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Background: As a large proportion of older adults are insufficiently active, it is imperative to identify ways to increase incidental physical activity. Men's Sheds, a mutual-aid, community-based organisation appear to be a promising approach for optimising wellbeing outcomes., Objectives: To investigate whether Men's Sheds attendance is associated with higher levels of physical activity, and the relationships between physical activity, health-related quality of life (HRQOL), and wellbeing in Men's Shed members., Methods: Participants (N = 45) wore a hip accelerometer (Actigraph GTX-9) for 11 days. The majority (n = 30, M age  = 72.3 ± 9.4) also consented to complete an online questionnaire investigating HRQOL and wellbeing., Results: Linear mixed models revealed members, on average, spent an additional 34 min in light physical activity, had an extra six breaks in sedentary behaviour, and took an extra 1193 steps on days they attended Men's Sheds, though, these effects were small. Physical activity was not significantly associated with HRQOL and wellbeing., Conclusion: Men's Sheds appear to be a valuable approach for increasing light intensity physical activity, breaks in sedentary behaviours, and step count in older adults. However, additional Men's Shed activities specifically targeting increased movement may be required to realise greater impacts on health-related quality of life and wellbeing. SO WHAT?: Men's Sheds may provide a valuable opportunity to increase some indices of physical activity, which may contribute to better overall health. While these effects may be small for active Men's Shed members, these effects may be more appreciable for more sedentary individuals., (© 2025 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Emotional labour is the process by which people regulate emotions congruently with occupational requirements. Research consistently links emotional labour to greater levels of burnout. However, we argue this literature is potentially confounded by measurement error. We sought to validate an English adaptation of a recent emotional labour measure that addresses measurement error concerns in an under-researched sample at risk of burnout-psychologists providing psychotherapy. We termed this measure the Perth Emotional Labour Scale (PELS) which is based upon Andela and colleagues' (2015) original measure. Additionally, we explored what factors of emotional labour contributed most to burnout in this group. We recruited 418 psychologists (81.58% female, 17.46% male, 0.96% non-binary) across Australia (N = 362, 86.60%) and New Zealand (N = 56, 13.40%). Factor analyses and correlational analyses examined the PELS' reliability and validity. Hierarchical multiple regression analysis explored whether each component of emotional labour contributed unique variance to emotional exhaustion (EE). Preliminary support for the PELS' psychometric properties was found and emotional dissonance was found to be the only emotional labour factor that uniquely contributed to EE. We demonstrate preliminary psychometric support for the PELS but recommend further development and argue our findings have unique implications for research and practice., (© 2024 The Author(s). Stress and Health published by John Wiley & Sons Ltd.)

The impact of leadership on members' mental health outcomes in community-based mutual-aid organizations such as Men's Shed is unknown. We analyzed (a) whether identity leadership is associated with Shed members' mental health, and (b) whether these links are mediated by psychological safety, social network quality, and social identity. Path analysis on data collected from 162 Australian Men's Shed members revealed statistically significant associations between identity leadership and each mechanism, and our model accounted for significant variance in mental health outcomes (14%-24%, p s < .001). Only social network quality and psychological safety were associated with unique variance in mental health outcomes. All indirect effects via social network quality and psychological safety were significant. These findings suggest the proposed mechanisms explain the relationship between identity leadership mental health outcomes in mutual-aid organizations such as Men's Sheds., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. Talbot, and J. Wild are employed by Men’s Sheds of WA. Although they contributed to the design and paper drafts, they did not access the raw data and did not conduct any analyses. We have no other known conflicts of interest to disclose.

