Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length ...(TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.
The adaptive significance of acute pain (to withdraw from tissue-damaging or potentially tissue-damaging external stimuli, and to enhance the salience of the stimulus resulting in escape and ...avoidance learning) and tonic pain (to enforce recuperation by punishing movement) are well-accepted 1. Pain researchers, however, generally assert that chronic pain has no adaptive significance, representing instead a pathophysiological state. This belief was recently challenged by the observation 2 that nociceptive sensitization caused by a chronic pain-producing injury reduced predation risk in squid (Doryteuthis pealeii). In that study, injury to an arm (removal of the tip with a scalpel) 6 hours prior led to increased targeting by black sea bass, resulting in decreased survival of the squid in a 30-minute trial featuring free interaction between predator and prey. The surprising finding was that anesthesia during surgery, preventing the chronic nociceptor sensitization associated with such injuries, led to even lower probability of survival. That is, the likely presence of pain increased apparent fitness, and the authors concluded that the chronic pain state and its associated nociceptive sensitization represented an adaptive function. Pain-induced defensive behaviors affecting fitness have also been reported in crustaceans (Gammarus fossarum) 3. It is, however, currently unknown whether this may also be true in any other species, including in Mammalia.
Studies in invertebrates suggest that the adaptive value of chronic pain may lie in producing hypervigilance to predation. Lister et al. test the hypothesis that chronic pain may produce hypervigilance in mice. Using an octagonal maze, they show that mouse avoidance of fox urine is increased after experimental nerve injury producing chronic pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is strong evidence indicating that the social environment triggers changes to the psychological stress response and glucocorticoid receptor function. Considerable literature links the ...subsequent changes in stress resiliency to physical health. Here, converging evidence for the modulatory role of chronic psychological stress in the recovery process following spinal cord injury (SCI) is presented. Despite the considerable advances in SCI research, we are still unable to identify the causes of variability in patients' recovery following injury. We propose that individuals' past and present life experiences (in the form of stress exposure) may significantly modulate patients' outcome post-SCI. We propose a theoretical model to explain the negative impact of chronic psychological stress on physical and psychological recovery. The stress experienced in life prior to SCI and also as a result of the traumatic injury, could compromise glucocorticoid receptor sensitivity and function, and contribute to high levels of inflammation and apoptosis post-SCI, decreasing the tissue remaining at the injury site and undermining recovery of function. Both stress-induced glucocorticoid resistance and stress-induced epigenetic changes to the glucocorticoid receptor can modulate the nuclear factor-kappa B regulated inflammatory pathways and the Bcl-2 regulated apoptosis pathways. This model not only contributes to the theoretical understanding of the recovery process following injury, but also provides concrete testable hypotheses for future studies.
Mental health is neglected in most parts of the world. For the Indigenous Peoples of Latin America, the plight is even more severe as there are no specific mental health services designed for them ...altogether. Given the high importance of mental health for general health, the status quo is unacceptable. Lack of research on the subject of Indigenous Peoples' mental health means that statistics are virtually unavailable. To illustrate their mental health status, one can nonetheless point to the high rates of poverty and extreme poverty in their communities, overcrowded housing, illiteracy, and lack of basic sanitary services such as water, electricity and sewage. At the dawn of the XXI century, they remain poor, powerless, and voiceless. They remain severely excluded from mainstream society despite being the first inhabitants of this continent and being an estimated of 48 million people. This paper comments, specifically, on the limited impact of the Pan American Health Organization's mental health initiative on the Indigenous Peoples of Latin America.
The Pan American Health Organization's sponsored workshop "Programas y Servicios de Salud Mental en Communidades Indígenas" Mental Health Programs and Services for the Indigenous Communities in the city of Santa Cruz, Bolivia on July16 - 18, 1998, appeared promising. However, eleven years later, no specific mental health program has been designed nor developed for the Indigenous Peoples in Latin America. This paper makes four specific recommendations for improvements in the approach of the Pan American Health Organization: (1) focus activities on what can be done; (2) build partnerships with the Indigenous Peoples; (3) consider traditional healers as essential partners in any mental health effort; and (4) conduct basic research on the mental health status of the Indigenous Peoples prior to the programming of any mental health service.
