Casein phosphopeptide/antimicrobial peptide co-modified SrTiO3 nanotubes for prevention of bacterial infections and repair of bone defects.

Endowing titanium surfaces with multifunctional properties can reduce implant-related infections and enhance osseointegration. In this study, titanium dioxide nanotubes with strontium doping (STN) were first created on the titanium surface using anodic oxidation and hydrothermal synthesis techniques. Next, casein phosphopeptide (CCP) and an antimicrobial peptide (HHC36) were loaded into the STN with the aid of vacuum physical adsorption (STN-CP-H), giving the titanium surface a dual function of "antimicrobial-osteogenic". The surface of STN-CP-H has a suitable roughness and good hydrophilicity, which is conducive to osteoblasts. STN-CP-H had a 99 % antibacterial rate against S. aureus and E. coli and effectively prevented the growth of bacterial biofilm. Meanwhile, the antibacterial mechanism of STN-CP-H was initially explored with the help of transcriptome sequencing technology. STN-CP-H could greatly increase osteoblast adhesion, proliferation, and expression of osteogenic markers (alkaline phosphatase, runt-related transcription) when CCP and Sr worked together synergistically. In vivo, the STN-CP-H coating could effectively promote new osteogenesis around titanium implant bone and had no toxic effects on heart, liver, spleen, lung and kidney tissues. A potential anti-infection bone healing material, STN-CP-H bifunctional coating developed in this work efficiently inhibited bacterial infection of titanium implants and encouraged early osseointegration.

Investigation of the intrinsic cannabinoid activity of hemp-derived and semisynthetic cannabinoids with ß-arrestin2 recruitment assays-and how this matters for the harm potential of seized drugs.

Cultivation of industrial low-Δ9-tetrahydrocannabinol (Δ9-THC) hemp has created an oversupply of cannabidiol (CBD)-rich products. The fact that phytocannabinoids, including CBD, can be used as precursors to synthetically produce a range of THC variants-potentially located in a legal loophole-has led to a diversification of cannabis recreational drug markets. 'Hemp-compliant', 'hemp-derived' and 'semisynthetic' cannabinoid products are emerging and being advertised as (legal) alternatives for Δ9-THC. This study included a large panel (n = 30) of THC isomers, homologs, and analogs that might be derived via semisynthetic procedures. As a proxy for the abuse potential of these compounds, we assessed their potential to activate the CB1 cannabinoid receptor with a ß-arrestin2 recruitment bioassay (picomolar-micromolar concentrations). Multiple THC homologs (tetrahydrocannabihexol, THCH; tetrahydrocannabiphorol, THCP; tetrahydrocannabinol-C8, THC-C8) and THC analogs (hexahydrocannabinol, HHC; hexahydrocannabiphorol, HHCP) were identified that showed higher potential for CB1 activation than Δ9-THC, based on either higher efficacy (Emax) or higher potency (EC50). Structure-activity relationships were assessed for Δ9-THC and Δ8-THC homologs encompassing elongated alkyl chains. Additionally, stereoisomer-specific differences in CB1 activity were established for various THC isomers (Δ7-THC, Δ10-THC) and analogs (HHC, HHCP). Evaluation of the relative abundance of 9(S)-HHC and 9(R)-HHC epimers in seized drug material revealed varying epimeric compositions between batches. Increased abundance of the less active 9(S)-HHC epimer empirically resulted in decreased potency, but sustained efficacy for the resulting diastereomeric mixture. In conclusion, monitoring of semisynthetic cannabinoids is encouraged as the dosing and the relative composition of stereoisomers can impact the harm potential of these drugs, relative to Δ9-THC products.

The use of host defense peptides in root canal therapy in rats.

OBJECTIVES: In order to evaluate host defense peptides (HDPs) HHC-10 and synoeca-MP activity in in vitro osteoclastogenesis process and in vivo induced apical periodontitis, testing the effect of molecules in the inflammatory response and in apical periodontitis size/volume after root canal treatment. MATERIALS AND METHODS: In vitro osteoclastogenesis was assessed on bone marrow cell cultures extracted from mice, while in vivo endodontic treatment involved rats treated with Ca(OH)2 or HDPs. In vitro osteoclasts were subjected to TRAP staining, and in vivo samples were evaluated by radiographic and tomographic exams, as well as histologic analysis. RESULTS: None of the substances downregulated the in vitro osteoclastogenesis. Nevertheless, all treatments affected the average of apical periodontitis size in rats, although only teeth treated with HDPs demonstrated lower levels of the inflammatory process. These results demonstrated the in vivo potential of HDPs. Radiographic analysis suggested that HHC-10 and synoeca-MP-treated animals presented a similar lesion size than Ca(OH)2-treated animals after 7-day of endodontic treatment. However, tomography analysis demonstrated smaller lesion volume in synoeca-MP-treated animals than HHC-10 and Ca(OH)2-treated animals, after 7 days. CONCLUSIONS: These molecules demonstrated an auxiliary effect in endodontic treatment that might be related to its immunomodulatory ability, broad-spectrum antimicrobial activity, and possible induction of tissue repair at low concentrations. These results can encourage further investigations on the specific mechanisms of action in animal models to clarify the commercial applicability of these biomolecules for endodontic treatment. CLINICAL SIGNIFICANCE: HDPs have the potential to be adjuvant substances in endodontic therapy due to its potential to reduce inflammation in apical periodontitis.

HOme-based Longitudinal Investigation of the multidiSciplinary Team Integrated Care (HOLISTIC): protocol of a prospective nationwide cohort study.

BACKGROUND: The use of home health care (HHC) is increasing worldwide. This may have an impact not only on patients and their caregivers' health but on care resource utilization and costs. We lack information on the impact of HHC on the broader dimensions of health status and care resource utilization. More understanding of the longitudinal HHC impact on HHC patients and caregivers is also needed. Moreover, we know little about the synergy between HHC and social care. Therefore, the present study aims to observe longitudinal changes in health, care resource utilization and costs and caregiving burden among HHC recipients and their caregivers in Taiwan. METHODS: A prospective cohort study "Home-based Longitudinal Investigation of the Multidisciplinary Team Integrated Care (HOLISTIC)" will be conducted and 600 eligible patient-caregiver dyads will be recruited and followed with comprehensive quantitative assessments during six home investigations over two years. The measurements include physical function, psychological health, cognitive function, wellbeing, shared decision making and advance care planning, palliative care and quality of dying, caregiving burden, continuity and coordination of care, care resource utilization, and costs. DISCUSSION: The HOLISTIC study offers the opportunity to comprehensively understand longitudinal changes in health conditions, care resource utilization and costs and caregiving burden among HHC patients and caregivers. It will provide new insights for clinical practitioners and policymakers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020.

Biological and pharmacological effects of hexahydrocurcumin, a metabolite of curcumin.

Curcumin, one of the most precious pharmacologically relevant natural products, has gained considerable attention among scientists for decades because of its multi-pharmacological activities in the clinical. However, critical studies on its pharmacological and toxicological activities are needed to understand how this compound can have these biological functions considering its poor oral bioavailability and the low plasma concentration. Moreover, curcumin undergoes extensive and rapid metabolism in vivo, indicating that the pharmacological activity of consuming curcumin might be mediated partly by its metabolites. And as one of the major curcumin metabolites, hexahydrocurcumin (HHC), exhibits similar or more potent bioactivity than curcumin by in vitro and in vivo studies, such as antioxidant, anti-inflammatory, antitumor and cardiovascular protective properties, which may provide important information for us to have a profound comprehension of the effectiveness of curcumin. This review mainly summarizes the current knowledge and underlying molecular mechanisms of the biological activities of HHC and its potential effects on the development of various human diseases.

The effectiveness of home health care for reducing readmissions: an integrative review.

This integrative review analyzes research on the relationship of Home Health Care (HHC) to readmissions, specifically, identifying moderating and mediating factors and measurement constraints influencing effectiveness evaluations of HHC in reducing readmissions. HHC patients' readmission rates are higher than patients not receiving home health services but measurement of effectiveness is confounded by both practice variation and comparisons using noncomparable control groups. Effectiveness evaluations of HHC in reducing readmission requires attention to sample comparability and control for mediating variables. Establishing evidence of effectiveness clarifies the utility of HHC as a strategy to reduce readmissions.

Mechanisms of Vasorelaxation Induced by Hexahydrocurcuminin Isolated Rat Thoracic Aorta.

This study was designed to examine the vasorelaxant effects of hexahydrocurcumin (HHC), one of the major natural metabolites of curcumin from Curcuma longa, on rat isolated aortic rings, and the underlying mechanisms. Isometric tension of the aortic rings was recorded using organ bath system. HHC (1 nM to 1 mM) relaxed the endothelium-intact aortic rings pre-contracted with PE and KCl in a concentration-dependent manner. Removal of the endothelium did not alter the effect of HHC-induced relaxation. In Ca(2+)-free Krebs solution, HHC significantly inhibited the CaCl2-induced contraction in high K(+) depolarized rings and suppressed the transient contraction induced by PE and caffeine in a concentration-dependent manner. HHC was also observed to relax phobal-12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC), precontracted aortic rings in a concentration-dependent manner with EC50 values equivalent to 93.36 ± 1.03 µM. In addition, pre-incubation with propranolol (a ß-adrenergic receptor blocker) significantly attenuated the HHC-induced vasorelaxation. These results suggest that the vasorelaxant effect of HHC is mediated by the endothelium-independent pathway, probably because of the inhibition of extracellular Ca(2+) influx through voltage-operated Ca(2+) channels and receptor-operated Ca(2+) channels, the inhibition of Ca(2+) mobilization from intracellular stores, as well as inhibition of PKC-mediated Ca(2+)-independent contraction. Moreover, HHC produces vasorelaxant effects probably by stimulating the ß-adrenergic receptor.

Hexahydrocannabinol and closely related semi-synthetic cannabinoids: A comprehensive review.

Since the early 2000s, there has been a turmoil on the global illicit cannabinoid market. Parallel to legislative changes in some jurisdictions regarding herbal cannabis, unregulated and cheap synthetic cannabinoids with astonishing structural diversity have emerged. Recently, semi-synthetic cannabinoids manufactured from hemp extracts by simple chemical transformations have also appeared as recreational drugs. The burst of these semi-synthetic cannabinoids into the market was sparked by legislative changes in the United States, where cultivation of industrial hemp restarted. By now, hemp-derived cannabidiol (CBD), initially a blockbuster product on its own, became a "precursor" to semi-synthetic cannabinoids such as hexahydrocannabinol (HHC), which appeared on the drug market in 2021. The synthesis and cannabimimetic activity of HHC were first reported eight decades ago in quest for the psychoactive principles of marijuana and hashish. Current large-scale manufacture of HHC is based on hemp-derived CBD extract, which is converted first by cyclization into a Δ8 /Δ9 -THC mixture, followed by catalytic hydrogenation to afford a mixture of (9R)-HHC and (9S)-HHC epimers. Preclinical studies indicate that (9R)-HHC has THC-like pharmacological properties. The animal metabolism of HHC is partially clarified. The human pharmacology including metabolism of HHC is yet to be investigated, and (immuno)analytical methods for the rapid detection of HHC or its metabolites in urine are lacking. Herein, the legal background for the revitalization of hemp cultivation, and available information on the chemistry, analysis, and pharmacology of HHC and related analogs, including HHC acetate (HHC-O) is reviewed.

Identification of hexahydrocannabinol (HHC), dihydro-iso-tetrahydrocannabinol (dihydro-iso-THC) and hexahydrocannabiphorol (HHCP) in electronic cigarette cartridge products.

PURPOSE: Since 2021, products claiming to contain hexahydrocannabinol (HHC) and hexahydrocannabiphorol (HHCP), which are tetrahydrocannabinol (THC) analogs, have been distributed via the Internet. Owing to the presence of three asymmetric carbons in their structure, HHC and HHCP have multiple stereoisomers. This study aimed to identify the actual stereoisomers of HHC and HHCP isolated from electronic cigarette cartridge products using nuclear magnetic resonance (NMR) spectroscopy. METHODS: Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-photodiode array-mass spectrometry (LC-PDA-MS) were used for the analyses of two major peaks and one minor peak in product A and two major peaks in product B. These five compounds were isolated by silica gel column chromatography, and their structures were analyzed by 1H, 13C-NMR and various two-dimensional NMR techniques, i.e., H-H correlation spectroscopy, heteronuclear multiple quantum coherence, heteronuclear multiple-bond correlation, and nuclear Overhauser effect spectroscopy. RESULTS: Three compounds isolated from product A were identified as rel-(6aR,9R,10aR)-hexahydrocannabinol (11ß-hexahydrocannabinol; 11ß-HHC), rel-(6aR,9S,10aR)-hexahydrocannabinol (11α-hexahydrocannabinol, 11α-HHC), and a minor compound (2R,5S,6R)-dihydro-iso-tetrahydrocannabinol (dihydro-iso-THC). Meanwhile, the structural isomers of the major compound isolated from product B were identified as rel-(6aR, 9R, 10aR)-hexahydrocannabiphorol (11ß-hexahydrocannabiphorol; 11ß-HHCP) and rel-(6aR, 9S, 10aR)-hexahydrocannabiphorol (11α-hexahydrocannabiphorol; 11α-HHCP). CONCLUSIONS: The presence of both 11ß-HHC and 11α-HHC in the HHC products analyzed in this study suggests that they were most likely synthesized via the reduction reaction of Δ8-THC or Δ9-THC. Dihydro-iso-THC was probably obtained as a byproduct of the synthesis of Δ8-THC or Δ9-THC from cannabidiol. Similarly, 11ß-HHCP and 11α-HHCP in the HHCP product could stem from Δ9-tetrahydrocannabiphorol.

An emerging trend in Novel Psychoactive Substances (NPSs): designer THC.

Since its discovery as one of the main components of cannabis and its affinity towards the cannabinoid receptor CB1, serving as a means to exert its psychoactivity, Δ9-tetrahydrocannabinol (Δ9-THC) has inspired medicinal chemists throughout history to create more potent derivatives. Initially, the goal was to synthesize chemical probes for investigating the molecular mechanisms behind the pharmacology of Δ9-THC and finding potential medical applications. The unintended consequence of this noble intent has been the proliferation of these compounds for recreational use. This review comprehensively covers the most exhaustive number of THC-like cannabinoids circulating on the recreational market. It provides information on the chemistry, synthesis, pharmacology, analytical assessment, and experiences related to the psychoactive effects reported by recreational users on online forums. Some of these compounds can be found in natural cannabis, albeit in trace amounts, while others are entirely artificial. Moreover, to circumvent legal issues, many manufacturers resort to semi-synthetic processes starting from legal products extracted from hemp, such as cannabidiol (CBD). Despite the aim to encompass all known THC-like molecules, new species emerge on the drug users' pipeline each month. Beyond posing a significantly high public health risk due to unpredictable and unknown side effects, scientific research consistently lags behind the rapidly evolving recreational market.

Disposition of Hexahydrocannabinol Epimers and Their Metabolites in Biological Matrices following a Single Administration of Smoked Hexahydrocannabinol: A Preliminary Study.