Background: Concerning levels of stress, strain, and poorer mental health are observed in family carers of patients diagnosed with high-grade glioma (HGG). Understanding the reported unmet needs of these carers will enable future interventions to address such needs to improve their preparedness for care and well-being. In this secondary analysis, we aimed to explore: (i) what carers of people with HGG perceive could improve their preparedness to care ; and (ii) what needs carers reported they required additional support with., Methods: Responses from 188 carers of patients with HGG participating in a randomized controlled trial of the Care-IS intervention were analyzed to identify reported unmet needs. Of this larger sample, 92 participants answered a qualitative question seeking to identify perceived unmet needs in carer preparedness over 12 months. These responses comprised the data for the current secondary analysis. Content analysis was used to analyze the qualitative data and observe trends across participant responses., Results: Five overarching themes were identified: carer needs , providing emotional and practical care , coping with uncertainty , coping with the consequences of illness progression , and processing and supporting end-of-life care. Notably, the content analysis identified differences in response numbers between groups in the Care-IS trial, particularly with the control group having more needs regarding illness progression and end-of-life care., Conclusions: Future interventions aimed at improving the well-being and preparedness of carers of people with HGG should consider providing better support centered on carer needs, their changed circumstances, living with uncertainty, and care transition., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Reducing rates of depressive symptoms in older adults is a public health priority. Men's Sheds are a community organisation that may protect against depressive symptoms in older men. It is currently unclear how social anxiety and behavioural activation may relate to depressive symptoms for Men's Shed members. We employed a cross-sectional design to explore whether the relationships between social anxiety, behavioural activation and depressive symptoms were contingent upon Shed social network quality in a sample of 164 Men's Shed members. Conditional effects analysis found social anxiety (B = -0.08, p < 0.01) and behavioural activation's (B = 0.02, p < 0.001) relationships with depression to be contingent on Shed social network quality. Additionally, we found evidence for a conditional effect of social anxiety on the relationship between behavioural activation and depression (B = -0.03, p < 0.01) such that this relationship was stronger for those with higher levels of social anxiety. Our findings suggest that a strong social network within a Men's Shed weakens the association between social anxiety and depression, that the relationship between behavioural activation and depression is stronger in those with poorer Shed social networks, and that the relationship between behavioural activation and depression may be stronger for those with higher levels of social anxiety. We suggest that our findings contribute to increasing quantitative support for the mental health benefits of Men's Shed membership, highlight the potential importance of Shed social network quality and explore how social anxiety may affect the mental health outcomes for members., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The condensative cyclization of sp 3 C-O bonds in per-silylated hexitols is investigated by computation. Conformer searches using the Monte Carlo algorithm, followed by successively higher levels of theory (MMFF, PM3, and B3LYP), of -SiR 3 + - and -Bcat + -activated substrates lead to structures primed for intramolecular chemistry. Silane activation features O4 to C1 attack, while borane activation suggests boronium ions that activate O5 to C2 reactivity. This, in conjunction with Boltzmann population analysis, parallels reported reactivity for sorbitol, mannitol, and galactitol. Calculations using the meta-hybrid M06-2X functional additionally provide free-energy profiles for each cyclization event. In most of the cases presented, precyclization conformers that position a nucleophilic oxygen less than 3.0 Å from the C-O leaving group correlate to efficient experimental reactivities. Two examples of galactitol containing bridging silyl groups are analyzed computationally, and the experimental outcomes match predictions. The computational regime presented is a step closer to providing predictive power for the reduction of per-functionalized molecules.

A novel diastereoselective, Lewis acid catalyzed 1,6-difunctionalization of galactose and mannose derivatives has been developed in one pot, via sequential nucleophile additions. Our studies point to the formation of a 3,6-anhydrosugar intermediate as key to the 1,6-site-selectivity. Starting material-specific reactivity occurs when competitive ring-opening C-O cleavage is possible, owed to basicity and stereoelectronic stabilization differences. Lastly, Mayr nucleophilicity parameter values helped predict which reaction conditions would be most suitable for specific nucleophiles.

