Background Sexual health remains one of the most overlooked areas of life for people with intellectual disability. In recent years there has been an increasing expectation that this issue will be addressed by disability service providers. In this paper we examine the barriers to sexual health provision of people with intellectual disability as experienced by disability service providers and clinicians. Method This research uses a constructionist grounded theory approach. It was conducted in 2 phases using semistructured qualitative interviews to collect data from disability service managers and clinicians working with people with intellectual disability in New South Wales, Australia. Findings and Discussion Key themes within the interviewsincluding funding shortages and a lack of policy guidelineswere identified as significant administrative barriers to sexual health provision. Myths about the sexual health of people with intellectual disability, family attitudes, and lack of staff training were also identified as barriers.

Protein adducts have the potential to serve as unique biomarkers of exposure to compounds of interest. Many xenobiotics (or their metabolites) are electrophilic and therefore reactive with nucleophilic amino acid residues on proteins. Nitrogen mustards are reactive xenobiotics with potential use as chemical warfare agents (CWA) or agents of terrorist attack, in addition to being employed as chemotherapeutic agents. The present study utilized cysteine-, lysine-, and histidine-containing model peptides to characterize in vitro adduction of the nitrogen mustards mechloroethamine (HN-2) and tris-(2-chlorethyl)amine (HN-3) to these nucleophilic amino acid residues by means of liquid chromatography-tandem mass spectrometry. The study assessed the structure of adducts formed, the time course of adduct formation, concentration-response relationships, and temporal stability of adducts. Adduction was hypothesized to occur on all three model peptides via initial formation of a reactive aziridinium intermediate for both mechloroethamine and tris-(2-chlorethyl)amine, followed by covalent adduction to nucleophilic residues. While adduction was found to occur most readily with cysteine, it was also observed at lysine and histidine, demonstrating that adduction by mechloroethamine and tris-(2-chlorethyl)amine is possible at multiple nucleophilic sites. Following solid phase extraction cleanup, adducts formed with mechloroethamine were stable for up to three weeks. Adducts formed with tris-(2-chlorethyl)amine were less stable; however, hydrolyzed secondary adducts were observed throughout the three week period. This study demonstrates that the nitrogen mustards mechloroethamine and tris-(2-chlorethyl)amine form stable adducts with reactive protein nucleophiles other than cysteine.

M ost patients with lung metastases have unresectable disease (1). Patients with unresectable and unablatable lung metastases have poor survival and limited treatment options when the metastases stop responding to systemic chemotherapy (2).Transarterial chemoembolization (TACE) of the pulmonary or bronchial arteries is an emerging treatment option for large and multifocal lung tumors (Table E1 [online]). Like the liver, the lung has a dual blood supply. However, unlike liver tumors, which are mostly supplied by the hepatic artery, lung tumors can be supplied by either the bronchial artery or pulmonary artery (3). Response rates are 17% after pulmonary artery chemoembolization (4,5) and 39% after bronchial artery chemoembolization (6-8), bland embolization (9), or chemoinfusion (10-12). The highest reported response rates have been seen with primary lung cancer, treated via the bronchial artery (Table E1 [online]).A major limitation of existing studies of lung chemoembolization is the low response rate. We hypothesize that the low response rate is because of the dual blood supply of lung tumors. Lung tumors primarily supplied by the pulmonary artery will presumably have a low response rate to bronchial artery chemoembolization and Background: Lung chemoembolization is an emerging treatment option for lung tumors, but the optimal embolic, drug, and technique are unknown.Purpose: To determine the technical success rate and safety of bronchial or pulmonary artery chemoembolization of lung metastases using ethiodized oil, mitomycin, and microspheres. Materials and Methods:Patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this prospective, single-center, single-arm, phase I clinical trial (December 2019-September 2020). Pulmonary and bronchial angiography was performed to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed using an ethiodized oil and mitomycin emulsion, followed by microspheres. The primary objectives were technical success rate and safety, according to the National Cancer Institute Common Terminology Criteria for Adverse Events. CIs of proportions were estimated with the equal-tailed Jeffreys prior interval, and correlations were evaluated with the Spearman test. Results:Ten participants (median age, 60 years; interquartile range, 52-70 years; six women) were evaluated. Nine of the 10 participants (90%) had lung metastases supplied by the bronchial artery, and one of the 10 participants (10%) had lung metastases supplied by the pulmonary artery. The technical success rate of intratumoral drug delivery was 10 of 10 (100%) (95% CI: 78, 100). There were no severe adverse events (95% CI: 0, 22). The response rate of treated tumors was one of 10 (10%) according to the Response Evaluation Criteria in Solid Tumors and four of 10 (40%) according to the PET Response Criteria in Solid Tumors. Ethiodized oil retention at 4-6 w...

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MS-based proteomic analysis was combined with in silico quantum mechanical calculations to improve understanding of protein adduction by N-phenylhydroxylamine (PhNHOH) and nitrosobenzene (NOB), metabolic products of aniline. In vitro adduction of model peptides containing nucleophilic sidechains (Cys, His, and Lys) and selected proteins (bovine and human hemoglobin and β-lactoglobulin-A) were characterized. Peptide studies identified the Cys thiolate as the most reactive nucleophile for these metabolites, a result consistent with in silico calculations of reactivity parameters. For PhNHOH, sulfinamides were identified as the primary adduction products, which were stable following tryptic digestion. Conversely, reactions with NOB yielded an additional oxidized adduct, the sulfonamide. In vitro exposure of human whole blood to PhNHOH and NOB demonstrated that only sulfinamides were formed. In addition to previously reported adduction of β93Cys of human Hb, two novel sites of adduction were found; α104Cys and β112Cys. We also report CD and UV-Vis spectroscopy studies of adducted human Hb that revealed loss of α-helical content and deoxygenation. The results provide additional understanding of the covalent interaction of aromatic amine metabolites with protein nucleophiles.