini reaction) under mechanochemical activation to produce several α-acyloxycarboxamide derivatives in high to excellent yields within 15 min of milling. Mechanochemistry, when combined with the diversity provided by multicomponent reactions, enables the efficient synthesis of the target compounds, with great atom economy, shorter reaction times, and experimental simplicity. The method allows for the rapid production of a vast library of complex compounds from a limited number of substrates.

N-Formamide as a carbonyl precursor in the catalytic synthesis of Passerini adducts under aqua and mechanochemical conditions.

A new simple, efficient, and environmentally friendly protocol is presented for the catalytic synthesis of α-acyloxycarboxamides using N-formamides as a carbonyl precursor under aqua and mechanochemical conditions. Immobilized sulfuric acid on silica gel was employed for the synthesis of desired products, via the reaction of benzoic acid, 1-napthylisocyanide and various heterocyclic N-formamides. After a careful optimization of the reaction conditions, the desired Passerini products were obtained in high to excellent yields in short reaction times (10-30 min) at room temperature. The highly efficient and environmentally friendly method provides a facile access to a library of α-acyloxycarboxamides derivatives for future research on bioactivity screening.

Cytotoxicity and antimicrobial activity of isolated compounds from Monsonia angustifolia and Dodonaea angustifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Monsonia angustifolia is traditionally used to treat anthrax, heartburn, diarrhea, eye infections and hemorrhoids. Dodonaea angustifolia is frequently used as a treatment for dental pain, microbial infections and jungle fever. The two plant species were selected due to the presence of secondary metabolites such as coumarins, flavonoids, terpenoids, saponins and polyphenolics from the crude extracts, which exhibit pharmacological significance. The pure isolated compounds from the crude extracts are known for their diverse structures and interesting pharmacophores. AIM: To isolate and identify antibacterial and antifungal chemical constituents from Monsonia angustifolia and Dodonaea angustifolia plant extracts and evaluate the cytotoxicity of pure compounds from the crude extracts. MATERIALS AND METHODS: Extractives from M. angustifolia and D. angustifolia plants were isolated using chromatographic techniques and structures were elucidated based on NMR, IR and MS spectroscopic techniques. A microplate serial dilution method was used to evaluate the antibacterial activity of extracts and pure compounds against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and antifungal activity against Candida albicans and Cryptococcus neoformans. The cytotoxicity was determined using the 3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The dichloromethane, ethyl acetate and methanol crude extracts from the plants exhibited significant inhibition of microbial growth. The phytochemical investigation of these active crude extracts led to the isolation of five pure active compounds, 5-methoxyjusticidin A (1), cis-phytyl diterpenoidal fatty acid ester (2), stigmasterol (3), ß-sitosterol (4) and 5-hydroxy-7,4'-dimethoxyflavone (5). Stigmasterol (3) showed good antifungal activity against Cryptococcus neoformans with a minimum inhibition concentration (MIC) of 25 µg/mL and Candida albicans (MIC = 50 µg/mL). CONCLUSION: Compounds (1-5) isolated from Monsonia angustifolia and Dodonaea angustifolia showed antibacterial and antifungal activities and were non-toxic against Madin-Darby canine kidney (MDCK) cells and VERO monkey kidney (VERO) cells.

When Do We Perform Elective Total Knee Arthroplasty? General and Demographic-Specific Trends of Preoperative Pain and Function among 10,327 Patients.