Mesoionic carbene-stabilized borenium ions efficiently reduce substituted pyridines to piperidines in the presence of a hydrosilane and a hydrogen atmosphere. Control experiments and deuterium labeling studies demonstrate reversible hydrosilylation of the pyridine, enabling full reduction of the N-heterocycle under milder conditions. The silane is a critical reaction component to prevent adduct formation between the piperidine product and the borenium catalyst.

Existing literature examining burnout in psychotherapists has not adequately considered the contributing role of emotional labor. Similarly, emotional labor research has not sufficiently explored how this construct operates in the context of psychologists who provide individual psychotherapy. To address these existing gaps in the literature, thematic analysis was conducted on interviews with 24 psychologists who provide individual psychotherapy to determine the perceived consequences of emotional labor identified by the participants. Participants discussed personal growth, feeling depleted and exhausted, and craving space free from people and work-related emotion as consequences of emotion management in the context of providing individual psychotherapy. The findings suggest that emotional labor can exert positive, negative, and neutral effects on psychologists providing psychotherapy and is worthy of attention as a variable in efforts to promote positive well-being. In the occupational group of psychologists providing individual psychotherapy, performing emotional labor can lead to personal growth, emotional exhaustion, and a need to distance oneself from work-related emotion. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aldimines and ketimines containing electron-donating and electron-withdrawing groups can be hydrosilylated with borenium catalysts at as low as 1 mol% catalyst loading at room temperature, providing the corresponding secondary amines in excellent yields. Reactions with 2-phenylquinoline gave the 1,4-hydrosilylquinoline product selectively which can be further functionalized in a one-pot synthesis to give unique γ-amino alcohol derivatives. Control experiments suggest that the borenium ion catalyzes both the hydrosilylation and subsequent addition to the aldehyde.

Palaeorecords suggest that the climate system has tipping points, where small changes in forcing cause substantial and irreversible alteration to Earth system components called tipping elements. As atmospheric greenhouse gas concentrations continue to rise as a result of fossil fuel burning, human activity could also trigger tipping, and the impacts would be difficult to adapt to. Previous studies report low global warming thresholds above pre-industrial conditions for key tipping elements such as ice-sheet melt. If so, high contemporary rates of warming imply that exceeding these thresholds is almost inevitable, which is widely assumed to mean that we are now committed to suffering these tipping events. Here we show that this assumption may be flawed, especially for slow-onset tipping elements (such as the collapse of the Atlantic Meridional Overturning Circulation) in our rapidly changing climate. Recently developed theory indicates that a threshold may be temporarily exceeded without prompting a change of system state, if the overshoot time is short compared to the effective timescale of the tipping element. To demonstrate this, we consider transparently simple models of tipping elements with prescribed thresholds, driven by global warming trajectories that peak before returning to stabilize at a global warming level of 1.5 degrees Celsius above the pre-industrial level. These results highlight the importance of accounting for timescales when assessing risks associated with overshooting tipping point thresholds.

We report the ruthenium-catalyzed cyclization of 1,6-diynes with two molecules of carbon monoxide and water to give a variety of catechols. This reaction likely proceeds through the intermediacy of the water-gas shift reaction to generate an yne-diol-type intermediate followed by a [4 + 2] cycloaddition with 1,6-diynes. The reaction requires no external reductants or hydride sources and provides a novel and valuable method for the synthesis of a variety of catechols.

