7,11,15,28-Tetra­methyl-1,21,23,25-tetra­kis(2-phenyl­ethyl)resorcin[4]arene ethyl acetate clathrate

The title compound, C68H64O8·C4H8O2, is a new resorcin­[4]arene cavitand synthetic precursor, obtained by alkyl­ation of a previously reported resorcin[4]arene. The additional alkyl bridges significantly rigidify the structure and enforce a ‘bowl’ shape on the mol­ecular cavity. In the crystal structure, the mol­ecule lies on a crystallographic mirror plane, and a single ethyl acetate mol­ecule (also lying on the mirror plane) is present within the compound cavity, illustrating the host capabilities of the mol­ecule

Sleep Medication Use by people with Cerebral Palsy: A Population Level DataLinkage Study

Objectives To (1) compare proportions of the population dispensed sleep medication, and rate (dispensations/month) and amount (milligrams/month) of dispensed sleep medication, in individuals with and without cerebral palsy (CP); and (2) describe dispensation of sleep medication within CP and non-CP cohorts with respect to sociodemographic and clinical characteristics. Approach Individuals aged 6 -36 years (aligning with those known to the Northern Ireland CP Register [NICPR]), registered with a general practitioner at 01-January-2018, were identified within the National Health Application and Infrastructure System.  Sleep medications dispensed 01-January-2018 to 31-December-2019 were extracted from the Enhanced Prescribing Database.  Analysis was limited to melatonin due to small counts in other medications.  Routine healthcare data was sourced from the Honest Broker Service (HBS).  NICPR clinical data (CP-type, Gross Motor Function Classification System (GMFCS), gestation and birthweight) were linked to routine healthcare data using the Health and Care Number by HBS. Descriptive statistics are presented. Results Complete matching was achieved between NICPR and healthcare data using the HCN.  Final cohorts consisted of 1,598 individuals with CP and 790,097 without CP. A greater proportion of those with CP were dispensed melatonin compared to those without CP (4.6% vs 1.0%).  The CP cohort were also dispensed melatonin at a greater rate (median(IQR) CP 0.33(0.71) vs non-CP 0.25(0.54) dispensations/month) and in greater amounts (median(IQR) CP 30(74.7) vs non-CP 17.5(55.0) mg/month).  Within the CP cohort, differences in melatonin dispensation were observed across sociodemographic groups (male 5.1% vs female 3.9%; children 8.2% vs young adults 2.2%; urban 6.5% vs rural 5.0%); deprived 5.1% vs affluent 4.2%).  Clinical characteristics associated with greatest dispensation of melatonin were non-spastic CP (6.83%), GMFCS IV&V (5.29%), or extremely premature birth (6.85%). Conclusion Individuals with CP, particularly children, are more likely to be dispensed sleep medications compared to the general population.  Awareness of this disparity could encourage further research on assessment and management of sleep in CP and facilitate discussions between healthcare providers and families on underlying causes of sleep problems

7,11,15,28-Tetra­kis[(2-formyl­phen­oxy)methyl]-1,21,23,25-tetra­methyl­resorcin[4]arene cavitand ethyl acetate clathrate at 173 K

The title compound, C68H56O16, was synthesized as a novel synthetic inter­mediate towards deeper and more elaborate resorcin[4]arene cavitands. The structure is the first reported example of a resorcin[4]arene cavitand bearing aromatic aldehyde functional groups at the extra-annular rim of the mol­ecule. The 2-formyl­phen­oxy residues are found to assume two different orientations above the mol­ecular cavity. One half of the resorcin[4]arene cavitand mol­ecule appears in the asymmetric unit; the complete resorcin[4]arene cavitand structure was generated across a mirror plane. In addition, a highly disordered ethyl acetate solvent mol­ecule is present within the mol­ecular cavity

Towards the Identification of an In Vitro Tool for Assessing the Biological Behavior of Aerosol Supplied Nanomaterials

Nanoparticles (NP)-based inhalation systems for drug delivery can be administered in liquid form, by nebulization or using pressurized metered dose inhalers, and in solid form by means of dry powder inhalers. However, NP delivery to the lungs has many challenges including the formulation instability due to particle-particle interactions and subsequent aggregation, causing poor deposition in the small distal airways and subsequent alveolar macrophages activity, which could lead to inflammation. This work aims at providing an in vitro experimental design for investigating the correlation between the physico-chemical properties of NP, and their biological behavior, when they are used as NP-based inhalation treatments, comparing two different exposure systems. By means of an aerosol drug delivery nebulizer, human lung cells cultured at air-liquid interface (ALI) were exposed to two titanium dioxide NP (NM-100 and NM-101), obtained from the JRC repository. In parallel, ALI cultures were exposed to NP suspension by direct inoculation, i.e., by adding the NP suspensions on the apical side of the cell cultures with a pipette. The formulation stability of NP, measured as hydrodynamic size distributions, the cell viability, cell monolayer integrity, cell morphology and pro-inflammatory cytokines secretion were investigated. Our results demonstrated that the formulation stability of NM-100 and NM-101 was strongly dependent on the aggregation phenomena that occur in the conditions adopted for the biological experiments. Interestingly, comparable biological data between the two exposure methods used were observed, suggesting that the conventional exposure coupled to ALI culturing conditions offers a relevant in vitro tool for assessing the correlation between the physico-chemical properties of NP and their biological behavior, when NP are used as drug delivery systems

