Primates and disability: Behavioral flexibility and implications for resilience to environmental change.

Congenital malformations, conditions, injuries, and illness can lead to long-term physical impairment and disability in nonhuman primates. How individual primates change their behaviors flexibly to compensate for their disabilities can inform our understanding of their resilience and ability to adjust to environmental change. Here, we synthesize the literature on nonhuman primates and disability, addressing the questions: how does disability influence behavior in primates? What insights can we take from the literature to better understand and predict the capacity of primates to modify their behaviors in the face of human-induced environmental change? We conducted a systematic review of the literature on spontaneous physical impairment and disability in captive, free-ranging, and wild primates. We surveyed 2807 articles on Web of Science and Scopus and identified 114 studies that fit our predetermined inclusion criteria. Behavioral plasticity, maternal and conspecific care, and the potential for innovation of novel behaviors allow many primates with disabilities to compensate when faced with challenges that are outside the scope of usual circumstances. We also found that 60% of the publications connected primate physical impairment and disability to human activities, suggesting an entangled relationship among humans, the environment, and primate disability. Disability and physical impairments provide an opportunity to examine how primates modify their behavior when presented with challenging conditions, and their potential resilience to a changing environment.

No food left behind: foraging route choices among free-ranging Japanese macaques (Macaca fuscata) in a multi-destination array at the Awajishima Monkey Center, Japan.

Animals must make route choices every day when moving through their habitat while foraging. Choosing an optimal route can be cognitively costly, and primates and other animals have been shown to use simple heuristics, "rules of thumb", to make foraging route choices. We investigated the potential use of heuristics among foraging free-ranging Japanese monkeys (Macaca fuscata) during solitary foraging trials. We also investigated the potential influence of individual variables (age and sex) and social variables (presence in the central group, presence of potential inter- and intraspecific competitors), on the use of heuristics, route length and trial time. We used a multi-destination foraging experiment with 6 platforms in a (4 m × 8 m) Z-array, completed by 29 Japanese macaques in 155 runs at the Awajishima Monkey Center in Japan. Our results showed that the macaques chose routes consistent with heuristics (e.g. nearest neighbour heuristic 19.4%, convex hull heuristic 4.5%) and selected optimal routes (shortest path in 23.9% of the trials). We also identified a potential new heuristic that was used most frequently, that we termed the "sweep heuristic" (27.1% of trials), which we interpreted as a strategy to deal with competitive foraging trade-offs - choosing routes to prioritize not leaving isolated food pieces behind. Age was significantly related to trial time; juvenile macaques were faster than adults and young adults, using speed to gain access to resources. Solitary trials with conspecifics present took significantly longer routes. Our results suggest that contextual factors led to variation in Japanese macaque decision-making, and we suggest that the preferential use of a sweep heuristic may have been a response to high intragroup competition.

Mothers of disabled infants had higher cortisol levels in a free-ranging group of Japanese macaques (Macaca fuscata).

Glucocorticoids (GCs) are hormones released in response to stressors and can provide insight into an organism's physiological well-being. Experiencing chronic challenges to homeostasis is associated with significant deviations from baseline fecal GCs (fGCs) in many species, providing a noninvasive biomarker for assessing stress. In the group of free-ranging Japanese macaques (Macaca fuscata) at the Awajishima Monkey Center in Japan, ~17% have congenital limb malformations. We collected 646 fecal samples from 27 females over three consecutive birth seasons (May-August) and analyzed them using enzyme immunoassay to extract fGCs. We explored the relationship between fGC levels and individual (physical impairment and reproductive status), social (dominance rank and availability of kin for social support), and ecological variables (exposure to potential predators, rainfall, and wild fruit availability). A disabled infant was associated significantly with higher fGC in the mother; however, physical impairment in adult females was not significantly related to fGC levels. Females with higher dominance rank had significantly lower fGC levels than lower ranking females. Other factors did not relate significantly to fGC. These results suggest that providing care that meets the support needs of disabled infants poses a physiological challenge for mothers and suggests that physically impaired adults are able to effectively compensate for their disabilities with behavioral plasticity. Once an individual with congenital limb malformations survives infancy through their mother's care, physical impairment does not appear to influence fGC values, while social variables like dominance rank significantly influenced cortisol values in free-ranging female Japanese macaques.