Formation of radical-radical cocrystals is an important step towards the design of organic ferrimagnets. We describe a simple approach to generate radical-radical cocrystals through the identification and implementation of well-defined supramolecular synthons which favor cocrystallization over phase separation. In the current paper we implement the structure-directing interactions of the E-E bond (E=S, Se) of dithiadiazolyl (DTDA) and diselenadiazolyl (DSDA) radicals to form close contacts to electronegative groups. This is exemplified through the preparation and structural characterization of three sets of radical cocrystals; the 2:2 cocrystal [PhCNSSN] 2 [MBDTA] 2 (4) [MBDTA=methyl benzodithiazolyl] and the 2:1 cocrystals [C 6 F 5 CNEEN] 2 [TEMPO] (E=S, 5; E=Se, 6). In 4 the two types of radical are linked via bifurcated inter-dimer δ+ S⋅⋅⋅N δ- interactions whereas 5 and 6 exhibit a set of five-centre δ+ E⋅⋅⋅O δ- contacts (E=S, Se)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A formal N-heterocyclic carbene insertion into the B-H bond of 9-BBN followed by a ring expansion reaction is reported. NHC-9-BBN adducts were reacted in one or two steps to give the corresponding di- or triazaborines. Hydride abstraction of selected species with [Ph 3 C] + is facile, giving rise to 6π-aromatic cations with Lewis acidity comparable to Lewis acids commonly employed in frustrated Lewis pairs.

The discovery of a natural quasicrystal, icosahedrite (Al63Cu24Fe13), accompanied by khatyrkite (CuAl2) and cupalite (CuAl) in the CV3 carbonaceous chondrite Khatyrka has posed a mystery as to what extraterrestrial processes led to the formation and preservation of these metal alloys. Here we present a range of evidence, including the discovery of high-pressure phases never observed before in a CV3 chondrite, indicating that an impact shock generated a heterogeneous distribution of pressures and temperatures in which some portions reached at least 5 GPa and 1,200 °C. The conditions were sufficient to melt Al-Cu-bearing minerals, which then rapidly solidified into icosahedrite and other Al-Cu metal phases. The meteorite also contains heretofore unobserved phases of iron-nickel and iron sulphide with substantial amounts of Al and Cu. The presence of these phases in Khatyrka provides further proof that the Al-Cu alloys are natural products of unusual processes that occurred in the early solar system.

Objectives: The rate of smoking among incarcerated adults is more than 3 times that of the general population. Negative health consequences of smoking have prompted many correctional facilities to become tobacco-free. This presents a unique opportunity to examine health conditions associated with motivation to remain tobacco-free after release from prison. We examined this association among individuals who participated in the WISE randomized clinical trial., Methods: A total of 247 participants completed a baseline questionnaire asking about illnesses (both smoking-related and non-smoking-related), family history of smoking-related illnesses, demographics, and smoking history. Smoking status was assessed 3 weeks postrelease., Results: Approximately 38% of participants reported having an illness caused by or worsened by smoking and 53.0% reported having "moderate" to "a lot" of concern about their health due to smoking; 22.9% reported having asthma and 26.8% reported hypertension. The adjusted odds of remaining tobacco-free at 3 weeks postrelease from a tobacco-free prison was significant only for individuals with a family history of smoking-related illnesses (odds ratio [OR] = 0.28; 95% confidence interval [CI], 0.12-0.68). For individuals with smoking-related conditions, the adjusted odds of remaining tobacco-free was nonsignificant (OR = 1.91; 95% CI, 0.85-4.27). Similarly, the adjusted odds of remaining tobacco-free for participants with non-smoking-related medical conditions was nonsignificant (OR = 0.27; 95% CI, 0.06-1.22)., Conclusions: These results offer a first look at understanding health conditions as a motivator to remain tobacco-free after release from prison. Although these findings require additional investigation, these results suggest that providing treatment to prisoners with chronic disease and specifically targeting smoking-related illnesses might be beneficial with regard to smoking cessation success.