In 2023, hexahydrocannabinol (HHC) attracted the attention of international agencies due to its rapid spread in the illegal market. Although it was discovered in 1940, less is known about the pharmacology of its two naturally occurring epimers, 9(R)-HHC and 9(S)-HHC. Thus, we aimed to investigate the disposition of hexahydrocannabinol epimers and their metabolites in whole blood, urine and oral fluid following a single controlled administration of a 50:50 mixture of 9(R)-HHC and 9(S)-HHC smoked with tobacco. To this end, six non-user volunteers smoked 25 mg of the HHC mixture in 500 mg of tobacco. Blood and oral fluid were sampled at different time points up to 3 h after the intake, while urine was collected between 0 and 2 h and between 2 and 6 h. The samples were analyzed with a validated HPLC-MS/MS method to quantify 9(R)-HHC, 9(S)-HHC and eight metabolites. 9(R)-HHC showed the highest Cmax and AUC0-3h in all the investigated matrices, with an average concentration 3-fold higher than that of 9(S)-HHC. In oral fluid, no metabolites were detected, while they were observed as glucuronides in urine and blood, but with different profiles. Indeed, 11nor-9(R)-HHC was the most abundant metabolite in blood, while 8(R)OH-9(R) HHC was the most prevalent in urine. Interestingly, 11nor 9(S) COOH HHC was detected only in blood, whereas 8(S)OH-9(S) HHC was detected only in urine.

Human metabolism of the semi-synthetic cannabinoids hexahydrocannabinol, hexahydrocannabiphorol and their acetates using hepatocytes and urine samples.

Hexahydrocannabinol (HHC), hexahydrocannabiphorol (HHCP) and their acetates, HHC-O and HHCP-O, respectively, are emerging in Europe as alternatives to tetrahydrocannabinol (THC). This study aimed to elucidate the metabolic pathways of the semi-synthetic cannabinoids HHC, HHCP, HHC-O and HHCP-O from incubation with human hepatocytes. The metabolites of HHC were also identified in authentic urine samples. HHC, HHCP, HHC-O and HHCP-O were incubated with primary human hepatocytes for 1, 3 and 5 h. Authentic urine samples from cases screened positive for cannabis in blood using ELISA but confirmed negative were analysed both non-hydrolysed and hydrolysed for HHC metabolites. Potential metabolites were identified using ultra-high performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight mass spectrometer (QToF-MS). HHC and HHCP were primarily metabolised through monohydroxylation (monoOH), followed by oxidation to a carboxylic acid metabolite. HHC-O and HHCP-O were rapidly metabolised to HHC and HHCP, respectively. In authentic urine samples, 18 different metabolites were identified, and 99.3% of hydroxylated metabolites were glucuronidated. 11-OH-HHC, 5'OH-HHC and another metabolite with a monoOH on the side chain were the only metabolites present in all 16 urine samples. The metabolism of HHC and HHCP were similar, although the longer alkyl side chain of HHCP (heptyl) led to greater hydroxylation on the side chain than HHC (pentyl). The use of HHC and HHCP can be differentiated from the use of THC and other phytocannabinoids, but the use of the acetate analogues may not be differentiable from their non-acetate analogues.

Isolation and characterization of synthesis intermediates and side products in hexahydrocannabiphorol.

After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC-MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)-HHCP, iso-HHCP, cis-HHCP, and abn-HHCP) and two ketones (possible intermediates to (9R)-HHCP and abn-HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)-HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn-HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso-HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.

Timeliness metrics for screening and preventing TB in household contacts of pulmonary TB patients in Kenya.

BACKGROUND: The study assessed whether a "7-1-7" timeliness metric for screening and TB preventive therapy (TPT) could be implemented for household contacts (HHCs) of index patients with bacteriologically confirmed pulmonary TB under routine programmatic settings in Kenya. METHODS: A longitudinal cohort study conducted among index patients and their HHCs in 12 health facilities, Kiambu County, Kenya. RESULTS: Between January and June 2023, 95% of 508 index patients had their HHCs line-listed within 7 days of initiating anti-TB treatment ("First 7"). In 68% of 1,115 HHCs, screening outcomes were ascertained within 1 day of line-listing ("Next 1"). In 65% of 1,105 HHCs eligible for further evaluation, anti-TB treatment, TPT or a decision for no drugs was made within 7 days of screening ("Second 7"). Altogether, 62% of screened HHCs started TPT during the "7-1-7" period compared with 58% in a historical cohort. Main barriers to TPT uptake were HHCs not consulting clinicians, HHCs being unwilling to initiate TPT and drug shortages. Healthcare workers felt that a timeliness metric was valuable for streamlining HHC management and proposed "3-5-7" as a workable alternative. CONCLUSIONS: The national TB programme must generate awareness about TPT, ensure uninterrupted drug supplies and assess whether the "3-5-7" metric can be operationalised.

CONTEXTE: L'étude a évalué si une mesure de rapidité "7-1-7" pour le dépistage et le traitement préventif de la TB (TPT) pouvait être mise en œuvre pour les contacts familiaux des patients index atteints de TB pulmonaire confirmée bactériologiquement dans le cadre d'un programme de routine au Kenya. MÉTHODES: Étude de cohorte longitudinale menée auprès de patients index et de leurs contacts familiaux dans 12 établissements de santé du comté de Kiambu, au Kenya. RÉSULTATS: Entre janvier et juin 2023, 95% des 508 patients index ont eu leur centre de santé inscrit sur la liste dans les 7 jours suivant le début du traitement antituberculeux (« First 7 ¼ ). Dans 68% des 1 115 centres de santé, les résultats du dépistage ont été vérifiés dans le jour suivant l'inscription sur la liste (« Next 1 ¼). Dans 65% des 1 105 centres de santé éligibles pour une évaluation plus approfondie, le traitement antituberculeux, le TPT ou la décision de ne pas prendre de médicaments a été prise dans les 7 jours suivant le dépistage (« Second 7 ¼). Au total, 62% des patients dépistés ont commencé un traitement antituberculeux au cours de la période « 7-1-7 ¼, contre 58% dans une cohorte historique. Les principaux obstacles à l'adoption du TPT étaient les suivants : les centres de santé ne consultaient pas les cliniciens, les centres de santé n'étaient pas disposés à commencer le TPT et les pénuries de médicaments. Les professionnels de la santé ont estimé qu'une mesure de la rapidité d'exécution était utile pour rationaliser la gestion des centres de santé et ont proposé le « 3-5-7 ¼ comme solution de rechange viable. CONCLUSION: Le programme national de lutte contre la TB doit sensibiliser au TPT, garantir un approvisionnement ininterrompu en médicaments et évaluer si la mesure « 3-5-7 ¼ peut être mise en œuvre.

Detection and quantification of synthetic cannabinoids in seven illicitly sourced disposable vapes submitted by an individual presenting to a UK drug and alcohol service.

BACKGROUND AND AIMS: In the United Kingdom and internationally, synthetic cannabinoids (SCs) are a common adulterant in illicitly sourced vaping products. Recently, their use is increasingly being linked to severe health effects, particularly among children. Here, we aimed to conduct the first detection and quantification of SCs in illicit disposable vaping products. METHODS: A cross-section of seven illicitly sourced disposable vape samples that were initially sold as cannabis products was submitted for analysis by a single individual presenting to a drug and alcohol service in the United Kingdom. Qualitative and quantitative analyses of these samples were conducted using nuclear magnetic resonance and gas chromatography/electron ionization-mass spectrometry. RESULTS: Qualitative analysis identified the SC 5F-MDMB-PICA in all seven samples, in the absence of any other pharmacologically active compounds. Quantitative analysis revealed that the median concentration of 5F-MDMB-PICA was 0.85 mg/ml (range = 0.59-1.63). The external appearance of these vape samples closely resembled regulated vaping products, and the presence of SCs was not identifiable by any labelling or packaging. CONCLUSIONS: The SC 5F-MDMB-PICA was detected at a median concentration of 0.85 mg/ml in seven disposable vapes which were illegally sourced in the United Kingdom, were mis-sold as cannabis products and closely resembled legal, regulated products.