Total knee arthroplasty (TKA) is the sole disease-modifying intervention for end-stage osteoarthritis. However, the temporal trends and stratification of age and patient demographics of pain and function levels at which surgeons perform TKA have not been characterized. The present investigation aimed to analyze the temporal trends of preoperative pain and functional patient-reported outcomes measures (PROMs) over the past 5 years when stratifying patient demographics. A prospective cohort of all patients who underwent primary elective TKA between January 2016 and December 2020 at a North American integrated tertiary health care system was retrospectively reviewed. The primary outcome was quarterly baseline (preoperative) pain and function PROM values before primary elective TKA. Evaluated PROMs included Knee Osteoarthritis Outcome Score (KOOS)-pain and KOOS-physical function shortform (PS) for the 5-year study period and were stratified by patient demographics (age, sex, race, and body mass index [BMI]). A total of 10,327 patients were analyzed. Preoperative pain levels remained unchanged over the study period for patients in the 45- to 64-year category (P-trend = 0.922). Conversely, there was a significant improvement in preoperative pain levels in the 65+ years group. Sex-stratified trends between males and females did not demonstrate a significant change in pre-TKA baseline pain over the study period (P-trend = 0.347 and P-trend = 0.0744). Both white and black patients demonstrated consistent KOOS-pain levels throughout the study period (P-trend = 0.0855 and P-trend = 0.626). Only white patients demonstrated improving preoperative KOOS-PS (P-trend = 0.0001), while black and "other" patients demonstrated consistent lower preoperative functional levels throughout the study period (P-trend = 0.456 and P-trend = 0.871). All BMI categories demonstrated relatively consistent preoperative KOOS-pain and KOOS-PS except for overweight and obese patients who demonstrated progressive improvement in preoperative KOOS-PS over the study period. Patients and surgeons are electing to perform primary TKA at higher levels of preoperative function. Stratification by race showed black patients did not experience a similar trend of improving function and exhibited a consistently lower functional level versus white patients. This disparity is likely to be multifactorial but may indicate underlying barriers to TKA access.

"After viral load testing, I get my results so I get to know which path my life is taking me": qualitative insights on routine centralized and point-of-care viral load testing in western Kenya from the Opt4Kids and Opt4Mamas studies.

BACKGROUND: Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed. METHODS: We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing's faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders. CONCLUSION: The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs. TRIAL REGISTRATION: NCT03820323, 29/01/2019.

In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1-3), along with four known ones (4-7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC50 = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC50 = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC50 = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (-121.8 and -131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (-116 and -100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.

13-amino derivatives of dehydrocostus lactone display greatly enhanced selective toxicity against breast cancer cells and improved binding energies to protein kinases in silico.

The biological activities of dehydrocostus lactone and its analogues are suggested to be mediated by the lactone ring and α,ß-methylene-γ-lactone. However, few studies exist on the structure-activity relationship of 13-amino derivatives of dehydrocostus latone. In this study new 13-amino derivatives of dehydrocostus lactone DHLC (1-4) were synthesized through Michael addition reactions, and were screened against three different breast cancer cell lines, namely hormone receptor positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12A) cell lines. Dehydrocostus lactone (DHLC) exhibited IC50 values of 1.11 (selectivity index (SI) = 0.06), 24.70 (SI = 0.01) and 0.07 µM against HCC70, MCF-7 and MCF-12A cells, respectively. All the amino derivatives, except DHLC-3 displayed low micromolar IC50 values (ranging from 0.07-4.24 µM) against both breast cancer cell lines, with reduced toxicity towards MCF-12A non-tumorigenic mammary epithelial cells (SI values ranging from 6.00-126.86). DHLC-1 and DHLC-2 demonstrated the greatest selectivity for the MCF-7 cells (with SI of 121 and 126.86 respectively) over the MCF-12A cells. This reveals that, overall, the derivatives display greatly improved selectivity for breast cancer over non-tumorigenic mammary epithelial cells, with between 100-fold and 12 000-fold higher SI values. The improved docking scores were recorded for all the 13-amino dehydrocostus lactone derivatives for the enzymes analyzed. Compounds DHLC-4, and DHLC-3 recorded higher docking scores of -7.33 and -5.97 Kca/mol respectively, compared to the parent structure, dehydrocostus lactone (-5.34 Kca/mol) for protein kinase (PKC) theta (1XJD) and -6.22 and -5.88 Kca/mol, respectively for protein kinase iota (1RZR). The compounds further showed promising predicted adsorption, distribution, metabolisms and excretion (ADME) properties. Predicting the ADME properties of these derivatives is of importance in evaluating their drug-likeness, which could in turn be developed into potential drug candidates.

Effects of Tartrazine on Some Sexual Maturation Parameters in Immature Female Wistar Rats.