The persistent neglect of the Indigenous Peoples' mental health in Latin America raises serious concerns of moral and human rights violations. Since the Pan American Health Organization' Health of the Indigenous Peoples Initiative 16 years ago, no mental health service designed for them has yet been created.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Highlights • Three groups emerged post SCI: (1) depression, (2) depression/anxiety, (3) neither. • Inflammation post SCI was associated with decreased psychological well-being. • Depression-like ...profiles were associated with peripheral inflammation. • Anxiety/depression-like profiles were associated with brain/spinal inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
There is an estimated 30 million indigenous peoples in South America. Most of them live in the Andes. Regional states and governments neglect their health care needs and exclude them from the ...conventional Western health services in general and mental health care in particular. This review first describes this population's current situation of social exclusion, poverty and poor health. The problem of mental health care inequities in the region is illustrated through the case of the Quichua people. Indeed, for the population of over 5 million Quichua people in Ecuador, there are no psychiatric services. There are no culturally sensitive services offered in the Quichua language. The doctor–Quichua patient communication is poor and interactions are loaded with prejudice. The review provides a rationale for the Quichuas' reluctance to seek medical doctors in Ecuador. Finally, traditional healers' contribution to the mental health care of indigenous peoples is stressed, as well as their preference for a form of medical pluralism, mainly combining both traditional Quichua medicine and Western medicine. Woeful inequalities and inaccessibility to psychological and biomedical psychiatric care still widely affect the children of the sun in the Pacific Rim.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite an increased incidence of depression in patients after spinal cord injury (SCI), there is no animal model of depression after SCI. To address this, we used a battery of established tests to ...assess depression after a rodent contusion injury. Subjects were acclimated to the tasks, and baseline scores were collected before SCI. Testing was conducted on days 9-10 (acute) and 19-20 (chronic) postinjury. To categorize depression, subjects' scores on each behavioral measure were averaged across the acute and chronic stages of injury and subjected to a principal component analysis. This analysis revealed a two-component structure, which explained 72.2% of between-subjects variance. The data were then analyzed with a hierarchical cluster analysis, identifying two clusters that differed significantly on the sucrose preference, open field, social exploration, and burrowing tasks. One cluster (9 of 26 subjects) displayed characteristics of depression. Using these data, a discriminant function analysis was conducted to derive an equation that could classify subjects as "depressed" on days 9-10. The discriminant function was used in a second experiment examining whether the depression-like symptoms could be reversed with the antidepressant, fluoxetine. Fluoxetine significantly decreased immobility in the forced swim test (FST) in depressed subjects identified with the equation. Subjects that were depressed and treated with saline displayed significantly increased immobility on the FST, relative to not depressed, saline-treated controls. These initial experiments validate our tests of depression, generating a powerful model system for further understanding the relationships between molecular changes induced by SCI and the development of depression.
Mice with experimental nerve damage can display long-lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length ...(TL) reduction and p53-mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53-positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male-specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male-specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53-specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male-specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.
Gaming environments have been used to teach mathematical topics such as addition and division in a fun manner**http://www.thefreedictionary.com/fun.. However, when it comes to college level ...mathematical concepts such as the use of the quadratic formula, there are very few software that explain these concepts in a fun way. In this paper, we present a first step towards using video game elements and Artificial Intelligence Tutoring system techniques to teach mathematical concepts such as factoring and the quadratic formula. These concepts are explained in a way that helps learners make a connection between the mathematical concepts and their real life experience. These methods of learning are supported by several studies (Bonwell & Eison, 1991; Donovan & Bransford, 2004; Scarlatos, 2006). We use gamification techniques during the training and test phases to help students learn the mathematical concepts. We then compare the performance of students who used our system (MathDungeon) with that of students who used the most popular math tutoring programs used in US colleges: Assessment and Learning, K-12, Higher Education (ALEKS). The number of students who used MathDungeon and scored above the median score on the test of math performance was greater than the number of students who used ALEKS and scored higher than the median score.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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