Key modifications to in vitro genetic toxicology testing have been made in the last 5 years including the use of optimization approaches such as structure-activity relationships and screening assays to identify and eliminate potentially genotoxic chemicals from further consideration, better guidance on cytotoxicity assessment and dose selection, and greater use of p53-competent human cells. To determine the effect of these changes on testing outcomes, the pattern of positive results across assays conducted by BioReliance from 2005 to 2010 was examined. Data were tabulated for good laboratory practice (GLP)-compliant Ames, mouse lymphoma (MLA), chromosome aberration in Chinese hamster ovary (CHO) cells, and in human peripheral blood lymphocytes (HPBL) assays along with non-GLP screening Ames assays. A decrease in percentage of positive results in MLA and CHO chromosome aberration assays was observed, whereas the percentage of positive Ames assays remained consistent. This was not unexpected because MLA and CHO cytogenetic assays have undergone the most substantive changes (e.g., the establishment of the Global Evaluation Factor for the MLA and the use of the relative increase in cell counts in CHO chromosome aberration assays). Over the last 5 years, there has been an increase in the percentage of positive results observed in the chromosome aberration assay in HPBL. It is speculated that this may have led to an increase in HPBL-positive results if the chemicals routed to HPBL had previous positive genotoxicity results. Another factor may be the lack of a reliable cytotoxicity measurement in the HPBL assay., (Copyright © 2012 Wiley Periodicals, Inc.)

2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) is a fully chlorinated, non-coplanar biphenyl. To demonstrate that PCB 209 is not likely to exhibit human health hazards common to coplanar PCBs it was tested for cytochrome P450 (P450) enzyme induction potentials, genetic toxicity, and endocrine-modulating activity. PCB 209 (dose from 0.005 to 5000 ng/mL) did not significantly induce P450 CYP1A, 2A, 2B, 3A, or 4A enzyme activities in primary cultured rat hepatocytes. In contrast, Aroclor 1260, a PCB mixture that contains approximately 60% chlorine by weight, showed significant induction of P450 CYP1A, 2A, 2B, and 3A within the same dose range. PCB 209 (dose from 100 to 5000 microg/plate) was negative in the bacterial mutagenicity (Ames) test in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 or in Eschericia coli strain WP2uvrA. PCB 209 (dose from 25 to 150 microg/mL) was also negative for forward mutations at the thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cells. The Ames and the mouse lymphoma assays were both conducted in the absence and presence of rat liver S9 fraction. PCB 209 (dose from 500 to 2000 mg/kg by single dose oral gavage) did not induce an increase in the frequency of micronuclei in polychromatic erythrocytes in mouse bone marrow in vivo. PCB 209 did not induce estrogenic effects when administered by gavage to ovariectomized adult female rats at 500 and 1000 mg/kg for 4 days, nor did it produce alterations consistent with endocrine-modulating activity in adult intact male rats when administered by gavage at 500 and 1000 mg/kg for 15 consecutive days.

Diacetyl (2,3-butanedione) is a yellowish liquid that is usually mixed with other ingredients to produce butter flavor or other flavors in a variety of food products. Inhalation of butter flavoring vapors was first associated with clinical bronchiolitis obliterans among workers in microwave popcorn production. Recent findings have shown irreversible obstructive lung disease among workers not only in the microwave popcorn industry, but also in flavoring manufacture, and in chemical synthesis of diacetyl, a predominant chemical for butter flavoring. It has been reported that perfluorochemicals utilized in food packaging are migrating into foods and may be sources of oral exposure. Relatively small quantities of perfluorochemicals are used in the manufacturing of paper or paperboard that is in direct contact with food to repel oil or grease and water. Because of recent concerns about perfluorochemicals such as those found on microwave popcorn bags (e.g. Lodyne P208E) and diacetyl in foods, we evaluated both compounds for mutagenicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells. Lodyne P208E was less toxic than diacetyl and did not induce a mutagenic response. Diacetyl induced a highly mutagenic response in the L5178Y mouse lymphoma mutation assay in the presence of human liver S9 for activation. The increase in the frequency of small colonies in the assay with diacetyl indicates that diacetyl causes damage to multiple loci on chromosome 11 in addition to functional loss of the thymidine kinase locus.

Kava (Piper methysticum) is a member of the pepper family and has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. Traditionally, kava extracts are prepared by grinding or chewing the rhizome and mixing with water and coconut milk. The active constituents of kava are a group of approximately 18 compounds collectively referred to as kavalactones or kava pyrones. Kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the six major kavalactones. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver toxicity in humans, including several who required liver transplants after using kava supplements. In order to study the toxicity and mutagenicity, two commercial samples of kava, Kaviar and KavaPure, and the six pure kavalactones including both D-kawain and DL-kawain, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation.

As previously reported [Cameron, T. P., Rogers-Back, A. M., Lawlor, T. E., Harbell, J. W., Seifried, H. E., and Dunkel, V. C. (1991) Gentoxicity of multifunctional acrylates in the Salmonella/mammalian-microsome assay and mouse lymphoma TK+/- assay. Environ. Mol. Mutagen. 17, 264-271], the National Cancer Institute (NCI) shares the responsibility of selecting the most significant chemicals for carcinogenicity testing by the National Toxicology Program (NTP) and has used data from Salmonella and mouse lymphoma mutagenicity assays to aid in the selection and prioritization of chemicals to be further evaluated in chronic 2 year rodent studies. In addition, a number of antineoplastic and anti-AIDS drugs in preclinical evaluation were tested for the NCI's Division of Cancer Treatment Toxicology Branch. In the NCI/NTP chemical selection process, it is no longer necessary to test chemicals prior to sending them to the NTP so the NCI program has ceased performing mutagenicity tests. Some of the testing data has been made available in summary form in the Chemical Carcinogenisis Research Information System (CCRIS), which is searchable on the NLM TOXNET system. The limitations in using this source are that only summary results are available and many negative test results are not included. A summary table that presents the results for each compound is provided in the Appendix with raw data provided in the Supporting Information. The Appendix table contains the compound name, CAS number, and a summary of the data from the Ames test and the mouse lymphoma assay.

Chromium picolinate (CrPic, Chromax) is a dietary supplement that has been commercially available for the past two decades. CrPic has potential benefits for reducing insulin dependence in diabetics by increasing sensitivity of insulin receptors and in stimulating insulin binding. In this study, CrPic was tested for its ability to produce chromosomal aberrations in vitro using Chinese hamster ovary K1 (CHO) cells. CHO cells were exposed to a range of cytotoxic to non-cytotoxic concentrations of CrPic for 4 or 20h in the absence of metabolic (S9) activation or for 4h in the presence of S9 activation. CrPic was solubilized with dimethyl sulfoxide (DMSO) to attain the highest possible solubility for maximizing the test doses. Cells were treated with 96.25, 192.5, 385 or 770 microg/mL of CrPic for 4 h in the presence of S9 activation, and for 4 or 20 h in the absence of S9 activation. A distinct precipitate of CrPic was evident in the cell culture medium at 770 microg/mL, which was the highest dose tested. Results showed no statistically significant increases in structural or numerical chromosome aberrations were produced at any test dose level with CrPic in 4-h treatments up to a precipitating dose of 770 microg/mL in either the presence or absence of S9 activation. Additionally no aberrations were observed up to 385 microg/mL (the maximum analyzable dose) following treatment for 20 h in the absence of S9 activation. The percentage of cells with structural or numerical aberrations in CrPic treated cultures was not statistically different (p>0.05) from that quantified in controls at any dose level. The absence of significant differences from control levels demonstrates that CrPic did not induce structural or numerical chromosome aberrations up to doses that were insoluble in the culture medium.

Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9.