Over the past century, the average age for onset of puberty has declined. Several additives present in our food are thought to contribute significantly to this early puberty which is recognized to also affect people's health in later life. On this basis, the impact of 40-days unique oral administration of the food dye tartrazine (7.5, 27, and 47 mg/kg BW doses) was evaluated on some sexual maturation parameters on immature female Wistar rats. Vaginal opening was evaluated during the treatment period. At the end of the treatments, animals were sacrificed (estrus phase) and the relative weight of reproductive organs, pituitary gonadotrophin and sexual steroids level, cholesterol level in ovaries and folliculogenesis were evaluated. Compared to the control group, animals receiving tartrazine (47 mg/kg BW) showed significantly high percentage of early vaginal opening from day 45 of age, and an increase in the number of totals, primaries, secondaries, and antral follicles; a significant increase in serum estrogen, LH and in uterine epithelial thickness. Our findings suggest that tartrazine considerably disturbs the normal courses of puberty. These results could validate at least in part the global observations on increasingly precocious puberty in girls feeding increasingly with industrially processed foods.

Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz.

Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance.

Catalytic Performance of Immobilized Sulfuric Acid on Silica Gel for N-Formylation of Amines with Triethyl Orthoformate.

In the search for convenient, green, and practical catalytic methods for the current interest in organic synthesis, a simple, green, and highly efficient protocol for N-formylation of various amines was carried out in the presence of immobilized sulfuric acid on silica gel (H2SO4-SiO2). All reactions were performed in refluxing triethyl orthoformate (65 °C). The product formamides were obtained with high-to-excellent yields within 4 min to 2 h. The current approach is advantageous, due to its short reaction time and high yields. The catalyst is recyclable with no significant loss in catalytic efficiency.

A Critical Review of the Antimicrobial and Antibiofilm Activities of Green-Synthesized Plant-Based Metallic Nanoparticles.

Metallic nanoparticles (MNPs) produced by green synthesis using plant extracts have attracted huge interest in the scientific community due to their excellent antibacterial, antifungal and antibiofilm activities. To evaluate these pharmacological properties, several methods or protocols have been successfully developed and implemented. Although these protocols were mostly inspired by the guidelines from national and international regulatory bodies, they suffer from a glaring absence of standardization of the experimental conditions. This situation leads to a lack of reproducibility and comparability of data from different study settings. To minimize these problems, guidelines for the antimicrobial and antibiofilm evaluation of MNPs should be developed by specialists in the field. Being aware of the immensity of the workload and the efforts required to achieve this, we set out to undertake a meticulous literature review of different experimental protocols and laboratory conditions used for the antimicrobial and antibiofilm evaluation of MNPs that could be used as a basis for future guidelines. This review also brings together all the discrepancies resulting from the different experimental designs and emphasizes their impact on the biological activities as well as their interpretation. Finally, the paper proposes a general overview that requires extensive experimental investigations to set the stage for the future development of effective antimicrobial MNPs using green synthesis.

A New Chalcone and Antimicrobial Chemical Constituents of Dracaena stedneuri.

Microbial infections are leading causes of death and morbidity all over the world due to the development of the resistance to antibiotics by certain microorganisms. In this study, the chemical exploration of the ethanol (EtOH) extract of the aerial part of Dracaena stedneuri (Dracaenaceae) led to the isolation of one previously unreported chalcone derivative, i.e., 2',4'-dihydroxy-2,3'-dimethoxychalcone (1), together with 12 known compounds: 8-(C)-methylquercetagetin-3,6,3'-trimethyl ether (2), methylgalangine (3), quercetin (4), kaempferol (5), 6,8-dimethylchrysin (6), ombuine-3-O-rutinoside (4',7-dimethylquercetin-3-O-α-L-rhamnopyranosyl-(1 → 6) -ß-D-glucopyranoside) (7), alliospiroside A (8), ß-sitosterol 3-O-glucopyranoside (9), ishigoside (10), betulinic acid (11), oleanolic acid (12), and lupeol (13). The structures were determined by spectroscopic and spectrometric analysis including 1- and 2-Dimensional Nuclear Magnetic Resonance (1D- and 2D-NMR), High-Resolution Electrospray Ionization Mass Spectrometry (HRESIMS), and comparison with literature data. The isolated secondary metabolites and crude extract displayed antibacterial activity against some multidrug-resistant strains with minimal inhibitory concentration (MIC) values ranging from 32 to 256 µg/mL. The antibacterial activity of compound 13 against Enterobacter aerogenes ATCC13048 (MIC value: 32 µg/mL) was higher than that of chloramphenicol used as the reference drug (MIC = 64 µg/mL).