Multidimensional mapping of spin-exchange optical pumping in clinical-scale batch-mode 129Xe hyperpolarizers.

We present a systematic, multiparameter study of Rb/(129)Xe spin-exchange optical pumping (SEOP) in the regimes of high xenon pressure and photon flux using a 3D-printed, clinical-scale stopped-flow hyperpolarizer. In situ NMR detection was used to study the dynamics of (129)Xe polarization as a function of SEOP-cell operating temperature, photon flux, and xenon partial pressure to maximize (129)Xe polarization (PXe). PXe values of 95 ± 9%, 73 ± 4%, 60 ± 2%, 41 ± 1%, and 31 ± 1% at 275, 515, 1000, 1500, and 2000 Torr Xe partial pressure were achieved. These PXe polarization values were separately validated by ejecting the hyperpolarized (129)Xe gas and performing low-field MRI at 47.5 mT. It is shown that PXe in this high-pressure regime can be increased beyond already record levels with higher photon flux and better SEOP thermal management, as well as optimization of the polarization dynamics, pointing the way to further improvements in hyperpolarized (129)Xe production efficiency.

XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use.

Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1L/h) (129)Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The 'hyperpolarizer' is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode-making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell (129)Xe nuclear spin polarization values of ~30%-90% have been measured for Xe loadings of ~300-1600Torr. Typical (129)Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long (129)Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine.

A 3D-printed high power nuclear spin polarizer.

Three-dimensional printing with high-temperature plastic is used to enable spin exchange optical pumping (SEOP) and hyperpolarization of xenon-129 gas. The use of 3D printed structures increases the simplicity of integration of the following key components with a variable temperature SEOP probe: (i) in situ NMR circuit operating at 84 kHz (Larmor frequencies of (129)Xe and (1)H nuclear spins), (ii) <0.3 nm narrowed 200 W laser source, (iii) in situ high-resolution near-IR spectroscopy, (iv) thermoelectric temperature control, (v) retroreflection optics, and (vi) optomechanical alignment system. The rapid prototyping endowed by 3D printing dramatically reduces production time and expenses while allowing reproducibility and integration of "off-the-shelf" components and enables the concept of printing on demand. The utility of this SEOP setup is demonstrated here to obtain near-unity (129)Xe polarization values in a 0.5 L optical pumping cell, including ∼74 ± 7% at 1000 Torr xenon partial pressure, a record value at such high Xe density. Values for the (129)Xe polarization exponential build-up rate [(3.63 ± 0.15) × 10(-2) min(-1)] and in-cell (129)Xe spin-lattice relaxation time (T1 = 2.19 ± 0.06 h) for 1000 Torr Xe were in excellent agreement with the ratio of the gas-phase polarizations for (129)Xe and Rb (PRb ∼ 96%). Hyperpolarization-enhanced (129)Xe gas imaging was demonstrated with a spherical phantom following automated gas transfer from the polarizer. Taken together, these results support the development of a wide range of chemical, biochemical, material science, and biomedical applications.

Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI.

The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP(129)Xe) make it attractive for a number of magnetic resonance applications; moreover, HP(129)Xe embodies an alternative to rare and nonrenewable (3)He. However, the ability to reliably and inexpensively produce large quantities of HP(129)Xe with sufficiently high (129)Xe nuclear spin polarization (P(Xe)) remains a significant challenge--particularly at high Xe densities. We present results from our "open-source" large-scale (∼1 L/h) (129)Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this "hyperpolarizer" is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell P(Xe) values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. P(Xe) values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long "in-bag" (129)Xe polarization decay times have been measured (T1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)--more than sufficient for a variety of applications.