Chromium picolinate (CrPic, Chromax) is a dietary supplement that is stable and more bioavailable than other commercially available forms of chromium. Chromium supplementation is known to enhance the action of insulin, particularly in insulin resistance and type 2 diabetes mellitus. A previous study reported that CrPic produced increases in mutations of the hypoxanthine phosphoribosyltransferase (Hprt) gene in Chinese hamster ovary (CHO) cell mutation tests. This study, however, evaluated CrPic produced by the testing laboratory and used an atypical 48 h exposure period for this test system. The current study evaluated the mutagenic potential of the most widely utilized commercial form of CrPic in CHO/Hprt mutation tests following International Conference on Harmonisation (ICH) Guidelines (+/-S9 metabolic activation with a 5h exposure) in addition to repeating the test with a 48 h exposure period -S9 activation. CrPic was suspended in dimethyl sulfoxide (DMSO) up to a concentration of 50 mg/mL; exposures were conducted under conditions in which precipitate was not evident and under conditions in which some precipitate of CrPic was visually evident in the cell culture medium at the highest concentrations (500 microg/mL). The concentrations evaluated for mutagenicity ranged from 15.6 to 500 microg/mL (+S9 and -S9) for the 5 h exposure and 31.3-500 microg/mL for the 48 h exposure (-S9). Only a slight degree of cytotoxicity was seen in the standard tests up to the limit of solubility in the medium. Toxicity, i.e., cloning efficiency < or =50% of the solvent control, but no mutagenic increases were observed at 500 microg/mL following a 48 h exposure period. The results of these studies showed that CrPic was non-mutagenic in two independent CHO/Hprt assays and in an assay using a 48 h exposure period.

Quinacrine has been used for voluntary female non-surgical sterilization for its ability to produce tubal occlusion. Safety issues regarding quinacrine have been raised because it has been shown to intercalate with DNA. Therefore, safety issues need to be resolved by appropriate toxicology studies to support a review for human transcervical use. Such toxicology studies include mutagenicity assays. Here we report an evaluation of the genotoxicity of quinacrine dihydrochloride dihydrate (QH) using a battery of assays. In the bacterial mutagenicity assay, QH was strongly positive in Salmonella typhimurium tester strain TA1537 with and without S9-activation and in S. typhimurium tester strain TA98 with S9-activation; QH was also strongly positive in Escherichia coli WP2 uvrA without S9-activation. QH was not mutagenic in S. typhimurium tester strains TA100 and TA1535 with and without S9-activation. QH was mutagenic in the mouse lymphoma assay in the absence of S9-activation. QH was clastogenic in Chinese hamster ovary (CHO) cells, with and without S9-activation. QH was negative for polyploidy in the same chromosome aberration test. Using a triple intraperitoneal injection treatment protocol in both male and female mice, QH was negative in the in vivo mouse micronucleated erythrocyte (micronucleus) assay. These results confirm that QH is mutagenic and clastogenic in vitro and suggest a potential risk to human health due to QH exposure after intrauterine exposure.

To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without the addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na2EDTA, phytic acid, and ferrozine.

The present paper discusses some of the difficulties in working with people with an intellectual disability and an alcohol problem, and draws on the sparse literature about alcohol problems in people with intellectual disability. Four individuals drawn from the current clinical case loads of medical practitioners in UK community intellectual disability services are described. Some suggestions for staff training, patient education and health promotion, and therapeutic approaches are made.

The design and use of iron(III) chelates in the oral treatment of iron-deficiency anemia is discussed in terms of the following criteria: (1) the ability of a chelate to exist as a monomeric species even at physiological pH values, (2) the rate of transfer of iron from the chelate to the iron-transporting protein-apotransferrin, (3) the rate of depolymerization of ferric citrate polymer by the free ligand, and (4) its nontoxicity and ability to regenerate hemoglobin levels in anemic rats. Detailed species distribution studies, stability constants, and kinetic data for iron(III) acetohydroxamate (criteria 1-3 above) show that it remains monomeric at physiological pH values and undergoes very rapid iron transfer with apotransferrin. Detailed animal studies show a significant increase in regeneration of hemoglobin in rats fed 2 ml of 4 mM Fe(III) acetohydroxamate daily when compared to rats fed similarly with Fe(III) citrate. A strong potential is thus indicated for Fe(III) acetohydroxamate as a source of iron in the anemic animal.