Cultural connectedness protects mental health against the effect of historical trauma among Anishinabe young adults.

OBJECTIVES: Canada's Indian Residential School (IRS) system aimed to annihilate Indigenous culture among Indigenous children. Negative health impacts have been documented not only among survivors but also among their descendants. Reconnection with culture has been promoted as a means to recovery for people affected by this historical trauma. This study aimed to assess whether cultural connectedness has a specific protective effect on mental health among the descendants of IRS survivors. STUDY DESIGN: Cross-sectional survey. METHODS: A randomly selected cross section of Anishinabe people, aged 18-39 years, from one community were invited to complete a brief questionnaire. Associations were calculated between IRS attendance, cultural connectedness, and mental health. RESULTS: A total of 147 people participated. Among participants without a family history of IRS attendance, cultural connectedness was not significantly associated with improved mental health. Among participants with a family history of IRS attendance, a high level of cultural connectedness was significantly associated with a 31% greater probability of reporting high mental health and mental health status similar to those with no family history of IRS attendance. CONCLUSIONS: Cultural connectedness appears to act as a strong and specific protective factor against the intergenerational effects of IRS on the mental health of Anishinabe young adults, providing epidemiological support for the notion of 'culture as treatment.'

Management of a hospital outbreak of extensively drug-resistant Acinetobacter baumannii using a multimodal intervention including daily chlorhexidine baths.

BACKGROUND: Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) is an increasingly important cause of healthcare-associated infection. Uncertainties remain concerning optimal control measures for healthcare-associated outbreaks. AIM: To describe the epidemiology and control of an XDR-Ab outbreak that involved multiple units of a large hospital from March 2012 to January 2014. METHODS: Case-finding included screening of rectum, groin, throat, nose, wounds, iatrogenic portals of entry, and catheterized sites. Antimicrobial susceptibility was evaluated by disc diffusion and E-test. Resistance genes were detected by polymerase chain reaction. Clonality was assessed by pulsed-field gel electrophoresis. Charts of cases were reviewed to identify risk factors for invasive infection. Control measures included isolation and cohorting of cases, hand hygiene reinforcement, environmental decontamination, and source control with daily baths using wipes pre-impregnated with chlorhexidine gluconate. FINDINGS: A single clonal strain of XDR-Ab colonized or infected 29 patients. Five patients died of XDR-Ab bacteraemia. Transmission occurred primarily on two wards. Colonization was detected at all anatomical screening sites; only 57% (16/28) of cases were rectal carriers. Advanced malignancy was a risk factor for bacteraemia (relative risk: 5.8; 95% confidence interval: 1.2-27.0). Transmission ended following implementation of the multimodal control strategy. No additional nosocomial cases occurred during the following 20 months. CONCLUSION: Our study highlights the need to screen multiple anatomic sites to diagnose carriage and identifies risk factors for XDR-Ab bacteraemia. A multimodal intervention that included daily chlorhexidine baths for cases was rapidly followed by the termination of the outbreak. Hospitals should consider similar interventions when managing future XDR-Ab outbreaks.

Primary hemangiosarcoma of the iliopsoas muscle eliciting a peripheral neuropathy.

An eight-year-old, male castrated bullmastiff presented to the Kansas State University Veterinary Medical Teaching Hospital with left hind-limb paralysis. A mass was identified in the left paralumbar soft tissue adjacent to the fourth (L4) to sixth (L6) lumbar vertebrae by magnetic resonance imaging. The iliopsoas muscle contained the mass which was identified as a hemangiosarcoma on histopathological examination. Hemangiosarcoma is rarely reported as a primary tumor arising from muscle vascular endothelium.

Inhibition of brain choline acetyltransferase in vivo: (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (B115), a depot form of a potent inhibitor.

The quaternary ammonium salt (E)-4-(1-naphthylvinyl)pyridine hydroxyethyl bromide (B111) and the tertiary amine salt (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (B115), both previously shown to protect against organophosphate (OP) toxicity, were examined in vivo for effects on rat brain choline acetyltransferase (CAT) activity and acetylcholine (ACh) levels. When administered iv, but not when given ip, B111 was able to inhibit brain CAT 29% and reduce brain ACh levels 25%, yet was unable to prevent soman-induced increases in ACh. B115, which may serve as a depot form of a quaternary ammonium analogue, was able to decrease CAT activity as much as 80% upon multiple ip administration. This CAT inhibitory potency was unprecedented for a tertiary amine salt of its structure. However, ACh levels were reduced by no more than 25% and B115 was ineffective in preventing soman- and sarin-induced increases in ACh. Since the degree of inhibition of CAT activity produced by B111 and B115 was not accompanied by a corresponding decrease in ACh levels, the protection afforded by these compounds against OP toxicity is most likely not related to CAT inhibition. B115 was also tested for its ability to affect cholinergic receptor binding. B115 was administered to rats ip, twice daily, at low doses throughout a 3-week period. Analysis of cortex tissue revealed a 45% increase in nicotinic receptor binding with no change in either total muscarinic receptor binding (M-1 and M-2) or high-affinity muscarinic receptor binding (M-2 alone).