Increasing access to erectile dysfunction treatment via pharmacies to improve healthcare provider visits and quality of life: Results from a prospective real-world observational study in the United Kingdom

OBJECTIVES: The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P. METHODS: Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months. RESULTS: Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months. CONCLUSION: Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude

Activated Functionalized Carbon Nanotubes and 2D Nanostructured MoS2 Hybrid Electrode Material for High‐Performance Supercapacitor Applications

Alkali-activated functionalized carbon nanotubes (AFCNTs) and 2D nanostructured MoS2 are investigated as a novel hybrid material for energy-storage applications. The nanoflower-like 2D MoS2 is grown on the surface of AFCNT using the controlled one-step hydrothermal technique. The activation of functionalized carbon nanotubes results in greater performance due to the improved surface area. The Brunauer–Emmett–Teller (BET) surface area of the AFCNTs is found to be 594.7 m2 g−1 which is almost 30 times of the as-prepared carbon nanotubes (CNTs). The improved surface area with attached hydroxyl and carboxylic functional groups helps in the attachment of MoS2 nanoflowers onto the AFCNT, thus reducing the interfacial resistance and providing an easy path for electron transfer. The electrochemical analysis shows a high specific capacitance of 516 F g−1 at 0.5 A g−1 with a corresponding energy density of 71.76 Wh kg−1, which is an encouraging reported value from AFCNT and MoS2 hybrid material. To the best of our knowledge, herein, the first report on AFCNTs and 2D MoS2 nanostructured hybrid electrode material for supercapacitor applications is provided, and promising results in terms of specific capacitance, energy density, and power density by boosting the properties of individual material are explained

Estrogenicity of resin-based composites and sealants used in dentistry.

We tested some resin-based composites used in dentistry for their estrogenic activity. A sealant based on bisphenol-A diglycidylether methacrylate (bis-GMA) increased cell yields, progesterone receptor expression, and pS2 secretion in human estrogen-target, serum-sensitive MCF7 breast cancer cells. Estrogenicity was due to bisphenol-A and bisphenol-A dimethacrylate, monomers found in the base paste of the dental sealant and identified by mass spectrometry. Samples of saliva from 18 subjects treated with 50 mg of a bis-GMA-based sealant applied on their molars were collected 1 hr before and after treatment. Bisphenol-A (range 90-931 micrograms) was identified only in saliva collected during a 1-hr period after treatment. The use of bis-GMA-based resins in dentistry, and particularly the use of sealants in children, appears to contribute to human exposure to xenoestrogens

Tuberculosis in UK cities: workload and effectiveness of tuberculosis control programmes

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB) has increased within the UK and, in response, targets for TB control have been set and interventions recommended. The question was whether these had been implemented and, if so, had they been effective in reducing TB cases.</p> <p>Methods</p> <p>Epidemiological data were obtained from enhanced surveillance and clinics. Primary care trusts or TB clinics with an average of > 100 TB cases per year were identified and provided reflections on the reasons for any change in their local incidence, which was compared to an audit against the national TB plan.</p> <p>Results</p> <p>Access to data for planning varied (0-22 months). Sputum smear status was usually well recorded within the clinics. All cities had TB networks, a key worker for each case, free treatment and arrangements to treat HIV co-infection. Achievement of targets in the national plan correlated well with change in workload figures for the commissioning organizations (Spearman's rank correlation R = 0.8, P < 0.01) but not with clinic numbers. Four cities had not achieved the target of one nurse per 40 notifications (Birmingham, Bradford, Manchester and Sheffield). Compared to other cities, their loss to follow-up during treatment was usually > 6% (χ²= 4.2, P < 0.05), there was less TB detected by screening and less outreach. Manchester was most poorly resourced and showed the highest rate of increase of TB. Direct referral from radiology, sputum from primary care and outreach workers were cited as important in TB control.</p> <p>Conclusion</p> <p>TB control programmes depend on adequate numbers of specialist TB nurses for early detection and case-holding.</p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/9/127</url></p

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection