Suicide in Cancer Patients in California, 1997–2006

The objective of this study was to measure suicide risk in cancer patients and compare it with the general population. Suicide rates were based on 1,168 suicides in 1,123,528 cancer patients in California from 1997–2006 and were studied by race/ethnicity, sex, site, stage, and marital status. Suicide in cancer patients is 2.3 times the general population with 81% in the non-Hispanic Whites, and half within the first 2 years post diagnosis. In men, it rapidly increases by age to a high plateau in the early forties. Metastatic cancers and those of the prostate, lung and bronchus, pancreas, stomach, esophagus, and oral cavity in men and breast in women were associated with significantly higher risk. Cancer patients are at higher risk of suicide and should be specifically targeted for preventive efforts post diagnosis.     

Trends in Self-Harm in Kuala Lumpur, 2005–2011

Acts of self-harm are not routinely tracked in Malaysia. The present study investigates the prevalence of self-harm in Kuala Lumpur, Malaysia, over a 7-year period. The aims were to: (a) assess the prevalence of self-harm; (b) examine any changes over a period of 7 years, and (c) identify correlates of methods of self-harm. Data were extracted from the hospital records of Kuala Lumpur Hospital to review trends in self-harm between 2005 and 2011. There were 918 episodes of self-harm across the 7-year period, with a significant peak in 2007–2009. The average rate of self-harm (7.7 per 100,000 population per year) was similar or lower than the rate of suicide (6–8 or 8–13 per 100,000) suggesting that genuine cases of self-harm are often attributed to other causes. Nevertheless, over-representation of young people, women and Indians suggest areas in which resources to prevent self-harm might usefully be targeted. Estimating rates of self-harm are fraught with problems and further research is needed to understand the economic and cultural barriers around seeking treatment for self-harm, reporting self-harm and classifying self-harm.     

Iron,Dopamine, and α-Synuclein Interactions in at-Risk Dopaminergic Neurons in Parkinson's Disease

正Parkinson’s disease(PD)is recognized as the second most common neurodegenerative disorder after Alzheimer disease.Although a fascinating 200-year journey of research has revealed the multifaceted nature of PD[1,2],its fundamental features are the loss of dopaminergic neurons in the substantia nigra pars compacta(SNpc)and depletion of dopamine(DA)in the striatum.Iron accumulates in normal brains with aging.Such     

Assessment of additional endpoints for trials in acute stroke - what, when, where, in who?

Functional outcome in acute stroke trials among others is usually measured on the modified Rankin Scale. However, new onset of depression, cognitive decline, and communication deficits alone or in combination affect more than 25% of patients. This report summarizes the findings and conclusions of a workshop by the European Stroke Organization held in February 2011 We propose that assessment of mood disorders, cognitive impairment/dementia, language or communication dysfunction, and quality of life should supplement outcome measures after acute stroke.     

Gangliosides in nervous system development,regeneration, and pathologies

Gangliosides, sialic acid-containing sphingolipids, are major constituents of neuronal membranes. According to the number of sialic acids and the structure of the oligosaccharide chain, gangliosides can be classified as simple or complex and grouped in different ganglio-series. Hundreds of gangliosides have been identified in vertebrate cells, with different expression patterns during development and related to several physiological processes, especially in the nervous system. While GD3 and its ...     

Neuroinflammation in the peripheral nerve: Cause,modulator, or bystander in peripheral neuropathies?

The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under‐researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets. GLIA 2016;64:475–486     

Trends in Attempted Suicide in Adolescents and Young Adults in Gent, 1986–1995

This paper describes gender-specific trends in the occurrence and methods of attempted suicide in adolescents and young adults between 1986 and 1995 in Gent. The overall pattern emerging from this study is that following a decrease in the rates of attempted suicide in the second half of the 1980s, rates have clearly increased in the 1990s, especially among adolescent males. A slight predominance of female attempters was found in the 15 to 19 age group while among young adults the female to male ratio was approximately 1.0. Deliberate self-poisoning was involved in the vast majority of attempts, although among young adults significantly more males than females used deliberate self-injury to attempt suicide. In view of increasing rates of suicide among young people in many countries and of the association between attempted suicide and suicide, further study of trends and characteristics of attempted suicide among young people is warranted.     

Stressed-out,or in (utero)?

The molecular and cellular mechanisms by which plasticity is induced in the mature CNS (and, specifically, in the hippocampus) by environmental input are progressively being elucidated. However, the mechanisms - and even the existence - of functional and structural effects of environmental input (and, particularly, stress) early in life are incompletely understood. Here, we discuss recent evidence that stressful stimuli have a significant impact on neonatal (rat) and prenatal (human) hippocampal function and integrity. Stressful signals provoke expression and release of neuromodulators, including the peptide corticotropin-releasing hormone (CRH), leading to activation of CRH receptors on principal hippocampal neurons. Although physiological activation of these receptors promotes synaptic efficacy, pathological levels of CRH at hippocampal synapses contribute to neuronal death. Thus, early-life stress could constitute a 'double-edged sword': mild stress might promote hippocampal-dependent cognitive function, whereas severe stress might impair neuronal function and survival, both immediately and in the long-term. Importantly, these CRH-mediated processes could be targets of preventive and interventional strategies.     

Mini-Mental State Examination performance in frail, pre-frail, and non-frail community dwelling older adults in Ermelino Matarazzo, São Paulo, Brazil

ABSTRACT Background: Frailty in older adults is a multifactorial syndrome defined by low metabolic reserve, less resistance to stressors, and difficulty in maintaining organic homeostasis due to cumulative decline of multiple physiological systems. The relationship between frailty and cognition remains unclear and studies about Mini-Mental State Examination (MMSE) performance and frailty are scarce. The objective was to examine the association between frailty and cognitive functioning as assessed by the MMSE and its subdomains. Methods: A cross-sectional population-based study (FIBRA) was carried out in Ermelino Matarazzo, a poor subdistrict of the city of S?o Paulo, Brazil. Participants were 384 community dwelling older adults, 65 years and older who completed the MMSE and a protocol to assess frailty criteria as described in the Cardiovascular Health Study (CHS). Results: Frail older adults had significantly worse performance on the MMSE (p < 0.001 for total score). Linear regression analyses showed that the MMSE total score was influenced by age (p < 0.001), education (p < 0.001), family income (p < 0.001), and frailty status (p < 0.036). Being frail was associated more significantly with worse scores in Time Orientation (p < 0.004) and Immediate Memory (p < 0.001). Conclusions: Our data suggest that being frail is associated with worse cognitive performance, as assessed by the MMSE. It is recommended that the assessment of frail older adults should include the investigation of their cognitive status.     

Suicide mortality in second-generation migrants,Australia, 2001–2008

Purpose

Generally, due to limited availability of official statistics on the topic, little is known about suicide mortality in second-generation migrants. A recent study from Sweden showed that these people could be at a high suicide risk. In a generalised phenomenon, this aspect would represent an important issue in suicide prevention. This paper aims to report the profile of second-generation migrants who died by suicide and the suicide risk differentials of second-generation migrants with other Australians.

Methods

Official suicide data from 2001 to 2008 were linked with State/Territory registries to collect information about the birthplace of the deceased’s parents to differentiate migration status (first, second or third-plus generation). The profile and suicide risk of second-generation migrants were compared with other generations by logistic and Poisson regression.

Results

Suicide in second-generation migrants accounted for 811 cases (14.6 %). These tended to be represented by younger subjects, more often never married, as compared to the other cases. Second-generation males aged 25–39 years tended to have a higher suicide risk than first-generation migrants, but the risk was lower when compared with the third-plus generation. Second-generation migrants aged 60+ tended to have a lower suicide risk than first-generation migrants.

Conclusion

In Australia, second-generation migrants are not at a higher suicide risk as compared to first-generation migrants or locals (third-plus-generation). In males aged 25–39, a lower suicide risk was found in second-generations as compared to Australian-born third generation, which may be explained by their more advantageous socioeconomic status and the flexibility and resources rendered by having grown up in a bicultural environment. The higher suicide rates found amongst older first-generation migrants require further examination.     

Management,administration, leadership: What's in a name?

In summary, I have argued that while research and publications in the field have tended to deal with management and administration--examining issues as if they were predominately structural, organizational and authority-oriented, the area that cries out for further attention is that of leadership. For, while managers can do, and administrators oversee--it is only leaders who can move us ahead. The field is in for a turbulent, difficult, but I suspect, exhilarating next new years. Our work is truly very different from that in most businesses--and while good "managers" may make money for business enterprises, for us, leadership is the critical ingredient. (I'm not even so sure that despite some experts disclaimer of the lack of importance of leadership in business, a closer look would not inevitably reveal a Kroc, Hewlett, DiLorenzo or Iacocca behind every successful corporate initiative anyway). With that in mind, we should increase both our study of the development of leaders and our attention to their development. To do less is to increase our difficulties, court further new disasters, and have even less control over our work and our future. We deserve and can achieve a better destiny.     

The neurotoxin, MPP+, induces hyperphosphorylation ofTau, in the presence of α-Synuclein, in SH-SY5Y neuroblastoma cells

Alzheimer's disease (AD) is characterized, in part, by intracellular neurofibrillary tangles composed of hyperphosphorylated filamentous aggregates of the microtubule-associated protein, Tau. Such hyperphosphorylated Tau is also found in Lewy bodies (LBs), and cytoplasmic inclusion bodies in certain forms of Parkinson's disease (PD). Further, LBs also contain aggregates of alpha-synuclein (alpha-Syn), also a microtubule-associated protein, which has been linked to the genesis of PD. To investigate a specific correlation between Tau phosphorylation and alpha-Syn, we generated a SH-SY5Y cell line that stably expresses human wild type alpha-Syn. Protein expression levels in the stably transfected cell line (SHalpha-Syn) were within the physiological range of alpha-Syn expression found in Substantia nigra. We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion) cell model of parkinsonism, a time- and dose-dependent increase in the hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau), concomitant with increased accumulation of alpha-Syn, upon treatment of cells with the neurotoxin. This increase in p-Tau was strictly dependent on the presence of alphaSyn, since in transfected cells not expressing any alpha-Syn, MPP+ failed to induce an increase in PHF-1-reactive Tau. The production of p-Tau caused increased cytotoxicity as indexed by reduced cell viability. Moreover, in the absence of alpha-Syn, the cells were more resistant to MPP+ -induced cell death. The increased levels of both p-Tau and alpha-Syn led to diminished levels of these proteins associated with the cytoskeleton, which was accompanied by enhanced presence of the proteins in the cytoskeletal-free fractions. These data indicate that alpha-Syn and p-Tau modulate the pathogenicity of one another, suggesting a novel convergent mechanism of neurodegeneration.     

Using advances in neuroimaging to detect,understand, and monitor disease progression in Huntington’s disease

Trangenic mouse models and other screens are being used to identify potential therapeutic agents for use in clinical trials in Huntington’s disease (HD). The development of surrogate markers that can be used in clinical therapeutics is an active area of research. Because HD is relatively uncommon and only a portion of available subjects meet inclusion and exclusion criteria, therapeutic trials are limited by the availability of potential subjects as well as the relative insensitivity of the clinical measures used. Neuroimaging methods offer the potential to provide noninvasive, reproducible, and objective methods not only to better understand the disease process but also to follow in clinical studies to determine if a drug is effective in slowing down disease progression or perhaps even in delaying onset. Following is a review of the literature, which highlights the studies that have been published to date.     

The role of the estrogen receptor α in the medial preoptic area in sexual incentive motivation, proceptivity and receptivity, anxiety, and wheel running in female rats

Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor α (ERα) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they were tested in the light/dark choice procedure, and after another 2 weeks they were subjected to a test in a brightly lit open field. Finally, the females were given free access to a running wheel for 88h. The females were treated with estradiol benzoate (EB), 18 or 1.5μg/kg, in randomized order 52h before each test except the running wheel. In that experiment, they were given EB 48h after introduction into the wheel cage. They were given progesterone, 1mg/rat, about 4h before all tests, except the running wheel. The shRNA reduced the number of ERα with 83%. Females with few ERα in the MPOA showed increased lordosis quotient after the 1.5μg/kg dose of EB. There was no effect on proceptive behaviors or on rejections. When given the 18μg/kg EB dose, there was no difference between females with few preoptic ERα and controls. In the test for sexual incentive motivation, females with few preoptic ERα approached the castrated male incentive more than controls, regardless of EB dose. They also moved a shorter distance. In the light/dark choice test as well as in the open field, females with few ERα in the MPOA showed signs of reduced fear/anxiety, since they spent more time in the light part of the dark/light box and in the center of the open field. Finally, the data from the running wheel showed that females with few preoptic ERα failed to show enhanced activity after treatment with EB. These data show that the preoptic ERα inhibits lordosis in females with an intermediate level of receptivity while it fails to do so in fully receptive females. The ERα in the MPOA seems to be necessary for selective approach to a sexual incentive. Finally, activation of this receptor appears to have anxiogenic effects in the procedures employed here. A hypothesis for how all these actions of the preoptic ERα contributes to efficient reproductive behavior is outlined.     

Amyotrophic lateral sclerosis in Sardinia, insular Italy, 1995–2009

Recent genetic studies suggest a Sardinian type of amyotrophic lateral sclerosis (ALS). Thus, ALS incidence, prevalence and survival were investigated in a large population of Sardinians aimed to disclose population-specific patterns and their temporal changes. This is a population-based incidence and prevalence study in northern and central Sardinia, insular Italy (over 700,000 population). Incidence rates were computed for the time interval 1995–2009 and by quinquennia. Prevalence was computed for prevalence days 31 December 2004 and 2009. Onset-based survival for 1995–2009 is also reported. All ALS patients (El Escorial Criteria) in the study area were retrospectively included. The ALS crude incidence from 2005–2009 was 2.5 (95 % CIs: 0.1, 4.9), 3.4 in men and 1.6 in women. Onset occurred most often between the age of 65–74 years in men and 55–64 years in women. The ALS incidence tended to increase over the period 1995–2009. The mean age at onset was 61.7 years with no difference based on gender, varying significantly from 59.9 years in 1995–1999 to 63.9 years in 2005–2009. On December 31, 2009, the ALS crude prevalence was 10.8 per 100,000 (95 % CIs: 8.6, 13.1), 13.8 in men and 8.0 in women, whereas it was 6.3 per 100,000 (95 % CIs: 4.1, 8.6) on December 31, 2004 (M:F ratio of 0.95). Mean survival from onset was 37.0 months, with no difference based on gender, and a tendency to decrease during the period 1995–2009, in relation to type and age of onset. The population-based incidence and prevalence data of ALS in Sardinians indicate an increase of the disease occurrence over the past 40 years, providing support for a population-specific variant of ALS in Sardinia.     

Apolipoprotein E,amyloid-beta,and neuroinflammation in Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by the accumulation and deposition of amyloid-beta (Aβ) peptides in the brain. Neuroinflammation occurs in the AD brain and plays a critical role in the neurodegenerative pathology. Particularly, Aβ evokes an inflammatory response that leads to synaptic dysfunction, neuronal death, and neurodegeneration. Apolipoprotein E (ApoE) proteins are involved in cholesterol transport, Aβ binding and clearance, and synaptic functions in the brain. The ApoE4 isoform is a key risk factor for AD, while the ApoE2 isoform has a neuroprotective effect. However, studies have reached different conclusions about the roles of the isoforms; some show that both ApoE3 and ApoE4 have anti-inflammatory effects, while others show that ApoE4 causes a predisposition to inflammation or promotes an inflammatory response following lipopolysaccharide treatment. These discrepancies may result from the differences in models, cell types, experimental conditions, and inflammatory stimuli used. Further, little was known about the role of ApoE isoforms in the Aβ-induced inflammatory response and in the neuroinflammation of AD. Our recent work showed that ApoE isoforms differentially regulate and modify the Aβ-induced inflammatory response in neural cells, with ApoE2 suppressing and ApoE4 promoting the response. In this article, we review the roles, mechanisms, and interrelations among Aβ, ApoE, and neuroinflammation in AD.