Developing cellulose-based hydrophobic/hydrophilic composites for efficient adsorption of oils and heavy metals from water.

The oily wastewater and heavy metal ions have been increasingly discharged into water environment, posting a serious threat to ecosystems and human health. However, it remains challenging to use single separation technology to effectively remove oil and heavy metal ions in oil-water mixtures simultaneously. Herein, novel hydrophobic/hydrophilic composites (HHC) were successfully prepared by using A4 paper-derived hydrophilic cellulose as the modified matrix, modifying the polydopamine layer and in-situ growth nanoscale zero-valent iron as active adsorption materials, combined with oleic acid-modified hydrophobic magnetic hollow carbon microspheres, which were used to efficiently and rapidly adsorb heavy metals and oil in oil-water mixtures. Under the optimal adsorption conditions, the adsorption amounts of As(III), As(V), Pb(II) and Cu(II) were 289.6 mg/g, 341.9 mg/g, 241.2 mg/g and 277.5 mg/g, respectively, and the mass transfer rate of HHC to the target ions is fast. The HHC have efficient separation performance for layered oil-water mixtures and emulsified oil-water mixtures, with separation efficiency of 97 % and 92 %. At the same time, due to the abundant adsorption sites, the HHC also exhibit splendid regeneration performance for the four ions after multiple adsorption utilization. Our work designed a approach to achieving promising oil and heavy metal adsorbents with higher adsorption capacity and better regenerative properties.

Management implications of latent TB among under-five children at risk: Insights from a community study in Mumbai, India.

BACKGROUND: Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown. A community-based study in Mumbai's urban slums screened and managed under-five children at LTBI risk to understand its epidemiology and inform TB control interventions. METHODS: Total 369 eligible under-five children were enrolled for the study. LTBI screening was done using Tuberculin skin test and Interferon gamma release assay. Active TB was ruled out before initiation of TB preventive therapy among LTBI positives. Statistical tests like chi-square, logistic regression analysis and Hosmer-Lemeshow test were used. RESULTS: Overall, LTBI prevalence among under-five children was 12.4% by IGRA and 21.4% by TST. Undernourished children had significantly lower LTBI positivity by IGRA (p = 0.027), while those with household contacts, longer contact duration and drug-resistant tuberculosis (DR-TB) exhibited proportionally greater IGRA positivity (p = <0.001). CONCLUSION: The study found a lower LTBI prevalence among under-five children compared to adults, with key risk factors being HHC, DR-TB contact, and prolonged exposure. These findings suggest the need to revise or revisit the TPT framework for this age group in India, particularly by implementing a test-and-treat approach.

Organizational readiness for change towards implementing a sepsis survivor hospital to home transition-in-care protocol.

Background: Organizational readiness for change, defined as the collective preparedness of organization members to enact changes, remains understudied in implementing sepsis survivor transition-in-care protocols. Effective implementation relies on collaboration between hospital and post-acute care informants, including those who are leaders and staff. Therefore, our cross-sectional study compared organizational readiness for change among hospital and post-acute care informants. Methods: We invited informants from 16 hospitals and five affiliated HHC agencies involved in implementing a sepsis survivor transition-in-care protocol to complete a pre-implementation survey, where organizational readiness for change was measured via the Organizational Readiness to Implement Change (ORIC) scale (range 12-60). We also collected their demographic and job area information. Mann-Whitney U-tests and linear regressions, adjusting for leadership status, were used to compare organizational readiness of change between hospital and post-acute care informants. Results: Eighty-four informants, 51 from hospitals and 33 from post-acute care, completed the survey. Hospital and post-acute care informants had a median ORIC score of 52 and 57 respectively. Post-acute care informants had a mean 4.39-unit higher ORIC score compared to hospital informants (p = 0.03). Conclusions: Post-acute care informants had higher organizational readiness of change than hospital informants, potentially attributed to differences in health policies, expertise, organizational structure, and priorities. These findings and potential inferences may inform sepsis survivor transition-in-care protocol implementation. Future research should confirm, expand, and examine underlying factors related to these findings with a larger and more diverse sample. Additional studies may assess the predictive validity of ORIC towards implementation success.