Prevalence of opioid dispensings and concurrent gastrointestinal medications in Quebec.

BACKGROUND: Opioids are frequently prescribed for moderate to severe pain. A side effect of opioid usage is the inhibition of gastrointestinal (GI) motility, known as opioid-induced bowel dysfunction (OBD). OBD is typically treated prophylactically with laxatives and/or acid suppressants. AIM: The present study describes the prevalence of outpatient opioid dispensing, opioid patient demographics, and concomitant dispensing of opioids and GI medications in the Quebec Public Prescription Drug Insurance Plan in 2005. METHODS: Using a retrospective cohort design, opioid dispensings were identified using claims and reimbursement data. Laxative and acid suppressant dispensings were also identified. Concurrent use was defined as having at least one 'GI medication-exposed day' overlapping an 'opioid-exposed day'. RESULTS: More than 11% of the drug plan population was dispensed an opioid in 2005, and dispensings increased with age. Approximately two-thirds of patients who received an opioid were given codeine. Approximately one-third of opioid patients were concomitantly dispensed a GI medication, yet only 2% were dispensed a laxative. CONCLUSIONS: Although the GI side effects of opioids are well known, these side effects appear to increase with age and duration of opioid use. Opioid-related side effects, particularly OBD, should be effectively managed so as not to lead to the cessation of opioid therapy.

Regulation of Dexras1 expression by endogenous steroids.

Dexras1, a newly identified member of the Ras superfamily of proteins, was discovered in AtT-20 corticotrope cells because its expression was induced in response to glucocorticoids (dexamethasone; Dex). As yet, the function of Dexras1 is unknown, but its rapid induction in response to glucocorticoids suggests the possibility that it may be involved in negative feedback regulation of corticotropin secretion. To better understand the control of Dexras1 expression, possible effects of other steroid hormones on its expression were studied in both AtT-20 cells and in mouse pituitaries. AtT-20 cells were treated with each of 6 steroids [aldosterone, corticosterone (Cort), Dex, beta-estradiol (E(2)), progesterone and testosterone] for 2 h. Dexras1 expression was assessed using both reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis. Expression of the gene was only induced in response to glucocorticoid treatment (Dex or Cort). The 6 steroids were also injected into mice, pituitaries were harvested and total RNA was obtained for RT-PCR analysis. Surprisingly, treatment with E(2), not only injection of glucocorticoids, induced Dexras1 expression in mouse pituitary. Other steroids were without effect. The results suggest that in AtT-20 corticotropes, Dexras1 expression is only induced by glucocorticoid-type steroids. In pituitary glands of mice, the gene's expression is also responsive to E(2). We conclude that either Dexras1 expression in corticotropes from normal mice is regulated differently from that in AtT-20 cells, or that Dexras1 is also expressed in other pituitary cells than corticotropes.

Healthcare for lesbians: attitudes and experiences.

This article reviews the literature relating to healthcare provision for lesbians. The author discusses the attitudes of healthcare providers to this client group and the experiences of these women in a prejudiced healthcare system.

A practical technique for disinfecting electrical stimulation apparatuses used in wound treatment.

BACKGROUND AND PURPOSE: Electrical stimulation (ES) is used in wound management. Concerns, however, have been raised about the possible role ES might play in promoting or exacerbating wound infections, especially bacterial infections. The purpose of this study was to address these concerns by evaluating the efficacy of a method for disinfecting ES electrodes used in wound treatment. METHODS: Samples were taken from each wound treated in this study prior to and after ES and from sponges used with the ES electrodes prior to treatment, after treatment, and after 20 minutes of chemical disinfection. The presence and types of bacteria recovered were determined through standard microbiological techniques. RESULTS: In this study of 25 patient samples, large numbers (ie, thousands) of bacteria were recovered from the pretreatment and posttreatment wound samples and from the posttreatment sponges. Following disinfection, however, bacteria were absent from the sponges in 23 of the 25 patient samples. In the remaining 2 samples, no more than two bacterial colonies were recovered after disinfection. CONCLUSION AND DISCUSSION: Immersion of the electrodes and sponges for 20 minutes in the disinfectant resulted in reduction of bacteria to safe, noninfective levels. Disinfection either completely eliminated all bacteria from the sponges (in 92% of the samples) or eliminated nearly all bacteria (in the remaining 8% of the samples), compared with predisinfection samples, which contained very large numbers of bacteria. These results demonstrate that the disinfection method used in this study is efficacious, and it appears to be cost-effective, practical, and safe for clinical use.

The sexual needs of elderly people: addressing the issue.

The subject of sexuality and elderly people has until recently, largely been ignored by nurses. This article stresses the importance of acknowledging that sexual activity and interest changes with ageing and that to deny that it exists is detrimental to the holistic care nurses should aim to provide.

Importance of communication training for psychiatric residents and mental health trainees.

Through the illustration of a clinical vignette and excerpts from interviews with trainees, this paper suggests that communication and communication disorders are essential issues in child psychiatry training. The vignette shows how communication issues pervade a multidisciplinary psychoeducational day treatment program. The importance of communication in the clinical experience and its impact on the professional preparation of psychiatry residents and mental health trainees are examined, and conclusions and recommendations for the goals of a training program in child psychiatry are presented which expand upon those findings.

Transfacial transpterygomaxillary access to foramen rotundum, sphenopalatine ganglion, and the maxillary nerve in the management of atypical facial pain.

Post-traumatic atypical facial pain syndromes are refractory to medical therapy and thus challenging to treat. Some of these patients have a facial causalgia syndrome that may include autonomic as well as trigeminal fibers as the anatomic mediators. A procedure that may be of both diagnostic and therapeutic benefit is a nerve block in the region of the foramen rotundum. This allows access to both the maxillary nerve and the sphenopalatine ganglion. A simple technique developed to perform this procedure is described, and the results in a series of six patients are presented.

Optimization of submillimeter-resolution MR imaging methods for the inner ear.

Submillimeter-resolution magnetic resonance (MR) imaging of the inner ear is valuable for diagnosis and treatment planning. Its main advantage for investigations of underlying disease is that it can directly depict the fluid spaces of the membranous labyrinth rather than define only the bony canal, as does computed tomography. A systematic evaluation of factors influencing high-resolution three-dimensional (3D) gradient-echo imaging of the inner ear with a standard clinical MR system is presented. This includes the evaluation of various radio-frequency coils, the design of steady-state pulse sequences, and the optimization of acquisition parameters. A quantitative analysis was facilitated by computer simulations and image processing. The highest signal-to-noise ratio for the membranous labyrinth was obtained with a single 3-inch (7.6-cm) receiver coil and a 3D GRASS (gradient-recalled acquisition in the steady state) sequence with the minimal achievable TR msec/TE msec of 25/7 and a 40 degrees--60 degrees flip angle, which yielded acceptable images with minimal voxel volumes of 0.1 mm3 in 14 minutes.

The extracranial facial nerve: high resolution three-dimensional Fourier transform MR imaging.

PURPOSE: To investigate the use of high-resolution three-dimensional Fourier transform gradient-echo MR in evaluation of the extracranial facial nerve. METHODS: Nine normal subjects and one clinical patient were scanned. Several imaging parameters, including echo time, field-of-view, and the use of Gd-DTPA, were manipulated to determine the optimal technique. Adequate results were obtained in less than 7 minutes acquisition time using a T1-weighted (50/5.3) gradient-echo technique, with a 30 degree flip angle, a 12-cm field of view, 128 x 256 matrix, and 28 or 60 1.0-mm-thick contiguous sections. RESULTS: Gd-DTPA administration was not found useful in identifying the normal extracranial facial nerve. The proximal extracranial facial nerve was seen as a branching low signal intensity tubular structure on 10 to 20 contiguous images in all five volunteers in which this optimal technique was employed. Postprocessing of the images to produce curved oblique planar reconstructed images was useful to display long segments of the facial nerve on a single image. CONCLUSION: Our experience with high resolution three-dimensional Fourier transform MR imaging indicates that it can consistently demonstrate the intraparotid facial nerve on multiple contiguous images.

Developmental brain anomalies in schizophrenia and bipolar disorder: a controlled MRI study.

Many of the structural brain abnormalities found in schizophrenia (SC) and bipolar disorder (BD) over the past decade are believed to represent impaired neurodevelopmental processes. The authors hypothesized that incidental developmental anomalies would be more frequently present in the brains of subjects with SC and BD compared with healthy control subjects. The authors systematically assessed the MRI scans of 167 subjects (SC = 67, BD/schizoaffective = 63, healthy control subjects = 37) for the presence of 23 developmental anomalies involving cortical and subcortical structures. No excess neurodevelopmental anomalies were found in the schizophrenic or bipolar/schizoaffective groups. These findings do not support the hypothesis that SC and BD are associated with an excess of gross neurodevelopmental brain anomalies.

Peroxisomal beta-oxidation of branched chain fatty acids in human skin fibroblasts.

Human skin fibroblasts in suspension are able to degrade [1-14C]-labeled alpha- and gamma-methyl branched chain fatty acids such as pristanic and homophytanic acid. Pristanic acid was converted to propionyl-CoA, whereas homophytanic acid was beta-oxidized to acetyl-CoA. Incubation of skin fibroblasts with [1-14C]-labeled fatty acids for longer periods produced radiolabeled carbon dioxide, presumably by further degradation of acetyl-CoA or propionyl-CoA generated by beta-oxidation. Under the same conditions similar products were produced from very long chain fatty acids, such as lignoceric acid. Inclusion of digitonin (> 10 micrograms/ml) in the incubations strongly inhibited carbon dioxide production but stimulated acetyl-CoA or propionyl-CoA production from fatty acids. ATP, Mg2+, coenzyme A, NAD+ and L-carnitine stimulated acetyl-CoA or propionyl-CoA production from [1-14C]-labeled fatty acids in skin fibroblast suspensions. Branched chain fatty acid beta-oxidation was reduced in peroxisome-deficient cells (Zellweger syndrome and infantile Refsum's disease) but they were beta-oxidized normally in cells from patients with X-linked adrenoleukodystrophy (ALD). Under the same conditions, lignoceric acid beta-oxidation was impaired in the above three peroxisomal disease states. These results provide evidence that branched chain fatty acid, as well as very long chain fatty acid, beta-oxidation occurs only in peroxisomes. As the defect in X-linked ALD is in a peroxisomal fatty acyl-CoA synthetase, which is believed to be specific for very long chain fatty acids, we postulate that different synthetases are involved in the activation of branched chain and very long chain fatty acids in peroxisomes.

Is plasma serine a marker for psychosis?

There is some disagreement in the literature concerning the use of plasma serine concentrations as a biological marker for psychoses including schizophrenia. The groups studying this phenomenon have used different methodologies, including gas chromatography and classical amino acid analysis. In the present study, using high pressure liquid chromatography to analyze plasma amino acids from schizophrenics and controls, we found no difference in plasma serine concentrations. None of the plasma amino acid concentrations that were measured differed significantly between schizophrenics and controls but the basic amino acids tended toward higher concentrations in schizophrenics.

Fulminant hepatic failure related to omeprazole.

Omeprazole is a new hydrogen-potassium adenosine triphosphatase antagonist with indications for severe reflux esophagitis and Zollinger-Ellison syndrome. Side effects involving the liver have consisted of minimal elevations of hepatocellular enzymes with higher dosages. We present what we believe is the first reported case of fulminant hepatic failure related to omeprazole.