Non-Hermitian Spatial Symmetries and Their Stabilized Normal and Exceptional Topological Semimetals.

We study non-Hermitian spatial symmetries-a class of symmetries that have no counterparts in Hermitian systems-and study how normal and exceptional semimetals can be stabilized by these symmetries. Different from internal ones, spatial symmetries act nonlocally in momentum space and enforce global constraints on both band degeneracies and topological quantities at different locations. In deriving general constraints on band degeneracies and topological invariants, we demonstrate that non-Hermitian spatial symmetries are on an equal footing with, but are essentially different from Hermitian ones. First, we discover the nonlocal Hermitian conjugate pair of exceptional or normal band degeneracies that are enforced by non-Hermitian spatial symmetries. Remarkably, we find that these pairs lead to the symmetry-enforced violation of the Fermion doubling theorem in the long-time limit. Second, with the topological constraints, we unravel that a certain exceptional manifold is only compatible with and stabilized by non-Hermitian spatial symmetries but is intrinsically incompatible with Hermitian spatial symmetries. We illustrate these findings using two three-dimensional models of a non-Hermitian Weyl semimetal and an exceptional unconventional Weyl semimetal. Experimental cold-atom realizations of both models are also proposed.

Outcomes and Survivorship at a Median of 8.9 Years Following Hip Arthroscopy in Adolescents with Femoroacetabular Impingement: A Matched Comparative Study with Adults.

BACKGROUND: Because of the unique theoretical surgical risks, including osteonecrosis, acute iatrogenic slipped capital femoral epiphysis, and epiphyseal injury, the optimal treatment strategy for femoroacetabular impingement (FAI) in growing adolescents has yet to be established. The aim of this study was to compare the clinical outcomes of primary arthroscopic treatment of FAI in growing adolescents with a matched adult group. METHODS: Patients with FAI who underwent arthroscopic treatment with a minimum follow-up of 2 years were included. Patients with previous ipsilateral hip surgery, an Outerbridge grade of ≥3, a preoperative Tönnis grade of ≥2, or evidence of dysplasia (lateral center-edge angle of <25°) were excluded. Eligible patients who were ≤19 years old and whose proximal femoral physis had not yet closed were matched to adult (20 to 40-year-old) counterparts in a 1:1 ratio by sex, body mass index, and time of surgery. For the adolescents, cam resection was performed with a physeal-sparing approach. Outcome scores, including the modified Harris hip score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and HOS-Sports-Specific Subscale (HOS-SSS), were prospectively collected. RESULTS: Of the 196 eligible adolescents, 157 (80%) were pair-matched to adult controls, with a median postoperative follow-up of 8.9 and 6.6 years, respectively. Fourteen (9%) of the adolescents required revision hip arthroscopy compared with 18 adults (11%) (p = 0.46). No patient in the adolescent group had conversion to a total hip arthroplasty (THA), while 3 in the adult group had a THA (p = 0.25). For adolescents without subsequent hip surgery, the median mHHS improved from 59 preoperatively to 96 postoperatively; the HOS-ADL, from 71 to 98; and the HOS-SSS, from 44 to 94 (p < 0.001), which were significantly higher postoperative scores than those of the matched adults (p < 0.05) despite similar or inferior baseline scores. No complications were found during the office visit or at the final follow-up. CONCLUSIONS: Hip arthroscopy performed with a physeal-sparing approach for FAI in growing adolescents is safe and effective and yields superior clinical outcomes compared with those in a matched adult group. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Midterm Outcomes After Hip Labral Augmentation in Revision Hip Arthroscopy.