A Survey Study of Individuals Using Hexahydrocannabinol Cannabis Products: Use Patterns and Perceived Effects.

Introduction: Across the cannabis market, multiple cannabinoids have seen rapid growth. Considering the differing effects between specific cannabinoids, it is critical to assess effects on an individual level. Hexahydrocannabinol (HHC) is one intoxicating cannabinoid that became more accessible due to regulatory shifts. The purpose of the current study was to provide descriptive data regarding HHC use patterns and perceived effects within a sample of participants who endorsed recent HHC use. Methods: One hundred nine individuals self-reported use of an HHC-cannabis product at least once within 6 months and completed an HHC use questionnaire via Prolific, an online crowdsourcing platform. Results: Findings suggest recent HHC users are using HHC relatively frequently (∼10 days during the past month) for various indications, including anxiety and pain. HHC was perceived to yield more good than bad effects, including relaxation and euphoria. Approximately 17% of the sample reported adverse effects, and ∼20% of those who stopped using HHC experienced some withdrawal symptoms. Few meaningful sex differences in subjective effect ratings were observed. Discussion: The current study provides critical preliminary data about consumer use patterns and perceived effects related to HHC. Such data are needed to further research on the potential therapeutic as well as detrimental effects of HHC and to better inform the consumers, health professionals, and regulators about a cannabinoid that is widely available the market.

Identification of human hexahydrocannabinol metabolites in urine.

Hexahydrocannabinol (HHC) is a cannabinoid that has been known since 1940 but has only recently found its way into recreational use as a psychoactive drug. HHC has been used as a legal alternative to tetrahydrocannabinol (THC) in many countries, but first countries already placed it under their narcotic substances law. Our aim was to evaluate a reliable analytical method for the proof of HHC consumption by LC-MS/MS and GC-MS. We identified the two epimers of HHC and metabolites after HHC consumption by two volunteers (inhalation by use of a vaporizer and oral intake). LC-HR-MS/MS, LC-MS/MS and GC-MS with literature data (EI-MS spectra of derivatives) and reference compounds - as far as commercially available - were used for metabolite identification. Phase-II-metabolites (glucuronides) of HHC and OH-HHC were found in urine samples with LC-HR-MS/MS and LC-MS/MS. The main metabolite was tentatively identified with GC-MS as 4'OH-HHC (stereochemistry on C9 and C4' unknown). Another major side-chain hydroxylated metabolite found by LC-MS/MS could not be unambiguously identified. Both epimers of 11-OH-HHC were found in considerable amounts in urine. (8R, 9R)-8-OH-HHC was identified as a minor metabolite with GC-MS and LC-MS/MS. While (9S)-HHC was found in urine after oral intake and inhalation of HHC, the more psychoactive epimer (9R)-HHC was only found in urine after inhalation. Several other minor metabolites were detected but not structurally identified. We found that after oral or inhalative consumption the urinary main metabolites of a diastereomeric mixture of HHC are different from the respective, major Δ9-THC metabolites (11-OH-Δ9-THC and 11-nor-9-carboxy-Δ9-THC). Although a sensitive LC-MS/MS and GC-SIM-MS method were set-up for the reference compounds (9R)-11-nor-9-carboxy-HHC and (9S)-11-nor-9-carboxy-HHC, these oxidation products were not detected in urine with these techniques. To further increase sensitivity, a GC-MS/MS method was developed, and the 11-nor-9-carboxy metabolites of HHC were confirmed to be present as minor metabolites.