Cardiovascular effects of 1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride.

1-Methyl-4-(1-naphthylvinyl)piperidine (B-120) produced a dose related decrease in blood pressure in cats. B-120 did not alter the cardiovascular response to acetylcholine or vagal stimulation. It did not affect the response of the nictitating membrane to both pre- and post-ganglionic stimulation. In isolated cortical synaptosomes, B-120 decreased calcium flux below basal levels. Thus, the blockade of calcium channels appeared to be related to the production of hypotension and may be the mechanism by which B-120 protected against organophosphate toxicity.

Approaches to protection against nerve agent poisoning. (Naphthylvinyl)pyridine derivatives as potential antidotes.

Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1-naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (22), and (E)-1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride (23), were found to afford significant protection against sarin in the mouse and against soman in the guinea pig. However, protection was apparently not related to CAT inhibition. Compound 23, our most effective compound in protecting against nerve agent, was without CAT inhibitory activity. Compound 22, which proved to be a potent CAT inhibitor, most likely owed this activity to being dehydrogenated back to the pyridinium quaternary salt by oxidative enzymes. Several of the (naphthylvinyl)pyridine quaternary salts, but not their tertiary amine analogues, were found to be effective in slowing the rate of aging of soman-inhibited acetylcholinesterase. Ability to slow the rate of aging was enhanced by introduction of methoxy substituents on the aryl moiety whereas the aging rate was actually accelerated by chloro substituents. To date, our most effective compound in slowing the rate of aging, (E)-4-[(4-methoxy-1-naphthyl)vinyl]pyridine methochloride (6), did not provide significant protection against soman in the mouse.

Synthesis of some quaternary ammonium alkylating agents and their effects on soman-inhibited acetylcholinesterase.

A number of compounds were synthesized and tested for their ability to realkylate the phosphonate anion of "aged", soman-inhibited acetylcholinesterase. None were found able to do so, but two of the compounds in particular, [2-(4-pyridyl)ethyl]diethylmethylammonium iodide (6) and its 2-isomer 7, proved able to slow the rate of aging significantly.

Steroid antifertility agents. Ionic complexes of basic derivatives for prolonged action.

Ethynylestradiol 3-dimethylaminopropionate (1), norethindrone 3-(O-dimethylaminopropyl)oxime (syn and anti isomers, 2a and 2b), and testosterone 3-(O-dimethylaminopropyl)oxime (3) have been prepared and converted to zinc and aluminum tannate complexes as potentially long-acting prodrug forms of the parent steroids. The basic derivatives and the complexes showed the appropriate hormonal activities although they were less active in acute tests than the respective parents. The complexes of 1 showed prolonged activities and, in particular, the zinc tannate showed a prolonged duration of antifertility activity in the rat on subcutaneous administration in an aluminum monostearate gel.

Intracutaneous cornifying epithelioma ("keratoacanthoma") of dogs and keratoacanthoma of man.

The intracutaneous cornifying epithelioma ("keratoacanthoma") of dogs was compared with keratoacanthoma of man based on findings in the literature and in house studies. The two tumors differ at the following points: epithelium of origin, rate of growth, infiltration, spontaneous involution, breed predisposition (Norwegian Elkhound, generalized form), occurrence in dogs at a younger or middle age. The development of this tumor in dogs seems to be comparable with the development of so-called keratoacanthoma in Mastomys natalensis, which is virus-induced. Further investigations have been initiated to uncover the possible virus nature of the intracutaneous cornifying epthelioma (so-called keratoacanthoma) in dogs.

Long-acting narcotic antagonist complexes.

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is a suspension in an aluminum monostearate gel.

Long-acting narcotic antagonist complexes.

We evaluated the ability of close to 100 organic acids to form water-soluble salts with methadone, cyclazocine, naloxone, naltrexone and, more recently, diprenorphine. About half the acids yielded insoluble salts. Polybasic acids affording insoluble salts were evaluated for their ability to form drug:acid:metal complexes with the polyvalent metal ions, Zn++, Al+++, Mg++ and Ca++. Optimum conditions for forming complexes have been developed and the consistency of their composition has been established. Salts were analyzed spectrophotometrically for drug content, and complexes were analyzed for drug and metal content. The in vitro degree of dissociation at equilibrium was measured for the preparations suspended in a simulated physiological buffer, pH 7.3. Preparations of the narcotic antagonist drugs showing relatively low degrees of dissociation in vitro, since it early appeared that a high degree of dissociation contraindicated a prolonged duration of pharmacological action, were evaluated in mice after intramuscular administration at several dose levels by the mouse tail-flick test for the potency and duration of their morphine antagonist activity. Our most promising preparations to date, showing the most prolonged durations of action without evidence of gross toxicity, are naltrexone zinc tannate and naltrexone aluminum tannate. These are undergoing detailed evaluation as potential clinical candidates. Thus far, the most useful of several dosage forms studied is s suspension in an aluminum monostearate gel.