BACKGROUND: Labral augmentation has emerged as an essential procedure to address a deficient or irreparable labrum while preserving native labral tissue and restoring the hip suction seal mechanism. PURPOSE: To evaluate midterm outcomes of arthroscopic hip labral augmentation for labral insufficiency after previous hip arthroscopy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients were identified from a prospectively collected database who underwent arthroscopic hip labral augmentation between January 2011 and January 2017 with a minimum 3-year follow-up. Pre- and postoperative patient-reported outcome scores were compared and included the 12-Item Short Form Health Survey physical and mental component summaries, Western Ontario and McMaster Universities Osteoarthritis Index, modified Harris Hip Score (mHHS), and Hip Outcome Score (HOS) (Activities of Daily Living [ADL] and Sport). Postoperative Tegner Activity Scale and patient satisfaction (1-10) scores were also evaluated. The minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) between the preoperative and minimum 3-year follow-up scores were calculated. RESULTS: A total of 88 patients (39 men, 49 women) underwent revision hip arthroscopy with labral augmentation. The average age was 32.8 ± 11 years. Of these, 77 patients (88%) were available for the minimum 3-year follow-up. The survivorship (absence of conversion to total hip arthroplasty) at 3 years and 5 years was 93% at both time points, with a mean survival time of 8.5 years (95% CI, 8.0-8.9). Eleven patients (14%) required revision arthroscopic surgery for continued pain. Revisions occurred at a mean of 2.6 ± 1.4 years after augmentation. The mean follow-up was 5.2 ± 1.2 years (range, 3-9 years). For patients not requiring subsequent surgery (n = 61), all patient-reported outcome measures significantly improved, which included a 20-point increase in HOS-ADL (MCID, 82%; PASS, 72%) and mHHS (MCID, 78%; PASS, 70%). The median postoperative Tegner score was 4 (range, 1-10). The median postoperative patient satisfaction score was 9 out of 10 (range, 1-10). CONCLUSION: Arthroscopic hip labral augmentation is a successful treatment option for patients with labral insufficiency after previous hip arthroscopy, demonstrating improved patient-reported outcomes and survivorship of 93% at 3 years and 5 years. This technique provides a valuable labral preservation option when addressing hip labral pathology when viable native labral tissue remains.

In vitro antibacterial and cytotoxic effects of Euphorbia grandicornis Blanc chemical constituents.

BACKGROUND: Euphorbia grandicornis is widely utilized in traditional medicine for the treatment of microbial infections including sexually transmitted diseases such as syphilis, gonorrhoea and for healing of wounds. OBJECTIVE: The aim of this work was to isolate and evaluate the antibacterial and anticancer activities of Euphorbia grandicornis chemical constituents. METHODS: Chemical constituents were isolated and identified using various spectroscopic techniques such as IR, MS, and NMR. The single point growth inhibitory potential of the compounds was determined using a 96-well plate based assay. RESULTS: The CH2Cl2 crude extracts exhibited potent antibacterial activity against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538 with percentage growth of 94.90 ± 4.24 and 29.47 ± 4.89 respectively. Hence, the CH2Cl2 crude extract was further subjected to column chromatography which resulted in the isolation of methyl 2,5-dihydroxybenzoate (1), n-octyl benzoate (2), friedelanol (3), and germanicol (4) and identification of compounds 12-24 for the first time in the species based on the LC-MS/MS spectroscopic data. The purified compounds (1-4), and previously reported compounds (5-11) were evaluated for antibacterial activities against S. aureus and E. coli, as well as the cytotoxicity effects against HeLa cells. Of the purified compounds, methyl 2,5-dihydroxybenzoate (1), was the most active against E.coli and S. aureus with a percentage growth of 19.12 ± 0.65 and 23.32 ± 0.23 respectively. ß-amyrin (6), and ß-sitosterol (8), were active against S. aureus with percentage growth of 27.17 ± 0.07, and 47.79 ± 2.99 respectively. CONCLUSION: The results obtained from this study indicate that E. grandicornis, is a rich source of chemical constituents that may provide new lead compounds for the development of antibacterial agents.